Heterocyclic compounds

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

or

or to their pharmaceutically acceptable salts, where ring A, R2, R3, R4 and X are as defined in the description. The disclosed compounds are useful as 11βHSD1 inhibitor. The invention also relates to a pharmaceutical composition, an agent for treating or preventing pathology related to glucocorticoids, a 11βHSD1 inhibitor containing the disclosed compound or its pharmaceutically acceptable salt, and use of the disclosed compounds.

EFFECT: compounds are highly effective.

40 cl, 48 tbl, 191 ex

 

The scope of the invention

The present invention relates to heterocyclic compounds, in particular heterocyclic compounds useful as HSD1 inhibitors.

The level of technology

As is usually noticed when Cushing's syndrome, excessive systemic glucocorticoids cause metabolic abnormalities, such as the accumulation of visceral fat, the characteristic changes in the distribution of adipose tissue in the body, insulin resistance, diabetes, hyperlipidemia, high blood pressure, etc.

For more than half a century it is known that glucocorticoids play a key role in diabetes and, for example, removal of the pituitary or adrenal glands in animals with diabetes leads to a weakening of the most severe forms of diabetes and also decrease the concentration of glucose in the blood (see Long, .D. and F.D.W. Leukins (1936), J. Exp. Med. 63: 465-490 and Houssay, B.A. (1942), Endocrinology, 30: 884-892).

It is known that glucocorticoids (1) are required for the differentiation of adipocytes and inhibition, as is typical hormone-antagonist of insulin caused by insulin of glucose metabolism and fat at different stages, (2) lead to an increase in blood pressure after induction of the synthesis of angiotensinogen, which is the substrate of renin, increased expression of angiotensin II receptors and the like, (3) cause the guy is anorexia and obesity, being a powerful antagonist Latino etc. (seeRinshoivol. 30 no 9, 2004; 1782-1787).

In addition, pay attention to the fact that the action pathologically activated glucocorticoids on adipose tissue are involved in the pathogenesis of the metabolic syndrome, which combines many metabolic diseases such as diabetes hyperlipidemia, hypertension, fatty liver infiltration, etc. in one individual (see Moller DE. New drug targets for 2 diabetes and the metabolic syndrome, Nature 2001; 414: 821-7).

These facts suggest that the reduction effect of glucocorticoids are useful for treatment or prevention of metabolic diseases such as diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, fatty infiltration of the liver, etc. and metabolic syndrome, combining metabolic diseases in one individual, and moreover, fatal vascular events, representing myocardial infarction and stroke associated with these diseases.

Active glucocorticoid (cortisol in humans and corticosterone in rodents) demonstrating glucocorticoid action is synthesized from cortisone 11-dehydrocorticosterone, each of which is inactive 11-citometria, through the action of converting enzyme 11β-hydroxysteroiddehydrogenase type 1 (11βHSD1), not that the are in the adrenal glands, but also in various tissues and cells (see Agurwal et al., J. Biol. Chem 264, 18939-46, 1989). Because knockout on mouse 11βHSD1 can't convert entered the inactive glucocorticoid in active form, as shown, this enzyme is only active enzyme that converts glucocorticoids in vivo (see Kotelevtsev, Y et al.: Proc. Natl. Acad. Sci. USA, 94: 14924, 1997). There is a message about the case of pituitary Cushing's disease with hyperglyceridemia, in which manifestations of Cushing's syndrome was not observed due to the significantly reduced by coincidence activity of 11βHSD1 (see Tomlinson, JW et al.: J. Clin. Endocrinol. Metab., 87: 57, 2002).

These results demonstrate that regulation of the activity of 11βHSD1 is essential for the action of glucocorticoids. In other words, regulation of the activity of 11βHSD1 is useful for the treatment and prevention of metabolic diseases such as diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, fatty infiltration of the liver, etc. and metabolic syndrome with a combination of metabolic diseases in one individual, and moreover, fatal vascular events, representing myocardial infarction and stroke associated with these diseases.

It was found that transgenic mice that demonstrate overexpression of 11βHSD1, have the same level of the, as in subjects with obesity, only in adipose tissue, and have significant symptoms of the metabolic syndrome, such as obesity visceral type, insulinorezistentne diabetes, hyperlipidemia, hypertension, fatty liver infiltration, etc. (see Masuzaki, H et al.: Science 2001; 294: 2166-70 and Masuzaki H et al.: J. Clin. Invest 2003; 112: 83-90). In addition, transgenic mice, have liver-specific overexpression of 11βHSD1, do not exhibit the phenotype of obesity visceral type, but demonstrate insulin resistance and abnormalities in the form of hypertension, fatty infiltration of the liver, etc. (see Janice M. Paterson et al.: PNAS 2004; 101: 7088-7093). On the contrary, knock-out by 11βHSD1 mice show resistance to induction of hepatic enzymes of gluconeogenesis (PEPCK, G6-phosphatase etc), due to the impact of stress or exposure to a diet high in fat, and demonstrate a distinct resistance to the development of diabetes (see Kotelevtsev, Y et al.: Proc. Natl. Acad. Sci. USA, 94: 14924, 1997).

Moreover, knock-out by 11βHSD1 mice demonstrate decreased levels of triglycerides in the blood and elevated levels of HDL-cholesterol in the blood, whereas expression of the molecular groups associated with the catabolism of fat, and coordinating the transcription factor PPARα increased significantly. It is shown that knockout on mouse 11βHSD1 demonstrate a distinct weakening of the accumulation of visceral adipose TC is neither and development of metabolic abnormalities, caused by exposure to a diet high in fat (see Morton NM et al. J. Biol. Chem. 2001; 44: 41293-301).

In fact, since insulin sensitivity is increased when the deficit 11βHSD1, it is expected that the inhibition of this enzyme would be useful in the treatment or prophylaxis of non-insulin-dependent diabetes and obesity (see Seckl, JR et al. Eur. J. Biochem. 249: 361, 1997 and Morton NM et al. Diabetes 2004; 53: 931-938).

These findings indicate that the decrease in 11βHSD1 is beneficial for treatment and prevention of metabolic diseases such as diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, fatty infiltration of the liver, etc. and metabolic syndrome with a combination of metabolic diseases in one individual, and moreover, fatal vascular events, representing myocardial infarction and stroke associated with these diseases.

Destruction of the adrenal glands reduces the effect of starvation, which increases food intake and expression of hypothalamic neuropeptide Y. This confirms the role of glucocorticoids in increasing food intake and suggests that inhibition of 11βHSD1 in the brain will increase the uptake and thereby reduce food consumption (see Woods, S.. et al. (1998) Science, 280:1378-1383). This means that the reduction steps 11βHSD1, as expected, the field is but for the treatment or prevention hyperorexia.

Stress and glucocorticoids damage cognitive function (see de Quervain, D.J.-F., B. Roozendaal, J.L. McGaugh (1998), Nature, 394: 787-790). In fact, knockout on mouse 11βHSD1 demonstrate a significant improvement in cognitive dysfunction caused by aging (see Yau J L et al. PNAS 2001; 98: 4716-4721), and the last message indicates that non-specific 11βHSD1 inhibitor karbenoksolon is effective for cognitive dysfunction in the elderly (see Sandeep T et al. PNAS 2004; 101: 6734-6739). In addition, 11βHSD1 regulates the actions of glucocorticoids in the brain, thus contributing to neurotoxicity (see Rajan, V., .R.W. Edwards and J.R. Seckl, J. (1996), Neuroscience, 16:65-70 and Seckl, J.R., Front. (2000), Neuroendocrinol, 18:49-99). Moreover, inhibition of 11βHSD1 in the brain leads to decrease anxiety, which is based on the above known action of glucocorticoids in the brain (see Tronche, F. et al. (1999), Nature Genetics, 23:99-103). Thus, these facts, taken together, suggest that the reduction steps 11βHSD1 in the brain prevents the reactivation of cortisone to cortisol, and is useful in the treatment or prevention of disorders cognitive, neurodegenerative diseases associated with loss of nerve cells, and emotional disorders such as anxiety, depression, mania, etc., schizophrenia, disorders of the nervous functions, including the stimulation of appetite and so on

Well known is n fact, that glucocorticoids suppress the immune system. Therefore, the reduction effect of 11βHSD1, assumed to be useful in the treatment or prevention of disease, showing a weakening of the immune system, such as immunodeficiency, etc. or for the treatment or prevention of diseases requiring activation of the immune system.

Recent data suggests that the levels of receptor targets of glucocorticoids and enzyme 11βHSD1 determine predisposition to glaucoma. (Stokes, J. Et al. (2000), Invest. Ophthalmol. 41: 1629-1638). Therefore, it was proposed to reduce the effect of 11βHSD1 gives an excellent effect for the treatment or prevention of glaucoma.

Although glucocorticoids play an integral role in the growth and function of the skeleton, excess glucocorticoids harmful. Glucocorticoid-induced bone loss is at least partially mediated through inhibition of bone formation, including the suppression of growth of osteoblasts and collagen synthesis (see Kim, S., S.L. Cheng, and G.-S. Kim (1999), J. Endocrinol, 162: 371-379).

Negative effect on the formation of ostional can be blocked with non-specific inhibitors of 11βHSD1 carbenoxolone, which suggests an important role of 11βHSD1 in the action of glucocorticoids (see Bellows, .G., A. Ciaccia, and J.N.M. Heersche, (1998), Bone, 23: 119-125). Therefore, the reduction steps 11βHSD1, assumed to be useful in the treatment or prevention of the OST is of porous.

Accordingly, we can say that a substance having the ability to reduce the effect of 11βHSD1, applicable as drugs for the treatment or prophylaxis of a pathology associated with glucocorticoids, such as

1) metabolic diseases, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, and fatty infiltration of the liver,

2) metabolic syndrome,

3) fatal vascular events, representing myocardial infarction and stroke associated with such diseases,

4) hyperorexia,

5) diseases involving impaired cognitive ability, neurodegenerative diseases, accompanied by loss of nerve cells, and emotional disorders such as anxiety, depression, mania, etc., schizophrenia and disorders of the nervous functions, including stimulation of appetite,

6) of the disease requiring treatment, or prevention of immune enhancing immunity, such as HIV, etc.,

7) glaucoma,

8) osteoporosis

and similar to them.

As heterocyclic compounds, for example, known. For example, WO99/43663 reveals the following heterocyclic compound as compounds with NHE1 inhibitor activity.

As is known, for example, which may be mentioned the following 11βHSD1 inhibitors. WO2004/089470 discloses the following compounds as compounds having inhibitory effect on 11βHSD1:

Disclosure of invention

There is a great need to develop compounds that are suitable as an agent for the prophylaxis or treatment of metabolic diseases such as diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, fatty liver infiltration, etc. etc. that have preferable properties than existing drugs, efficacy, duration of action, specificity, low toxicity, absorption and ingestion, pharmacokinetics, etc.

Thus, an object of the present invention is a compound having inhibitory activity against HSD1, etc. and is applicable as an agent for the prophylaxis or treatment of metabolic diseases such as diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, fatty liver infiltration, etc. etc. that has a different chemical structure than the known compounds including the above-mentioned compounds and their application.

It was first discovered in accordance with the present invention, a heterocyclic compound, mentioned below, has a powerful the inhibitory effect against HSD1, and is suitable as an agent for the prevention and treatment of metabolic diseases such as diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, fatty liver infiltration, etc. etc. studies have Been conducted based on these findings, and based on completed this invention. Accordingly, the present invention specifically relates to the next.

1. The compound represented by the following formula [1']:

where

ring A represents a

(1) nitrogen-containing, saturated, monocyclic, heterocyclic group, or

(2) cycloalkyl group,

the specified ring A is optionally substituted by one or more identical or different substituents R1,

specified substituent R1represents a

1) a hydrogen atom,

2) -CONR5R6where R5and R6are the same or different and each represents

(a) a hydrogen atom,

(b) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6the alkyl group is shown With 1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, and (iii)1-6alkoxygroup)), and

e)1-6alkoxygroup,

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group, and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom, and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different and is Ohm halogen)),

d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group, and

(iv)1-6alkoxygroup),

e)1-6alkoxygroup, and

f) a carboxyl group)

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom, and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or With1-6alkyl group,

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is neobyazatelnostyu one or more identical or different substituents, selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl group, and

c) the carbonyl group),

(g)1-6alkoxygroup, or

(h) nitrogen-containing unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms),

or

(i) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or heterocyclic group, which is a condensed ring of the specified heterocycle and carbon rings (both of these heterocyclic groups are optionally substituted by one or more, same or different substituents selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, and (iii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22 23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R24and R25optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup),

3) -COOR10where R10represents a

(a)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) through d):

(a) a hydroxyl group,

b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic groups is,

c1-6alkoxygroup, and

d) aryl group), or

(b) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl group, and

c) the carbonyl group),

4) -COR11where R11represents a

(a)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to h):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R 30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

e)1-6alkoxygroup,

f) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii)1-6alkoxygroup and (iv)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

g) a carboxyl group, and

(h) alloctype),

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (this is 1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3)1-6alkoxygroup), or

(e) a carboxyl group,

5)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (d):

(a) carboxyl group,

(b) cycloalkyl group (specified cycloalkyl GRU the PA is optionally substituted by one or more, same or different-CO-NR 32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),

6) cycloalkyl group,

7) -S(=O)2-R12 where R12represents a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)or aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

8) -C(=NCN)-R13where R13represents a C1-6alkyl group,

9) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

10) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (f):

(a) carboxyl group,

(b) halogen atom,

(c)1-6alkyl group (specified With1-6alkylen the I group is optionally substituted by one or more identical or different substituents, selected from the following group: a) hydroxyl group, (b) halogen atom, and c1-6alkoxygroup),

(d) -NR38R39where R38and R39are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-NR40R41where R40and R41are the same or different and each represents a hydrogen atom, a C1-6alkyl group or a C1-6alkoxygroup, or R40and R41optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or-S(=O)2-R42where R42represents a C1-6alkyl group, or R38and R39optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more oxoprop),

(e) -CO-NR43R44where R43and R44are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R43and R44optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, is heterocyclics group, and

(f) -COO-C1-6alkyl group), or

11) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) to (h):

(a) carboxyl group,

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup),

(c) cycloalkyl group,

(d) halogen atom,

(e) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R45and R46optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

(f) -COO-C1-6alkyl groups,

(g) ceanography and

(h)1-6alkoxygroup);

-X - represents

(1) -N(R1)-, where R1is as defined above, or

(2) -C(R7R8)-, where R7and R8are the same or different and each represents with the fight

1) a hydrogen atom,

2) -NR16R17where R16and R17are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-NR36R37where R36and R37are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R36and R37optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or R16and R17optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

3) -CONR18R19where R18and R19are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted one or more carboxyl groups) or aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more identical or R is slichnih halogen atoms), or R18and R19optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group, or

5) a carboxyl group;

R2represents a

(1) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following groups: 1)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) a hydroxyl group and (b) (C1-6alkoxygroup), and 2)1-6alkoxygroup); and

R3and R4are the same or different and each represents

(1) a hydrogen atom,

(2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: 1) halogen atom, 2) a hydroxyl group, 3)1-6alkoxygroup and 4) -OCO-C1-6alkyl group),

(3) aryl group (this aryl group is optionally Zam is illuminated by one or more identical or different substituents, selected from the following 1) to 6):

1) halogen atom,

2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) halogen atom, (b) hydroxyl groups, and (c) With1-6alkoxygroup),

3)1-6alkoxygroup (specified With1-6alkoxygroup is optionally substituted by one or more, same or different halogen atoms),

4) carboxyl group,

5) -COO-C1-6alkyl groups and

6) ceanography),

(4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following group: 1) halogen atom and 2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

(5) a hydroxyl group, or

(6)1-6alkoxygroup],

or its salt.

2. The compound represented by the following formula [1]:

where

-X - represents

(1) -N(R1)-, where R1is Wal-Christ.

1) a hydrogen atom,

2) -CONR5R6where R5and R6are the same or different and each represents

(a) a hydrogen atom,

(b) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup) and

e)1-6alkoxygroup),

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, identical or different is cnyh substituents, selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group and

(iv)1-6alkoxygroup),

e)1-6alkoxygroup and

f) a carboxyl group)

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one the or more identical or different substituents, selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or With1-6alkyl group,

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

(g)1-6alkoxygroup or

(h) nitrogen-containing unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms),

or

(i) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or heterocyclic group, which is a condensed ring of the specified heterocycle and carbon rings (both of these heterocyclic groups are optionally substituted by one or more, same or different Zam is stitely, selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R24and R25optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup),

3) -COOR10where R10represents a

(a)1-6alkyl group (specified With1-6an alkyl group is optional is tion substituted by one or more identical or different substituents, selected from the following a) through d):

(a) a hydroxyl group,

b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

c1-6alkoxygroup and

d) aryl group), or

(b) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

4) -COR11where R11represents a

(a)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to h):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl the second group, or-S(=O) 2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

e)1-6alkoxygroup,

f) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii)1-6alkoxygroup and (iv)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

g) a carboxyl group, and

(h) alloctype),

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is obazatelno substituted by one or more identical or different substituents, selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3)1-6alkoxygroup), or

(e) a carboxyl group,

5)1-6alkyl the second group (specified With 1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (d):

(a) carboxyl group,

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

(d) aryl group (this aryl group is not necessarily samewe the Noah one or more identical or different substituents, selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),

6) cycloalkyl group,

7) -S(=O)2-R12where R12represents a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)or aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

8) -C(=NCN)-R13where R13represents a C1-6alkyl group,

9) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

10) aryl group is u (mentioned aryl group is optionally substituted by one or more identical or different substituents, selected from the following (a) to (f):

(a) carboxyl group,

(b) halogen atom,

(c)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) hydroxyl group, (b) halogen atom, and c1-6alkoxygroup),

(d) -NR38R39where R38and R39are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-NR40R41where R40and R41are the same or different and each represents a hydrogen atom, a C1-6alkyl group or a C1-6alkoxygroup, or R40and R41optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or-S(=O)2-R42where R42represents a C1-6alkyl group, or R38and R39optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more oxoprop)),

(e) -CO-NR43R44where R43 and R44are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R43and R44optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

(f) -COO-C1-6alkyl group), or

11) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) to (h):

(a) carboxyl group,

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup),

(c) cycloalkyl group,

(d) halogen atom,

(e) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R45and R46optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

(f) -CO-C 1-6alkyl groups,

(g) ceanography and

(h)1-6alkoxygroup), or

(2) -C(R7R8)-, where R7and R8are the same or different and each represents

1) a hydrogen atom,

2) -NR16R17where R16and R17are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-NR36R37where R36and R37are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R36and R37optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or R16and R17optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

3) -CONR18R19where R18and R19are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted one or more carboxyl groups) or aryl group (this aryl group is optionally substituted by one or more identical or different substituents, selected the data from the following groups: (a) halogen atom and (b) (C 1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or R18and R19optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group, or

5) a carboxyl group;

R2represents a

(1) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following groups: 1)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) a hydroxyl group and (b) (C1-6alkoxygroup), and 2)1-6alkoxygroup); and

R3and R4are the same or different and each represents

(1) a hydrogen atom,

(2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: 1) atom g is lagena, 2) a hydroxyl group, 3)1-6alkoxygroup and 4) -OCO-C1-6alkyl group),

(3) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following 1) to 6):

1) halogen atom,

2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) halogen atom, (b) hydroxyl groups, and (c) With1-6alkoxygroup),

3)1-6alkoxygroup (specified With1-6alkoxygroup is optionally substituted by one or more, same or different halogen atoms),

4) carboxyl group,

5) -COO-C1-6alkyl groups and

6) ceanography),

(4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following group: 1) halogen atom and 2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

(5) hydro is a strong group, or

(6)1-6alkoxygroup],

or its salt.

3. The compound according to any one of above items 1 and 2, where-X - is-C(R7R8)-, where R7and R8are those, as in the above item 1 or its salt.

4. The compound according to any one of above items 1 to 3, where R8represents a

1) -NR16R17where R16and R17are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R16and R17optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

2) -CONR18R19where R18and R19are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R18and R19optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or

3) 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group,

or its salt.

5. The compound according to any one of above items 1 or 2, X represents-N(R1)-, where R1is that as in the above item 1 or its salt.

6. The compound according to any one of the above items , 2 and 5, where R1represents a

1) a hydrogen atom,

2) -CONR5R6where R5and R6are the same or different and each represents

(a) a hydrogen atom,

(b) aryl group (this aryl group is substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup) and

e)1-6alkoxygroup),

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, identical is whether different substituents, selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group and

(iv)1-6alkoxygroup),

e)1-6alkoxygroup and

f) a carboxyl group)

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one the or more identical or different substituents, selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or With1-6alkyl group, or

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group), or

(g) nitrogen-containing unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms),

or

(h) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl GRU the PA is optionally substituted by one or more identical or different substituents, selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R24and R25optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup) (provided that R5and R6are not simultaneously hydrogen atoms),

3) -COOR10where R10represents a

(a)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) through d):

(a) a hydroxyl group,

b) -NR26R27where R26and R27vlahuta the same or different and each represents a hydrogen atom or a C 1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

c1-6alkoxygroup and

d) aryl group), or

(b) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

4) -COR11where R11represents a

(a)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to h):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, Goethe is acyclically group,

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

e)1-6alkoxygroup,

f) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii)1-6alkoxygroup and (iv)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

g) a carboxyl group, and

(h) alloctype),

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6Alki the other group is optionally substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

(d) aryl group (this aryl group is substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3)1-6alkoxygroup), or

(e) a carboxyl group,

5)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (d):

(a) carboxyl group,

(b) cycloalkyl the th group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR 32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),

6) cycloalkyl group,

7) -S(=O)2-R12 where R12represents a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)or aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

8) -C(=NCN)-R13where R13represents a C1-6alkyl group,

9) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

10) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (f):

(a) carboxyl group,

(b) halogen atom,

(c)1-6alkyl group (specified With1-6alkylen the I group is optionally substituted by one or more identical or different substituents, selected from the following group: a) hydroxyl group, (b) halogen atom, and c1-6alkoxygroup),

(d) -NR38R39where R38and R39are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-NR40R41where R40and R41are the same or different and each represents a hydrogen atom, a C1-6alkyl group or a C1-6alkoxygroup, or R40and R41optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or-S(=O)2-R42where R42represents a C1-6alkyl group), or R38and R39optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more oxoprop),

(e) -CO-NR43R44where R43and R44are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R43and R44optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, is heterocyclics group, and

(f) -COO-C1-6alkyl group), or

11) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) to (h):

(a) carboxyl group,

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup),

(c) cycloalkyl group and

(d) halogen atom,

(e) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R45and R46optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

(f) -COO-C1-6alkyl groups,

(g) ceanography and

(h)1-6alkoxygroup),

or its salt.

7. The compound according to any one of above items 1, 2 and 5, where R1represents a

1) -CONR5R6where R5and R6are the same or different and each p is ecstasy a

(a) a hydrogen atom,

(b) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup) and

e)1-6alkoxygroup),

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this is ilina group is optionally substituted by one or more identical or different substituents, selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group and

(iv)1-6alkoxygroup),

e)1-6alkoxygroup and

f) a carboxyl group)

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted one or more what kolichestvo identical or different halogen atoms)), or1-6alkyl group, or

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

(g)1-6alkoxygroup or

(h) nitrogen-containing unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms)

or

(i) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R24and R25optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup) (provided that R5and R6are not any combination of substituents selected from the following group: (i) a hydrogen atom and (ii) unsubstituted With1-6alkyl group),

2) -COOR10where R10represents a

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) through d):

(a) a hydroxyl group,

b) -NR26R27where R26and R27ablauts the same or different and each represents a hydrogen atom or a C 1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

c1-6alkoxygroup and

d) aryl group), or

(b) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

3) -COR11where R11represents a

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to h):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic is the Rupp,

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

e)1-6alkoxygroup,

f) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii)1-6alkoxygroup and (iv)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

g) a carboxyl group, and

(h) alloctype),

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6Alki the other group is optionally substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3)1-6alkoxygroup), or

(e) a carboxyl group,

4)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) to (d):

(a) carboxyl group,

(b) cycloalkyl the th group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR 32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),

5) cycloalkyl group,

6) -S(=O)2-R12 where R12represents a C1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different halogen atoms)or aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

7) -C(=NCN)-R13where R13represents a C1-6alkyl group,

8) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or

9) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is substituted by one or more, same or different substituents selected from the following (a) to (g):

(a)1-6alkyl group (specified With1-6alkyl g is the SCP is substituted by one or more identical or different substituents, selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup),

(b) cycloalkyl group,

(c) halogen atom,

(d) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R45and R46optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

(e) -COO-C1-6alkyl groups,

(f) ceanography and

(g)1-6alkoxygroup),

or its salt.

8. The compound according to any one of above items 1, 2 and 5, where R1represents a

1) -CONR5R6where R5and R6are the same or different and each represents

(a) a hydrogen atom,

(b) aryl group (this aryl group is substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) the atom Galaga is a, (ii) a hydroxyl group, and (iii)1-6alkoxygroup) and

e)1-6alkoxygroup),

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6Alki is inuu group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group and

(iv)1-6alkoxygroup),

e)1-6alkoxygroup and

f) a carboxyl group)

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or With1-6alkyl group, or

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups and

b) -CO-C1-6alkyl groups and

c) the carbonyl group), or

(g) nitrogen-containing unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms)

or

(h) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) in the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R24and R25optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup) (provided that R5and R6are not simultaneously hydrogen atoms),

2) -COOR10where R10represents a

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) through d):

(a) a hydroxyl group,

b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

c1-6alkoxygroup and

d) aryl group), or

(b) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more numbers is the your identical or different substituents, selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

3) -COR11where R11represents a

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to h):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

e)1-6alkoxygroup,

f) aryl group (this aryl group is optionally substituted one or more to the number of identical or different substituents, selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii)1-6alkoxygroup and (iv)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

g) a carboxyl group, and

(h) alloctype),

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is one the Xia optionally substituted by one or more identical or different substituents, selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3)1-6alkoxygroup), or

(e) a carboxyl group,

4)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) to (d):

(a) carboxyl group,

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) the 1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),

5) cycloalkyl group,

6) -S(=O)2-R12where R12represents a C1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different halogen atoms)or aryl group (this aryl group is optionally substituted by one or more identical or different substituents, the curse of the following groups: a) halogen atom and (b) (C 1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

7) -C(=NCN)-R13where R13represents a C1-6alkyl group,

8) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or

9) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is substituted by one or more, same or different substituents selected from the following (a) to (g):

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup),

(b) cycloalkyl group,

(c) halogen atom,

(d) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or alkyl group, or R45and R46optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

(e) -COO-C1-6alkyl groups,

(f) ceanography and

(g)1-6alkoxygroup),

or its salt.

9. The compound according to any one of above items 1 to 8, where R2represents cyclopropyl group or 1-methylcyclopropyl group or its salt.

10. The compound according to any one of above items 1 to 9, where R3and R4are the same or different and each represents

(1) a hydrogen atom,

(2)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following group: 1) halogen atom and (2) -OCO-C1-6alkyl group),

(3) aryl group (this aryl group is substituted by one or more, same or different substituents selected from the following 1) to 5):

1) With the1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following group: (a) halogen atom and (b) a hydroxyl group),

2)1-6Alcock is gruppy (specified With 1-6alkoxygroup is substituted by one or more, same or different halogen atoms),

3) carboxyl group,

4) -COO-C1-6alkyl groups and

5) ceanography) or

(4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is substituted by one or more, same or different substituents selected from the following group: 1) halogen atom and 2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

(provided that R3and R4are not simultaneously hydrogen atoms),

or its salt.

11. The connection at the above paragraph 1, where R1represents a

1) -CONR5R6where R5and R6are the same or different and each represents

(a) a hydrogen atom,

(b) aryl group (this aryl group is substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6alkyl group (specified With1-6the alkyl group is a long is the super substituted by one or more identical or different substituents, selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup) and

e)1-6alkoxygroup),

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, the 1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group and

(iv)1-6alkoxygroup),

e)1-6alkoxygroup and

f) a carboxyl group)

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or With1-6alkyl group, or

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

(g)1-6alkoxygroup or

(h) nitrogen-containing unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms), or

(i) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23optional form together with the nitrogen atom to which they are vasani, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R24and R25optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup) (provided that R5and R6are not simultaneously hydrogen atoms),

2) -COOR10where R10represents a

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) through d):

(a) a hydroxyl group,

b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

c1-6alkoxygroup and

d) aryl group), or

(b) nitrogen-containing, saturated, monocyclic, heterocyclic group (indicated what data heterocyclic group is optionally substituted by one or more identical or different substituents, selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group)),

3) -COR11where R11represents a

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to h):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

e)1-6alkoxygroup,

f) aryl group (this aryl group is optionally substituted one or more what kolichestvo identical or different substituents, selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii)1-6alkoxygroup and (iv)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

g) a carboxyl group, and

(h) alloctype),

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is one the Xia optionally substituted by one or more identical or different substituents, selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3)1-6alkoxygroup), or

(e) a carboxyl group,

4)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) to (d):

(a) carboxyl group,

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) the 1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),

5) cycloalkyl group,

6) -S(=O)2-R12where R12represents a C1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different halogen atoms)or aryl group (this aryl group is optionally substituted by one or more identical or different substituents, the curse of the following groups: a) halogen atom and (b) (C 1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

7) -C(=NCN)-R13where R13represents a C1-6alkyl group,

8) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

9) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (f):

(a) carboxyl group,

(b) halogen atom,

(c)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) hydroxyl group, (b) halogen atom, and c1-6alkoxygroup),

(d) -NR38R39where R38and R39are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-NR40R 41where R40and R41are the same or different and each represents a hydrogen atom, a C1-6alkyl group or a C1-6alkoxygroup, or R40and R41optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or-S(=O)2-R42where R42represents a C1-6alkyl group), or R38and R39optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more oxoprop),

(e) -CO-NR43R44where R43and R44are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R43and R44optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

(f) -COO-C1-6alkyl group), or

10) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is substituted by one or more, same or different substituents selected from the following is (a) to (h):

(a) carboxyl group,

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup),

(c) cycloalkyl group,

(d) halogen atom,

(e) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R45and R46optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

(f) -COO-C1-6alkyl groups,

(g) ceanography and

(h)1-6alkoxygroup),

or its salt.

12. The connection at the above paragraph 1 or its salt, selected from the following:

(1) 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine,

(2) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(3) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(4) 1-[1-(1-carbamoylbiphenyl-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(5) 1-{1-[1-(2-carboxyphenylazo)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(6) 1-{5-cyclopropyl-1-[1-(2-hydroxymethyluracil)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(7) 1-{5-cyclopropyl-1-[1-(1-hydroxymethylpropane)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(8) 1-{5-cyclopropyl-1-[1-(2-hydrooximethylcarbamil)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(9) 1-{5-cyclopropyl-1-[1-(2-hydroxy-1,1-dimethylthiocarbamyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(10) 1-{1-[1-(2-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(11) of the hydrochloride of 1-{1-[1-(2-aminoethylamino)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(12) 1-{5-cyclopropyl-1-[1-(1,1-diocletianopolis-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(13) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoethanol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(14) 1-{5-cyclopropyl-1-[1-(4-hydroxypiperidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(15) 1-{1-[1-(azetidin-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(16) 1-{5-cyclopropyl-1-[1-(3-hydroxypyrrolidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(17) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-piperidine-1-iletileri)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(18) 1-{5-cyclopropyl-1-[1-(4,4-deformability-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(19) 1-{5-cyclopropyl-1-[1-(3,3-debtorprovidian-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(20) 1-{5-cyclopropyl-1-[1-(3-hydroxyazetidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(21) 1-(5-cyclopropyl-1-{1-[(R)-3-hydroxypyrrolidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(22) 1-(5-cyclopropyl-1-{1-[(S)-3-hydroxypyrrolidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(23) 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxy-1-methylethylketon]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(24) 1-{5-cyclopropyl-1-[1-(4-hydroxyethylpiperazine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidin is and,

(25) 1-{1-[1-(4-carboxypeptidase-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(26) 1-{5-cyclopropyl-1-[1-(3-oxopiperidin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(27) 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxyethylpyrrolidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(28) 1-{5-cyclopropyl-1-[1-(3-hydroxymethylation-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(29) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(4-methylpiperazin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(30) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(4-isopropylpiperazine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(31) 1-{1-[1-(4-acetylpiperidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(32) 1-(5-cyclopropyl-1-{1-[(R)-3-hydroxypiperidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(33) 1-{1-[1-(4-carbamoylbiphenyl-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(34) 1-{1-[1-(3-carbamoylation-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptime ylphenyl)]pyrrolidine,

(35) of the hydrochloride of 1-{1-[1-(4-aminopiperidin-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(36) of the hydrochloride of 1-{1-[1-(3-aminopyrrolidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(37) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-yl-carbarnoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(38) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(4-dimethylaminopyridine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(39) 1-{1-[1-(4-acetylaminophenol-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(40) 1-{1-[1-(3-acetylpyrrolidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(41) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(3-dimethylaminopropan-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(42) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-yl-carbarnoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(43) 1-{1-[1-(1-acetylpiperidine-4-yl-carbarnoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(44) 1-{5-cyclopropyl-1-[1-(4-oxopiperidin-1-carbonyl)shall piperidin-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(45) 1-{1-[1-(3-acetylaminoacetylenes-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(46) 1-{5-cyclopropyl-1-[1-(3-oxopyrrolidin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(47) 1-{5-cyclopropyl-1-[1-(2,2,2-triptoreline)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(48) 1-{5-cyclopropyl-1-[1-(3,3,4,4-tetrafluoropyridine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(49) 1-(5-cyclopropyl-1-{1-[(S)-1-hydroxymethyl-2-methylpropionyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(50) 1-(1-{1-[(S)-1-benzyl-2-hydrooximethylcarbamil]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(51) 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxy-1-phenylethanol]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(52) 1-(5-cyclopropyl-1-{1-[(S)-1-hydroxymethyl-3-methylbutanoyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(53) 1-{5-cyclopropyl-1-[1-(2-hydroxyphenylarsonic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(54) 1-{5-cyclopropyl-1-[1-(1-hydroxymethylglutaryl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline who yl)]pyrrolidine,

(55) 1-[1-(1-pensacolanewsjournal.com-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(56)1-[5-cyclopropyl-1-(1-methanesulfonylaminoethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(57) 1-[5-cyclopropyl-1-(1-ethoxycarbonylpyrimidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(58) 1-{5-cyclopropyl-1-[1-(2-hydroxyethoxyethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(59) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoethoxide)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(60) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-piperidine-1-yl-etoxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(61) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-yl-oxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(62) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-yl-oxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(63) 1-{1-[1-(1-acetylpiperidine-4-yl-oxycarbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(64) 1-[1-(1-cyclopropanecarbonitrile-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptorelin is)]pyrrolidine,

(65) 1-{5-cyclopropyl-1-[1-(2-hydroxyacyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(66) 1-(5-cyclopropyl-1-{1-[1-(4-forfinal)cyclopropanecarbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(67) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoacetyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(68) 1-{1-[1-(2-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(69) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(70) 1-{1-[1-(2-acetylamino-2-methylpropionyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(71) 1-(1-{1-[(S)-2-acetylaminophenol]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(72) 1-(1-{1-[(S)-2-acetylamino-3-methylbutyryl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(73) 1-{5-cyclopropyl-1-[1-(3,3,3-triptocaine)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(74) 1-(5-cyclopropyl-1-{1-[(S)-5-oxopyrrolidin-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(75) 1-{1-[1-(3-acetylaminophenol)piperidine-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(76) 1-{5-cyclopropyl-1-[1-(3-hydroxy-2,2-dimethylpropionic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(77) of the hydrochloride of 1-{1-[1-(2-aminoacetyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(78) 1-{5-cyclopropyl-1-[1-(1-hydroxymethylpropane)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(79) of the hydrochloride of 1-{1-[1-(2-amino-2-methylpropionyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(80) 1-{5-cyclopropyl-1-[1-(4-hydroxybutyryl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(81) of the hydrochloride of 1-(5-cyclopropyl-1-{1-[(S)-pyrrolidin-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(82) of the hydrochloride of 1-(5-cyclopropyl-1-{1-[(S)-1-methylpyrrolidine-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(83) of the hydrochloride of 1-{1-[1-(3-aminopropyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(84) hydrochloride 1-(1-{1-[(S)-2-amino-3-methylbutyryl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(85) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-methylaminomethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptorelin is)]pyrrolidine,

(86) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(87) 1-{5-cyclopropyl-1-[1-(2-isobutylamino)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(88) 1-{1-[1-(2-cyclopropanecarboxylate)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(89) 1-(1-{1-[(S)-1-acetylpyrrolidine-2-carbonyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(90) 1-{5-cyclopropyl-1-[1-(2-methanesulfonylaminoethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(91) 1-{1-[1-(1-acetylpiperidine-4-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(92) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(93) 1-{1-[1-(3-carbamoylbiphenyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(94) of the hydrochloride of 1-[1-(1-carbamoylmethyl-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(95) of the hydrochloride of 1-[5-cyclopropyl-1-(1-methylcarbamoylmethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(96) the Hydra is chloride 1-{1-[1-(1-carbarnoyl-1-methylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(97) of the hydrochloride of 1-{1-[1-(2-carbamoylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(98) of the hydrochloride of 1-[5-cyclopropyl-1-(1-cyclopropylmethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(99) of the hydrochloride of 1-[5-cyclopropyl-1-(1-cyclopropylidene-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(100) of the hydrochloride of 1-[5-cyclopropyl-1-(1-dimethylcarbamodithioato-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(101) of the hydrochloride of 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(102) of the hydrochloride of 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(103) of the hydrochloride of 1-{1-[1-(1-carbamoylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(104) of the hydrochloride of 1-{1-[1-(2-carboxy-2-methylpropyl " piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(105) of the hydrochloride of 1-{1-[1-(2-carbarnoyl-2-methylpropyl " piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(106) of the hydrochloride of 1-{1-[1-(1-carbamoylmethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]Pyrrhus is Lidia,

(107) of the hydrochloride of 1-(5-cyclopropyl-1-{1-[1-(2-hydrooximethylcarbamil)cyclopropylmethyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(108) 1-[5-cyclopropyl-1-(1-triftormetilfullerenov-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(109) 1-{5-cyclopropyl-1-[1-(2,2,2-cryptogramophone)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(110) 1-{1-[1-(1-cyanoimino)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(111) 1-(1-{1-[cyanoimino(methylamino)methyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(112) 1-{1-[1-(N-cyanocarbonimidate)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(113) 4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid,

(114) 3-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid,

(115) 5-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiophene-2-carboxylic acid,

(116) 2-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiazole-4-carboxylic acid,

(117) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-methyl-4H-[1,2,4]triazol-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(118) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-cyclopropyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(119) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-hydroxymethyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(120) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-trifluoromethyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(121) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine,

(122) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine,

(123) 1-{5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine,

(124) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(125) 1-{5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(126) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(127) of the hydrochloride of (-)-3-(4-forfinal)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}PIR is alidina,

(128) of the hydrochloride of (+)-3-(4-forfinal)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,

(129) of the hydrochloride of 1-[5-cyclopropyl-1-(1-pyrazin-2-reparacin-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(130) 1-[1-(TRANS-4-carbamoylmethyl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(131) 1-[5-cyclopropyl-1-(TRANS-4-reidiculously)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(132) 1-{5-cyclopropyl-1-[TRANS-4-(1H-tetrazol-5-yl)cyclohexyl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(133) 1-{5-(1-methylcyclopropyl)-1-[1-(4-cryptomaterial)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(134) 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(1-methoxycyclohexyl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(135) 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-phenyl-3-triftormetilfullerenov,

(136) 3-(2-chlorophenyl)-1-{5-cyclopropyl-1-[1-(2,4-differencemaker)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,

(137) 3-(2-chloropyridin-3-yl)-1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,

(138) 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(2,2,3,3-tetramethylcyclopropane)-1H-pyrazole-4-carbon is l}-3-(pyridin-3-yl)pyrrolidine,

(139) 1-{5-cyclohexyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(140) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-trifloromethyl)pyrrolidine,

(141) 1-{5-cyclopropyl-1-[1-(4-cryptomaterial)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(142) 1-(5-cyclopropyl-1-{1-[((S)-1-carboxy-2-methylpropyl)methylcarbamoyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(2-triptoreline)pyrrolidine,

(143) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-methoxy-3-(2-triptoreline)pyrrolidine,

(144) 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(1-hydroxymethylglutaryl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(145) 1-{5-cyclopropyl-1-[1-(thiazol-2-ylcarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(146) 1-{1-[1-(isopropoxycarbonyl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(147) 1-{5-cyclopropyl-1-[1-(4-verbesserbar)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(148) 1-{1-[1-(2,3-dihydroindol-1-carbonyl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(149) 1-{1-[1-(2,3-dihydro[1,4]oxazin-4-carbonyl)piperidine-4-yl]-5-(1-metill sapropel)-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(150) 1-{5-cyclopropyl-1-[1-(2,6-dichloropyridine-3-ylcarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(151) 1-{5-(1-methylcyclopropyl)-1-[1-(2,3,4,5-tetrahydrobenzo[b]azepin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(152) ethyl-4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoate,

(153) 1-[1-(1-benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine,

(154) 1-{1-[1-(3-carboxy-3-methylbutyryl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(155) 1-{5-cyclopropyl-1-[1-(2-phenoxyacetyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(156) 1-{1-[1-(3-chlorobenzoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(157) 1-{1-[1-(2-chlorobenzoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(158) 1-[5-cyclopropyl-1-(1-oxalipatin-4-yl)-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidine,

(159) 1-{1-[1-(4-chlorobenzoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(160) 1-(5-cyclopropyl-1-{1-[2-(4-forfinal)acetyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(pyridin-3-yl)pyrrolidine,

(161) 1-{5-cyclopropyl-1-[1-(3-trifloromethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(who iridin-3-yl)pyrrolidine,

(162) 1-{5-cyclopropyl-1-[1-(3-methoxybenzoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(163) of the hydrochloride of 1-{1-[1-(4-terbisil)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(164) 1-[1-(1-benzosulfimide-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine,

(165) 1-{1-[1-(4-carbamoylphenoxy)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(166) 1-{5-cyclopropyl-1-[1-(4-hydroxymethylene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(167) 1-{1-[1-(5-carbamoylation-2-yl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(168) 1-{1-[1-(4-AMINOPHENYL)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(169) 1-(5-cyclopropyl-1-{1-[4-(2-oxoacridine-3-yl)phenyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(2-triptoreline)pyrrolidine,

(170) 1-(5-cyclopropyl-1-{1-[4-(3-metaxourgeio)phenyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(2-triptoreline)pyrrolidine,

(171) 1-{5-cyclopropyl-1-[1-(4-methanesulfonylaminoethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(172) 1-[1-(1-ethoxycarbonylpyrimidine-4-yl)-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidine,

(173) 1-[1-(5-habiri the Jn-2-yl)azetidin-3-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidine,

(174) 1-{1-[1-(5-chloropyridin-2-yl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-methoxymethyl-3-phenylpyrrolidine,

(175) 1-{1-[1-(5-cyano-2-yl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(176) of the hydrochloride of 3-(2-acetoxyethyl)-3-(4-forfinal)-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,

(177) hydrochloride {(3S*,4R*)-3-methyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-4-phenylpyrrolidine,

(178) methyl-6-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)nicotinate,

(179) methyl-2-{1-[5-(1-methylcyclopropyl)-1-(1-pyrimidine-2-reparacin-4-yl)-1H-pyrazole-4-carbonyl]pyrrolidin-3-yl}benzoate,

(180) of the hydrochloride of 3-(2-hydroxymethylene)-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,

(181) 1-[5-cyclopropyl-1-(1-pyridin-2-reparacin-4-yl)-1H-pyrazole-4-carbonyl]-3-hydroxy-3-(pyridin-3-yl)pyrrolidine,

(182) 1-{1-[1-(4-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,

(183) 4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)-3-perbenzoate sodium

(184) 3-(2-cyanophenyl)-1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}p is rolidone,

(185) of the hydrochloride of 3-hydroxymethyl-1-{1-[1-(4-methoxypyridine-2-yl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-phenylpyrrolidine,

(186) of the hydrochloride of 3-(3,5-differenl)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,

(187) 1-{1-[1-(3-chloropyridin-2-yl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(188) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(thiazol-2-yl)pyrrolidine,

(189) (S)-2-[(TRANS-4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}-cyclohexanecarbonyl)methylamino]-3-methylmalonic acid,

(190) 1-{5-(1-methylcyclopropyl)-1-[TRANS-4-(2-tortenelmebol)cyclohexyl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine and

(191) CIS-4-{5-(1-methylcyclopropyl)-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl)-cyclohexanecarboxylic acid.

13. A pharmaceutical composition comprising a compound according to any one of above items 1 to 12 or its salt.

14. 11βHSD1 inhibitor containing the compound according to any one of above items 1 to 12 or its salt.

15. Agent for the treatment or prophylaxis of a pathology involving glucocorticoid containing any connection with the above items 1 to 12, or their salt.

16. The agent shows you the e to the point 15, for which the pathology associated with glucocorticoid, is:

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including myocardial infarction or stroke,

(4) hyperorexia,

(5) disease with impaired nerve function including impaired cognitive abilities, neurodegenerative diseases, emotional disorders, schizophrenia or stimulation of appetite,

(6) a disease associated with reduced immune function,

(7) glaucoma or

(8) osteoporosis.

17. The method of inhibition of 11βHSD1, which includes the introduction of a pharmaceutically effective amount of a compound according to any one of above items 1 to 12 or its salts.

18. The method of treatment or prophylaxis of a pathology involving glucocorticoid, which includes the introduction of a pharmaceutically effective amount of a compound according to any one of above items 1 to 12 or its salts.

19. The method according to item 18, wherein the pathology associated with glucocorticoid, is one of the following:

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hipertensi is or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including myocardial infarction or stroke,

(4) hyperorexia,

(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, emotional disorders, schizophrenia or stimulation of appetite,

(6) a disease associated with reduced immune function,

(7) glaucoma or

(8) osteoporosis.

20. The use of any of the compounds according to the above items 1 to 12 or its salt to obtain 11βHSD1 inhibitor.

21. The use of any of the compounds according to the above items 1 to 12 or its salt to obtain agent for the treatment or prophylaxis of a pathology involving glucocorticoid.

22. Application under paragraph 21, in which the pathology associated with glucocorticoid is one of the following:

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including myocardial infarction or stroke,

(4) hyperorexia,

(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, emotional disorders, schizophrenia restimulation appetite,

(6) a disease associated with reduced immune function,

(7) glaucoma or

(8) osteoporosis.

23. Commercial pack that includes a written statement stating that the pharmaceutical composition according to paragraph 13 can or should be used for the treatment or prevention of a disease selected from the following:

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including myocardial infarction or stroke,

(4) hyperorexia,

(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, emotional disorders, schizophrenia or stimulation of appetite,

(6) a disease associated with reduced immune function,

(7) glaucoma or

(8) osteoporosis.

24. The pharmaceutical composition according to paragraph 13 for use in combination with from 1 to 3 agents selected from the agents in the following paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for L. the treatment or prophylaxis of hypertension.

25. 11βHSD1 inhibitor according to item 14, for use in combination with from 1 to 3 agents selected from the agents in the following paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

26. The agent according to the above paragraphs 15 or 16 for use in combination with from 1 to 3 agents selected from the agents in the following paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

27. The method according to item 17, characterized in that it additionally includes an introduction from 1 to 3 agents selected from the agents in the following paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

28. Pharmaceutical agent, comprising from 1 to agents, the selected agent in the following paragraphs (1) through (5) and compounds according to any one of items 1 to 12, or salts thereof:

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

29. The method of treatment or prophylaxis of a pathology involving glucocorticoid, in the above paragraphs 18 or 19, characterized in that it additionally includes an introduction from 1 to 3 agents selected from the agents in the following paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

30. The application of paragraph 20, which combined with the use of from 1 to 3 agents selected from the following items (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

31. the label in the above paragraphs 21 or 22, which combined with the use of from 1 to 3 agents selected from the following items (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

32. The pharmaceutical composition according to paragraph 13, characterized in that it is used to suppress the increase of the level of glucocorticoids in the blood by use in combination with a pharmaceutical agent that increases the level of glucocorticoids in the blood.

33. 11βHSD1 inhibitor according to item 14, which is used to suppress the increase of the level of glucocorticoids in the blood by use in combination with a pharmaceutical agent that increases the level of glucocorticoids in the blood.

34. The method according to item 17, characterized in that it further includes the introduction of a pharmaceutical agent that increases the level of glucocorticoids in the blood.

35. Application under paragraph 21 to suppress the increase of the level of glucocorticoids in the blood in combination with a pharmaceutical agent that increases the level of glucocorticoids in the blood.

36. The method of suppressing the level of glucocorticoids in the blood from rising, which includes the introduction of a pharmaceutical agent that increases preventglycation in the blood and 11βHSD1 inhibitor according to item 14.

37. Dimethyl-2-[(S)-2-nitro-1-(2-triptoreline)ethyl]malonate.

38. Methyl-(S)-2-oxo-4-(2-triptoreline)pyrrolidin-3-carboxylate.

39. (S)-4-(2-triptoreline)pyrrolidin-2-it.

40. (S)-3-(2-triptoreline)pyrrolidin or its salt.

41. A method of producing dimethyl-2-[(S)-2-nitro-1-(2-triptoreline)ethyl]malonate, which includes the stage of interaction of 1-((E)-2-nitrovinyl)-2-cryptomelane with diethylmalonate in the presence of 1-(3,5-bis-triptoreline)-3-((1S,2S)-2-dimethylaminoethoxy)thiourea.

42. The way to obtain methyl(S)-2-oxo-4-(2-triptoreline)pyrrolidin-3-carboxylate, which includes the stage of restoration and ring closure dimethyl-2-[(S)-2-nitro-1-(2-triptoreline)ethyl]malonate.

43. The method of obtaining (S)-4-(2-triptoreline)pyrrolidin-2-it, which includes a step of hydrolysis and decarboxylation of methyl-(S)-2-oxo-4-(2-triptoreline)pyrrolidin-3-carboxylate.

44. The method of obtaining salt (S)-3-(2-triptoreline)pyrrolidine, which includes the stage of restoration (S)-4-(2-triptoreline)pyrrolidin-2-she and the stage of processing of the obtained compound with acid to form salt.

The present invention also encompasses the following :

45. The compound represented by the following formula [2]:

where

-X - represents

(1) -N(R1)-, where R represents a

1) a hydrogen atom,

2) -CONR5R6where R5and R6are the same or different and each represents

(a) a hydrogen atom,

(b) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup) and

e)1-6alkoxygroup),

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more the same or different substituents, selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group and

(iv)1-6alkoxygroup),

e)1-6alkoxygroup and

f) a carboxyl group)

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one the or more identical or different substituents, selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or With1-6alkyl group, or

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group), or

(g) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group or heterocyclic group, which is a condensed ring of the specified heterocycle and carbon rings (both of these heterocyclic groups are optionally substituted by one or more, same or different substituents selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different mandated the residents, selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R24and R25optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup),

3) -COOR10where R10represents a

(a)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

(a) a hydroxyl group,

b) -NR26R27where R26and R27are the same or different and each represents with the battle of the atom of hydrogen or C 1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

c1-6alkoxygroup), or

(b) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

4) -COR11where R11represents a

(a)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) through (g):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

e)1-6alkoxygroup,

f) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii)1-6alkoxygroup and (iv)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and

g) a carboxyl group)

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6an alkyl group is obazatelno substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

5)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (d):

(a) carboxyl group,

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents is selected from the following group: (i) a hydroxyl group and (ii) 1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

(d) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),

6) cycloalkyl group,

7) -S(=O)2-R12where R12represents a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)or aryl group (this aryl group is optionally substituted by one or more, same or different, z is mustiala, selected from the following group: a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

8) -C(=NCN)-R13where R13represents a C1-6alkyl group,

9) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

10) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (f):

(a) carboxyl group,

(b) halogen atom,

(c)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) hydroxyl group, (b) halogen atom, and c1-6alkoxygroup),

(d) -NR38R39where R38and R39are the same or different and each represents a hydrogen atom, a C1-6Alki is inuu group, -CO-C1-6alkyl group, -CO-NR40R41where R40and R41are the same or different and each represents a hydrogen atom, a C1-6alkyl group or a C1-6alkoxygroup, or R40and R41optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or-S(=O)2-R42where R42represents a C1-6alkyl group), or R38and R39optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more oxoprop),

(e) -CO-NR43R44where R43and R44are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R43and R44optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

(f) -COO-C1-6alkyl group), or

11) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more of Isakovich or different substituents, selected from the following (a) to (g):

(a) carboxyl group,

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup),

(c) cycloalkyl group,

(d) halogen atom,

(e) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R45and R46optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

(f) -COO-C1-6alkyl groups and

(g) ceanography) or

(2) -C(R7R8)-, where R7and R8are the same or different and each represents

1) a hydrogen atom,

2) -NR16R17where R16and R17are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-NR36R37where R36and R37are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R36and R37optional form instead of the e with the nitrogen atom, with which they are associated, nitrogen-containing, saturated, monocyclic, heterocyclic group, or R16and R17optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

3) -CONR18R19where R18and R19are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted one or more carboxyl groups) or aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) halogen atom and (b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), or R18and R19optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group, or

5) a carboxyl group;

R2represents a

(1) cycloalkyl group (specified cycloalkyl group I which is optionally substituted by one or more, same or different With 1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) a hydroxyl group and (b) (C1-6alkoxygroup)); and

R3and R4are the same or different and each represents

(1) a hydrogen atom,

(2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: 1) halogen atom, 2) a hydroxyl group, and (3) With1-6alkoxygroup),

(3) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following 1) to 6):

1) halogen atom,

2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) halogen atom, (b) hydroxyl groups, and (c) With1-6alkoxygroup),

3)1-6alkoxygroup (specified With1-6alkoxygroup is optionally substituted by one or more identical or different atoms of Galaga is a)

4) carboxyl group,

5) -COO-C1-6alkyl groups and

6) ceanography), or

(4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following group: 1) halogen atom and 2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

or its salt.

46. The connection at the above paragraph 45, which is represented by the following formula [2]:

where

-X - represents

(1) -N(R1)-, where R1represents a

1) a hydrogen atom,

2) -CONR5R6where R5and R6are the same or different and each represents

(a) a hydrogen atom,

(b) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or is a large number of the same or of different substituents, selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup) and

e)1-6alkoxygroup),

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

d) -NR20R21where R20and R21are the same or different and each represents the volume of hydrogen, With1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group and

(iv)1-6alkoxygroup) and

e)1-6alkoxygroup),

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or With1-6alkyl group, or

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b)-CO-C 1-6alkyl groups and

c) the carbonyl group), or

(g) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, and R 24and R25optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup),

3) -COOR10where R10is,

(a)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

(a) a hydroxyl group,

b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

c1-6alkoxygroup), or

(b) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

4) -COR11where R11is,

(a)1-6alkyl group (specified With1-6alkiline the group is optionally substituted by one or more identical or different substituents, selected from the following a) to e):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

e)1-6alkoxygroup),

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl groups (decree of the Fes 1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

5)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (c):

(a) carboxyl group,

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (this is 1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group), and

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

6) cycloalkyl group,

7) -S(=O)2-R12where R12represents a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms),

8) -C(=NCN)-R13where R13represents a C1-6alkyl group,

9) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15optional form together with the nitrogen atom to which anivesary, nitrogen-containing, saturated, monocyclic, heterocyclic group,

10) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms) and (3) a carboxyl group), or

11) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) to (c):

(a) carboxyl group,

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup), and

(c) cycloalkyl group), or

(2) -C(R7R8)-, where R7and R8are the same or different and each represents

1) a hydrogen atom,

2) -NR16R17where R16and R17are Odie is akovali or different and each represents a hydrogen atom, With1-6alkyl group or-CO-NR36R37where R36and R37are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R36and R37optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or R16and R17optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

3) -CONR18R19where R18and R19are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R18and R19optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or

4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group;

R2represents a

(1) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups); and

R3and R4are the same or different and each represents

(1) a hydrogen atom,

(2)1-6alkyl group (pointed to by the I 1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup),

(3) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following 1) and 2):

1) halogen atom, and

2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or

(4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group,

or its salt.

47. The connection in the above paragraphs 45 or 46, where-X - is-C(R7R8)-, where R7and R8are those, as in the above paragraph 46, or its salt.

48. The compound according to any one of the above paragraphs 45 to 47, where R8represents a

1) -NR16R17where R16and R17are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R16and R17optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic gr the PPU,

2) -CONR18R19where R18and R19are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R18and R19optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or

3) 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group),

or its salt.

49. The connection in the above paragraphs 45 or 46, where-X - represents-N(R1)-, where R1is that as in the above paragraph 46), or its salt.

50. The compound according to any one of the above paragraphs 45, 46 and 49, where R1represents a

1) a hydrogen atom,

2) -CONR5R6where R5and R6are the same or different and each represents

(a) a hydrogen atom,

(b) aryl group (this aryl group is substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) and the Ohm halogen, (ii) a hydroxyl group, and (iii)1-6alkoxygroup) and

e)1-6alkoxygroup),

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6Alki is inuu group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group and

(iv)1-6alkoxygroup), and

e)1-6alkoxygroup),

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or With1-6alkyl group, or

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group), or

(g) Rsup> 5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R24and R25optional form together with at the IOM nitrogen, with which they are associated, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup) (provided that R5and R6are not simultaneously hydrogen atoms),

3) -COOR10where R10represents a

(a)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

(a) a hydroxyl group,

b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

c1-6alkoxygroup), or

(b) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

4) -COR11where R11represents a

(a)1-6alkyl group (specified With alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to e):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

e)1-6alkoxygroup),

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is optionally substituted by one or more of Isakovich or different substituents, selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

5)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (c):

(a) carboxyl group,

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same elerslie and each represents a hydrogen atom, With1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group), and

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

6) cycloalkyl group,

7) -S(=O)2-R12where R12represents a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms),

8) -C(=NCN)-R13where R13represents a C1-6alkyl group,

9) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15not necessarily about the will is formed together with the nitrogen atom, with which they are associated, nitrogen-containing, saturated, monocyclic, heterocyclic group,

10) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms) and (3) a carboxyl group), or

11) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) to (c):

(a) carboxyl group,

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup), and

(c) cycloalkyl group)

or its salt.

51. The compound according to any one of the above paragraphs 45, 46 and 49, where R1represents a

1) -CONR5R6where R5and R6are the same who or different and each represents

(a) a hydrogen atom,

(b) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup) and

e)1-6alkoxygroup),

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this is ilina group is optionally substituted by one or more identical or different substituents, selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group and

(iv)1-6alkoxygroup), and

e)1-6alkoxygroup),

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or the hypoxia halogen atoms)), or1-6alkyl group, or

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group), or

(g) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23not necessarily about the will is formed together with the nitrogen atom, with which they are associated, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R24and R25optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup) (provided that R5and R6are not simultaneously hydrogen atoms and unsubstituted1-6alkyl groups),

2) -COOR10where R10represents a

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to c):

(a) a hydroxyl group,

b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

c1-6alkoxygroup), or

(b) nitrogen-containing, saturated, is monocyclics, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

3) -COR11where R11represents a

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to e):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic will stifle, heterocyclic group, and

e)1-6alkoxygroup),

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

4)1-6alkyl group (specified With1-6 an alkyl group is substituted by one or more, same or different substituents selected from the following (a) to (c):

(a) carboxyl group,

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group), and

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

5) cycloalkyl group,

6) -S(=O)2-R12where R12represents a C1-6and kilou group (specified With 1-6an alkyl group is substituted by one or more, same or different halogen atoms),

7) -C(=NCN)-R13where R13represents a C1-6alkyl group,

8) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or

9) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is substituted by one or more, same or different substituents selected from the following (a) and (b):

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup) and

(b) cycloalkyl group)

or its salt.

52. The compound according to any one of the above paragraphs 45, 46 and 49, where R1represents a

1) -CONR5R6where R5and R6are the same or different and each represents the t of a

(a) a hydrogen atom,

(b) aryl group (this aryl group is substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) a carboxyl group,

d)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup) and

e)1-6alkoxygroup),

(c) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),

(d)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following groups:

(a) a hydroxyl group,

(b) halogen atom,

c) aryl group (this aryl group is neo Astelin substituted by one or more identical or different substituents, selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),

d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) to (iv):

(i) halogen atom,

(ii) a hydroxyl group,

(iii) the carbonyl group and

(iv)1-6alkoxygroup), and

e)1-6alkoxygroup),

(e) -S(=O)2-R9where R9represents an aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or the hypoxia halogen atoms)), or1-6alkyl group, or

(f) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group), or

(g) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):

a) halogen atom,

b) a hydroxyl group,

c1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup),

d) a carboxyl group,

(e) -CO-C1-6alkyl groups,

f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R22and R23not necessarily about the will is formed together with the nitrogen atom, with which they are associated, nitrogen-containing, saturated, monocyclic, heterocyclic group,

g) the carbonyl group,

h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R24and R25optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

i)1-6alkoxygroup) (provided that R5and R6are not simultaneously hydrogen atoms and unsubstituted1-6alkyl groups),

2) -COOR10where R10represents a

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to c):

(a) a hydroxyl group,

b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, and

c1-6alkoxygroup), or

(b) nitrogen-containing, saturated, is monocyclics, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

3) -COR11where R11represents a

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to e):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group, or R28and R29optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,

d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic will stifle, heterocyclic group, and

e)1-6alkoxygroup),

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and

(b) (C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or

(c) nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group),

4)1-6alkyl group (specified With1-6 an alkyl group is substituted by one or more, same or different substituents selected from the following (a) to (c):

(a) carboxyl group,

(b) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup), or R32and R33optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group), and

(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group),

5) cycloalkyl group,

6) -S(=O)2-R12where R12represents a C1-6and kilou group (specified With 1-6an alkyl group is substituted by one or more, same or different halogen atoms),

7) -C(=NCN)-R13where R13represents a C1-6alkyl group,

8) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R14and R15optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, or

9) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is substituted by one or more, same or different substituents selected from the following (a) and (b):

(a)1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to c):

a) halogen atom,

b) a hydroxyl group, and

c1-6alkoxygroup) and

(b) cycloalkyl group)

or its salt.

53. The compound according to any one of above items from 45 to 52, where R2represents cyclopropyl group, or 1-methylcyclopropyl group, or its salt.

54. The compound according to any one of the azannyh above paragraphs 45 through 53, where R3and R4are the same or different and each represents

(1) a hydrogen atom,

(2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup),

(3) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following 1) and 2):

1) halogen atom, and

2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or

(4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group,

or its salt.

55. The connection at the above paragraph 45 or its salt, which is selected from the following compounds:

(1) 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine,

(2) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(3) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,

(4) 1-[1-(1-carbamoylbiphenyl is n-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(5) 1-{1-[1-(2-carboxyphenylazo)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(6) 1-{5-cyclopropyl-1-[1-(2-hydroxymethyluracil)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(7) 1-{5-cyclopropyl-1-[1-(1-hydroxymethylpropane)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(8) 1-{5-cyclopropyl-1-[1-(2-hydrooximethylcarbamil)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(9) 1-{5-cyclopropyl-1-[1-(2-hydroxy-1,1-dimethylthiocarbamyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(10) 1-{1-[1-(2-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(11) of the hydrochloride of 1-{1-[1-(2-aminoethylamino)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(12) 1-{5-cyclopropyl-1-[1-(1,1-diocletianopolis-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(13) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoethanol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(14) 1-{5-cyclopropyl-1-[1-(4-hydroxypiperidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,/p>

(15) 1-{1-[1-(azetidin-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(16) 1-{5-cyclopropyl-1-[1-(3-hydroxypyrrolidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(17) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-piperidine-1-yl-ethylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(18) 1-{5-cyclopropyl-1-[1-(4,4-deformability-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(19) 1-{5-cyclopropyl-1-[1-(3,3-debtorprovidian-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(20) 1-{5-cyclopropyl-1-[1-(3-hydroxyazetidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(21) 1-(5-cyclopropyl-1-{1-[(R)-3-hydroxypyrrolidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(22) 1-(5-cyclopropyl-1-{1-[(S)-3-hydroxypyrrolidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(23) 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxy-1-methylethylketon]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(24) 1-{5-cyclopropyl-1-[1-(4-hydroxyethylpiperazine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidin is and,

(25) 1-{1-[1-(4-carboxypeptidase-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(26) 1-{5-cyclopropyl-1-[1-(3-oxopiperidin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(27) 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxyethylpyrrolidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(28) 1-{5-cyclopropyl-1-[1-(3-hydroxymethylation-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(29) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(4-methylpiperazin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(30) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(4-isopropylpiperazine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(31) 1-{1-[1-(4-acetylpiperidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(32) 1-(5-cyclopropyl-1-{1-[(R)-3-hydroxypiperidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(33) 1-{1-[1-(4-carbamoylbiphenyl-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(34) 1-{1-[1-(3-carbamoylation-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptime ylphenyl)]pyrrolidine, (35) of the hydrochloride of 1-{1-[1-(4-aminopiperidin-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(36) of the hydrochloride of 1-{1-[1-(3-aminopyrrolidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(37) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-yl-carbarnoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(38) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(4-dimethylaminopyridine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(39) 1-{1-[1-(4-acetylaminophenol-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(40) 1-{1-[1-(3-acetylpyrrolidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(41) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(3-dimethylaminopropan-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(42) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-yl-carbarnoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(43) 1-{1-[1-(1-acetylpiperidine-4-yl-carbarnoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(44) 1-{5-cyclopropyl-1-[1-(4-oxopiperidin-1-carbonyl)PIP is ridin-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(45) 1-{1-[1-(3-acetylaminoacetylenes-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(46) 1-{5-cyclopropyl-1-[1-(3-oxopyrrolidin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(47) 1-{5-cyclopropyl-1-[1-(2,2,2-triptoreline)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(48) 1-{5-cyclopropyl-1-[1-(3,3,4,4-tetrafluoropyridine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(49) 1-(5-cyclopropyl-1-{1-[(S)-1-hydroxymethyl-2-methylpropionyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(50) 1-(1-{1-[(S)-1-benzyl-2-hydrooximethylcarbamil]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(51) 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxy-1-phenylethanol]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(52) 1-(5-cyclopropyl-1-{1-[(S)-1-hydroxymethyl-3-methylbutanoyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(53) 1-{5-cyclopropyl-1-[1-(2-hydroxyphenylarsonic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(54) 1-{5-cyclopropyl-1-[1-(1-hydroxymethylglutaryl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline who yl)]pyrrolidine,

(55) 1-[1-(1-pensacolanewsjournal.com-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(56)1-[5-cyclopropyl-1-(1-methanesulfonylaminoethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(57) 1-[5-cyclopropyl-1-(1-ethoxycarbonylpyrimidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(58) 1-{5-cyclopropyl-1-[1-(2-hydroxyethoxyethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(59) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoethoxide)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(60) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-piperidine-1-yl-etoxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(61) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-yl-oxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(62) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-yl-oxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(63) 1-{1-[1-(1-acetylpiperidine-4-yl-oxycarbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(64) 1-[1-(1-cyclopropanecarbonitrile-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptorelin is)]pyrrolidine,

(65) 1-{5-cyclopropyl-1-[1-(2-hydroxyacyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(66) 1-(5-cyclopropyl-1-{1-[1-(4-forfinal)cyclopropanecarbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(67) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoacetyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(68) 1-{1-[1-(2-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(69) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(70) 1-{1-[1-(2-acetylamino-2-methylpropionyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(71) 1-(1-{1-[(S)-2-acetylaminophenol]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(72) 1-(1-{1-[(S)-2-acetylamino-3-methylbutyryl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(73) 1-{5-cyclopropyl-1-[1-(3,3,3-triptocaine)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(74) 1-(5-cyclopropyl-1-{1-[(S)-5-oxopyrrolidin-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(75) 1-{1-[1-(3-acetylaminophenol)piperidine-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(76) 1-{5-cyclopropyl-1-[1-(3-hydroxy-2,2-dimethylpropionic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(77) of the hydrochloride of 1-{1-[1-(2-aminoacetyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(78) 1-{5-cyclopropyl-1-[1-(1-hydroxymethylpropane)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(79) of the hydrochloride of 1-{1-[1-(2-amino-2-methylpropionyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(80) 1-{5-cyclopropyl-1-[1-(4-hydroxybutyryl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(81) of the hydrochloride of 1-(5-cyclopropyl-1-{1-[(S)-pyrrolidin-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(82) of the hydrochloride of 1-(5-cyclopropyl-1-{1-[(S)-1-methylpyrrolidine-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(83) of the hydrochloride of 1-{1-[1-(3-aminopropyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(84) hydrochloride 1-(1-{1-[(S)-2-amino-3-methylbutyryl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(85) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-methylaminomethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptorelin is)]pyrrolidine,

(86) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(87) 1-{5-cyclopropyl-1-[1-(2-isobutylamino)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(88) 1-{1-[1-(2-cyclopropanecarboxylate)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(89) 1-(1-{1-[(S)-1-acetylpyrrolidine-2-carbonyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(90) 1-{5-cyclopropyl-1-[1-(2-methanesulfonylaminoethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(91) 1-{1-[1-(1-acetylpiperidine-4-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(92) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(93) 1-{1-[1-(3-carbamoylbiphenyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(94) of the hydrochloride of 1-[1-(1-carbamoylmethyl-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(95) of the hydrochloride of 1-[5-cyclopropyl-1-(1-methylcarbamoylmethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(96) the Hydra is chloride 1-{1-[1-(1-carbarnoyl-1-methylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(97) of the hydrochloride of 1-{1-[1-(2-carbamoylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(98) of the hydrochloride of 1-[5-cyclopropyl-1-(1-cyclopropylmethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(99) of the hydrochloride of 1-[5-cyclopropyl-1-(1-cyclopropylidene-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(100) of the hydrochloride of 1-[5-cyclopropyl-1-(1-dimethylcarbamodithioato-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(101) of the hydrochloride of 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(102) of the hydrochloride of 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(103) of the hydrochloride of 1-{1-[1-(1-carbamoylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(104) of the hydrochloride of 1-{1-[1-(2-carboxy-2-methylpropyl " piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(105) of the hydrochloride of 1-{1-[1-(2-carbarnoyl-2-methylpropyl " piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(106) of the hydrochloride of 1-{1-[1-(1-carbamoylmethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]Pyrrhus is Lidia,

(107) of the hydrochloride of 1-(5-cyclopropyl-1-{1-[1-(2-hydrooximethylcarbamil)cyclopropylmethyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(108) 1-[5-cyclopropyl-1-(1-triftormetilfullerenov-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(109) 1-{5-cyclopropyl-1-[1-(2,2,2-cryptogramophone)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(110) 1-{1-[1-(1-cyanoimino)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(111) 1-(1-{1-[cyanoimino(methylamino)methyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,

(112) 1-{1-[1-(N-cyanocarbonimidate)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(113) 4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid,

(114) 3-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid,

(115) 5-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiophene-2-carboxylic acid,

(116) 2-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiazole-4-carboxylic acid,

(117) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-methyl-4H-[1,2,4]triazol-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(118) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-cyclopropyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(119) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-hydroxymethyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(120) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-trifluoromethyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(121) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine,

(122) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine,

(123) 1-{5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine,

(124) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(125) 1-{5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(126) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,

(127) of the hydrochloride of (-)-3-(4-forfinal)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}PIR is alidina,

(128) of the hydrochloride of (+)-3-(4-forfinal)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,

(129) of the hydrochloride of 1-[5-cyclopropyl-1-(1-pyrazin-2-reparacin-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(130) 1-[1-(TRANS-4-carbamoylmethyl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,

(131) 1-[5-cyclopropyl-1-(TRANS-4-reidiculously)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidin and

(132) 1-{5-cyclopropyl-1-[TRANS-4-(1H-tetrazol-5-yl)cyclohexyl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine.

56. A pharmaceutical composition comprising a compound according to any one of above items from 45 to 55 or its salt.

57. 11βHSD1 inhibitor comprising the compound according to any one of items 45 through 55, or its salt.

58. Agent for the treatment or prophylaxis of a pathology involving glucocorticoid, which comprises the compound according to any one of items 45 through 55, or its salt.

59. The agent according to item 58, for which the pathology associated with glucocorticoid is:

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including infer the t infarction or stroke, associated with these diseases,

(4) hyperorexia,

(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, accompanied by loss of nerve cells, emotional disorders, including anxiety, depression, or mania, schizophrenia or stimulation of appetite,

(6) disease requiring treatment or prophylaxis of impaired immunity or immunity, including immunodeficiency,

(7) glaucoma, or

(8) osteoporosis.

60. The method of inhibition of 11βHSD1, which includes the introduction of a pharmaceutically effective amount of a compound according to any one of items 45 55 or its salts.

61. The method of treatment or prophylaxis of a pathology involving glucocorticoid, which includes the introduction of a pharmaceutically effective amount of a compound according to any one of paragraphs 45-55 or its salts.

62. The method according to item 61, wherein the pathology associated with glucocorticoid, is:

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including myocardial infarction or stroke associated with these diseases,

(4) hyperorexia,

(5) the illness is updated with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, accompanied by loss of nerve cells, emotional disorders, including anxiety, depression, or mania, schizophrenia or stimulation of appetite,

(6) disease requiring treatment or prophylaxis of impaired immunity or immunity, including immunodeficiency,

(7) glaucoma or

(8) osteoporosis.

63. The use of compounds according to the above points, from 45 to 55 or its salt to obtain 11βHSD1 inhibitor.

64. The use of compounds according to any one of above items from 45 to 55 or its salt to obtain agent for the treatment or prophylaxis of a pathology involving glucocorticoid.

65. The application of the above paragraph 64, in which the pathology associated with glucocorticoid, is:

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including myocardial infarction or stroke associated with these diseases,

(4) hyperorexia,

(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, accompanied by loss of the nerve to etok, emotional disorders, including anxiety, depression, or mania, schizophrenia or stimulation of appetite,

(6) a disease that requires treatment or prophylaxis of impaired immunity or immunity, including immunodeficiency,

(7) glaucoma or

(8) osteoporosis.

66. Commercial pack that includes a written statement stating that the pharmaceutical composition according to paragraph 56 can or should be used for the treatment or prevention of a disease selected from the following:

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including myocardial infarction or stroke associated with these diseases,

(4) hyperorexia,

(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, accompanied by loss of nerve cells, emotional disorders, including anxiety, depression, or mania, schizophrenia or stimulation of appetite,

(6) a disease that requires treatment or prophylaxis of impaired immunity or immunity, including immunodeficiency,

(7) glaucoma or

(8) osteoporosis.

67. Pharmaceutical whom azizia at the above paragraph 56, characterized in that it is used in combination with from 1 to 3 agents selected from the following agents paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

68. 11βHSD1 inhibitor according to the above paragraph 57, characterized in that it is used in combination with from 1 to 3 agents selected from the following agents paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

69. The agent according to the above paragraphs 58 or 59, which is used in combination with from 1 to 3 agents selected from the following items (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

70. The method according to the above paragraph 60, the best of the decomposing those which further includes an introduction from 1 to 3 agents selected from the agents in the following paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

71. A pharmaceutical agent containing from 1 to 3 agents selected from the following agents paragraphs (1) through (5), and the compound according to any one of above items from 45 to 55 or its salt in combination:

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

72. The method of treatment or prophylaxis of a pathology involving glucocorticoid in the above paragraphs 61 or 62, characterized in that it additionally includes an introduction from 1 to 3 agents selected from the agents in the following paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) an agent for treatment or prevention is complicated by the th of diabetes,

(5) the agent for the treatment or prophylaxis of hypertension.

73. The application of the above paragraph 63, which combined with the use of from 1 to 3 agents selected from the following agents paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

74. Use the above paragraphs 64 or 65, which combined with the use of from 1 to 3 agents selected from the following agents paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

75. The pharmaceutical composition according to the above paragraph 56, characterized in that it is used to suppress the increase of the level of glucocorticoids in the blood by using in combination with a pharmaceutical agent that increases the level of glucocorticoids in the blood.

76. 11βHSD1 inhibitor according to the above paragraph 57, characterized in that it is used to suppress the increase of the level of Glu is corticoids in blood by use in combination with a pharmaceutical agent, increase the level of glucocorticoids in the blood.

77. The method according to the above paragraph 60, characterized in that it further includes the introduction of a pharmaceutical agent that increases the level of glucocorticoids in the blood.

78. The application of the above paragraph 64 to suppress the increase of the level of glucocorticoids in the blood by use in combination with a pharmaceutical agent that increases the level of glucocorticoids in the blood.

79. The method of suppressing the increase of the level of glucocorticoids in the blood, which includes the introduction of a pharmaceutical agent that increases the level of glucocorticoids in the blood and 11βHSD1 inhibitor according to the above paragraph 57.

The present invention also includes the following.

80. The compound represented by the following formula [3]:

where

R1represents a

(1) -CONR5R6where R5and R6are the same or different and each represents

1) a hydrogen atom,

2)1-6alkyl group,

3) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups) or

4) aryl group (this aryl group is optionally substituted by one or more, Odinak is new or different halogen atoms),

(2) aryl group (this aryl group is optionally substituted one or more carboxyl groups) or

(3) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more carboxyl groups);

R2represents a

(1) cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different With1-6alkyl groups); and

R3and R4are the same or different and each represents

(1) a hydrogen atom,

(2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more hydroxyl groups),

(3) aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from a halogen atom and C1-6alkyl group optionally substituted by one or more halogen atoms) or

(4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group,

or its pharmaceutically acceptable salt.

81. The connection at the above paragraph 0, in which R1represents a

(1) -CONR5R6where R5and R6are the same or different and each represents

1) a hydrogen atom,

2)1-6alkyl group,

3) cyclopropyl group (specified cyclopropyl group is optionally substituted by one or more, same or different With1-6alkyl groups) or

4) a phenyl group (this phenyl group is optionally substituted by one or more, same or different halogen atoms),

(2) a phenyl group (this phenyl group is optionally substituted one or more carboxyl groups) or

(3) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more carboxyl groups or its pharmaceutically acceptable salt.

82. The connection at the above paragraph 80, in which R2represents cyclopropyl group or methylcyclopropyl group, or their pharmaceutically acceptable salt.

83. The connection at the above paragraph 80, in which R3and R4are the same or different and each represents

(1) a hydrogen atom,

(2)1-6 alkyl group (specified With1-6alkyl group is optionally substituted by one or more hydroxyl groups),

(3) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from a halogen atom and C1-6alkyl group optionally substituted by one or more halogen atoms) or

(4) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group, or its pharmaceutically acceptable salt.

84. The connection at the above paragraph 80, or their pharmaceutically acceptable salt, which is selected from the following compounds:

(1) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-(3-pyridin-3-yl)pyrrolidine,

(2) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-{(R)-3-(2-triptoreline)}pyrrolidine,

(3) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-{(R)-3-(2-triptoreline)}pyrrolidine,

(4) 1-{5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-{(R)-3-(2-triptoreline)}pyrrolidine,

(5) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-{(S)-3-(2-triptoreline)}pyrrolidine,

(6) 1-{5-cyclepro the Il-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-{(S)-3-(2-triptoreline)}pyrrolidine,

(7) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-{(S)-3-(2-triptoreline)}pyrrolidine,

(8) hydrochloride (-)1-{5-(1-methylcyclopropyl)-1-[(1-pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(4-forfinal)-3-hydroxyethylpyrrolidine,

(9) hydrochloride (+)1-{5-(1-methylcyclopropyl)-1-[(1-pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(4-forfinal)-3-hydroxyethylpyrrolidine,

(10) 4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid,

(11) 3-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid,

(12) 5-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiophene-2-carboxylic acid and

(13) 2-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiazole-4-carboxylic acid.

85. A pharmaceutical composition comprising a compound according to any one of the above paragraphs 80 to 84 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

86. 11βHSD1 inhibitor containing the compound according to any one of the above paragraphs 80 to 84 or its pharmaceutically acceptable salt, as an active ingredient.

87. Agent for the treatment or prophylaxis of a pathology associated with glucocorticoid is, which includes a compound according to any one of the above paragraphs 80-84 or its pharmaceutically acceptable salt as an active ingredient.

88. The agent at the above paragraph 87, for which the pathology associated with glucocorticoids, is:

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including myocardial infarction or stroke associated with these diseases,

(4) hyperorexia,

(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, accompanied by loss of nerve cells, emotional disorders, including anxiety, depression, or mania, schizophrenia or stimulation of appetite,

(6) a disease that requires treatment or prophylaxis of impaired immunity or immunity, including immunodeficiency,

(7) glaucoma or

(8) osteoporosis.

89. The pharmaceutical composition according to the above paragraph 85, characterized in that it is used in combination with from 1 to 3 agents selected from the following agents paragraphs (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) the agent for treatment is or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

90. 11βHSD1 inhibitor according to the above paragraph 86, wherein it is used in combination with from 1 to 3 agents selected from the following items (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

91. The agent according to the above paragraphs 87 or 88, which is used in combination with 1 to 3 agents selected from the following items (1) through (5):

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications,

(5) the agent for the treatment or prophylaxis of hypertension.

92. The pharmaceutical composition according to the above paragraph 85, wherein it is used to suppress the increase of the level of glucocorticoids in the blood in combination with a pharmaceutical agent that increases the level of glucocorticoids in the blood.

93. 11βHSD1 inhibitor according to the above paragraph is 86, characterized in that it is used to suppress the increase of the level of glucocorticoids in the blood by use in combination with a pharmaceutical agent that increases the level of glucocorticoids in the blood.

The best way to embodiments of the invention

The present invention is described in detail as follows.

The present invention uses the following definitions of the substituents.

The term “C1-6alkyl group represents an alkyl group with a linear or branched chain, having from 1 to 6 carbon atoms and, for example, can be mentioned methyl group, ethyl group, through the group, isopropyl group, bucilina group, isobutylene group, Deut.-bucilina group, tert-bucilina group, pencilina group, isopentyl group, neopentyl group, tert-pencilina group, 1,2-dimethylpropylene group, exilda group, 1,3-dimethylbutyl group and the like, preferably creating a linear or branched chain alkyl groups having from 1 to 4 carbon atoms.

For R1the preferred “C1-6alkyl group is a methyl group, ethyl group, isopropyl group or isobutylene group.

For R3or R4the preferred “C1-6alkyl group is a methyl group.

For R5Il is R 6the preferred “C1-6the alkyl group is an ethyl group, isopropyl group, tert-bucilina group, 1,2-dimethylpropylene group, or 1,3-dimethylbutyl group.

For R9the preferred “C1-6alkyl group is a methyl group.

For R10the preferred “C1-6alkyl group is methyl group or ethyl group.

For R11the preferred “C1-6alkyl group is a methyl group, ethyl group, through the group, isopropyl group, isobutylene group or tert-bucilina group.

For R12the preferred “C1-6alkyl group is methyl group or ethyl group.

For R13the preferred “C1-6alkyl group is a methyl group.

For R14or R15the preferred “C1-6alkyl group is a methyl group.

The term “C2-6Alchemilla group” represents alkenylphenol group with a linear or branched chain, having from 2 to 6 carbon atoms and, for example, can be mentioned vinyl group, n-protanilla group, isopropylene group, n-bucinellina group, isobutylene group, sec-bucinellina group, tert-bucinellina group, n-penttila group, isopentenyl group, n is openarena group, 1-methylpropenyl group, n-examilia group, isohexyl group, 1,1-dimethylbutyl group, 2,2-dimethylbutyl group, 3,3-dimethylbutyl group, 3,3-dimethylpropylene group, 2-ethylbutylamine group and the like.

The term “C1-6alkoxygroup is alkoxygroup, where the alkyl residue is “C1-6alkyl group”defined above and, for example, can be mentioned a methoxy group, ethoxypropan, propoxylate, isopropylacetate, butoxypropan, isobutylacetate, tert-butylacrylate, pentyloxy, hexyloxy and the like.

The term “halogen atom” is a fluorine atom, chlorine atom, bromine atom or iodine atom. Preferred is a fluorine atom or a chlorine atom, and more preferred is a fluorine atom.

The term “aryl group” is an aromatic hydrocarbon group having 6 to 14 carbon atoms and, for example, may be mentioned phenyl group, naftalina group, antenna group, atulananda group, phenanthroline group and the like. Preferred is a phenyl group.

The term “alloctype is alloctype, where the aryl residue is the “aryl group”defined above and, for example, can be mentioned fenoxaprop, naphthyloxy the group, and the like.

The term “cycloalkyl group” represents cycloalkyl group having from 3 to 8 carbon atoms and, for example, can be mentioned cyclopropyl group, cyclobutyl group, cyclopentenone group, tsiklogeksilnogo group, cycloheptyl group, cyclooctyl group and the like. It is preferable cycloalkyl group having from 3 to 6 carbon atoms, such as cyclopropyl group, cyclobutyl group, cyclopentenone group and tsiklogeksilnogo group. Especially preferred are cyclopropyl group and cyclopentenone group.

The term “5-membered or 6-membered unsaturated, monocyclic, heterocyclic group” represents a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group having, besides carbon atom, at least one, preferably from 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom. Unsaturation includes partial desaturation and full desaturation. For example, there may be mentioned 5-membered, monocyclic aromatic heterocyclic group such as furilla group, thienyl group, pyrrolidine group, pyrazolidine group, imidazolidinyl group, oxazoline group, isoxazolyl group, thiazolidine group, isothiazolinone group, Tria is ailina group, oxadiazolidine group, tetrataenia group, thiadiazolyl group and the like, and a 6-membered, monocyclic aromatic heterocyclic group such as Peregrina group, pyridazinyl group, pyrimidinyl group, piratininga group, trainline group, teinila group, oxydianiline group, Pernilla group, copernicia group and the like. As a 5-membered, monocyclic aromatic heterocyclic group, preferred is a thienyl group or thiazolidine group. As a 6-membered, monocyclic aromatic heterocyclic group is preferred Peregrina group or pyrimidinyl group.

For R1preferred 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group” is Peregrina group, thienyl group, thiazolidine group, thiazolidine group (particularly preferred is 1,2,4-triazoline group), tetrataenia group, pyrimidinyl group or piratininga group.

For R3or R4preferred 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group” is Peregrina group or thiazolidine group. More preferred is Peregrina group.

The term “nitrogen-containing, n is sisenna, monocyclic, heterocyclic group” represents, for example, containing from 4 - to 6-member saturated, monocyclic heterocycle having at least one nitrogen atom, such as azetidinone group, pyrrolidinyl group, imidazolidinyl group, pyrazolidinone group, oxazolidinyl group, 2-oxopyrrolidin group, diazolidinylurea group, isothiazolinone group, piperideine group, piperazinilnom group, morpholinyl group, thiomorpholine group, 2-oxopiperidine group, 4-oxopiperidine group, 2,6-dioxopiperidin group and the like. Preferred nitrogen-containing, saturated, monocyclic, heterocyclic group” is azetidinone group, pyrrolidinyl group, piperideine group, piperazinilnom group or thiomorpholine group.

For-NR5R6preferred nitrogen-containing, saturated, monocyclic, heterocyclic group” is azetidinone group, pyrrolidinyl group, piperideine group, piperazinilnom group or thiomorpholine group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following groups: halogen atom,

hydroxyl g is uppy,

With1-6alkyl group, optionally substituted by one or more hydroxyl groups,

carboxyl group,

acetyl group,

carbamoyl group,

amino group, optionally substituted by one or more, same or different substituents selected from C1-6alkyl group and acetyl group and the carbonyl group).

For-NR20R21preferred nitrogen-containing, saturated, monocyclic, heterocyclic group” is azetidinone group, pyrrolidinyl group or piperideine group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from a halogen atom and a hydroxyl group).

For-NR26R27preferred nitrogen-containing, saturated, monocyclic, heterocyclic group” is piperideine group or pyrrolidinyl group, more preferred piperideine group.

For R10preferred nitrogen-containing, saturated, monocyclic, heterocyclic group” is piperideine group.

For R11preferred nitrogen-containing, saturated, monocyclic, heterocyclic group” is pyrrolidinyl group or piperidin the other group (this heterocyclic group is optionally substituted by one or more identical or different substituents, selected from C1-6alkyl group, -CO-C1-6the alkyl group and the carbonyl group).

The presence of the term “optionally substituted by one or more substituents” means that there is unsubstituted or optionally substituted by at least using from one to the maximum number of substituents. For example, in the case of a methyl group, that means there is an optional substituted from 1 to 3 substituents in the case of ethyl group, this means the presence optional substituted by 1 to 5 substituents. The substituents in the case of substitution of from two or more substituents may be the same or different and position of the substituents are not specifically limited and can be any.

The term “C1-6alkyl group, optionally substituted by one or more, same or different substituents” preferably represents C1-6alkyl group optionally substituted by the same or different 1 to 3 substituents. Especially, “1-6alkyl group, optionally substituted by one or more, same or different halogen atoms” preferably represents C1-6alkyl group optionally substituted by 1 to 3 halogen atoms, more preferably1-6the alkyl group is one the Xia optionally substituted by three halogen atoms and more preferably triptorelin group or 2,2,2-triptorelin group.

Preferred groups, each group are as follows.

[Preferred ring A]

Ring A represents a

(1) nitrogen-containing, saturated, monocyclic, heterocyclic group (i.e.,- X - represents-N(R1)-) or

(2) cycloalkyl group (i.e.,- X - represents-C(R7R8)-) and preferably

(1) azetidinone group or piperidino group or

(2) tsiklogeksilnogo group.

[Preferred R2]

R2preferably represents cyclopropyl group or tsiklogeksilnogo group, optionally substituted by one or more, same or different substituents selected from C1-6alkyl group (specified With1-6alkyl group is optionally substituted hydroxyl group) and C1-6alkoxygroup. More preferably, it is cyclopropyl group or tsiklogeksilnogo group, optionally substituted by one or more methyl groups (this methyl group is optionally substituted hydroxyl group) or methoxypropane. Especially preferably, it is cyclopropyl group, methylcyclopropyl group, methoxycyclohexene group, tetramethylcyclopropane group, hydroxymethylcellulose the function group or tsiklogeksilnogo group.

[Preferred R3and R4]

R3and R4preferably not simultaneously represent hydrogen atoms.

More preferably one of R3and R4represents a hydrogen atom, hydroxyl group, With1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from a halogen atom, a hydroxyl group, metoxygroup and acetyloxy) or (C1-6alkoxygroup and the other is not a hydrogen atom.

In addition, preferably one of R3and R4represents a hydrogen atom, hydroxyl group, With1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from a halogen atom, a hydroxyl group, metoxygroup and acetyloxy) or (C1-6alkoxygroup and the other is a Deputy selected from the following group, which is optionally substituted by one or more, same or different substituents selected from a halogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted one or more measure the ohms are the same or different halogen atoms or hydroxyl group), With1-6alkoxygroup (specified With1-6alkoxygroup is optionally substituted by one or more, same or different halogen atoms), C1-6alkoxycarbonyl group and ceanography:

• phenyl group,

• Peregrina group and

• thiazolidine group.

Particularly preferably, when one of R3and R4represents a hydrogen atom, hydroxyl group, With1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from a halogen atom, a hydroxyl group, metoxygroup and acetyloxy) or a methoxy group and the other represents a Deputy selected from the following group, which is optionally substituted by one or more, same or different substituents selected from a halogen atom, triptorelin group, cryptometer, methoxycarbonyl group, hydroxymethylene group and ceanography:

• phenyl group,

• Peregrina group and

• thiazolidine group.

[Preferred R5and R6]

R5and R6are preferably the same or different and each represents

• a hydrogen atom,

• phenyl group, neobyazatelnostyu one or more identical or different substituents, selected from hydroxyl group, halogen atom, carboxyl group and1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more hydroxyl groups or halogen atoms),

• cycloalkyl group having from 3 to 6 carbon atoms (indicated cycloalkyl group is optionally substituted C1-6alkyl group, optionally substituted by one or more hydroxyl groups),

1-6alkyl group, optionally substituted by one or more, same or different substituents selected from hydroxyl group, halogen atom, phenyl group (this phenyl group is optionally substituted by halogen atom), a carboxyl group, and-NR20R21(where R20and R21are those as defined for the formula [1]),

• -S(=O)2-R9where R9represents a phenyl group or a C1-6alkyl group,

• optional saturated With1-6alkoxygroup,

• pyridinyl group optionally substituted by a halogen atom at the 2-position and 6-position

• optionally substituted, nitrogen-containing unsaturated, heterocyclic group, or

• nitrogen-containing, saturated, monocyclic, heterocyclic the action group, optionally substituted by one or more, same or different substituents selected from C1-6alkyl groups and-CO-C1-6alkyl group, or

• R5and R6may form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group selected from azetidine group, pyrrolidinyl group, piperidino group, piperazinilnom group and thiomorpholine group or heterocyclic group selected from dihydroindole group, dihydro[1,4]oxazinyl group, tetrahydrobenzo[b]aspenlea group, which is a condensed ring of the specified heterocycle and carbon rings (both of these heterocyclic groups are optionally substituted by one or more, same or different substituents selected from the following groups:

the halogen atom,

hydroxyl group,

With1-6alkyl group, optionally substituted by one or more hydroxyl groups,

carboxyl group,

acetyl group,

carbamoyl group,

amino group, optionally substituted by one or more, same or different substituents selected from C1-6alkyl group and acetyl group, and

p> the carbonyl group).

More preferably, when R5and R6are the same or different and each represents

• a hydrogen atom,

• phenyl group, optionally substituted on the ortho-position and/or para-position substituents selected from hydroxyl group, halogen atom, carboxyl group and1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more hydroxyl groups or halogen atoms),

• cyclopropyl group or cyclopentyl group, optionally substituted C1-6alkyl group, optionally substituted by one or more hydroxyl groups,

1-6alkyl group, substituted by one or more, same or different substituents selected from hydroxyl group, halogen atom, phenyl group (this phenyl group is optionally substituted by halogen atom), a carboxyl group, and-NR20R21(where R20and R21are those as defined for the formula [1]),

• -S(=O)2-R9where R9represents a phenyl group or a methyl group,

1-6alkoxygroup,

• pyridinyl group substituted by a halogen atom at 2-position and 6-position,

• optional the nutrient rich thiazolino group or

• piperidine-4-ilen group, optionally substituted at the 1-position by one Deputy, selected from C1-6alkyl groups and-CO-C1-6alkyl group, or

• R5and R6may form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, selected from azetidin-1-ilen group, pyrrolidin-1-ilen group, piperidine-1-ilen group, piperazine-1-ilen group and thiomorpholine-4-ilen group or heterocyclic group selected from dihydroindol-1-ilen group, dihydro[1,4]oxazin-1-ilen group, tetrahydrobenzo[b]azepin-1-ilen group, which is a condensed ring of the specified heterocycle and carbon rings (both of these heterocyclic groups are optionally substituted by one or more, same or different substituents selected from the following groups:

the halogen atom,

hydroxyl group,

With1-6alkyl group, optionally substituted by one or more hydroxyl groups,

carboxyl group,

acetyl group,

carbamoyl group,

amino group, optionally substituted by one or more, same or different substituents selected from C1-6alkyl groups and acetyl g is uppy and

the carbonyl group).

Moreover, preferably, when R5and R6are the same or different and each represents

• a hydrogen atom,

• phenyl group, substituted at the ortho-position and/or para-position substituents selected from hydroxyl group, halogen atom, carboxyl group and1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more hydroxyl groups or halogen atoms),

• cyclopropyl group or cyclopentyl group, substituted C1-6alkyl group substituted by one or more hydroxyl groups,

1-6alkyl group, substituted by one Deputy, selected from hydroxyl group, halogen atom, phenyl group (this phenyl group is optionally substituted by halogen atom), a carboxyl group, and-NR20R21(where R20and R21are those as defined for the formula [1]),

• -S(=O)2-R9where R9represents a phenyl group or a methyl group,

1-6alkoxygroup,

• pyridine-3-ilen group substituted by a halogen atom at 2-position and 6-position,

• thiazolino group or

• piperidine-4-ilen group, optionally substituted in 1-position is the-CO-C 1-6alkyl group, or

• R5and R6may form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group, selected from azetidin-1-ilen group, pyrrolidin-1-ilen group, piperidine-1-ilen group, piperazine-1-ilen group and thiomorpholine-4-ilen group or heterocyclic group selected from dihydroindol-1-ilen group, dihydro[1,4]oxazin-1-ilen group, tetrahydrobenzo[b]azepin-1-ilen group, which is a condensed ring of the specified heterocycle and carbon rings (both of these heterocyclic groups are optionally substituted by one or more, same or different substituents selected from the following groups:

the halogen atom,

hydroxyl group,

With1-6alkyl group, optionally substituted by one or more hydroxyl groups,

carboxyl group,

acetyl group,

carbamoyl group,

amino group, optionally substituted by one or more, same or different substituents selected from C1-6alkyl group and acetyl group, and

the carbonyl group).

Particularly preferably, when R5and R6are the same or different and each isone

• a hydrogen atom,

• 2-florfenicol group,

• 2-carboxyphenyl group,

• 2-hydroxymethylamino group,

• 1-hydroxymethylpropane group,

• 2-hydroxyethyloxy group,

• 2-hydroxy-1,1-dimethylethylene group,

• 2-acetylaminophenol group,

• 2-aminoethyl group,

• 2-dimethylaminoethyl group,

• 2-piperidine-1-yl-ethyl group,

• 2-hydroxy-1-methylamino group,

• piperidine-4-ilen group,

• 1 methylpiperidin-4-ilen group,

• 1-acetylpiperidine-4-ilen group,

• 2,2,2-triptorelin group,

• 1-hydroxymethyl-2-methylpropyloxy group,

• 1-hydroxymethyl-2-phenylethylene group,

• 2-hydroxy-1-phenylethylene group,

• 1-hydroxymethyl-3-methylbutyl group,

• 2-hydroxyphenyl group,

• 1-hydroxymethylglutaryl group,

• benzosulfimide group,

• 4-triftormetilfullerenov group,

• 2,4-differenly group,

• 1-carboxy-2-methylpropyloxy group,

• thiazol-2-ilen group,

• isopropoxide,

• 4-forbindelse group,

• 2,6-dichloropyridine-3-ilen group,

• ethoxypropan or

• mesyl group, or

• R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, g is teracycline group, or heterocyclic group, which is a condensed ring of the specified heterocycle and the carbon ring, which is selected from the following groups:

azetidin-1-ilen group,

3-hydroxyazetidine-1-ilen group,

3-hydroxymethylation-1-ilen group,

3-acetylization-1-ilen group,

3-acetylaminoacetylenes-1-ilen group,

3-hydroxypyrrolidine-1-ilen group,

3,3-debtorprovidian-1-ilen group,

3,3,4,4-tetrafluoropyridine-1-ilen group,

2-hydroxyethylpyrrolidine-1-ilen group,

2-aminopyrrolidine-1-ilen group,

2-acetylpyrrolidine-1-ilen group,

2-dimethylaminopyridine-1-ilen group,

3-oxopyrrolidin-1-ilen group,

4-hydroxypiperidine-1-ilen group,

4,4-deformability-1-ilen group,

4-hydroxyethylpiperazine-1-ilen group,

4-carboxypeptidase-1-ilen group,

3-hydroxypiperidine-1-ilen group,

4-carbamoylbiphenyl-1-ilen group,

4-aminopiperidin-1-ilen group,

4-dimethylaminopyridine-1-ilen group,

4-acetylaminophenol-1-ilen group,

4-methylpiperazin-1-ilen group,

4-isopropylpiperazine-1-ilen group,

4-acetylpiperidine-1-ilen group,

1,1-diocletianopolis-4-ilen group,

3-oxopiperidin-1-ilen group,

4-oxopiperidin-1-ilen gr is PPI,

2,3-dihydroindol-1-ilen group,

2,3-dihydro[1,4]oxazin-1-ilen group and

2,3,4,5-tetrahydrobenzo[b]azepin-1-ilen group.

Moreover, preferably, when R5and R6are not simultaneously hydrogen atoms. More preferably one of R5and R6represents a hydrogen atom and the other is not a hydrogen atom.

[Preferred R10]

R10preferably represents

1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from hydroxyl group, phenyl group, and-NR26R27where R26and R27are the same or different and each represents a C1-6alkyl group, or R26and R27optional form piperidino group together with the nitrogen atom to which they relate), or

• piperidino group (specified piperideine group is optionally substituted by one or more, same or different substituents selected from C1-6alkyl groups and-CO-C1-6alkyl group).

R10more preferably represents a

1-6alkyl group (specified With1-6the alkyl group is a long is the super substituted by one or more identical or different substituents, selected from a hydroxyl group, phenyl group, and-NR26R27where R26and R27are the same or different and each represents a C1-6alkyl group, or R26and R27optional form piperidino group together with the nitrogen atom to which they relate), or

• piperidine-4-ilen group (specified piperidine-4-ilen group is optionally substituted by one or more, same or different substituents selected from C1-6alkyl groups and-CO-C1-6alkyl group).

R10in addition, preferably represents

1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from hydroxyl group, phenyl group, and-NR26R27where R26and R27are the same or different and each represents a C1-6alkyl group, or R26and R27optional form piperidino group together with the nitrogen atom to which they relate), or

• piperidine-4-ilen group (specified piperidine-4-ilen group is optionally substituted by one or more, same or different substituents selected from C1-6alkyl groups,- CO-C 1-6alkyl group).

R10represents a particularly preferred

• methyl group,

• 2-hydroxyethyloxy group,

• 2-dimethylaminoethyl group,

• 2-piperidine-1-ratelow group,

• piperidine-4-ilen group,

• 1 methylpiperidin-4-ilen group,

• benzyl group, or

• 1-acetylpiperidine-4-ilen group.

[Preferred R11]

R11preferably represents

1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) through (g):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,

d) carbamoyl group,

e) a carboxyl group,

(f) fenoxaprop and

g) forfamilies group)

• cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group, optionally Zam is illuminated by one or more, same or different halogen atoms and

(b) (C1-6alkyl group, optionally substituted by one or more hydroxyl groups),

• aryl group (this aryl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a) one or more identical or different halogen atoms,

(b) (C1-6alkyl group, optionally substituted by one or more, same or different halogen atoms and

c1-6alkoxygroup),

• carboxyl group, or

• nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group).

R11more preferably represents a

1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) through (g):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or the difference is different and each represents a hydrogen atom, With1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,

d) carbamoyl group,

e) a carboxyl group,

(f) fenoxaprop and

g) forfamilies group)

• cyclopropyl group (specified cyclopropyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group, optionally substituted by one or more, same or different halogen atoms and

(b) (C1-6alkyl group, optionally substituted by one or more hydroxyl groups),

• phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a) one or more identical or different halogen atoms,

(b) (C1-6alkyl group, optionally substituted by one or more, same or different halogen atoms and

c1-6alkoxygroup),

• carboxyl group, or

• nitrogen-containing, saturated, monocyclic, heterocyclic group selected from pyrrolidinyl group and piperidino group (specified heterocyclic the Skye group is optionally substituted by one or more identical or different substituents, selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group).

R11in addition, preferably represents

1-6alkyl group (specified With1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) through (g):

a) halogen atom,

b) a hydroxyl group,

c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,

d) carbamoyl group,

e) a carboxyl group,

(f) fenoxaprop and

g) forfamilies group)

• cyclopropyl group (specified cyclopropyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):

(a) aryl group, optionally substituted by one or more, same or different halogen atoms and

(b) (C1-6alkyl group, optionally substituted by one or more hydroxyl groups),

• phenyl group (this phenyl group is substituted on the him or more identical or different substituents, selected from the following a) to c):

a) one or more identical or different halogen atoms,

(b) (C1-6alkyl group, optionally substituted by one or more, same or different halogen atoms and

c1-6alkoxygroup),

• carboxyl group, or

• nitrogen-containing, saturated, monocyclic, heterocyclic group selected from pyrrolidin-2-ilen group and piperidine-4-ilen group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to c):

a)1-6alkyl groups,

b) -CO-C1-6alkyl groups and

c) the carbonyl group).

R11represents a particularly preferred

• 2,2,2-triptorelin group,

• hydroxymethylene group,

• 3-hydroxypropyl group,

• 2-hydroxy-1,1-dimethylethylene group,

• aminomethyl group,

• 2-aminoethyl group,

• 1-amino-1-methylamino group,

• 1-amino-2-methylpropyloxy group,

• methylaminomethyl group,

• dimethylaminomethylene group,

• acetamidomethyl group,

• 1-acetylaminophenol group,

• 2-acetylaminophenol group,

• 1-acetylamino-1-methylamino group,

• 1-acetyl what Ino-2-methylpropyloxy group,

• isobutylamino group,

• cyclopropanecarbonitrile group,

• methanesulfonylaminoethyl group,

• 2-carbamoylethyl group,

• cyclopropyl group,

• 1-(4-forfinal)cyclopropyl group,

• 1-methylcyclopropyl group,

• 1-hydroxymethylpropane group,

• pyrrolidin-1-ilen group,

• pyrrolidin-2-ilen group,

• piperidine-4-ilen group,

• 1 methylpyrrolidine-2-ilen group,

• 1 methylpiperidin-4-ilen group,

• 1-acetylpyrrolidine-2-ilen group,

• 1-acetylpiperidine-4-ilen group,

• 2-carboxy-2-methylpropyloxy group,

• phenoxymethyl group,

• 2-chloraniline group,

• 3-chloraniline group,

• 4-chloraniline group,

• carboxyl group,

• 4-forbindelse group,

• 3-triftormetilfullerenov group,

• 3-metoksifenilny group or

• 5-oxopyrrolidin-2-ilen group.

Salt of the compounds of the present invention preferably is a pharmaceutically acceptable salt. Salt of the compounds of the present invention represented by the formula [1'] can be obtained in the usual way. Salt of the compounds of the present invention represented by the formula [1'], can be obtained by the reaction of compounds of formula [1'] (hereinafter soy is inania [1'] and its salt all together, by definition, relate to the connection of the present invention), for example, inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, Hydrobromic acid and the like; organic acids such as oxalic acid, malonic acid, citric acid, fumaric acid, lactic acid, malic acid, succinic acid, tartaric acid, acetic acid, triperoxonane acid, gluconic acid, ascorbic acid, methanesulfonate acid, benzolsulfonat acid and the like; inorganic bases such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, ammonium hydroxide and the like; organic bases such as methylamine, diethylamine, triethylamine, triethanolamine, Ethylenediamine, Tris(hydroxymethyl)methylamine, guanidine, choline, cinchonine and the like; amino acids such as lysine, arginine, alanine and the like. The present invention also includes aqueous products, hydrate and a solvate of the compound of the present invention.

In addition, the compound of the present invention has various isomers. For example, E form and Z form can be represented as geometric isomers, when there is an asymmetric carbon atom, the enantiomer and the diastereoisomer presented as the stereoisomers of the compounds and can also be tautomers. The poet is, the present invention covers these isomers and their mixtures. Moreover, the present invention encompasses in addition to the compounds of the present invention, prodrugs of compounds and metabolites of the compounds as equivalent connection.

Used in this description, the term "prodrug" means a derivative, which has a chemically or metabolically tsepliaeva group, and manifesting pharmaceutical activity after decomposition by hydrolysis or solvolysis or under physiological conditions. The prodrug is used, for example, to improve absorption when administered orally or hit the target on the object. As such chemically or metabolically tsepliaeva group is used, and how it is embedded in the connection, are well studied in the field of pharmaceutical agents, such known methods can be used in this invention. As the functional group, which can be modified to obtain prodrugs of the compounds of this invention can be used highly reactive functional group such as hydroxyl group, carboxyl group, amino group, thiol group, etc. that can be specified for compounds of the present invention.

For example, there may be mentioned a derivative, where the cover is spruce, such as-CO-C1-6alkyl group, -CO2-C1-6alkyl group, -CONH-C1-6alkyl group, -CO-C2-6Alchemilla group, -CO2-C2-6Alchemilla group, -CONH-C2-6Alchemilla group, -CO-aryl group, -CO2-aryl group, -CONH-aryl group, -CO-heterocyclic group, -CO2-heterocyclic group, -CONH-heterocyclic group (C1-6alkyl group, a C2-6Alchemilla group, aryl group and heterocyclic group optionally substituted by a halogen atom, a C1-6alkyl group, a hydroxyl group, With1-6alkoxygroup, carboxyl group, amino group, amino acid residue, -PO3H2, -SO3H, residue-CO-poly (ethylene glycol), residue-CO2-glycol, the remainder monoalkyl ether-CO-polyethylene glycol, the remainder monoalkyl ether-CO2the polyethylene glycol and the like) and the like included in the hydroxyl group.

In addition, there may be mentioned a derivative, where the Deputy, such as-CO-C1-6alkyl group, -CO2-C1-6alkyl group, -CO-C2-6Alchemilla group, -CO2-C2-6Alchemilla group, -CO-aryl group, -CO2-aryl group, -CO-heterocyclic group, -CO2-heterocyclic group (C1-6alkyl group, a C2-6and chunilna group, aryl group and heterocyclic group optionally substituted by a halogen atom, a C1-6alkyl group, a hydroxyl group, With1-6alkoxygroup, carboxyl group, amino group, amino acid residue, -PO3H2, -SO3H, residue-CO-poly (ethylene glycol), residue-CO2-glycol, the remainder monoalkyl ether-CO-polyethylene glycol, the remainder monoalkyl ether-CO2-glycol-PO3H2and the like) and the like included in the amino group.

Moreover, there may be mentioned a derivative, where the Deputy, such as1-6alkoxygroup, alloctype (C1-6alkoxygroup and alloctype, optionally substituted by a halogen atom, a C1-6alkyl group, a hydroxyl group, With1-6alkoxygroup, carboxyl group, amino group, amino acid residue, -PO3H2, -SO3H, a residue of polyethylene glycol, the remainder monoalkyl ether of polyethylene glycol and the like) and the like included in the carboxyl group.

As indicated above, the term “heterocyclic group” is a 5-membered or 6-membered saturated or unsaturated (including partial desaturation and full desaturation), monocyclic, heterocyclic group having, besides carbon atom, at least one pre is respectfully from 1 to 4 heteroatoms, selected from nitrogen atom, oxygen atom and sulfur atom, or a condensed ring group of the heterocycle or a condensed ring group of the heterocycle and the carbon ring selected from benzene, cyclopentane and cyclohexane.

As the “5-membered or 6-membered saturated, monocyclic, heterocyclic group”, for example, can be mentioned pyrrolidinyl group, tetrahydrofuryl group, tetrahydroquinoline group, imidazolidinyl group, pyrazolidinone group, 1,3-DIOXOLANYL group, 1,3-occationally group, oxazolidinyl group, diazolidinylurea group, piperidinyl group, piperazinilnom group, tetrahydropyranyl group, tetrahydropyranyl group, dioxinlika group, morpholinyl group, thiomorpholine group, 2-oxopyrrolidin group, 2-oxopiperidine group, 4-oxopiperidine group, 2,6-dioxopiperidin group and the like.

As the “5-membered or 6-membered unsaturated, monocyclic, heterocyclic group”, for example, can be mentioned pyrrolidine group, furilla group, thienyl group, imidazolidinyl group, 1,2-dihydro-2-Oxymetazoline group, pyrazolidine group, diazolidinyl group, oxazoline group, isoxazolyl group, thiazolidine group, isothiazolin the th group, thiazolidine group (1,2,4-triazoline group, 1,2,3-triazoline group), tetrataenia group, 1,3,4-oxadiazolyl group, 1,2,4-oxadiazolyl group, 1,3,4-thiadiazolyl group, 1,2,4-thiadiazolyl group, furazolidine group, Peregrina group, pyrimidinyl group, 3,4-dihydro-4-oxopyrimidine group, pyridazinyl group, piratininga group, 1,3,5-trainline group, imidazolidine group, piratininga group, oxazolidine group (2-oxazolidinone group, 3-oxazolidine group, 4-oxazolidinone group), isooxazolyl group, thiazolidine group, isothiazolinone group, Pernilla group, 2-oxopyrimidine group, 2-oxo-2,5-dihydropyridine group and 1,1-dioxo-1H-isothiazolinone group.

As the “heterocyclic group which is a condensed ring, for example, can be mentioned indlela group (for example, 4-indlela group, 7-indlela group and so on), isoindoline group, 1,3-dihydro-1,3-dioxopiperidin group, benzofuranyl group (for example, 4-benzofuranyl group, 7-benzofuranyl group and so on), indazolinone group, isobenzofuranyl group, benzothiazoline group (for example, 4-benzothiophene group, 7-benzothiazoline group and so on), benzoxazolyl group (e.g. the measures 4-benzoxazolyl group, 7-benzoxazolyl group and so on), benzimidazolyl group (for example, 4-benzimidazolyl group, 7-benzimidazolyl group and so on), benzothiazolyl group (for example, 4-benzothiazolyl group, 7-benzothiazolyl group and so on), indolizinyl group, kinolinna group, izochinolina group, 1,2-dihydro-2-oxopyridine group, chinadaily group, khinoksalinona group, indolenine group, phthalazinone group, hyalinella group, pualina group, pteridinyl group, indolinyl group, isoindolyl group, 5,6,7,8-tetrahydroquinoline group, 1,2,3,4-tetrahydroquinoline group, 2-oxo-1,2,3,4-tetrahydroquinoline group, benzo[1,3]dioxooleana group, 3,4-methylenedioxyphenyl group, 4,5-ethylenediaminetetramethylene group, chromadorina group, chromadorina group, thrombilia group and the like.

The term "pharmaceutical composition" includes, in addition to determining the composition containing the active ingredient as a pharmaceutical agent and combined drug and the like, the combination agent with another lekarstvennym tool, etc. Needless to say that the pharmaceutical composition of the present invention can be used simultaneously with any other drug within the limits of acceptability in the Kli of the practical situation. Thus, the present pharmaceutical composition can also be seen as a pharmaceutical composition for combination with another drug.

Moreover, the pharmaceutical composition of the present invention can be introduced not only man, but also other mammals (mice, rats, hamsters, rabbits, cats, dogs, cows, horses, sheep, monkeys and so on). Therefore, the pharmaceutical composition of the present invention is also applicable as a pharmaceutical product for animals, not to mention the man.

The compound of the present invention and its salt can be mixed with a pharmaceutically acceptable carrier and administered orally or parenterally in the form of tablets, pills, powder, granule, suppository, injection, eye drops, solution, capsules, pastilles, aerosol, elixir, suspension, emulsion, syrup, etc.

As a "pharmaceutically acceptable carrier" used various organic or inorganic substances-media, usually used as the basic substance of the drug, which add as a neutral filler, lubricants, binders, razryhrytelya, solvent, auxiliary solvents, suspending agent, isotonic agent, buffer, soothing the Ghent etc. If necessary, auxiliary agents such as preservatives, antioxidants, colorants, sweeteners, etc. can also be used. As examples of the above-mentioned fillers may be mentioned lactose, sucrose, D-mannitol, starch, crystalline cellulose, light silicic anhydride and the like as the above-mentioned lubricants can be provided, for example, magnesium stearate, calcium stearate, talc, colloidal silica, etc. as examples of the above-mentioned binders may be described polymer compounds such as crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropylcellulose, hypromellose, polyvinylpyrrolidone, etc. as examples of the above-mentioned razryhrytelya can be brought starch, carboxymethyl cellulose, calcium carboxymethyl cellulose, crosscarmellose sodium, sodium carboxymethyl starch, etc. as examples of the above-mentioned solvents can be given water for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil, esters of propylene glycol and fatty acids, etc. as examples of the above contributing to the dissolved substances can be mentioned polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trilaminate, cholesterol, t is ethanolamine, sodium carbonate, sodium citrate, etc. as examples of the above-mentioned suspendida agents can be described surfactants, such as stearyl triethanolamine, sodium lauryl sulphate, lauryl-aminopropionic acid, lecithin, benzalkonium chloride, benzene chloride, glycerylmonostearate and the like; polyvinyl alcohol, polyvinylpyrrolidone, carboxymethylcellulose sodium, methylcellulose, hydroxymethylcellulose, etc. as examples of the above-mentioned isotonic agents may be given sodium chloride, glycerin, D-mannitol, etc. as examples of the aforementioned buffer substances can be given such buffers like phosphate, acetate, carbonate, citrate etc. as examples of the above-mentioned emollients can be brought benzyl alcohol, etc. as examples of the above-mentioned preservatives can be given peroxybenzoate, chlorbutanol, benzyl alcohol, fantroy alcohol, dehydroacetic acid, sorbic acid, etc. as examples of the above antioxidants may be given a sulfite, ascorbic acid, etc. as examples of the above-mentioned sweeteners can be given aspartame, saccharin sodium, stevia, etc. as examples of the above dyes can be given food colors such as Food Color Yellow No. 5,Food Color Red No. 2 and Food Color Blue No. 2 and the like, food lake colors, iron oxide, etc.

The term "11βHSD1 inhibitor" means the disappearance or weakening of the activity of 11βHSD1 by specific inhibition of its function as an enzyme, for example, the meaning of the specific inhibition of the functions of 11βHSD1 in terms of the following experimental example 1, and preferably means that the concentration required to achieve 50% inhibition of 11βHSD1 in the following conditions of experimental example 1 is less than 10 μm, preferably less than 1 μm, more preferably less than 100 nm and even more preferably less than 10 nm.

The term “pathology associated with glucocorticoid” means, for example,

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including myocardial infarction or stroke,

(4) hyperorexia,

(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, emotional disorders, schizophrenia or stimulation of appetite,

(6) the disease is associated with decreased immune function,

(7) glaucoma or

(8) osteoporosis

etc.

If soy is inania of the present invention is used as a medicine for the treatment or prophylaxis of a pathology, demonstrating the involvement of glucocorticoids, it can be introduced systemically, topically, orally or parenterally. Since the dose varies depending on age, body weight, condition, effect of treatment and the like, for example, the drug may be in the range from 0.1 to 1 g per reception grown from one to several times a day. The compound of the present invention can also be used as a drug for treatment or prevention of the aforementioned diseases in humans, other than those of animals, particularly in mammals. The same applies to the use of compounds of the present invention as a drug for treatment or prevention of the following diseases:

(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,

(2) metabolic syndrome,

(3) a fatal vascular event, including myocardial infarction or stroke,

(4) hyperorexia,

(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, emotional disorders, schizophrenia or stimulation of appetite,

(6) the disease is associated with decreased immune function,

(7) glaucoma, or

(8) osteoporosis

Etc.

To obtain the drug compounds of the present invention, such as a solid composition or a liquid composition for oral administration, or injections for parenteral administration, etc., this compound can be mixed with auxiliary substances, such as suitable diluent, dispersing agent, adsorbent, solubilizers tool, etc. in Addition, the pharmaceutical composition of the present invention may be of known form, such as tablets, pills, powder, granules, suppositories, injections, eye drops, solution, capsule, LPS, aerosol, elixir, suspension, emulsion, syrup, etc.

In cases where the pharmaceutical composition of the present invention is, for example, a solid preparation such as tablet, pill, powder, granules and the like, auxiliary substances include, for example, lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone, magnesium aluminometasilicate powder, silicic anhydride, etc. In the production of tablets or pills may be optionally used shell from dissolving in the stomach or intestines of a substance, such as sucrose, gelatin, hydroxypropylcellulose or phthalate of hydroxymethylcellulose etc. or can be made multi-layered tablet having two the Loya or more.

The compound, pharmaceutical composition or drug of the present invention can be used in combination with (here and hereinafter the term "combined use") another pharmaceutical composition or preparation (hereinafter used, the term "a combined preparation").

The duration of the pharmaceutical composition or drug of the present invention and the combined drug is not limited, and they can be administered to the subject in the form of a combined preparation, introduced simultaneously or in stages. Moreover, a pharmaceutical agent, which is a set containing pharmaceutical composition or drug of the present invention and the combined drug can be entered. Can be clinically applied dose combined preparation, which may be appropriately determined depending on the subject treated, the age and body weight, General condition, time of administration, dosage form, route of administration, combination, etc. the Way the introduction of the combined preparation is not specifically limited and may be any if the pharmaceutical composition and combining the drug combination.

The pharmaceutical agent consisting of 1-3 agents selected from the following items (1) through (5)and the connection for us is oedema invention or its salt in combination:

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,(4) an agent for treatment or prevention of diabetes complications,

(5) the agent for the treatment or prevention of hypertension

means pharmaceutical agents, such as the case where a "pharmaceutical agent" is a combination drug, case when "pharmaceutical agent" is a set containing preparation containing these "1-3 agent selected from paragraphs (1) through (5)and a drug containing the compound of the present invention, the case where a "pharmaceutical agent" and a drug containing the compound of the present invention, are administered simultaneously or at intervals, etc. This pharmaceutical agent, preferably an agent for the treatment or prophylaxis of a pathology associated with glucocorticoids.

As a combined preparation may be mentioned

(1) an agent for the treatment or prophylaxis of hyperlipidemia,

(2) an agent for treatment or prevention of obesity,

(3) the agent for the treatment or prevention of diabetes,

(4) the agent for the treatment or prevention of diabetes complications, and

(5) the agent for the treatment or prevention of hypertension,

and 1-3 agent, on their basis, and the connection is really the image the structure can be used in combination.

As "agent for the treatment or prophylaxis of hyperlipidemia can be mentioned, for example,

(1) fibrates (PPAR agonists α),

(2) agonists, PPAR-δ,

(3) inhibitors of microsomal protein carrier of triglycerides,

(4) inhibitors of protein-a carrier of aethers of cholesterol,

(5) statins (inhibitors of HMG-CoA reductase),

(6) anion exchange resin,

(7) probucol,

(8) nicotinic acid drugs,

(9) phytosterols,

(10) the inductors apolipoprotein-A1 (Apo-A1),

(11) an activator of lipoprotein lipase (LPL),

(12) inhibitors of endothelial lipase,

(13) ezetimib,

(14) IBAT inhibitors,

(15) inhibitors of squalene synthase,

(16) the ACAT inhibitors,

(17) agonists receptor LXR,

(18) agonists receptors FXR,

(19) FXR receptor antagonists, and

(20) agonists of the adenosine A1

and, in particular, can be referred to clofibrate, bezafibrat, fenofibrate, lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, pitavastatin, rosuvastatin, tseriwastatina, cholestyramine, colestimide, tocopherol nicotinate, nicomol, niceritrol, sisterol, gamma-oryzanol, etc.

As "agent for the treatment or prevention of obesity" can be mentioned, for example,

(1) leptin,

(2) inhibitors of pancreatic lipase,

(3) inhibitors of reuptake of norepinephrine and serotonin

(4) antagonis the s cannabinoid receptors,

(5) inhibitors of reuptake of monoamines,

(6) inhibitors of diacylglycerol acyltransferase (DGAT),

(7) receptor antagonists glukozooksidasa insulinotropic polypeptide (GIP),

(8) agonists, leptin receptor,

(9) agonists receptor bombezin subtype 3 (BRS-3),

(10) inhibitors of perilipin,

(11) inhibitors of acetyl-COA carboxylase 1 (ACC1),

(12) inhibitors of acetyl-COA carboxylase 2 (ACC2),

(13) inhibitors of fatty acid synthase,

(14) inhibitors sn-1-acyl-glycerol-3-phosphate acyltransferase (AGPAT),

(15) inhibitors of zoom phospholipase A2 (pPLA2), (16) agonists receptor melanocortin (MC), (17) receptor antagonists of neuropeptide Y5 (NPY5),

(18) the inductor or activators uncoupling protein (UCP),

(19) activators carnitine O-palmitoyltransferase 1 (CPT-1),

(20) agonists CCK1 (CCKA),

(21) ciliary neurotrophic factor (CNTF),

(22) agonists, CRF 2,

(23) receptor antagonists of the neuropeptide Y2 (NPY2),

(24) receptor antagonists of neuropeptide Y4 (NPY4),

(25) agonists beta-receptors of thyroid hormones,

(26) growth hormones

(27) inhibitors of ATP citrate liase,

(28) antagonists of 5-HT6, and

(29) agonist at 5-HT2C

and, in particular, can be referred to leptin, orlistat, sibutramine, rimonabant and mazindol, etc.

As "agent for the treatment or prevention of diabetes" can be mentioned, for example,

1) insulin (injection),

(2) oral drugs of low molecular weight insulin

(3) receptor agonists sulfonylureas (SU agents),

(4) desulfonylation tools that increase insulin secretion (SU agents),

(5) the opening kolisevski ATP-channels (KATP),

(6) inhibitors of α-glucosidase,

(7) inhibitors of α-amylase,

(8) a means of improving insulin sensitivity,

(9) low molecular weight agonists of receptors tGLP-1,

(10) the peptide analogues tGLP-1,

(11) inhibitors of dipeptidylpeptidase IV (DPP-IV)

(12) receptor antagonists of glucagon

(13) receptor antagonists glucorticosteroids,

(14) biguanides,

(15) inhibitors SGLUT,

(16) inhibitors of fructose - 1,6-biphosphate (FBPase),

(17) inhibitors of kinase 3 glikogensintetazy (GSK-3),

(18) inhibitors phosphoenolpyruvate carboxykinase (PEPCK),

(19) inhibitors patientinitiated 1B (PTPase 1B),

(20) inhibitors of SH2 dominatethe inositolfosfatov (SHIP2),

(21) inhibitors of glycogen phosphorylase (GP),

(22) activators of glucokinase,

(23) agonists of GPR40 receptor,

(24) inhibitors kinase piruvatdegidrogenazy (PDHK),

(25) inhibitors of glutamine-fructose-6-fosforamidokyanidaty (GFAT),

(26) antioxidants; acceptors of nitric oxide,

(27) inhibitors of carnitine-O-palmitoyltransferase 1 (CPT-1),

(28) the factors that stimulates growth hormone (GHRF),

(29) inhibitors triacyl is literalpath (hormone-sensitive lipase),

(30) agonists of PPAR γ,

(31) antagonists, PPAR γ,

(32) agonists, PPAR α/γ,

(33) activators of AMP-activated protein kinase,

(34) agonists of the receptors, adiponectin, and

(35) agonists, β3-adrenergic receptors,

and, in particular, can be mentioned insulin, tolbutamide, glimepiride, acetohexamide, hlorpropamid, glibedal, glibenclamide, gliclazide, glimepiride, mitiglinide, Repaglinide, nateglinide, voglibose, acarbose, miglitol, rosiglitazone maleate, Metformin hydrochloride, pioglitazone hydrochloride, buformin hydrochloride etc.

As "agent for the treatment or prevention of diabetic complications" can be mentioned, for example,

(1) the inhibitor of protein kinase C β (PKCβ),

(2) receptor antagonist of angiotensin II,

(3) the inhibitor alsoreported,

(4) the inhibitor of angiotensin converting enzyme (ACE)inhibitors,

(5) inhibitors of production of the end products of glycation (AGE),

(6) therapeutic agents for the treatment of neuropathy and

(7) therapeutic agents for the treatment of diabetic nephropathy

and, in particular, can be mentioned epalrestat (kinetic), meksiletina hydrochloride, imidapril hydrochloride etc.

As "agent for the treatment or prevention of hypertension" can be mentioned, for example,

(1) thiazide diuretics

(2) casinomodule diuretics,

(3) PE is left diuretics,

(4) potassium-sparing diuretics

(5) β-blockers,

(6) α,β-blockers,

(7) α-blockers,

(8) Central sympathetic neuropressure,

(9) peripheral sympathetic neuropressure (rauwolfia preparations),

(10) antagonists Ca (benzodiazepin),

(11) Ca antagonists (dihydropyridines),

(12) the vasodilator,

(13) the angiotensin converting enzyme (ACE),

(14) antagonists of receptors of angiotensin II,

(15) nitrates,

(16) receptor antagonists endothelin ETA,

(17) inhibitors endotelinzawisimogo enzyme; inhibitors neprilysin,

(18) prostaglandin; agonists of prostanoid FP,

(19) inhibitors of renin,

(20) a means of improving the expression of NOS3; analogues of prostacyclin,

(21) inhibitors of phosphodiesterase V (PDE5A),

(22) the analogues of prostacyclin, and

(23) aldosterone antagonists

and, in particular, can be mentioned hydrochlorothiazide, trichlormethiazide, benzylhydroxylamine, metakron, indapamide, tripamide, chlorthalidone, mefruside, furosemide, spironolactone, triamterene, atenolol, bisoprolol fumarate, betaxolol hydrochloride, bevantolol hydrochloride, metoprolol tartrate, acebutolol hydrochloride, celiprolol hydrochloride, nipradilol, tilisolol hydrochloride, nadolol, propranolol hydrochloride, indenolol hydrochloride, carteolol hydrochloride, pindolol, drug pindolol with medlennym release, bunitrolol hydrochloride, penbutolol sulfate, bopindolol malonate, amosulalol hydrochloride, arotinolol hydrochloride, carvedilol, labetalola hydrochloride, urapidil, terazosin hydrochloride, doxazosin mesilate, bunazosin hydrochloride, prazosin hydrochloride, fentolamina mesilate, clonidine hydrochloride, guanfacine hydrochloride, guanabenz acetate, hydrochlorothiazide methyldopa, reserpine, rescinnamine, amlodipine, besylate, aranidipine, efonidipine hydrochloride, cilnidipine, nicardipine hydrochloride, nisoldipine, nitrendipin, nifedipine drug nifedipine delayed release, nilvadipine, barnidipine hydrochloride, felodipine, benidipine hydrochloride, manidipine hydrochloride, azelnidipine, diltiazem hydrochloride, hydrazine hydrochloride, Colorline hydrochloride betalain, cadralazine, captopril, enalapril maleate, alacepril, delapril hydrochloride, cilazapril, lisinopril, benazepril hydrochloride, imidapril hydrochloride, temocapril hydrochloride, quinapril hydrochloride, trandolapril, perindopril erbumine, candesartanzapomnit, valsartan, telmisartan, olmesartan medoxomil, sodium nitroprusside, nitroglycerin, etc.

As a combined drug can be mentioned a drug that increases the level of glucocorticoids in the blood, such as corticosteroid adrenal etc. Glucocorti oidy blood means not only endogenous glucocorticoids, such as corticosterone, cortisol, etc. but also exogenous glucocorticoids, due to the introduction of corticosteroids in the adrenal gland. Thus, from 1 to 3 agents and the compound of the present invention can be used in combination.

The following are some examples of ways to produce compounds of the present invention. However, methods for obtaining the compounds of the present invention is not limited to these examples. Even in the absence of a description of the method of obtaining, if necessary, may be represented by an effective receipt by introducing a protective group into the functional group with a subsequent removal of the protection at the next stage by replacing the sequence of the respective stages. As a protective group, for example, can be mentioned carboxyamide group (in the present description carboxyamide group means the one usually used in the field of synthetic organic chemistry, such as methyl group, ethyl group, through the group, tert-bucilina group, benzyl group, p-methoxybenzyl group and the like, which are in the form of esters that can easily lead to a carboxylic acid by hydrolysis, catalytic hydrogenation and the like), aminosidine group (in the present description aminosidine group means that, to the verge, usually used in the field of synthetic organic chemistry, such as tert-butoxycarbonyl group, benzyloxycarbonyl group, benzyl group and the like, which can easily turn into an amino group by hydrolysis, catalytic hydrogenation and the like), hydroxylamine group (in the present description hydroxylamine group means the one usually used in the field of synthetic organic chemistry, such as tetrahydropyranyl group, methoxymethyl group, methoxyethoxymethyl group, benzoyloxymethyl group, benzyl group, p-methoxybenzyl group, p-nitrobenzyl group, trimethylsilyl group, tert-butyldimethylsilyl group, acetyl group, benzoline group, allyl group, tert-bucilina group and the like, which can easily turn into a hydroxyl group by hydrolysis, catalytic hydrogenation and the like) and the like. Treatment after the reaction at each stage can be performed in the usual way, where if necessary, perform isolation and purification by selecting or combining conventional methods such as crystallization, recrystallization, chromatography on silica gel, preparative HPLC and the like.

The method of obtaining 1

In the compound of the formula [1'] of the present from which retene, connection, where-X - is-NH-, can be obtained by performing the following steps.

where R' represents carboxyamide group (in the present description carboxyamide group means the one usually used in the field of synthetic organic chemistry, such as methyl group, ethyl group, through the group, tert-bucilina group, benzyl group, p-methoxybenzyl group and the like), ethers, can easily lead to a carboxylic acid by hydrolysis, catalytic hydrogenation and the like, R represents aminosidine group (in the present description aminosidine group means the one usually used in the field of synthetic organic chemistry, such as tert-butoxycarbonyl group, benzyloxycarbonyl group, benzyl group and the like), which can be easily removed by hydrolysis, catalytic hydrogenation and the like, and other values radicals such as defined above.

Stage 1

The compound of the formula (3) can be obtained by reacting β-keeeper (1), synthesized using known techniques, with dimethylacetal of dimethylformamide (2), in a solvent or in the absence of solvent. The solvent can be upon the chickpeas methanol, ethanol, benzene, toluene, xylene, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 250°C. the reaction Time is usually from one hour to 24 hours. The number of dimethylacetal of dimethylformamide (2), which must be used is usually from approximately 1.5 to approximately 3 mol per 1 mol of β-keeeper (1). The amount of solvent that must be used is not particularly limited and may be appropriately determined depending on the type and quantity of used reaction substrate (β-ketoester (1), dimethylacetal of dimethylformamide (2)), the temperature of the reaction mixture, the reaction time and the like (similar clarification regarding the amount of the solvent used at each stage is given below).

Stage 2: Stage circuit pyrazol ring

The compound of the formula (5) is produced by the interaction of hydrazine (4), synthesized using known methods with the compound of the formula (3), in a solvent. The solvent may be mentioned methanol, ethanol, n-propanol, n-butanol, isopropanol, acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dichloromethane, chloroform, benzene, toluene, xylene and the mixture of these RA the creators and the like. The temperature of the reaction mixture is usually in the range from 20°C to 250°C. the reaction Time is usually from one hour to 24 hours. The amount of hydrazine (4), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (3). When hydrazine (4) use as a salt, the reaction is carried out in the presence of a base (number of grounds for the introduction is typically between approximately 1 and approximately 2 mol per 1 mol of compound (3)), such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine and the like.

Stage 3: The stage of removing the protection of carboxyl groups

The compound of formula (6) is obtained by elimination carboxylamide group R' of the compound (5) using known methods.

Stage 4: Stage amidation

The compound of formula (8) are obtained by reacting the compound (6) with the amine (7) in a solvent in the presence of a condensing agent and an additive. As the condensing agent can be mentioned dicyclohexylcarbodiimide (DCC), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC·HCl), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI), diphenylphosphoryl (DPPA) and the like. In to the amount of additives can be mentioned 1-hydroxybenzotriazole (HOBT), N-hydrocortisone imide (HOSu), 4-dimethylaminopyridine (DMAP) and the like. The solvent may be mentioned dichloromethane, chloroform, acetonitrile, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 100°C. the reaction Time is usually from one hour to 24 hours. The amount of amine (7), which is used, is usually from about 1 and about 1.5 mol per 1 mol of compound (6). In addition, the amount of the condensing agent and an additive, which is used, is usually from about 1 and about 1.5 moles and about 1 and about 1.5 mole, respectively, per 1 mol of compound (6). When the amine (7) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine and the like. Alternatively, the carboxylic acid (6) can be translated in galoyanized acid or mixed acid anhydride and interact with the amine (7) in the presence of a base. The amount of base used is usually from about 1 and priblisitelno to 1.5 mol per 1 mol of compound (6).

Stage 5: The stage of removing the protection of the amino group

The compound of formula (9) is obtained by elimination aminosidine group R” of compound (8) using known techniques. If necessary, it can be converted into a salt using known techniques.

The method of obtaining 2

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)and R1is a-CONR5R6where R5represents a hydrogen atom, can be obtained by performing the following steps.

where each radical has the meaning as defined above.

Stage 1: The stage of deriving urea

1) When R6is not hydrogen

The compound of the formula (11) are obtained by reacting the compound (9) with the isocyanate (10) in a solvent. The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range of from 0°C. to 100°C. the reaction Time is usually from one hour to 24 hours. The number of isocyanate (10), which is used, is usually from approximately 1 and approximately 2 mo the ü on 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out in the presence of a base, such as triethylamine, N,N-diisopropylethylamine, pyridine and the like (the amount of base used is usually from about 1 and to about 2 mol per 1 mol of compound (9)). Alternatively, the compound of formula (9) can interact with 1,1'-carbonyl diimidazol (CDI) (the Number of CDI, which is used, is usually from approximately 1 and approximately 3 mol per 1 mol of compound (9)) and then communicates with the appropriate amine.

When R6represents an alkyl group, cycloalkyl group, aryl group, heterocyclic group and so forth, having a functional group, it can be properly protected by a protective group, and after obtaining a derivative of urea protection is removed. When an alkyl group, cycloalkyl group, aryl group, heterocyclic group and the like have substituents, they may be converted, after receiving a derivative of urea, into other functional groups by known methods. For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group to roxylenol group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

2) When R6is hydrogen

The compound of the formula (11) are obtained by reacting the compound (9) with cyanate in a solvent. The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, water, acetic acid and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range of from 0°C. to 100°C. the reaction Time is usually from one hour to 24 hours. The number of cyanate, which is used, is usually from about 1 and about 10 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine and the like (the amount of base used is usually from about 1 and to about 2 mol per 1 mol of compound (9)).

The method of obtaining 3

The compound of the present invention [1'], where X - represents-N(R1)and R1is a-CONR5R6

where each radical has the meaning as defined above.

Stage 1: The stage of obtaining phenylcarbamate

The compound of formula (13) are obtained by reacting the compound (9) with 4-nitrophenylphosphate (12) in a solvent in the presence of a base. The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. As grounds may be mentioned triethylamine, N,N-diisopropylethylamine, pyridine and the like. The temperature of the reaction mixture is usually in the range of from 0°C. to 100°C. the reaction Time is usually from one hour to 24 hours. Number 4-nitrophenylphosphate (12), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (9). The amount of base used is usually from about 1 and to about 2 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out with basis in the amount of approximately 2 and approximately 4 mol per 1 mol of compound (9).

Stage 2: The stage of deriving urea

Sedimentary (11) is produced by the interaction of the intermediate phenylcarbamate (13) with the amine (14) in a solvent. The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N-organic, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 0°C to 150°C. the reaction Time is usually from one hour to 24 hours. The amount of amine (14), which is used, is usually from approximately 1 and approximately 3 mol per 1 mol of compound (9). When Amin (14) is a salt, the reaction is carried out in the presence of a base, such as triethylamine, N,N-diisopropylethylamine, pyridine and the like (the amount of base used is normally between approximately 1 and approximately 3 mol per 1 mol of compound (13)).

As another method, as shown in the formula 2), the compound of formula (15) are obtained in Stage 1 by reacting amine (14) with a 4-nitrophenylphosphate (12) in a solvent and the compound of formula (15) interacts with the amine (9) in Stage 2 with obtaining the compounds of formula (11).

Moreover, there may be used another charformat or 1,1'-carbonyldiimidazole (CDI) instead of 4-nitrophenylphosphate (12).

When R5and/or R6represent/represents an alkyl group, cycloalkyl group, Ari is inuu group, heterocyclic group, and so on, which have a functional group, they are properly protected with a protective group, and after obtaining a derivative of urea protection is removed. When an alkyl group, cycloalkyl group, aryl group, heterocyclic group and the like have a substituent(s), they can be converted to other functional groups after obtaining a derivative of urea using known techniques. For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

The method of obtaining 4

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)-, R1is a-CONR5R6where R5represents a hydrogen atom and R6=-S(=O)2R9), can be obtained by performing the following steps.

where each radical has the meaning as defined above.

Stage 1: Stage receiving sulfonylureas

Connection fo the formula (17) are obtained by reacting the compound (9) with sulforidazine (16) in a solvent. The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range of from 0°C. to 100°C. the reaction Time is usually from one hour to 24 hours. The number sulfonylation (16), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out in the presence of a base, such as triethylamine, N,N-diisopropylethylamine, pyridine and the like (the amount of base used is usually from about 1 and to about 2 mol per 1 mol of compound (9)).

The method of obtaining 5

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)and R1is a-COOR10can be obtained by performing the following steps.

where each radical has the meaning as defined above.

Stage 1: The stage of obtaining carbamate

The compound of formula (20) are obtained by reacting the compound (9) with chlorocarbonate (18) or carbonate (19) in the presence of a base, in a solvent or without the solvent. The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. As grounds may be mentioned triethylamine, N,N-diisopropylethylamine, pyridine and the like. The temperature of the reaction mixture is usually in the range from 0°C to 150°C. the reaction Time is usually from one hour to 24 hours. The number of chlorocarbonate (18) or carbonate (19), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (9). The amount of base used is usually from about 1 and to about 2 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out with basis in the amount of approximately 2 and approximately 4 mol per 1 mol of compound (9).

When R10represents an alkyl group, cycloalkyl group, aryl group, heterocyclic group and so forth, having a functional group, they are adequately protected by a protective group, and after receipt of the carbamate, the protection is removed. When an alkyl group, cycloalkyl group, aryl group, heterocyclic group and the like have a substituent(s), they can, after the floor is placed carbamate to be converted into other functional groups by known methods. For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

As another method, as shown in the formula 2), phenylcarbamate intermediate compound (13)obtained in the production Method of 3, stage 1 interacts with alcohol (21) in a solvent, in the presence of a base to obtain the compounds of formula (20). The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N-organic, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. As the base can be mentioned sodium hydride, potassium hydride, sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine and the like. The temperature of the reaction mixture is usually in the range from 0°C to 150°C. the reaction Time is usually from one hour to 24 hours. The number of alcohol (21), which is used, is usually from about 1 and AP is sustained fashion to 3 mol per 1 mol of the intermediate phenylcarbamate (13). The amount of base used is usually from about 1 and to about 2 mol per 1 mol of the intermediate phenylcarbamate (13).

When R10represents an alkyl group, cycloalkyl group, aryl group, heterocyclic group and so forth, having a functional group, protected properly with a protective group, and after receiving the carbamate protection is removed. When an alkyl group, cycloalkyl group, aryl group, heterocyclic group and the like have a substituent(s), they may be after receipt of the carbamate converted into other functional groups by known methods. For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

The method of obtaining 6

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)and R1represents-COR11can be obtained by performing the following steps.

where Kadyrova has the meaning as specified above.

Stage 1: Stage amidation

The compound of formula (23) are obtained by reacting the compound (9) with carboxylic acid (22) in a solvent in the presence of a condensing agent and an additive. As the condensing agent can be mentioned dicyclohexylcarbodiimide (DCC), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC·HCl), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI), diphenylphosphoryl (DPPA) and the like. As an additive may be mentioned 1-hydroxybenzotriazole (HOBT), N-hydroxysuccinimide (HOSu), 4-dimethylaminopyridine (DMAP) and the like. The solvent may be mentioned dichloromethane, chloroform, acetonitrile, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 100°C. the reaction Time is usually from one hour to 24 hours. The amount of carboxylic acid (22), which is used, is usually from about 1 and about 1.5 mol per 1 mol of compound (9). In addition, the amount of the condensing agent and an additive, which is used, is usually from about 1 and about 1.5 mole, and from about 1 and about 1.5 mole, respectively, per 1 mol of compound (9). When the compound of the formula (9) represents the t of a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine and the like. Moreover, carboxylic acid (22) can be translated in galoyanized acid or mixed acid anhydride and interact with the compound of the formula (9) in the presence of a base. The amount of base used is usually from about 1 and about 1.5 mol per 1 mol of compound (9).

When R11represents an alkyl group, cycloalkyl group, aryl group, heterocyclic group and so forth, having a functional group, they are protected properly protecting group and after amidation protection is removed. When an alkyl group, cycloalkyl group, aryl group, heterocyclic group and the like have a substituent(s), they can be converted to other functional groups after amidation using known methods.

For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in CT is auxillou group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

The method of obtaining 7

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)and R1represents a C1-6alkyl group or cycloalkyl group, can be obtained by performing the following steps.

where X' represents a halogen atom and the other radicals are as defined above.

Stage 1: Stage N-alkylation

The compound of formula (25) are obtained by reacting the compound (9) with alkylhalides (24) in a solvent in the presence of a base. As the base can be mentioned sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydride, potassium hydride, triethylamine, N,N-diisopropylethylamine, pyridine and the like. The solvent can be mentioned acetonitrile, acetone, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range of from 0°C. to 100°C. BP the two reactions is usually from 30 minutes to 24 hours. The number of alkylhalides (24), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (9). The amount of base used is usually from about 1 and to about 2 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out with basis in the amount of approximately 2 and approximately 4 mol per 1 mol of compound (9). This is possible to perform recovery amination of compound (9) with the appropriate aldehyde, ketone or their equivalent.

When R1represents an alkyl group having a functional group, it is properly protected with a protective group, and after N-alkylation protection is removed. When the alkyl group has a substituent(s), it can be converted into another functional group after N-alkylation by known methods. For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

The way to obtain 8

In which the Association of the formula [1'] of the present invention, connection, where-X - represents-N(R1)and R1represents a-S(=O)2R12can be obtained by performing the following steps.

where each radical has the meaning as defined above.

Stage 1: Stage sulfonylamine

The compound of formula (27) can be obtained by reacting compound (9) with sulphonylchloride (26) in a solvent in the presence of a base. As the base can be mentioned sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydride, potassium hydride, triethylamine, N,N-diisopropylethylamine, pyridine and the like. The solvent can be mentioned acetonitrile, acetone, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range of from 0°C. to 100°C. the reaction Time is usually from 30 minutes to 24 hours. The number of sulphonylchloride (26), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (9). The amount of base used is usually will bring the flax between 1 and approximately 2 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out with basis in the amount of approximately 2 and approximately 4 mol per 1 mol of compound (9). In addition, the compound of formula (9) may be subjected to interaction with the corresponding sulfonic acid anhydride.

When R12represents an alkyl group having a functional group, it is properly protected with a protective group, and after sulfonylamine protection is removed. When the alkyl group has a substituent(s), it can be converted into another functional group after sulfonylamine using known techniques. For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

The method of obtaining 9

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)and R1represents-C(=NCN)R13can be obtained by performing the following steps.

where each radical has the meaning as defined in the above.

Stage 1: The stage of obtaining N-cyanoaniline

The compound of the formula (29) are obtained by reacting the compound (9) with N-cyanometallates (28) in the solvent. The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range of from 0°C. to 100°C. the reaction Time is usually from one hour to 24 hours. The number of N-cyanometallates (28), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out in the presence of a base, such as triethylamine, N,N-diisopropylethylamine, pyridine and the like (the amount of base used is usually from about 1 and to about 2 mol per 1 mol of compound (9)).

The method of obtaining 10

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)and R1represents-C(=NCN)NR14R15can be obtained by performing the following steps.

where Ph represents a phenyl group and the other radicals are as defined the by above.

Stage 1

The compound of formula (31) are obtained by reacting the compound (9) with diphenyl-N-cyanocarbonimidate (30) in a solvent. The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range of from 0°C. to 100°C. the reaction Time is usually from one hour to 24 hours. The amount of diphenyl-N-cyanocarbonimidate (30), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (9). When the amine (9) is a salt, the reaction is carried out in the presence of a base, such as triethylamine, N,N-diisopropylethylamine, pyridine and the like (the amount of base used is usually from about 1 and to about 2 mol per 1 mol of compound (9)).

Stage 2: The stage of obtaining N-cyanoguanidine

The compound of formula (33) are obtained by reacting the compound (31) with the amine (32) in the solvent. The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, N-organic, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and the mixture of these RA the creators and the like. The temperature of the reaction mixture is usually in the range from 0°C to 150°C. the reaction Time is usually from one hour to 24 hours. The amount of amine (32), which is used, is usually from about 1 and about 5 mol per 1 mol of compound (31). When Amin (32) is a salt, the reaction is carried out in the presence of a base, such as triethylamine, N,N-diisopropylethylamine, pyridine and the like (the amount of base used is usually from about 1 and about 20 mol per 1 mol of compound (31)).

The method of obtaining 11

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)and R1represents an aryl group or a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group, can be obtained by performing the following steps.

where each radical has the meaning as defined above.

Stage 1: Stage circuit pyrazol ring of hydrazine (34) and the compounds of formula (3)

The compound of the formula (35) is produced by the interaction of hydrazine (34), synthesized using known methods with the compound of the formula (3)obtained in Method 1, step 1, in a solvent. The solvent may be mentioned methanol, ethanol, n-propanol, n-BU is anal, isopropanol, acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 250°C. the reaction Time is usually from one hour to 24 hours. The amount of hydrazine (34), which is used, is usually from approximately 1.5 to approximately 3 mol per 1 mol of compound (3). When hydrazine (34) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine and the like (the amount of base used is normally between approximately 1.5 and approximately 3 mol per 1 mol of compound (3)).

Stage 2: The stage of removing the protection of the carboxyl group R'

The compound of formula (36) is obtained by elimination of the protective group carboxyl R' using known methods.

Stage 3: Stage amidation

The compound of formula (37) are obtained by reacting the compound (36) with the amine (7) in a solvent in the presence of a condensing agent and an additive. As the condensing agent can be mention the s dicyclohexylcarbodiimide (DCC), hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC·HCl), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI), diphenylphosphoryl (DPPA) and the like. As an additive may be mentioned 1-hydroxybenzotriazole (HOBT), N-hydroxysuccinimide (HOSu), 4-dimethylaminopyridine and the like. The solvent may be mentioned dichloromethane, chloroform, acetonitrile, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 100°C. the reaction Time is usually from one hour to 24 hours. The amount of amine (7), which is used, is usually from about 1 and about 1.5 mol per 1 mol of compound (36). In addition, the amount of the condensing agent and an additive, which is used, is usually from about 1 and about 1.5 moles and about 1 and about 1.5 mole, respectively, per 1 mol of compound (36). When the amine (7) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine and the like. In addition, carboxylic acid (36) can be translated is in galoyanized acid and then vzaimodeistvie with the amine (7) in the presence of a base. The amount of base used is usually from about 1 and about 1.5 mol per 1 mol of compound (36).

When R1represents an aryl group or a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group having a functional group, it is properly protected with a protective group, and then the protection is removed. When the aryl group or a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group has a substituent(s), it can be converted into another functional group by known methods after this stage. For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

The method of obtaining 12

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)and R1represents an aryl group or a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group, can be obtained by performing the following steps.

where each radical has the meaning as defined above.

Stage 1: Stage amination by Buchwald/Hartwig, catalyzed by palladium

The compound of formula (39) are obtained by reacting the compound (9)obtained in the production Method of 1, and an aromatic halogen (38) in a solvent in the presence of a palladium catalyst and base. As the palladium catalyst can be mentioned a mixture of palladium acetate and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, dichloride, bis(diphenylphosphino)ferrocene palladium (II), Tris(dibenzylideneacetone) diplodia and the like. As the base can be mentioned tripotassium phosphate (K3PO4), sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, tert-piperonyl potassium and the like. The solvent may be mentioned 1,2-dimethoxyethane, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, tert-butanol and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 250°C. the reaction Time is usually from one hour to 24 hours. The number of aromatic halogen (38), which is used, is usually from about 1 and about 1.5 mol per 1 mol of compound (9). The amount of palladium catalyst and base is, which is used is usually about 0.01 and about 0.1 mol and approximately 1 and approximately 2 mol, respectively, per 1 mol of compound (9).

When R1represents an aryl group or a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group having a functional group, it is properly protected with a protective group, and then the protection is removed. When the aryl group or a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group has a substituent(s), it can be converted into another functional group after the specified stage using known methods.

For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

The method of obtaining 13

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)and R1represents an aryl group or a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group, may be is obtained by performing the following steps.

where R”' represents a substituent (for example, ethoxycarbonyl group, benzoline group, 9-fluorenylmethoxycarbonyl group and the like) on the nitrogen atom, and the other radicals are as defined above.

Stage 1: Stage fiorentinovia

The compound of formula (41) are obtained by reacting the compound (9)obtained in the production Method of 1, isothiocyanato (40) in the solvent and removal of the substituent (R') on the nitrogen atom by known methods. As isothiocyanate (40) can be mentioned ethoxycarbonylmethylene, benzoylisothiocyanate, 9-fluorenylmethoxycarbonyl and the like. The solvent can be mentioned acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range of from 0°C. to 100°C. the reaction Time is usually from one hour to 24 hours. The number of isothiocyanate (40), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (9). It is possible to expose the interaction of a compound of the formula (9) with thiophosgene (number of thiophosgene, which is used, is usually p is blithedale between 1 and about 1.5 mol per 1 mol of compound (9)), with subsequent treatment with ammonia.

Stage 2: Stage circuit thiazole ring

The compound of formula (43) is obtained by interaction of the compound (41) with halogenoalkanes (42) in the solvent. The solvent may be mentioned methanol, ethanol, n-propanol, n-butanol, isopropanol, acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 250°C. the reaction Time is usually from one hour to 24 hours. The number of halogenoalkane (42), which is used, is usually from about 1 and about 1.5 mol per 1 mol of compound (41).

Thiazolidine group having a functional group may be suitably protected by a protective group, and then the protection is removed. When thiazolidine group has a substituent(s), it can be converted into another functional group after the specified stage using known techniques. For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in the carboxyl group, aminocarbonyl gr the PPU, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

The method of obtaining 14

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)and R1represents a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group, can be obtained by performing the following steps.

where X' represents a halogen atom, alkyl represents a C1-6alkyl group, R””' represents a carboxyl group, With1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from a halogen atom and a hydroxyl group) or cycloalkyl group and the other radicals are as defined above.

Stage 1

Hydrohalic estimacion (45) are obtained by reacting compound (41)obtained in the production Method of 13, stage 1, with alkylhalides (44) in the solvent. The solvent can be mentioned acetonitrile, acetone, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. Pace is the atur reaction mixture is usually in the range of from 0°C. to 100°C. The reaction time is usually from 30 minutes to 24 hours. The number of alkylhalides (44), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (41).

Stage 2: The stage of creation of the triazole ring from estimacion and hydrazide

The compound of formula (47) can be obtained by interaction of hydrohalide estimacion (45) hydrazide (46), synthesized using a known method in a solvent in the presence of a base. The solvent may be mentioned methanol, ethanol, n-propanol, isopropanol, n-butanol, acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dimethylsulfoxide, dichloromethane, 1,2-dichloroethane, chloroform, benzene, chlorobenzene, O-dichlorobenzene, toluene, xylene, pyridine, 2,6-luthien, 2,4,6-kallidin, acetic acid, water and a mixture of these solvents and the like. As the base can be mentioned sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydride, potassium hydride, triethylamine, N,N-diisopropylethylamine, pyridine and the like. The temperature of the reaction mixture is usually in the range from 20°C to 250°C. the reaction Time is usually from 30 minutes to 24 hours. The number of hydrazide (46), which is th use is usually approximately 1 and approximately 2 mol per 1 mol of estimacion hydrohalides (45). The amount of base used is usually from about 1 and to about 2 mol per 1 mol of hydrohalide estimacion (45). When hydrazide (46) is a salt, the reaction is carried out with basis in the amount of approximately 2 and approximately 4 mol per 1 mol of hydrohalide estimacion (45).

Thiazolidine group having a functional group may be suitably protected by a protective group, and then the protection is removed. When thiazolidine group has a substituent(s), the substituent(s) may be converted by known methods into another functional group after this stage. For example, there can be mentioned the conversion of the hydroxyl group in alkoxygroup or ketone, amino groups in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

The method of obtaining 15

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-N(R1)-can be obtained by performing the following steps.

where each radical has the meaning as defined above.

Stage 1: The stage of removing the protection of the amino group

The compound of formula (48) is obtained by elimination aminosidine group R of the compound (5)obtained in the production Method of 1, stage 2.

Stage 2: Introduction R1

The compound of formula (49) is obtained by introducing R1in the compound of formula (48) in accordance with methods analogous to the methods specified in the Ways of getting from 2 to 10 and the Ways to get from 12 to 14.

Stage 3: The stage of removing the protection of carboxyl groups

The compound of formula (50) is obtained by elimination of the carboxy protective group R' of the compound (49) using known methods.

Stage 4: Stage amidation

The compound of formula (51) is produced by the interaction of the compound (50) with the amine (7) in a solvent in the presence of a condensing agent and an additive. As the condensing agent can be mentioned dicyclohexylcarbodiimide (DCC), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC·HCl), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI), diphenylphosphoryl (DPPA) and the like. As an additive may be mentioned 1-hydroxybenzotriazole (HOBT), N-hydroxysuccinimide (HOSu), 4-dimethylaminopyridine (DMAP) and the like. The solvent may be mentioned dichloromethane, hloroform, tetrahydrofuran, acetonitrile, 1,4-dioxane, N,N-dimethylformamide and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 100°C. the reaction Time is usually from one hour to 24 hours. The amount of amine (7), which is used, is usually from about 1 and about 1.5 mol per 1 mol of compound (50). In addition, the amount of the condensing agent and an additive, which is used, is usually from about 1 and about 1.5 moles and about 1 and about 1.5 mole, respectively, per 1 mol of compound (50). When the amine (7) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine and the like (the amount of base used is usually from about 1 and about 1.5 mol per 1 mol of compound (50)).

R1having a functional group, are adequately protected by a protective group, and then the protection is removed. When R1has a substituent(s), it can be converted into another functional group after the specified stage using known techniques. For example, mo is ut to be mentioned conversion of the hydroxyl group in alkoxygroup or ketone, of the amino group in alkylamino, alkylcarboxylic or alkylsulfonamides, alkoxycarbonyl group in the carboxyl group, aminocarbonyl group, alkylaminocarbonyl group or hydroxymethylene group and sulfide in sulfon or sulfoxide.

The method of obtaining 16

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-C(R7R8)-can be obtained by performing the following steps.

where each radical has the meaning as defined above, where R”” is carboxyamide group (in the present description carboxyamide group means the one usually used in the field of synthetic organic chemistry, such as methyl group, ethyl group, through the group, tert-bucilina group, benzyl group, p-methoxybenzyl group and the like, which is present in the form of esters, which can easily lead to the carboxylic acid by hydrolysis, catalytic hydrogenation and the like)

Stage 1: Reductive alkylation

The compound of formula (54) is produced by the interaction of the ketone (52) with tert-BUTYLCARBAMATE (53) in a solvent in the presence of a recovery agent. As a recovery agent can be in omanut sodium borohydride cyanoborohydride sodium, triacetoxyborohydride sodium, bananowy complex and the like. The solvent may be mentioned methanol, ethanol, n-propanol, n-butanol, isopropanol, dichloromethane, chloroform, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, benzene, toluene, xylene, acetic acid and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range of from 0°C. to 100°C. the reaction Time is usually from one hour to 24 hours. The number of recovery agent used is usually from about 2 and about 5 mol per 1 mol of compound (52).

Stage 2: removal of group-BOC (tert-butoxycarbonyl group)

The compound of formula (54) communicates with 4 N. solution of hydrochloric acid in ethyl acetate or 4 N. solution of hydrochloric acid in 1,4-dioxane to obtain hydrazine hydrochloride (55). In addition, after removing the group-BOC by exposure triperoxonane acid in the solvent, it can be converted into a hydrochloride. The solvent may be mentioned dichloromethane, chloroform and the like.

Stage 3: The stage of creation of the pyrazol ring from hydrazine hydrochloride (55) and the compounds of formula (3)

The compound of formula (56) is obtained by interaction of hydrazine hydrochloride (55) with the compound of the formula (3) is rastvoritele in the presence of a base. The solvent may be mentioned methanol, ethanol, n-propanol, n-butanol, isopropanol, acetonitrile, diethyl ether, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, dichloromethane, chloroform, benzene, toluene, xylene and a mixture of these solvents and the like. As the base can be mentioned sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine and the like. The temperature of the reaction mixture is usually in the range from 20°C to 250°C. the reaction Time is usually from one hour to 24 hours. The amount of hydrazine hydrochloride (55), which is used, is usually from about 1 and to about 2 mol per 1 mol of compound (3). The amount of base used is usually from about 1 and to about 2 mol per 1 mol of compound (3).

Stage 4: The stage of removing the protection of carboxyl groups

The compound of formula (57) is obtained by elimination of the carboxy protective group R' of the compound (56) using known methods.

Stage 5: Stage amidation

The compound of formula (58) is obtained by interaction of the compound (57) with the amine (7) in a solvent in the presence of a condensing agent and add the I. As the condensing agent can be mentioned dicyclohexylcarbodiimide (DCC), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC·HCl), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI), diphenylphosphoryl (DPPA) and the like. As an additive may be mentioned 1-hydroxybenzotriazole (HOBT), N-hydroxysuccinimide (HOSu), 4-dimethylaminopyridine (DMAP) and the like. The solvent may be mentioned dichloromethane, chloroform, acetonitrile, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 100°C. the reaction Time is usually from one hour to 24 hours. The amount of amine (7), which is used, is usually from about 1 and about 1.5 mol per 1 mol of compound (57). In addition, the amount of the condensing agent and an additive, which is used, is usually from about 1 and about 1.5 moles and about 1 and about 1.5 mole, respectively, per 1 mol of compound (57). When the amine (7) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-visapro ylethylamine, the pyridine and the like. In addition, carboxylic acid (57) can be entered in galoyanized acid or mixed acid anhydride and interact with the amine (7) in the presence of a base. The amount of base used is usually from about 1 and about 1.5 mol per 1 mol of compound (57).

Stage 6: The stage of removing the protection of carboxyl groups

Carboxylic acid (59) is obtained by elimination of the carboxy protective group R” of compound (58) using known methods.

Stage 7: Stage amidation

The compound of formula (61) are obtained by reacting carboxylic acid (59) with the amine (60) in a solvent in the presence of a condensing agent and an additive. As the condensing agent can be mentioned dicyclohexylcarbodiimide (DCC), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (WSC·HCl), diisopropylcarbodiimide, 1,1'-carbonyldiimidazole (CDI) or diphenylphosphoryl (DPPA) and the like. As an additive may be mentioned 1-hydroxybenzotriazole (HOBT), N-hydroxysuccinimide (HOSu), 4-dimethylaminopyridine (DMAP) and the like. The solvent may be mentioned dichloromethane, chloroform, acetonitrile, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide and a mixture of these solvents and the like. The temperature of the reaction mixture find the camping usually in the range from 20°C to 100°C. The reaction time is usually from one hour to 24 hours. The amount of amine (60), which is used, is usually from about 1 and about 1.5 mol per 1 mol of carboxylic acid (59). In addition, the amount of the condensing agent and an additive, which is used, is usually from about 1 and about 1.5 moles and about 1 and about 1.5 mole, respectively, per 1 mol of compound (59). When Amin (60) is a salt, the reaction is carried out in the presence of a base such as sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, potassium acetate, sodium hydroxide, potassium hydroxide, lithium hydroxide, triethylamine, N,N-diisopropylethylamine, pyridine and the like. Moreover, carboxylic acid (59) can be entered in galoyanized acid or mixed acid anhydride and interact with the amine (60) in the presence of a base. The amount of base used is usually from about 1 and about 1.5 mol per 1 mol of carboxylic acid (59).

The method of obtaining 17

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-C(R7R8)-can be obtained by performing the following steps.

where each radical has the meaning as is designated above.

Stage 1: The stage of deriving urea

Carboxylic acid (59) interacts with diphenylphosphorylacetate (DPPA) in a solvent in the presence of a base to translate into isocyanate which reacts with the amine (62) to give the urea (63). The solvent may be mentioned dichloromethane, chloroform, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, benzene, toluene, xylene and the like. As grounds may be mentioned triethylamine, N,N-diisopropylethylamine, pyridine and the like. The temperature of the reaction mixture for the stage, which gives the isocyanate is typically in the range from 20°C to 150°C and the stage, which gives the urea is generally in the range from 0°C to 100°C. the reaction Time is usually from one hour to 24 hours for both stages. The number of DPPA, which is used, is usually from about 1 and to about 2 mol per 1 mol of carboxylic acid (59). The amount of base used is usually from about 1 and to about 2 mol per 1 mol of carboxylic acid (59). The amount of amine (62), which is used, is usually from about 1 and about 5 mol per 1 mol of carboxylic acid (59).

The method of obtaining 18

In the compound of the formula [1'] of the present invention, the compounds, which-X - represents-C(R7/sup> R8)-can be obtained by performing the following steps.

where each radical has the meaning as defined above.

Stage 1: Stage cyanidation

Nitrile (64) is produced by the interaction of the amide (61) with the agent degidrirovaniya in a solvent in the presence of a base. As agent degidrirovaniya can be mentioned, anhydride triftormetilfullerenov acid, p-toluensulfonate, trichloroethylene, anhydride triperoxonane acid, phosphorus oxychloride, thionyl chloride and the like. As grounds may be mentioned triethylamine, N,N-diisopropylethylamine, pyridine and the like. The solvent may be mentioned dichloromethane, chloroform, tetrahydrofuran, 1,4-dioxane, N,N-dimethylformamide, pyridine and the mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 100°C. the reaction Time is usually from one hour to 24 hours. The number of agent degidrirovaniya that is used is usually from about 1 and to about 2 mol per 1 mol of amide (61). The amount of base used is usually from about 1 and to about 2 mol per 1 mol of amide (61).

Stage 2: Stage circuit tetrazole rings

Nitrile (64) communicates in RA is the solvent in the presence of the reagent of sideropenia with getting tetrazole (65). As a reagent sideropenia can be mentioned sodium azide, azitromicina, sidtribution, azitromicina and the like. The solvent may be mentioned dichloromethane, chloroform, tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, N,N-dimethylformamide, benzene, toluene, xylene and a mixture of these solvents and the like. The temperature of the reaction mixture is usually in the range from 20°C to 150°C. the reaction Time is usually from one hour to 24 hours. The amount of reagent sideropenia that is used is usually from about 1 and to about 2 mol per 1 mol of the nitrile (64).

Described in the present description means of obtaining represent examples of methods for producing compounds of the present invention, and compounds other than those listed above, can be obtained by combining known methods in synthetic organic chemistry.

EXAMPLES

Heterocyclic compounds and methods for their preparation the present invention disclosed in detail hereinafter, referring to examples, which should not be construed as restrictive.

Example 1

Obtaining 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine

Stage 1

Obtaining methyl-2-cyclopropanecarbonyl-3-dimethylamino what crylate

Methyl-3-cyclopropyl-3-oxopropionate (2.0 g) dissolved in toluene (20 ml). To the resulting solution add dimethylacetal of dimethylformamide (3.0 ml) and the resulting mixture is heated at the boil under reflux for 3 hours. The reaction mixture was allowed to cool, concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of n-hexane:acetone=2:1) to obtain the specified title compound as yellow oil (2,61 g).

Stage 2

Obtaining methyl-1-(1-benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carboxylate

Methyl-2-cyclopropanecarbonyl-3-diethylaminoacetate (1.0 g), obtained as described in the previous phase, and hydrochloride benzyl-4-hydrazinopyridazine-1-carboxylate (1,49 g)synthesized by known methods, is suspended in ethanol. To the suspension is added triethylamine (0,78 ml) and the resulting mixture is heated at the boil under reflux for 3.5 hours. To the reaction mixture, water is added and the mixture extracted with diethyl ether. A layer of diethyl ether, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate=2,5:1) to obtain specified in the connection header in widebase yellow (1,58 g).

Stage 3

Obtaining 1-(1-benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carboxylic acid

Methyl-1-(1-benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carboxylate (1,58 g), obtained as indicated in the preceding stage, dissolved in tetrahydrofuran (5 ml), methanol (5 ml) and water (10 ml), add the monohydrate of lithium hydroxide (834 mg) and the mixture was stirred at 50°C for 6 hours. The reaction mixture was concentrated under reduced pressure, to the obtained residue, add water, acidified with 2 N. hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the obtained residue is added diethyl ether and n-hexane and precipitated precipitated solid is collected by filtration and dried to obtain specified in the title compound as amorphous solid white (1.27 g).

Stage 4

Obtaining 1-[1-(1-benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine

1-(1-Benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carboxylic acid (800 mg), obtained as described in the previous phase, 1-hydroxybenzotriazole (332 mg) and the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (498 mg) dissolve Aut in N,N-dimethylformamide (10 ml) and the resulting mixture is stirred for 15 minutes. To the resulting solution was added 3-(pyridin-3-yl)pyrrolidin (330 mg) and 4-dimethylaminopyridine (catalytic amount) and the resulting mixture is stirred over night at room temperature. The reaction mixture was concentrated under reduced pressure, to the residue water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=11:1) to obtain the specified title compound as amorphous solid white (1.06 g).

Stage 5

Obtaining 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine

1-[1-(1-Benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidin (970 mg), obtained as indicated in the preceding stage, dissolved in methanol (12 ml), add 10% palladium on coal (50% water content) (200 mg) and the resulting mixture is stirred in hydrogen atmosphere for 2.5 hours. The catalyst is filtered off and the filtrate is concentrated under reduced pressure. The obtained residue is purified via chromatography (neutral alumina) (mixture of chloroform:methanol=7:1) to obtain specified in the connection header in the form of amorn the th solid white (718 mg).

Example 2

Obtain hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Stage 1

Obtain (S)-3-acetyl-4-isopropyl-5,5-diphenyloxazole-2-it

In the atmosphere of argon (S)-4-isopropyl-5,5-diphenyloxazole-2-he (1.56 g) is suspended in tetrahydrofuran (22 ml) and added dropwise a 1.6 M solution of n-utility/n-hexane (3,64 ml) under cooling with ice. After 10 minutes add acetylchloride (0,47 ml) and the resulting mixture is stirred overnight, during which the temperature of the mixture was allowed to gradually lowered to room. To the reaction mixture is added saturated aqueous solution of ammonium chloride and the resulting mixture was concentrated under reduced pressure. To the resulting residue, water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with 1 N. hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate and water and then dried over anhydrous magnesium sulfate. The ethyl acetate layer concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of n-hexane:ethyl acetate=4:1) to obtain the specified title compound as white crystals (1,69 g).

Stage 2

Obtain (S)-4-isopropyl-3-[(S)-4-nitro-3-(2-triptoreline)butyryl]-5,5-diphenyloxazole-2-it

(S-3-Acetyl-4-isopropyl-5,5-diphenyloxazole-2-he (4,74 g), received as stated on the previous stage is dissolved in dichloromethane (73 ml) in an argon atmosphere and added titanium tetrachloride (3,17 ml) and N,N-diisopropylethylamine (3,06 ml) at -78°C. the Mixture is gradually heated to a temperature of 0°C for 30 minutes, again cooled to a temperature of -78°C. and add a solution of 1-[(E)-2-nitrovinyl]-2-triptoreline (3.50 g) in dichloromethane (27 ml). Added titanium tetrachloride (3,17 ml) and after 2 hours the reaction mixture is added saturated aqueous solution of ammonium chloride. The mixture is extracted with ethyl acetate and the ethyl acetate layer was washed with 1 N. hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate and water and then dried over anhydrous magnesium sulfate. The mixture is concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of n-hexane:ethyl acetate=5:1) and crystallized from a mixture of diethyl ether:n-pentane to obtain specified in the title compound as white crystals (2,62 g).

Stage 3

Obtain (S)-4-(2-triptoreline)pyrrolidin-2-it

To (S)-4-isopropyl-3-[(S)-4-nitro-3-(2-triptoreline)butyryl]-5,5-diphenyloxazole-2-ONU (of 2.51 g), obtained as described in the previous phase, add ethanol (35 ml), ethyl acetate (35 ml), and then add Raney Nickel (50% in water) (2.8 g). After stirring for whom the night in an atmosphere of hydrogen, nerastvorim the product is filtered through celite and the filtrate concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=20:1) to obtain the specified title compound as white crystals (850 mg).

Stage 4

Obtain (S)-3-(2-triptoreline)pyrrolidine

To (S)-4-(2-triptoreline)pyrrolidin-2-ONU (803 mg), obtained as described in the previous phase, add tetrahydrofuran (7 ml), and then add sociallyengaged (200 mg). After heating at boiling under reflux for 1.5 hours, add water (0.2 ml), 4 N. aqueous sodium hydroxide solution (0.2 ml) and water (0.4 ml) under cooling with ice. Add anhydrous magnesium sulfate, the insoluble product is filtered through celite and the filtrate concentrated under reduced pressure to obtain specified in the connection header in the form of oil, pale yellow (722 mg).

[α]25D = +23,9 (c = 0,504, EtOH)

Stage 5

Obtaining 1-[1-(1-benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

1-(1-Benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carboxylic acid (235 mg)obtained in Example 1, step 3, 1-hydroxybenzotriazole (127 mg) and the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (59 mg) was dissolved in N,N-dimethylformamide (6 ml) and the mixture is stirred for 15 minutes. To the resulting solution was added (S)-3-(2-triptoreline)pyrrolidin (151 mg), obtained as described in the previous phase, and 4-dimethylaminopyridine (78 mg) and the mixture is stirred over night at room temperature. The reaction mixture was concentrated under reduced pressure, to the residue water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with water, 1 N. aqueous solution of potassium hydrosulfate, saturated aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of ethyl acetate:methanol=40:1) to obtain the specified title compound as amorphous solid white (287 mg).

Stage 6

Obtain hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

1-[1-(1-Benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (2.0 g)obtained as indicated in the previous stage is dissolved in methanol (14 ml), added palladium hydroxide on coal (0.2 g) and the resulting mixture is stirred in hydrogen atmosphere for 15 hours. The catalyst is filtered off through celite and the filtrate concentrated under reduced pressure. The residue RA is tworay in methanol (6.4 ml) and add 4 N. a solution of hydrochloric acid in ethyl acetate (1,32 ml). The mixture is concentrated under reduced pressure and crystallized from a mixture of ethyl acetate+diisopropyl ether to obtain specified in the title compound as white crystals (1.45 g).

Stage 7

(S)-3-(2-Triptoreline)pyrrolidin obtained in the above Stage 4, and its hydrochloride can be obtained in accordance with the next Stage.

Stage 7-1

Getting dimethyl-2-[(S)-2-nitro-1-(2-triptoreline)ethyl]malonate

Toluene (40 ml) are added to 1-((E)-2-nitrovinyl)-2-triptoreline (4,34 g) and then add diethylmalonate (3.4 ml) and 1-(3,5-bis-triptoreline)-3-((1S,2S)-2-dimethylaminoethoxy)thiourea (413 mg), disclosed in WO2005/000803 and J. Am. Chem. Soc., 2005, 127, 119-125 while cooling with ice. The mixture is stirred under ice cooling for 24 hours. The reaction mixture was concentrated under reduced pressure and the residue is crystallized from 2-propanol to obtain specified in the connection header (5.31g) in the form of white crystals.

This reaction can also be carried out using the catalysts disclosed in J. Am. Chem. Soc., 1999, 121, 10215-10216, J. Am. Chem. Soc., 2005, 127, 9958-9959, J. Am. Chem. Soc., 2006, 128, 1454-1455 and the like, instead of 1-(3,5-bis-triptoreline)-3-((1S,2S)-2-dimethylaminoethoxy)-thiourea.

Stage 7-2

Obtain methyl(S)-2-oxo-4-(2 - thrift methylphenyl)pyrrolidin-3-carboxylate

Dimethyl-2-[(S)-2-nitro-1-(2-triptoreline)ethyl]malonate (4.0 g), obtained as described in the previous phase, is added to a suspension of Raney Nickel (2.0 g) in a mixture of tetrahydrofuran (10 ml)/methanol (10 ml) and the resulting mixture is stirred in hydrogen atmosphere at a pressure of 3.5 atmospheres at room temperature for 24 hours. Insoluble products filtered over celite. The filtrate and washing are combined and concentrated under reduced pressure. To the residue is added toluene and the mixture was washed with 10% aqueous potassium carbonate solution and water and the organic layer concentrated under reduced pressure. The residue is crystallized from a mixture of toluene+n-hexane to obtain specified in the title compound (2.38 g) as white crystals.

This reaction can also be carried out using palladium on coal, instead of Raney Nickel in the presence of acid, such as acetic acid, toluensulfonate, methanesulfonate and the like.

Stage 7-3

Obtain (S)-4-(2-triptoreline)pyrrolidin-2-it

Methanol (3.8 ml) is added to methyl(S)-2-oxo-4-(2-triptoreline)pyrrolidin-3-carboxylate (1.0 g), obtained as described in the previous phase, then add 1 N. aqueous sodium hydroxide solution (3.8 ml) and the resulting mixture was stirred at 65°C for one hour. The reaction mixture it will centerour under reduced pressure and the obtained residue acidified with 1 N. solution of hydrochloric acid under ice cooling and extracted twice with butyl acetate. The organic layers are combined, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the residue newly added butyl acetate (10 ml) and the resulting mixture is stirred overnight at a temperature of 100°C. the Reaction mixture was concentrated under reduced pressure and the residue is crystallized from n-hexane to obtain specified in the header of the compound (667 mg) as white crystals.

Stage 7-4

Obtaining hydrochloride (S)-3-(2 - triptoreline)pyrrolidine

To a solution of (S)-4-(2-triptoreline)pyrrolidin-2-it (22.9 grams), obtained as described in the previous phase in THF (100 ml), added dropwise 1M solution of sociallyengaged in THF (100 ml) in an argon atmosphere at a temperature of 85°C for one hour and then the resulting mixture was stirred at the same temperature for one hour. After the mixture will allow to cool, add 50% aqueous solution of Rochelle salt under ice cooling and the resulting mixture was partitioned between water and ethyl acetate. The organic layer is separated and concentrated under reduced pressure. The residue is distributed between ethyl acetate and water and the organic layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the residue is dobavlaut ethyl acetate (60 ml), then add 4 n hydrochloric acid in ethyl acetate (37.5 ml) under ice cooling and the resulting mixture was stirred at room temperature. Precipitated precipitated crystals are collected by filtration to obtain specified in the title compound (20.6 g) in the form of white crystals.

[α]25D = +10,3 (c = 0,55, MeOH)

Example 3

Obtain 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

1-[5-Cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine (100 mg)obtained in Example 1, step 5, was dissolved in chloroform (2 ml), add triethylamine (38 μl) and 2-forgenerations (34 μl) and the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of chloroform:methanol=11:1) to obtain the specified title compound as amorphous solid white (111 mg).

Example 4

Obtaining 1-[1-(1-carbamoylbiphenyl-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

1-[5-Cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (1.0 g)obtained in accordance with methods analogous to the methods for obtaining compounds described the Anna in Example 1, Stage 5, is dissolved in acetic acid (3 ml) and water (6 ml)and then added dropwise an aqueous solution (6 ml), sodium cyanide (300 mg) at room temperature. The mixture is stirred at room temperature for 6 hours, during which add a further quantity of sodium cyanide (750 mg total. The mixture is extracted with ethyl acetate, the ethyl acetate layer was washed with 1 N. hydrochloric acid, water, saturated aqueous sodium bicarbonate, water and brine and dried over anhydrous magnesium sulfate. The mixture is concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of chloroform:methanol=10:1). Add diethyl ether (10 ml) and the resulting mixture was stirred at room temperature for 2 hours. Precipitated precipitated solid is collected by filtration and dried to obtain specified in the title compound as white crystals (581 mg).

Example 5

Obtain 1-{1-[1-(2-carboxyphenylazo)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

Hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (703 mg) from Example 2 is suspended in chloroform (7 ml) and add triethylamine (0,23 ml). While cooling with ice add 2 methoxycarbonyl phenylisocyanate (292 mg) and the resulting mixture was stirred at room temperature for 2 hours. The mixture is concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of chloroform:methanol=30:1) to give 1-{5-cyclopropyl-1-[1-(2-methoxycarbonylpropionyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (992 mg) as amorphous solid white color.

The obtained 1-{5-cyclopropyl-1-[1-(2-methoxycarbonylpropionyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (244 mg) was dissolved in tetrahydrofuran (0.4 ml) and methanol (0.2 ml), add 4 N. aqueous sodium hydroxide solution (0.4 ml) and the resulting mixture was stirred at 60°C for 4 hours. The mixture is concentrated under reduced pressure and the resulting residue is dissolved in water. Under ice cooling, the mixture is acidified with 2 N. hydrochloric acid and extracted with chloroform. The chloroform layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure. To the residue is added n-hexane, which leads to the loss of the crystal. The obtained crystal was washed with n-hexane and dried under reduced pressure to obtain specified in the title compound as amorphous solid white (181 mg).

Example 6

Obtain 1-{5-cyclopropyl-1-[1-(2-hydroxymethyluracil)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-tripto who were)]pyrrolidine

1-{5-Cyclopropyl-1-[1-(2-methoxycarbonylpropionyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (213 mg) obtained in Example 5 was dissolved in tetrahydrofuran (2 ml) and ethanol (2 ml) and added under ice cooling, the lithium chloride (30 mg) and sodium borohydride (26 mg). The mixture is stirred over night at room temperature. Fell into the residue, the insoluble product is collected by filtration and washed with chloroform. The filtrate and washing are combined and the resulting mixture was washed with water, saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=30:1) to obtain the specified title compound as amorphous solid white (109 mg).

Example 7

Obtain 1-{5-cyclopropyl-1-[1-(1-hydroxymethylpropane)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 5, is listed in the title compound obtained as an amorphous solid white (530 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (1.07 g) in Example 2.

Example 8

Obtain 1-{5-cyclopropyl-1-[1-(2-hydrooximethylcarbamil)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 5, is listed in the title compound obtained as an amorphous solid white (202 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (206 mg) according to Example 2.

Example 9

Obtain 1-{5-cyclopropyl-1-[1-(2-hydroxy-1,1-dimethylthiocarbamyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 5, is listed in the title compound obtained as an amorphous solid white (341 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (350 mg) according to Example 2.

Example 10

Obtain 1-{1-[1-(2-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

Stage 1

Obtain 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

The hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-Carbo is Il]-[(S)-3-(2-triptoreline)]pyrrolidine (5,04 g) from Example 2 is added chloroform (50 ml), N,N-diisopropylethylamine (4,68 ml) and then add 4-nitrophenylphosphate (2,39 g) under ice cooling and the resulting mixture was stirred at room temperature for one hour. The mixture is concentrated under reduced pressure, acidified with 1 N. hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=20:1) to obtain specified in the title compound in amorphous form pale yellow (5,41 g).

Stage 2

Obtain 1-{1-[1-(2-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

1-{5-Cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg), obtained as indicated in the preceding stage, dissolved in N-organic (1 ml) and add N-(2-amino-ethyl)ndimethylacetamide (96 μl). The mixture is stirred overnight at a temperature of 80°C. After the mixture is allowed to cool, add 10% aqueous potassium carbonate solution and the resulting mixture extracted with ethyl acetate. The ethyl acetate layer was washed with water, 1 N. hydrochloric acid and water, dried over anhydrous magnesium sulfate and concentrate the Ute under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=15:1) to obtain specified in the title compound in amorphous form white (65 mg).

Example 11

Obtain hydrochloride of 1-{1-[1-(2-aminoethylamino)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

1-{5-Cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg)obtained in Example 10, step 1, tert-butyl(2-amino-ethyl)carbamate (160 mg) was dissolved in acetonitrile (1 ml) and the resulting mixture is heated at the boil under reflux overnight. The mixture is diluted with chloroform, the mixture was washed with water, saturated aqueous potassium bicarbonate, water and brine and dried over anhydrous magnesium sulfate. The mixture is concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of chloroform:methanol=10:1). The obtained amorphous solid was dissolved in ethyl acetate (1 ml) and added 4 n hydrochloric acid in ethyl acetate (4 ml). Precipitated precipitated solid is collected by filtration and dried to obtain specified in the title compound as amorphous solid white (111 mg).

Example 12

Obtain 1-{5-cyclopropa the-1-[1-(1,1-diocletianopolis-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

1-{5-Cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (250 mg)obtained in Example 10, step 1 and thiomorpholine (0,13 ml) dissolved in N-organic (1 ml) and the resulting mixture is stirred over night at 100°C. After the mixture is allowed to cool, the mixture is diluted with diethyl ether, washed with water a 5% aqueous potassium carbonate solution and brine and dried over anhydrous sodium sulfate. The mixture is concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of ethyl acetate:methanol=30:1) to give 1-{5-cyclopropyl-1-[1-(thiomorpholine-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine in the form of an amorphous solid white color (224 mg). The obtained product is dissolved in chloroform (4 ml) and add m-chloroperbenzoic acid (319 mg) under ice cooling. The mixture is stirred for 3 hours, during which the temperature of the mixture was allowed to gradually lowered to room. Add saturated aqueous sodium thiosulfate solution and saturated aqueous sodium hydrogen carbonate solution and the resulting mixture extracted with chloroform. The chloroform layer is washed with brine and dried over anhydrous sodium sulfate. It is then concentrated under reduced pressure and obtained the initial residue purified via chromatography on silica gel (mixture of ethyl acetate:methanol=30:1) to obtain the specified title compound as amorphous solid white (198 mg).

Example 13

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoethanol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid yellow (130 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 14

Obtain 1-{5-cyclopropyl-1-[1-(4-hydroxypiperidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (176 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 15

Obtain 1-{1-[1-(azetidin-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidin

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (150 mg) from 1-{5-C is chlorophyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 16

Obtain 1-{5-cyclopropyl-1-[1-(3-hydroxypyrrolidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (175 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 17

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(2-piperidine-1-iletileri)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid pale yellow color (170 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 18

Obtain 1-{5-cyclopropyl-1-[1-(4,4-deformability-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as amorphous solids blignault color (132 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 19

Obtain 1-{5-cyclopropyl-1-[1-(3,3-debtorprovidian-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid pale yellow color (152 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 20

Obtain 1-{5-cyclopropyl-1-[1-(3-hydroxyazetidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (158 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 21

Obtaining 1-(5-cyclopropyl-1-{1-[(R)-3-hydroxypyrrolidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (171 m is from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 22

Obtaining 1-(5-cyclopropyl-1-{1-[(S)-3-hydroxypyrrolidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (172 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 23

Obtaining 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxy-1-methylethylketon]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid yellow (60 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 24

Obtain 1-{5-cyclopropyl-1-[1-(4-hydroxyethylpiperazine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (150 mg).

Example 25

Obtain 1-{1-[1-(4-carboxypeptidase-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (65 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (172 mg).

Example 26

Obtain 1-{5-cyclopropyl-1-[1-(3-oxopiperidin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (143 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 27

Obtaining 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxyethylpyrrolidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid yellow (150 mg) of 1 - {5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 28

Obtain 1-{5-cyclopropyl-1-[1-(3-hydroxymethylation-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid yellow (178 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 29

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(4-methylpiperazin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (66 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (150 mg).

Example 30

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(4-isopropylpiperazine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid substances is as white (50 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (150 mg).

Example 31

Obtain 1-{1-[1-(4-acetylpiperidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (56 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (150 mg).

Example 32

Obtaining 1-(5-cyclopropyl-1-{1-[(R)-3-hydroxypiperidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid yellow (170 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg).

Example 33

Obtain 1-{1-[1-(4-carbamoylbiphenyl-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (108 mg) from 1-{5-C is chlorophyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (150 mg).

Example 34

Obtain 1-{1-[1-(3-carbamoylation-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (93 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (171 mg).

Example 35

Obtain hydrochloride of 1-{1-[1-(4-aminopiperidin-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 11, specified in the title compound obtained as an amorphous solid white (302 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (478 mg).

Example 36

Obtain hydrochloride of 1-{1-[1-(3-aminopyrrolidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 11, specified in the title compound obtained as an amorphous solid, light color is brown-yellow (635 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (478 mg).

Example 37

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-yl-carbarnoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 11, specified in the title compound obtained as an amorphous solid white (59 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (478 mg).

Example 38

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(4-dimethylaminopyridine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound obtained as an amorphous solid white (74 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (478 mg).

Example 39

Obtain 1-{1-[1-(4-acetylaminophenol-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound obtained as an amorphous solid westvillage color (100 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (478 mg).

Example 40

Obtain 1-{1-[1-(3-acetylpyrrolidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound obtained as an amorphous solid white (127 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (478 mg).

Example 41

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(3-dimethylaminopropan-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound obtained as an amorphous solid light brown-yellow (141 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (478 mg).

Example 42

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-yl-carbarnoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound obtained as the isomorphous solid white (116 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (181 mg).

Example 43

Obtain 1-{1-[1-(1-acetylpiperidine-4-yl-carbarnoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound obtained as an amorphous solid white (41 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (181 mg).

Example 44

Obtain 1-{5-cyclopropyl-1-[1-(4-oxopiperidin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound obtained as an amorphous solid white (155 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (540 mg).

Example 45

Obtain 1-{1-[1-(3-acetylaminoacetylenes-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound obtained as an amorphous solid white (68 mg) from 1-{5-cycle is propyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (90 mg).

Example 46

Obtain 1-{5-cyclopropyl-1-[1-(3-oxopyrrolidin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound obtained as an amorphous solid white (155 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (300 mg).

Example 47

Obtain 1-{5-cyclopropyl-1-[1-(2,2,2-triptoreline)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

Stage 1

Getting 4-nitrophenyl-(2,2,2-triptorelin)carbamate

2,2,2-Triptorelin (392 mg) dissolved in chloroform (4 ml) and added dropwise pyridine (0.35 ml) and 4-nitrophenylphosphate (2,39 g) under cooling with ice. The mixture is stirred at room temperature for one hour. Its concentrated under reduced pressure, to the residue water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with 1 N. hydrochloric acid and water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the obtained residue, add diisopropyl ether, precipitated precipitated solid is collected by filtration and dried to obtain specified in the header is VCE connection in the form of solid white (501 mg).

Stage 2

Obtain 1-{5-cyclopropyl-1-[1-(2,2,2-triptoreline)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

4-Nitrophenyl-(2,2,2-triptorelin)carbamate (113 mg), obtained as described in the previous phase, and the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) from Example 2 is dissolved in pyridine (1 ml) and the resulting mixture is stirred at a temperature of 80°C for 2 hours. After the mixture is allowed to cool, add toluene and the resulting mixture was concentrated under reduced pressure. Add 10% aqueous potassium carbonate solution and the resulting mixture extracted with ethyl acetate. The ethyl acetate layer washed with 10% aqueous potassium carbonate solution, water, 1 N. hydrochloric acid and water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=15:1) to obtain specified in the title compound in amorphous form pale yellow (162 mg).

Example 48

Obtain 1-{5-cyclopropyl-1-[1-(3,3,4,4-tetrafluoropyridine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 47, specify the OU in the title compound obtained as an amorphous solid pale yellow color (138 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (468 mg) according to Example 2.

Example 49

Obtaining 1-(5-cyclopropyl-1-{1-[(S)-1-hydroxymethyl-2-methylpropionyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 47, indicated in the title compound obtained as an amorphous solid white (166 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (250 mg) according to Example 2.

Example 50

Obtaining 1-(1-{1-[(S)-1-benzyl-2-hydrooximethylcarbamil]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 47, indicated in the title compound obtained as an amorphous solid white (140 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (300 mg) according to Example 2.

Example 51

Obtaining 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxy-1-phenylethanol]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 47, indicated in the title compound obtained as an amorphous solid white what about the color (170 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (300 mg) according to Example 2.

Example 52

Obtaining 1-(5-cyclopropyl-1-{1-[(S)-1-hydroxymethyl-3-methylbutanoyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 47, indicated in the title compound obtained as an amorphous solid yellow color (256 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (250 mg) according to Example 2.

Example 53

Obtain 1-{5-cyclopropyl-1-[1-(2-hydroxyphenylarsonic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 47, indicated in the title compound obtained as an amorphous solid white (125 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 54

Obtain 1-{5-cyclopropyl-1-[1-(1-hydroxymethylglutaryl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 47, indicated in the title compound obtained as an amorphous solid white 92 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 55

Obtaining 1-[1-(1-pensacolanewsjournal.com-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Chloroform (3 ml) is added to the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (250 mg) from Example 2, then add triethylamine (81 μl) and toluensulfonate (78 μl) and the resulting mixture is stirred for 2 hours. Its concentrated under reduced pressure, to the residue water is added and the mixture extracted with chloroform. The chloroform layer is washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=10:1). The obtained solid is recrystallized from ethyl acetate to obtain specified in the connection header in the form of a solid pale yellow color (40 mg).

Example 56

Obtaining 1-[5-cyclopropyl-1-(1-methanesulfonylaminoethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 55, indicated in the title compound obtained as an amorphous solid pale yellow color (200 mg) of the hydrochloride of 1-[5-cyclopropyl is-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (500 mg) according to Example 2.

Example 57

Obtaining 1-[5-cyclopropyl-1-(1-ethoxycarbonylpyrimidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) from Example 2 is suspended in chloroform (2.0 ml) and add potassium carbonate (177 mg) under ice cooling. Add methylchloroform (49,4 μl) and the temperature of the obtained mixture was allowed to return to room temperature and stirred for 1.5 hours. Then add methylchloroform (49,4 μl) and the resulting mixture was stirred at room temperature for a period of 15.5 hours. To the reaction mixture is added saturated aqueous sodium hydrogen carbonate solution and the resulting mixture is extracted three times with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=30:1) to obtain the specified title compound as amorphous solid white (210 mg).

Example 58

Obtain 1-{5-cyclopropyl-1-[1-(2-hydroxyethoxyethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in the Example is 57, specified in the title compound obtained as an amorphous solid white (214 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S) - 3-(2-triptoreline)]pyrrolidine (300 mg) according to Example 2.

Example 59

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoethoxide)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (166 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (300 mg).

Example 60

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(2-piperidine-1-yl-etoxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 10, is indicated in the title compound obtained as an amorphous solid white (219 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (300 mg).

Example 61

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-yl-oxycarbonyl)piperidine-4-yl]-spirutal-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 11, specified in the title compound obtained as an amorphous solid pale yellow (53 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (102 mg).

Example 62

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-yl-oxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound obtained as an amorphous solid white (64 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (124 mg).

Example 63

Obtain 1-{1-[1-(1-acetylpiperidine-4-yl-oxycarbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method of obtaining the compound described in Example 12, is indicated in the title compound, obtained as an amorphous solid white (65 mg) from 1-{5-cyclopropyl-1-[1-(4-nitrophenoxyacetic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (122 mg).

Por the measures 64

Obtaining 1-[1-(1-cyclopropanecarbonitrile-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Chloroform (5 ml) and triethylamine (0,13 ml) are added to the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) from Example 2 and then add the acid chloride cyclopropanecarbonyl acid (0,047 ml) under cooling with ice. After stirring overnight at room temperature, the solvent is removed under reduced pressure, to the residue water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium bicarbonate and brine and dried over anhydrous sodium sulfate. The mixture is concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of ethyl acetate:methanol=10:1) to obtain the specified title compound as amorphous solid white (170 mg).

Example 65

Obtain 1-{5-cyclopropyl-1-[1-(2-hydroxyacyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

Chloroform (5 ml) and triethylamine (0.16 ml) is added to the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (250 mg) from Example 2 and acetoxyacetyl (0,069 ml) add the ri ice cooling. After stirring over night at room temperature the mixture is concentrated under reduced pressure, to the residue water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium bicarbonate and brine and dried over anhydrous sodium sulfate. The mixture is concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of ethyl acetate:methanol=10:1). The obtained amorphous solid was dissolved in tetrahydrofuran (2 ml), methanol (2 ml) and water (4 ml) and add monohydrate of lithium hydroxide (103 mg). The mixture is stirred at 60°C for 4 hours. The mixture is concentrated under reduced pressure, the obtained residue add 5% aqueous solution of potassium hydrosulfate and the resulting mixture extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine and dried over anhydrous sodium sulfate. The mixture is concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of ethyl acetate:methanol=20:1) to obtain the specified title compound as amorphous solid white (30 mg).

Example 66

Obtaining 1-(5-cyclopropyl-1-{1-[1-(4-forfinal)cyclopropanecarbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidin is and

In accordance with a technique similar to the method for obtaining compounds described in Example 64, indicated in the title compound obtained as an amorphous solid pale yellow color (193 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 67

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoacetyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 64, indicated in the title compound obtained as an amorphous solid pale yellow color (217 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 68

Obtain 1-{1-[1-(2-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 64, indicated in the title compound obtained as an amorphous solid light brown-yellow (119 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

P the emer 69

Obtain 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 64, indicated in the title compound obtained as an amorphous solid pale yellow color (178 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 70

Obtain 1-{1-[1-(2-acetylamino-2-methylpropionyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 64, indicated in the title compound obtained as an amorphous solid light brown-yellow (94 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 71

Obtaining 1-(1-{1-[(S)-2-acetylaminophenol]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 64, indicated in the title compound obtained as an amorphous solid white (183 mg) of g is drochloride 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 72

Obtaining 1-(1-{1-[(S)-2-acetylamino-3-methylbutyryl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 64, indicated in the title compound obtained as an amorphous solid pale yellow color (212 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 73

Obtain 1-{5-cyclopropyl-1-[1-(3,3,3-triptocaine)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 64, indicated in the title compound obtained as an amorphous solid pale yellow color (151 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (150 mg) according to Example 2.

Example 74

Obtaining 1-(5-cyclopropyl-1-{1-[(S)-5-oxopyrrolidin-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 64, indicated in the title compound obtained as an amorphous solid white (127 mg) and the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 75

Obtain 1-{1-[1-(3-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 64, indicated in the title compound obtained as an amorphous solid pale yellow color (263 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (355 mg) according to Example 2.

Example 76

Obtain 1-{5-cyclopropyl-1-[1-(3-hydroxy-2,2-dimethylpropionic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid white color (238 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (250 mg) according to Example 2.

Example 77

Obtain hydrochloride of 1-{1-[1-(2-aminoacetyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid pale yellow color (219 mg) and the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 78

1-{5-cyclopropyl-1-[1-(1-hydroxymethylpropane)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, specified in the header connection receive in the form of white crystals (168 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (250 mg) according to Example 2.

Example 79

Obtain hydrochloride of 1-{1-[1-(2-amino-2-methylpropionyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid light brown-yellow (154 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 80

Obtain 1-{5-cyclopropyl-1-[1-(4-hydroxybutyryl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid white (166 mg) of hydrochloride-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 81

Obtain hydrochloride of 1-(5-cyclopropyl-1-{1-[(S)-pyrrolidin-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid pale yellow color (569 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (450 mg).

Example 82

Obtain hydrochloride of 1-(5-cyclopropyl-1-{1-[(S)-1-methylpyrrolidine-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid pale yellow color (192 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (450 mg).

Example 83

Obtain hydrochloride of 1-{1-[1-(3-aminopropyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous Tverdov the substances pale yellow (414 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (355 mg) according to Example 2.

Example 84

Getting hydrochloride 1-(1-{1-[(S)-2-amino-3-methylbutyryl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid light brown-yellow (182 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (150 mg) according to Example 2.

Example 85

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(2-methylaminomethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid light brown-yellow (183 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (150 mg) according to Example 2.

Example 86

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as Amor the aqueous solids pale yellow (478 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (404 mg) according to Example 2.

Example 87

Obtain 1-{5-cyclopropyl-1-[1-(2-isobutylamino)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid light brown-yellow (214 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 88

Obtain 1-{1-[1-(2-cyclopropanecarboxylate)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid pale yellow color (190 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 89

Obtaining 1-(1-{1-[(S)-1-acetylpyrrolidine-2-carbonyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as amorphous solids is ledno yellow (189 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (450 mg).

Example 90

Obtain 1-{5-cyclopropyl-1-[1-(2-methanesulfonylaminoethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid white (134 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (152 mg).

Example 91

Obtain 1-{1-[1-(1-acetylpiperidine-4-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid pale yellow color (145 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (404 mg) according to Example 2.

Example 92

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid light measles is nebo-yellow (151 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (404 mg) according to Example 2.

Example 93

Obtain 1-{1-[1-(3-carbamoylbiphenyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 65, indicated in the title compound obtained as an amorphous solid white (61 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 94

Obtain hydrochloride of 1-[1-(1-carbamoylmethyl-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) from Example 2 was dissolved in N,N-dimethylformamide (2.5 ml) and add potassium carbonate (93 mg) and 2-bromoacetamide (50,7 mg). The resulting mixture was stirred at room temperature for 2 hours. To the reaction mixture, water is added and the mixture extracted three times with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=20:1) to give 1-[1-(1-carbamoylmethyl-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptime ylphenyl)]pyrrolidine (167 mg) as amorphous solid white color.

1-[1-(1-Carbamoylmethyl-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (154 mg), obtained as described in the preceding stage, dissolved in ethyl acetate (2 ml) and added 4 n hydrochloric acid in ethyl acetate (159 μl). The mixture is stirred for 10 minutes. Precipitated precipitated crystals are collected by filtration and dried to obtain specified in the title compound as amorphous solid white (109 mg).

Example 95

Obtain hydrochloride of 1-[5-cyclopropyl-1-(1-methylcarbamoylmethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (2.5 g) from Example 2 was dissolved in N,N-dimethylformamide (20 ml) and add potassium carbonate (1,62 g) and ethylbromoacetate (0,98 g). The mixture is stirred at room temperature for one hour. To the reaction mixture, water is added and the mixture extracted twice with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=25:1) to give 1-{5-cyclopropyl-1-[1-(ethoxycarbonylmethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]Pirro is Idina (2,79 g) as amorphous solid white color.

1-{5-Cyclopropyl-1-[1-(ethoxycarbonylmethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (1.4 g), obtained as described in the preceding stage, dissolved in tetrahydrofuran (5.5 ml) and methanol (2.7 ml) and add 4 N. aqueous sodium hydroxide solution (1.4 ml). The mixture is stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure and the resulting residue is dissolved in water. The layer of the aqueous solution is washed twice with diethyl ether, the pH adjusted to 5-6 with 2 n hydrochloric acid under ice cooling and extracted three times with chloroform. The chloroform layer is dried over anhydrous magnesium sulfate, concentrated under reduced pressure and to the residue is added n-hexane. Precipitated precipitated solid is collected by filtration and dried to obtain 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (1,17 g) as a solid white color.

N,N-Dimethylformamide (3.0 ml) are added to 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (150 mg), obtained as described in the previous phase, was added 1-hydroxybenzotriazole (61 mg), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (76 mg) and the resulting mixture premesis the Ute at room temperature within hours. Add 40% aqueous solution of methylamine (106 μl) and the resulting mixture is stirred for 5 hours, then add 40% aqueous solution of methylamine (318 μl) and the resulting mixture was stirred at room temperature for 13 hours. To the reaction mixture, water is added and the mixture extracted with chloroform. The organic layer was washed with saturated aqueous sodium bicarbonate, water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=20:1). The obtained amorphous solid was dissolved in ethyl acetate (2.0 ml), added with 4 n hydrochloric acid in ethyl acetate (100 ml) and the resulting mixture is stirred for 10 minutes. Precipitated precipitated crystals are collected by filtration and dried to obtain specified in the title compound as amorphous solid white (16,9 mg).

Example 96

Obtain hydrochloride of 1-{1-[1-(1-carbarnoyl-1-methylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

Cameramen (1.1 g) and triethylamine (1.2 ml) dissolved in chloroform (10 ml) and add a solution of 2-bromoisobutyrate (1.0 ml) in chloroform (2 ml) under ice cooling over 5 minutes. The mixture is stirred at room temperature for 15 minutes. It is then concentrated under reduced pressure, the obtained residue is added ethyl acetate and the resulting mixture was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained solid is white washed with diisopropyl ether and dried to obtain 2-bromo-2-methyl-N-(1-methyl-1-phenylethyl)propylamide in a solid white color (1.73 g).

Hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 was dissolved in tetrahydrofuran (5.5 ml) and add 60% solution of sodium hydride (104 mg). The mixture is stirred at 60°C for one hour and at room temperature for 5 minutes. Add 2-bromo-2-methyl-N-(1-methyl-1-phenylethyl)propylamide (329 mg), obtained as described in the previous phase, and the resulting mixture was stirred at 60°C for 22 hours. After the mixture is allowed to cool, to the reaction mixture, water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=20:1) to give 1-(5-cyclopropyl-1-{1-[1-methyl-1-(1-methyl-1-phenylethanol)ethyl]piperidine-4-yl}-1H-pyrazole-4-Carbo who yl)-[(S)-3-(2-triptoreline)]pyrrolidine in amorphous form pale yellow (78 mg).

1-(5-Cyclopropyl-1-{1-[1-methyl-1-(1-methyl-1-phenylethanol)ethyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidin obtained as indicated in the previous stage is dissolved in triperoxonane acid (2 ml) and the resulting mixture was stirred at 80°C for 8 hours. Then add triperoxonane acid (1 ml) and then the resulting mixture was stirred at 80°C for 8 hours. After the mixture is allowed to cool, the mixture was concentrated under reduced pressure and the resulting residue is dissolved in ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:acetone=4:5→mixture of chloroform:methanol=10:1). The resulting residue is dissolved in ethyl acetate (1 ml) and added 4 n hydrochloric acid in ethyl acetate (1 ml) and diethyl ether (1.5 ml). The obtained solid is collected by filtration and dried to obtain specified in the connection header in the form of a solid pale yellow color (36 mg).

Example 97

Obtain hydrochloride of 1-{1-[1-(2-carbamoylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In soo is required by the method, analogous to the methods for obtaining compounds described in Example 94, specified in the title compound obtained as an amorphous solid white color (149 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 98

Obtain hydrochloride of 1-[5-cyclopropyl-1-(1-cyclopropylmethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 94, specified in the header connection receive in the form of white crystals (133 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (150 mg) according to Example 2.

Example 99

Obtain hydrochloride of 1-[5-cyclopropyl-1-(1-cyclopropylidene-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 94, specified in the title compound obtained as an amorphous solid light brown-yellow (144 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 100

Obtain hydrochloride of 1-[5-cyclopropyl-1-(1-dimethy carbamoylbiphenyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 95, specified in the title compound obtained as an amorphous solid white (20 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (2.5 g) in Example 2.

Example 101

Obtain hydrochloride of 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Specified in the title compound obtained as an amorphous solid white color (24 mg) of 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (112 mg)obtained in Example 95.

Example 102

Obtain hydrochloride of 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 95, specified in the title compound obtained as an amorphous solid pale yellow color (295 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (350 mg).

Example 103

Obtain hydrochloride of 1-{1-[1-(1-carbamoylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[()-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 95, specified in the title compound obtained as an amorphous solid pale yellow color (146 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (350 mg).

Example 104

Obtain hydrochloride of 1-{1-[1-(2-carboxy-2-methylpropyl " piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 95, specified in the title compound obtained as an amorphous solid pale yellow color (71 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (400 mg).

Example 105

Obtain hydrochloride of 1-{1-[1-(2-carbarnoyl-2-methylpropyl " piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 95, specified in the title compound obtained as an amorphous solid white (52 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (400 mg).

Obtain hydrochloride of 1-{1-[1-(1-carbamoylmethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 95, specified in the title compound obtained as an amorphous solid white (82 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (400 mg).

Example 107

Obtain hydrochloride of 1-(5-cyclopropyl-1-{1-[1-(2-hydrooximethylcarbamil)cyclopropylmethyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 95, specified in the title compound obtained as an amorphous solid white (84 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (400 mg).

Example 108

Obtaining 1-[5-cyclopropyl-1-(1-triftormetilfullerenov-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) from Example 2 is dissolved in methylene chloride (2.0 ml) in an argon atmosphere of the races is a thief cooled to a temperature of -78°C, add triethylamine (178 μl) and the anhydride triftormetilfullerenov acid (78,8 μl), after which the resulting mixture was stirred for 2.5 hours. Then add the anhydride triftormetilfullerenov acid (78,8 μl) and the resulting mixture is stirred for 2 hours. To the reaction mixture is added saturated aqueous solution of sodium bicarbonate at a temperature of -78°C and the resulting mixture extracted with chloroform. The organic layer was washed with 1 N. hydrochloric acid, water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=20:1) to obtain the specified title compound as amorphous forms yellow (192 mg).

Example 109

Obtain 1-{5-cyclopropyl-1-[1-(2,2,2-cryptogramophone)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 108, specified in the title compound obtained as an amorphous solid yellow (29 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg) according to Example 2.

Example 110

Obtain 1-{1-[1-(1-cyanoimino)piperidine-4-yl]-5-cyclopropyl-1H-pee the azole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

Hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine of Example 2 (300 mg) dissolved in chloroform (5 ml) and then add triethylamine (97 μl) and methyl-N-cyanoacetamide (66 μl). Then after stirring at room temperature for 30 minutes and at a temperature of 45°C for 1.5 hours add triethylamine (97 μl) and methyl-N-cyanoacetamide (66 μl) and the resulting mixture is stirred at 45°C for 2 hours. The mixture is concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of chloroform:methanol=15:1) to obtain specified in the title compound in amorphous form pale yellow (214 mg).

Example 111

Obtaining 1-(1-{1-[cyanoimino(methylamino)methyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

Stage 1

Obtaining 1-(1-{1-[cyanoimino(phenoxy)methyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

Chloroform (5 ml) is added to the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine of Example 2 (500 mg) and then add triethylamine (rate £ 0.162 ml) and diphenyl-N-cyanocarbonimidate (284 mg). The mixture is stirred for 1.5 hours. Then her focus when pengendalian and the resulting residue purified via chromatography on silica gel (mixture of chloroform:acetone=1:1→2:3→1:2) obtaining specified in the title compound in amorphous form pale yellow (575 mg).

Stage 2

Obtaining 1-(1-{1-[cyanoimino(methylamino)methyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine

1-(1-{1-[Cyanoimino(phenoxy)methyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine (575 mg), obtained as indicated in the preceding stage, dissolved in chloroform (10 ml), added methylamine hydrochloride (81 mg) and triethylamine (0.31 in ml)and the resulting mixture was stirred at room temperature for 30 minutes and at a temperature of 55°C within 5 hours. Then add methylamine hydrochloride (81 mg) and triethylamine (2 ml) and the resulting mixture is stirred at a temperature of 55°C for one hour and at 60°C for 30 minutes. Then again added methylamine hydrochloride (162 mg) and the mixture was stirred at 60°C for 2.5 hours. After the mixture is allowed to cool, the mixture is concentrated under reduced pressure and the resulting residue is dissolved in chloroform and the resulting mixture was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=10:1) to obtain the specified title compound as amorphous solid white (242 mg).

Example 112

Recip is of 1-{1-[1-(N-cyanocarbonimidate)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 111, specified in the title compound obtained as an amorphous solid pale yellow color (249 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine from Example 2 (302 mg).

Example 113

Getting 4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid

Stage 1

Obtain tert-butyl-1-[1-(4-ethoxycarbonylphenyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carboxylate

tert-Butyl-2-cyclopropanecarbonyl-3-diethylaminoacetate (1.12 g)obtained in accordance with methods analogous to the methods for obtaining compounds described in Example 1, stage 1 and hydrochloride ethyl-4-(4-hydrazinopyridazine-1-yl)benzoate (692 mg)obtained by known methods, is suspended in ethanol (15 ml). To the resulting suspension is added triethylamine (0,81 ml) and the resulting mixture is heated at the boil under reflux overnight. The reaction mixture was concentrated under reduced pressure, to the residue water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained OST is OK purified using chromatography on silica gel (mixture of n-hexane:ethyl acetate=3:1) to obtain the specified title compound as yellow oil (673 mg).

Stage 2

Obtaining 1-[1-(4-ethoxycarbonylphenyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carboxylic acid

tert-Butyl-1-[1-(4-ethoxycarbonylphenyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carboxylate (673 mg), obtained as indicated in the preceding stage, dissolved in chloroform (4 ml), add triperoxonane acid (4 ml) under ice cooling and the resulting mixture is stirred at 40°C for 2 hours. The reaction mixture was concentrated under reduced pressure, to the residue water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the obtained residue is added diethyl ether and n-hexane and precipitated precipitated solid is collected by filtration and dried to obtain specified in the connection header in the form of a solid white color (556 mg).

Stage 3

Getting 5-cyclopropyl-1-{1-[1-(4-ethoxycarbonylphenyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-{3-(2-triptoreline)}pyrrolidine

5-Cyclopropyl-1-[1-(4-ethoxycarbonylphenyl)piperidine-4-yl]-1H-pyrazole-4-carboxylic acid (550 mg), obtained as described in the previous phase, 1-hydroxybenzotriazole (285 mg) and the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (357 mg) was dissolved in N,N-dimethylformamide ( ml). To the resulting solution was added 3-(2-triptoreline)pyrrolidin (308 mg) and the resulting mixture is stirred over night at room temperature. To the reaction mixture, water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (ethyl acetate) to obtain the specified title compound as amorphous solid white (757 mg).

Stage 4

Getting 4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid

1-{1-[1-(4-Ethoxycarbonylphenyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-{3-(2-triptoreline)}pyrrolidin (720 mg), obtained as indicated in the preceding stage, dissolved in tetrahydrofuran (3 ml) and methanol (1.5 ml) and add 4 N. aqueous sodium hydroxide solution (1.2 ml). The mixture is stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue is dissolved in water. The layer of the aqueous solution was washed with diethyl ether, acidified with 2 N. hydrochloric acid under ice cooling and extracted with ethyl acetate. The ethyl acetate layer is raybaut water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the obtained residue, add a mixture of diethyl ether:n-hexane (1:1) and precipitated precipitated solid is collected by filtration and dried to obtain specified in the connection header in the form of a solid white color (600 mg).

Example 114

Obtaining 3-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid

1-[5-Cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidin (195 mg)obtained in accordance with methods analogous to the methods for obtaining compounds described in Example 1 and ethyl-3-iodobenzoate (142 mg) was dissolved in 1,4-dioxane (1 ml) and tert-butanol (1 ml) and then added Tris(dibenzylideneacetone)dipalladium (14,2 mg), 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (24.3 mg) and cesium carbonate (235 mg). The mixture is heated at boiling under reflux overnight. After the mixture is allowed to cool, the insoluble product is filtered through celite and the filtrate concentrated under reduced pressure. To the obtained residue is added saturated aqueous sodium hydrogen carbonate solution and the resulting mixture extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure, the NII. The resulting residue is purified by chromatography on silica gel (mixture of n-hexane:acetone=1:1) to give ethyl-3-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoate as an amorphous solid white (179 mg).

Ethyl-3-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoate (179 mg), obtained as indicated in the preceding stage, dissolved in tetrahydrofuran (1 ml) and ethanol (1 ml) and add 4 N. aqueous sodium hydroxide solution (1 ml). The mixture is heated at the boil under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue is dissolved in water and acidified with 2 N. hydrochloric acid under ice cooling. Precipitated precipitated solid is collected by filtration, washed with water and dried under reduced pressure to obtain specified in the connection header in the form of a solid white color (165 mg).

Example 115

Getting 5-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiophene-2-carboxylic acid

1-[5-Cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidine (220 mg)obtained in accordance with methods analogous to the methods for obtaining compounds described, the example1 and ethyl-5-bromothiophene-2-carboxylate (137 mg) was dissolved in toluene (4 ml) and add palladium acetate (13 mg), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (36 mg) and cesium carbonate (265 mg). The mixture is heated at boiling under reflux for 6 hours. After the mixture is allowed to cool, the insoluble product is filtered through celite and the filtrate concentrated under reduced pressure. To the obtained residue is added saturated aqueous sodium hydrogen carbonate solution and the resulting mixture extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of n-hexane:acetone=1:1) to give ethyl-5-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiophene-2-carboxylate (162 mg) as amorphous solid white color.

Ethyl-5-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiophene-2-carboxylate (162 mg), obtained as described in the preceding stage, dissolved in tetrahydrofuran (1 ml) and ethanol (1 ml) and add 4 N. aqueous sodium hydroxide solution (1 ml). The mixture is heated at the boil under reflux for 3 hours. The reaction mixture was concentrated under reduced pressure and the resulting residue is dissolved in water and acidified with 2 N. hydrochloric acid under ice cooling. Fallen Vostok the solid is collected by filtration, washed with water and dried under reduced pressure. The obtained solid is purified by chromatography on silica gel (mixture of chloroform:acetone=6:1) and recrystallized from ethyl acetate to obtain specified in the connection header in the form of a solid pale green color (28 mg).

Example 116

Obtaining 2-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiazole-4-carboxylic acid

Stage 1

Getting 4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-thiocarboxamide

1-[5-Cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidin (420 mg)obtained in accordance with methods analogous to the methods for obtaining compounds described in Example 1, is dissolved in chloroform (10 ml) and add triethylamine (0,139 ml) and 9-fluorenylmethoxycarbonyl (285 mg) at room temperature. The mixture is stirred for one hour. The reaction mixture was concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of chloroform:methanol=50:1). The obtained purified product was dissolved in N,N-dimethylformamide (7 ml) and added piperidine (0.7 ml) at room temperature. The mixture is stirred for one hour and concentrated under reduced pressure. OST is OK dissolved in ethyl acetate and the resulting mixture was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. To the obtained residue is added diethyl ether and precipitated precipitated solid is collected by filtration, washed with water and dried under reduced pressure to obtain specified in the connection header in the form of a solid white color (287 mg).

Stage 2

Obtaining 2-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiazole-4-carboxylic acid

4-{5-Cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-thiocarboxamide (280 mg), obtained as described in the previous phase, suspended in ethanol (5 ml) and the resulting suspension add ethylbromide (0,09 ml). The mixture is heated at the boil under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure, to the residue water is added and the mixture extracted with chloroform. The chloroform layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=20:1) to obtain ethyl-2-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiazole-4-Carbo is power (361 mg) as amorphous solid white color.

Ethyl-2-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiazole-4-carboxylate (355 mg), obtained as indicated in the preceding stage, dissolved in tetrahydrofuran (0.6 ml) and methanol (0.3 ml)and add 4 N. aqueous sodium hydroxide solution (0,57 ml) at room temperature. The mixture is stirred for 3 hours. The reaction mixture was concentrated under reduced pressure and the obtained residue was added 1 N. aqueous sodium hydroxide solution and the resulting mixture was washed with diethyl ether. A layer of an aqueous solution acidified with 2 N. hydrochloric acid and precipitated precipitated solid is collected by filtration, washed with water and dried under reduced pressure to obtain specified in the connection header in the form of a solid white color (272 mg).

Example 117

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(5-methyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

Stage 1

Getting hydroiodide methyl-4-{5-cyclopropyl-4-[(S)-3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-iminodicarboxylate

4-{5-Cyclopropyl-4-[(S)-3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-thiocarboxamide (500 mg)obtained in accordance with methods analogous to the methods for obtaining compounds, op is pulling in Example 116, Stage 1, is dissolved in chloroform (5 ml) and add methyliodide (0.1 ml). The mixture is stirred over night at room temperature. Its concentrated under reduced pressure, the obtained residue is added diethyl ether, precipitated precipitated solid is collected by filtration and dried to obtain specified in the connection header in the form of a solid pale yellow color (654 mg).

Stage2

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(5-methyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

Hydroiodide methyl-4-{5-cyclopropyl-4-[(S)-3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-iminodicarboxylate (317 mg), obtained as described in the previous phase, acetic acid hydrazide (50 mg) and sodium acetate (43 mg) are suspended in dioxane (2 ml) and water (0.4 ml) and the resulting mixture is heated at the boil under reflux overnight. The solvent is removed under reduced pressure, to the residue water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with brine and dried over anhydrous magnesium sulfate. The mixture is concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of chloroform:methanol=10:1). The obtained amorphous solid was dissolved in those who acetate (1 ml) and add 4 N. a solution of hydrochloric acid in ethyl acetate (0.4 ml). Precipitated precipitated solid is collected by filtration and dried to obtain specified in the title compound as white crystals (72 mg).

Example 118

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(5-cyclopropyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 117, specified in the header connection receive in the form of white crystals (253 mg) from hydroiodide methyl-4-{5-cyclopropyl-4-[(S)-3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-iminodicarboxylate (475 mg).

Example 119

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(5-hydroxymethyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 117, specified in the header connection receive in the form of white crystals (25 mg) of hydroiodide methyl-4-{5-cyclopropyl-4-[(S)-3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-iminodicarboxylate (317 mg).

Example 120

Obtain hydrochloride of 1-{5-cyclopropyl-1-[1-(5-trifluoromethyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-what reformational)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 117, specified in the header connection receive in the form of white crystals (130 mg) of hydroiodide methyl-4-{5-cyclopropyl-4-[(S)-3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-iminodicarboxylate (317 mg).

Example 121

Obtain 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine

Stage 1

Obtaining methyl-5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carboxylate

Methyl-1-(1-benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carboxylate (15.9 g)obtained in Example 1, step 2, was dissolved in methanol (12 ml) and added palladium on coal (1.5 g). The mixture is stirred overnight in a hydrogen atmosphere. The catalyst is filtered off and the filtrate is concentrated under reduced pressure. To the obtained residue is added n-hexane and after filtration receive specified in the title compound as amorphous solid white (9,66 g).

Stage 2

Obtaining methyl-5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carboxylate

Methyl-5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carboxylate (2,82 g), obtained as indicated in the preceding stage, dissolved in chloroform (28 ml) and add Proc. of the ethylamine (1,58 ml).

To the mixture is added 2-forgenerations (1.4 ml) under ice cooling and the resulting mixture was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of n-hexane:ethyl acetate=2:3) to obtain the specified title compound as amorphous solid white (to 4.23 g).

Stage 3

Getting 5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carboxylic acid

Methyl-5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carboxylate (to 4.23 g), obtained as indicated in the preceding stage, dissolved in tetrahydrofuran (11 ml) and methanol (5 ml) and add 4 N. aqueous sodium hydroxide solution (11 ml). The mixture is stirred at 60°C for 6 hours. The reaction mixture was allowed to cool and concentrated under reduced pressure. The resulting residue is dissolved in water. The layer of the aqueous solution was washed with diethyl ether and acidified with concentrated hydrochloric acid while cooling with ice. Precipitated precipitated solid is collected by filtration, washed with water and n-hexane and dried under reduced pressure to obtain specified in the connection header in the form of a solid white color (to 3.89 g).

Stage 4

Paul is the significance of 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-{(R)-3-(2-triptoreline)}pyrrolidine

5-Cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carboxylic acid (101 mg), obtained as described in the previous phase, 1-hydroxybenzotriazole (46 mg), and hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (57 mg) was dissolved in N,N-dimethylformamide (15 ml). (R)-3-(2-Triptoreline)pyrrolidine (65 mg)and 4-dimethylaminopyridine (37 mg) are added to the resulting solution and the resulting mixture is stirred over night at room temperature. To the reaction mixture, water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=20:1) to obtain the specified title compound as amorphous solid white (136 mg).

[α]25D = +10,9 (c = 0,495, EtOH)

*(R)-3-(2-Triptoreline)pyrrolidin receive in accordance with methods analogous to the methods for obtaining compounds described in Example 2, Stage 1 through 4, and using (R)-4-isopropyl-5,5-diphenyloxazole-2-it.

[α]25D = -21,0 (c = 0,500, EtOH)

Example 122

Obtain 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidin the

Stage 1

Obtaining methyl-5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carboxylate

1-Methylcyclopropane-1-carboxylic acid (1,81 g), diphenylphosphoryl (4,67 ml) and triethylamine (2,77 ml) dissolved in toluene (30 ml) and the resulting mixture is heated at the boil under reflux for one hour to obtain isocyanate.

Methyl-5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carboxylate (1.50 g)obtained in Example 121, step 1, and triethylamine (0,84 ml) dissolved in tetrahydrofuran (15 ml) and add toluene solution of isocyanate obtained in advance, until there is no longer the original product (methyl-1-(piperidine-4-yl)-5-cyclopropyl-1H-pyrazole-4-carboxylate). The reaction mixture was concentrated under reduced pressure, to the residue water is added and the mixture extracted with chloroform. The chloroform layer was washed with saturated aqueous sodium bicarbonate and brine and dried over anhydrous magnesium sulfate. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=15:1) to obtain the specified title compound as amorphous solid white (1.92 g).

Stage 2

Getting 5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carboxylic acid

Methyl-5-cyclopropyl-1-[1-(1-methylcyclopropyl rebamol)piperidine-4-yl]-1H-pyrazole-4-carboxylate (1.92 g), received as stated on the previous stage is dissolved in tetrahydrofuran (20 ml) and methanol (10 ml) and add 4 N. aqueous sodium hydroxide solution (15 ml). The mixture is stirred at 60°C for 6 hours. The reaction mixture was allowed to cool and concentrated under reduced pressure. The resulting residue is dissolved in water and a layer of an aqueous solution washed with diethyl ether. Under ice cooling the resulting mixture was acidified with concentrated hydrochloric acid and extracted with chloroform. The chloroform layer is washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the obtained residue is added ethyl acetate, precipitated precipitated solid is collected by filtration and dried to obtain specified in the connection header in the form of a solid white color (1.68 g).

Stage 3

Obtain 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine

5-Cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carboxylic acid (91 mg), obtained as described in the previous phase, 1-hydroxybenzotriazole (46 mg), and hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (57 mg) was dissolved in N,N-dimethylformamide (1.5 ml). To the resulting solution was added (R)-3-(2-triptoreline)pyrrol the Dean (65 mg) and 4-dimethylaminopyridine (37 mg) and the resulting mixture is stirred over night at room temperature. To the reaction mixture, water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=15:1) to obtain the specified title compound as amorphous solid white color (123 mg).

[α]25D = +13,1 (c = 0,495, EtOH)

Example 123

Obtain 1-{5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine

Stage 1

Obtaining methyl-5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carboxylate

Methyl-5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carboxylate (1,87 g)obtained in Example 121, step 1, was dissolved in chloroform (20 ml) and add triethylamine (1,05 ml). To the resulting mixture add isopropyltoluene (0.7 ml) under ice cooling and then stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure and the resulting residue purified via chromatography on silica gel (mixture of chloroform:methanol=15:1) to obtain the specified title compound as amorphous solid white (2.00 d).

Stage 2/u>

Getting 5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carboxylic acid

Methyl-5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carboxylate (2.00 g)obtained as indicated in the previous stage is dissolved in tetrahydrofuran (6 ml) and methanol (3 ml)and add 4 N. aqueous sodium hydroxide solution (6 ml). The mixture is stirred at 60°C for 4.5 hours. The reaction mixture was allowed to cool and concentrated under reduced pressure. The resulting residue is dissolved in water and a layer of an aqueous solution washed with diethyl ether and acidified with concentrated hydrochloric acid while cooling with ice. The mixture is extracted with chloroform. The chloroform layer is washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the obtained residue is added n-hexane, precipitated precipitated solid is collected by filtration and dried to obtain specified in the connection header in the form of a solid white color (1,58 g).

Stage 3

Obtain 1-{5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine

5-Cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carboxylic acid (88 mg), obtained as described in the previous phase, 1-hydroxybenzotriazole (46 mg) and guide klorid 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (57 mg) was dissolved in N,N-dimethylformamide (1.5 ml). To the resulting solution was added (R)-3-(2-triptoreline)pyrrolidine (65 mg) and 4-dimethylaminopyridine (37 mg) and the resulting mixture is stirred over night at room temperature. To the reaction mixture are added water and then extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=15:1) to obtain the specified title compound as amorphous solid white (120 mg).

[α]25D = +14,2 (c = 0,500, EtOH)

Example 124

Obtain 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 121, step 4, is listed in the title compound obtained as an amorphous solid white (127 mg) from 5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carboxylic acid (123 mg), (S)-3-(2-triptoreline)pyrrolidine (78 mg).

[α]25D = -10,8 (c = 0,510, EtOH)

Example 125

Obtain 1-{5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrole the ina

In accordance with a technique similar to the method for obtaining compounds described in Example 123, step 3, is indicated in the title compound obtained as an amorphous solid white color (123 mg) from 5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carboxylic acid (107 mg), (S)-3-(2-triptoreline)pyrrolidine (79 mg).

[α]25D = -13,2 (c = 0,515, EtOH)

Example 126

Obtain 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 122, step 3, is indicated in the title compound obtained as an amorphous solid white color (149 mg) from 5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carboxylic acid (107 mg), (S)-3-(2-triptoreline)pyrrolidine (76 mg).

[α]25D = -13,6 (c = 0,500, EtOH)

Example 127

Obtaining hydrochloride (-)-3-(4-forfinal)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine

Stage 1

Getting atilano-(4-forfinal)acetate

Toluene (40 ml) is added to 4-perforaciones (15.0 g) and diethylmalonate (66,9 ml), then add the sodium ethylate (8,30 g). The mixture is stirred for 2 hours as evaporation, R is storytale at a temperature in the range from 110°C to 130°C. After the mixture is allowed to cool, the reaction mixture was poured into water and add acetic acid (13 ml). The mixture is stirred for 5 minutes and then it is extracted three times with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain specified in the connection header in the form of oil, pale yellow (25,0 g).

Stage 2

Getting diethyl-2-cyano-2-(4-forfinal)succinate

Tetrahydrofuran (40 ml) is added 60% sodium hydride (2,12 g) and added dropwise a solution of atilano(4-forfinal)acetate (10.0 g)obtained as described at the previous step in tetrahydrofuran (40 ml) under cooling with ice. The mixture is stirred for 40 minutes and add ethylbromoacetate (6,4 ml) under cooling with ice. The mixture is stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, to the residue water is added and the mixture extracted three times with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate=5:1) to obtain specified in the connection header in the form of oil, pale yellow (14,7 g).

Stage 3

The floor is giving ethyl-3-(4-forfinal)-5-oxopyrrolidin-3-carboxylate

A solution of diethyl-2-cyano-2-(4-forfinal)succinate (7.0 g), obtained as described in the previous phase, in ethanol (50 ml) was added to Raney Nickel (7.0 g) and the resulting mixture is stirred overnight in a hydrogen atmosphere. The reaction mixture was filtered through celite, the filtrate and washing are combined and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=25:1) and to the resulting solid residue is added a mixed solvent of diethyl ether and n-hexane. The mixture is filtered and dried to obtain specified in the title compound as white crystals (3,96 g).

Stage 4

Getting ethyl-1-benzyl-3-(4-forfinal)-5-oxopyrrolidin-3-carboxylate

Tetrahydrofuran (25 ml) is added 60% sodium hydride (1.63 g) and added dropwise a solution of ethyl-3-(4-forfinal)-5-oxopyrrolidin-3-carboxylate (10.3 g), obtained as described in the previous phase in a mixture of tetrahydrofuran (30 ml)/N,N-dimethylformamide (10 ml) under cooling with ice. The mixture is stirred for 10 minutes. While cooling with ice add benzylbromide (4,86 ml). The mixture is stirred at the same temperature for 30 minutes and at room temperature for 3.5 hours. The reaction mixture was concentrated under reduced pressure, to the residue water is added and the mixture extracted three times etelaat the om. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate=2:1) to obtain specified in the connection header in the form of oil is pale-yellow (12.1 g).

Stage 5

Obtain 1-benzyl-3-(4-forfinal)-3-hydroxyethylpyrrolidine

Tetrahydrofuran (20 ml) is added to sociallyengaged (1,16 g) and added dropwise a solution of ethyl-1-benzyl-3-(4-forfinal)-5-oxopyrrolidin-3-carboxylate (4,16 g), obtained as described in the previous step in tetrahydrofuran (20 ml) under cooling with ice. The mixture is stirred at the boil under reflux for 3.5 hours. After the mixture is allowed to cool, successively added water (0.9 ml), 4 N. aqueous sodium hydroxide solution (0.9 ml) and water (2.7 ml) under cooling with ice, and then add diethyl ether and magnesium sulfate. The mixture is stirred for 20 minutes and filtered through celite. The filtrate and washing are combined and concentrated under reduced pressure to obtain specified in the connection header in the form of oil, pale yellow (3,18 g).

Stage 6

Obtaining 3-(4-forfinal)-3-hydroxyethylpyrrolidine

To a solution of 1-benzyl-3-(4-forfinal)-3-hydroxyethylpyrrolidine (3,18 g), obtained as Asano on the previous stage, in methanol (30 ml) is added palladium hydroxide (300 mg) and the resulting mixture is stirred overnight in a hydrogen atmosphere (3 ATM). The reaction mixture was filtered through celite, the filtrate and washing are combined and concentrated under reduced pressure to obtain specified in the connection header in the form of oil, pale yellow (2.30 g).

Stage 7

Obtain tert-butyl-3-(4-forfinal)-3-hydroxyethylpyrrolidine-1-carboxylate

To 3-(4-forfinal)-3-hydroxyethylpyrrolidine (2.30 g), obtained as described in the previous phase, add tetrahydrofuran (40 ml) and triethylamine (5.7 ml), and then add di-tert-BUTYLCARBAMATE (4,60 g) under cooling with ice. The mixture is stirred over night at room temperature. The reaction mixture was concentrated under reduced pressure and add ethyl acetate. The mixture is washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate=2:1) to obtain the specified title compound as a colourless oil (2.70 g).

Stage 8

Obtaining (-)-3-(4-forfinal)-3-hydroxyethylpyrrolidine

To tert-butyl 3-(4-forfinal)-3-hydroxyethylpyrrolidine-1-carboxylate (1,02 g), obtained as described in the previous phase, add chloroform(10 ml), the triethylamine (962 mm) and 4-dimethylaminopyridine (421 mg) and then add (S)-(+)-3,3,3-Cryptor-2-methoxy-2-phenylpropionate (969 μl) under ice cooling. The mixture is stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure, to the residue water is added and the mixture extracted three times with ethyl acetate. The organic layer was washed with an aqueous solution of potassium hydrosulfate, with water, aqueous sodium hydrogen carbonate solution and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of n-hexane:diethyl ether=5:3) to give the less polar diastereoisomer as a colourless oil (871 mg). In addition, the more polar diastereoisomer obtained as a colorless oil (781 mg).

Colorless oil (871 mg) of the less polar diastereoisomer was dissolved in tetrahydrofuran (4 ml) and methanol (2 ml) and then add 4 N. aqueous sodium hydroxide solution (2.6 ml). The mixture is stirred at 60°C for 40 minutes. The reaction mixture was concentrated under reduced pressure and to the residue water is added. The mixture is extracted three times with diethyl ether. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain a colorless oil (481 is g).

To the resulting colorless oil (481 mg) is added methanol (3 ml) and 4 n hydrochloric acid in ethyl acetate (3.3 ml) and the resulting mixture is stirred over night at room temperature. The reaction mixture was concentrated under reduced pressure and to the residue water is added. The mixture was washed with diethyl ether and the water layer solution is alkalinized 2 N. aqueous sodium hydroxide solution. The mixture is extracted 5 times with chloroform. The organic layer was washed with brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain specified in the title compound as a colourless oil (312 mg).

[α]25D = -9,70 (c = 0,598, EtOH)

Obtain (+)-3-(4-forfinal)-3-hydroxyethylpyrrolidine

By using a technique similar to the method for producing (-)-3-(4-forfinal)-3-hydroxyethylpyrrolidine, and using colorless oil (781 mg) more polar diastereoisomer specified in the title compound obtained as a colorless oil (251 mg).

[α]25D = +10,37 (c = 0,588, EtOH)

Stage 9

Obtain tert-butyl-5-(1-methylcyclopropyl)-1-(1-pyrimidine-2-reparacin-4-yl)-1H-pyrazole-4-carboxylate

tert-Butyl-5-(1-methylcyclopropyl)-1-(piperidine-4-yl)-1H-pyrazole-4-carboxylate (1,15 g)obtained in accordance with methods analogous to the methods for obtaining compounds described in Example 121, step , and 2-chloropyrimidine (700 mg) was dissolved in 1,4-dioxane (12 ml) and add palladium acetate (85 mg), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (352 mg) and cesium carbonate (1.84 g). The mixture is heated at the boil under reflux for 3 hours. After the mixture is allowed to cool, the insoluble product is filtered through celite and the filtrate concentrated under reduced pressure. To the obtained residue is added saturated aqueous sodium hydrogen carbonate solution and the resulting mixture extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate=2:1) to obtain the specified title compound as amorphous solid white (922 mg).

Stage 10

Getting hydrochloride 5-(1-methylcyclopropyl)-1-(1-pyrimidine-2-yl-piperidine-4-yl)-1H-pyrazole-4-carboxylic acid

tert-Butyl-5-(1-methylcyclopropyl)-1-(1-pyrimidine-2-yl-piperidine-4-yl)-1H-pyrazole-4-carboxylate (922 mg), obtained as indicated in the preceding stage, dissolved in chloroform (2 ml) and add triperoxonane acid (4 ml). The mixture is stirred over night at room temperature. The reaction mixture was concentrated under reduced pressure and the obtained crystal was dissolved in Tetra is drofuran. Added 4 n hydrochloric acid in ethyl acetate (2 ml) and the resulting mixture was concentrated under reduced pressure. The resulting crystalline residue is washed in suspension with ethyl acetate (10 ml) for one hour to obtain specified in the connection header in the form of a solid white color (800 mg).

Stage 11

Obtaining hydrochloride (-)-3-(4-forfinal)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine

Hydrochloride 5-(1-methylcyclopropyl)-1-(1-pyrimidine-2-reparacin-4-yl)-1H-pyrazole-4-carboxylic acid (150 mg), obtained as described in the previous phase, 1-hydroxybenzotriazole (81 mg), and hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (102 mg) was dissolved in N,N-dimethylformamide (3 ml). To the resulting solution was added (-)-3-(4-forfinal)-3-hydroxyethylpyrrolidine (88 mg)obtained in Stage 8, triethylamine (0,057 ml) and 4-dimethylaminopyridine (50 mg) and the resulting mixture is stirred over night at room temperature. To the reaction mixture are added water and then extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is purified by chromatography on silica gel (mixture of chloroform:methanol=0:1) and the resulting free base was dissolved in methanol (3 ml). Added 4 n hydrochloric acid in 1,4-dioxane (0.2 ml) and the resulting mixture was concentrated under reduced pressure. The resulting crystalline residue is washed in suspension with ethyl acetate (3 ml) for 15 minutes to obtain specified in the title compound as white crystals (203 mg).

[α]25D = -21,3 (c = 0,506, MeOH)

Example 128

Obtaining hydrochloride (+)-3-(4-forfinal)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine

In accordance with a technique similar to the method for obtaining compounds described in Example 127, step 11, specified in the header connection receive in the form of white crystals (198 mg) of the hydrochloride of 5-(1-methylcyclopropyl)-1-(1-pyrimidine-2-yl-piperidine-4-yl)-1H-pyrazole-4-carboxylic acid (150 mg), (+)-3-(4-forfinal)-3-hydroxyethylpyrrolidine (88 mg)obtained in Example 127, step 8.

[α]25D = +26,0 (c = 0,508, MeOH)

Example 129

Obtain hydrochloride of 1-[5-cyclopropyl-1-(1-pyrazin-2-yl-piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Specified in the title compound obtained as an amorphous solid yellow (165 mg) of the hydrochloride of 1-[5-cyclopropyl-1-(1-pyrazin-2-yl-piperidine-4-yl)-1H-pyrazole-4-carboxylic acid (281 mg)obtained in accordance with methods similar to the methods of the ICA obtain compounds described in Example 127.

Example 130

Obtaining 1-[1-(TRANS-4-carbamoylmethyl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Stage 1

Getting ethyl-TRANS-4-(2-tert-butoxycarbonylamino)cyclohexanecarboxylate

Ethyl-4-cyclohexanecarboxylate (8.0 g) and tert-BUTYLCARBAMATE (6.2 g) was dissolved in chloroform (150 ml) and acetic acid (5.4 ml) and then add triacetoxyborohydride sodium (30 g) under cooling with ice. The temperature of the mixture was allowed to gradually return to room temperature and then stirred for 7 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate solution and the resulting mixture extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate=4:1) to obtain specified in the connection header in the form of a solid white color (4,63 g).

Stage 2

Getting hydrochloride ethyl-TRANS-4-hydrazinecarboxamide

Ethyl TRANS-4-(2-tert-butoxycarbonylamino)cyclohexanecarboxylate (4,63 g), obtained as indicated in the preceding stage, dissolved in ethanol (30 ml) and added 4 n hydrochloric acid in ethyl acetate (82 m is). The mixture is stirred for 5.5 hours. Its concentrated under reduced pressure and to the residue is added diethyl ether. The mixture is filtered and dried to obtain specified in the title compound as white powder (3,86 g).

Stage 3

Obtain tert-butyl-1-(TRANS-4-ethoxycarbonylmethoxy)-5-cyclopropyl-1H-pyrazole-4-carboxylate

Hydrochloride ethyl-TRANS-4-hydrazinecarboxamide (3.80 g), obtained as described in the previous phase, and tert-butyl-2-cyclopropanecarbonyl-3-diethylaminoacetate (3,71 g)synthesized in accordance with methods analogous to the methods for obtaining compounds described in Example 1, step 1, was dissolved in ethanol (50 ml) and add triethylamine (4,32 ml). The mixture is stirred at the boil under reflux for one hour. After the mixture is allowed to cool, the mixture is concentrated under reduced pressure and to the residue water is added. The mixture is extracted three times with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of n-hexane:ethyl acetate=5:1) to obtain specified in the title compounds as a yellow liquid (4,80 g).

Stage 4

Obtain 1-(TRANS-4-ethoxycarbonylethyl is Xan)-5-cyclopropyl-1H-pyrazole-4-carboxylic acid

To a solution of tert-butyl 1-(TRANS-4-ethoxycarbonylmethoxy)-5-cyclopropyl-1H-pyrazole-4-carboxylate (4,80 g), obtained as described in the previous phase, in chloroform (14 ml) is added triperoxonane acid (14 ml) and the resulting mixture is heated to a temperature of 40°C and stirred for 1.5 hours. After the mixture is allowed to cool, the mixture is concentrated under reduced pressure and subjected to the azeotropic distillation with toluene. To the residue is added ethyl acetate, which allows you to land crystals. The mixture is once concentrated under reduced pressure, to the residue is added n-hexane, the crystals are collected by filtration and dried to obtain specified in the title compound as white powder (to 3.09 g).

Stage 5

Obtain 1-{5-cyclopropyl-1-(TRANS-4-ethoxycarbonylphenyl)-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

1-(TRANS-4-ethoxycarbonylmethoxy)-5-cyclopropyl-1H-pyrazole-4-carboxylic acid (1.50 g)obtained as described in the previous phase, and (S)-3-(2-triptoreline)pyrrolidin (1,16 g) dissolved in N,N-dimethylformamide (15 ml) and add 1-hydroxybenzotriazole (825 mg), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1,03 g) and 4-dimethylaminopyridine (658 mg). The mixture is stirred at room temperature for 14 hours. To the reaction mixture are added ethyl acetate and receive the complete mixture is washed twice with water. The organic layer was washed with 1 N. hydrochloric acid, water, saturated aqueous sodium bicarbonate, water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=20:1) to obtain the specified title compound as an amorphous substance brown (2,34 g).

Stage 6

Obtaining 1-[1-(TRANS-4-carboxylicacid)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

1-{5-Cyclopropyl-1-(TRANS-4-ethoxycarbonylphenyl)-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine (2,34 g), obtained as indicated in the preceding stage, dissolved in tetrahydrofuran (12 ml) and methanol (6 ml) and then add a solution of the monohydrate of lithium hydroxide (973 mg) in water (12 ml). The mixture is stirred at 45°C for one hour. Its concentrated under reduced pressure and to the residue water is added. The mixture is washed twice with diethyl ether layer and an aqueous solution acidified with 2 N. hydrochloric acid and extracted three times with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the obtained residue is added ethyl acetate and n-hexane and precipitated the precipitate solid is collected by filtration and dried to obtain specified in the connection header in the form of a solid milky white color (2,13 g).

Stage 7

Obtaining 1-[1-(TRANS-4-carbamoylmethyl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

1-[1-(TRANS-4-carboxylicacid)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (300 mg), obtained as described in the previous stage is dissolved in N,N-dimethylformamide (3.5 ml) and add 1-hydroxybenzotriazole (106 mg), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (133 mg), ammonium chloride (80 mg) and triethylamine (0,105 ml). The mixture is stirred at room temperature for 15 hours. To the reaction mixture are added ethyl acetate and the resulting mixture was washed successively with water, 1 N. hydrochloric acid, water, saturated aqueous sodium bicarbonate, water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. to the resulting solid residue is added diethyl ether and the resulting mixture is stirred for 10 minutes. The solid is collected by filtration and dried to obtain specified in the title compound as amorphous solid white (171 mg).

Example 131

Obtaining 1-[5-cyclopropyl-1-(TRANS-4-reidiculously)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

Toluene (3.0 ml) are added to 1-[1-(TRANS-4-carboxylicacid)-5-cyclopropyl-1H-pyrazole-4-arbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (200 mg), obtained in Example 130, step 6, and then add triethylamine (76 μl) and diphenylphosphoryl azide (118 ml) in an argon atmosphere. The mixture is heated at the boil under reflux for 2 hours. After the mixture is allowed to cool, the solution of toluene is added dropwise to 28% aqueous ammonia solution (10 ml) and ethyl acetate (4 ml) under ice cooling and the resulting mixture was stirred at the same temperature for 30 minutes. To the reaction mixture, water is added and the mixture extracted three times with chloroform. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography on silica gel (mixture of chloroform:methanol=10:1). To the resulting solid residue is added diethyl ether and the resulting mixture is stirred for 10 minutes. The solid is collected by filtration and dried to obtain specified in the title compound as amorphous solid white (135 mg).

Example 132

Obtain 1-{5-cyclopropyl-1-[TRANS-4-(1H-tetrazol-5-yl)cyclohexyl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

Stage 1

Obtaining 1-[1-(TRANS-4-cyanocyclohexyl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine

1-[1-(TRANS-4-carbamoylmethyl)-5-cyclopropyl-1H-pee the azole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (514 mg), obtained in Example 130, step 7, is dissolved in tetrahydrofuran (6 ml) and add pyridine (180 ml) and the anhydride triftormetilfullerenov acid (220 ml). The mixture is stirred at room temperature for one hour. Then add pyridine (180 ml) and the anhydride triftormetilfullerenov acid (220 ml) and the resulting mixture was stirred at room temperature for one hour. The mixture is concentrated under reduced pressure and add 1 N. aqueous solution of potassium hydrosulfate. The mixture is extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography (mixture of chloroform:methanol=15:1) to obtain specified in the title compound in amorphous form pale yellow (207 mg).

Stage 2

Obtain 1-{5-cyclopropyl-1-[TRANS-4-(1H-tetrazol-5-yl)cyclohexyl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine

1-[1-(TRANS-4-cyanocyclohexyl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine (207 mg), obtained as described in the previous stage is dissolved in 1,4-dioxane (2.5 ml) and add sidtribution (188 mg). The mixture is heated at boiling under reflux overnight. Then add sidtribution (94 mg) and the resulting mixture is heated at boiling from about ATiM refrigerator for 4 hours. The mixture is concentrated under reduced pressure, was added 1 n hydrochloric acid and the resulting mixture is extracted twice with chloroform. The chloroform layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue is purified by chromatography (mixture of chloroform:methanol=25:2) and concentrated under reduced pressure. To the obtained residue, add diisopropyl ether, precipitated precipitated solid is collected by filtration and dried to obtain specified in the title compound as amorphous solid white (122 mg).

Example 133

Obtain 1-{5-(1-methylcyclopropyl)-1-[1-(4-cryptomaterial)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 3 mentioned in the title compound is obtained from the corresponding starting compound.

Example 134

Obtain 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(1-methoxycyclohexyl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 3 mentioned in the title compound is obtained from the corresponding starting compound.

Example 135

Obtain 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-feast of the evil-4-carbonyl}-3-phenyl-3-triftormetilfullerenov

In accordance with a technique similar to the method described in Example 3 mentioned in the title compound is obtained from the corresponding starting compound.

Example 136

Obtaining 3-(2-chlorophenyl)-1-{5-cyclopropyl-1-[1-(2,4-differencemaker)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine

In accordance with a technique similar to the method described in Example 3 mentioned in the title compound is obtained from the corresponding starting compound.

Example 137

Obtaining 3-(2-chloropyridin-3-yl)-1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine

In accordance with a technique similar to the method described in Example 3 mentioned in the title compound is obtained from the corresponding starting compound.

Example 138

Obtain 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(2,2,3,3-tetramethylcyclopropane)-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 3 mentioned in the title compound is obtained from the corresponding starting compound.

Example 139

Obtain 1-{5-cyclohexyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 3, specified in the header is the connection obtained from the corresponding starting compound.

Example 140

Obtain 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-trifloromethyl)pyrrolidine

In accordance with a technique similar to the method described in Example 3 mentioned in the title compound is obtained from the corresponding starting compound.

Example 141

Obtain 1-{5-cyclopropyl-1-[1-(4-cryptomaterial)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 3 mentioned in the title compound is obtained from the corresponding starting compound.

Example 142

Obtaining 1-(5-cyclopropyl-1-{1-[((S)-1-carboxy-2-methylpropyl)methylcarbamoyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 12, is indicated in the title compound is obtained from the corresponding starting compound.

Example 143

Obtain 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-methoxy-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 3 mentioned in the title compound is obtained from the corresponding starting compound.

Example 144

Obtain 1-{1-[1-(2-torfin carbamoyl)piperidine-4-yl]-5-(1-hydroxymethylglutaryl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 3 mentioned in the title compound is obtained from the corresponding starting compound.

Example 145

Obtain 1-{5-cyclopropyl-1-[1-(thiazol-2-ylcarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 10, is indicated in the title compound is obtained from the corresponding starting compound.

Example 146

Obtain 1-{1-[1-(isopropoxycarbonyl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 10, is indicated in the title compound is obtained from the corresponding starting compound.

Example 147

Obtain 1-{5-cyclopropyl-1-[1-(4-verbesserbar)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 10, is indicated in the title compound is obtained from the corresponding starting compound.

Example 148

Obtain 1-{1-[1-(2,3-dihydroindol-1-carbonyl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in the Example is 10, specified in the title compound is obtained from the corresponding starting compound.

Example 149

Obtain 1-{1-[1-(2,3-dihydro[1,4]oxazin-4-carbonyl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 10, is indicated in the title compound is obtained from the corresponding starting compound.

Example 150

Obtain 1-{5-cyclopropyl-1-[1-(2,6-dichloropyridine-3-ylcarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 10, is indicated in the title compound is obtained from the corresponding starting compound.

Example 151

Obtain 1-{5-(1-methylcyclopropyl)-1-[1-(2,3,4,5-tetrahydrobenzo[b]azepin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 10, is indicated in the title compound is obtained from the corresponding starting compound.

Example 152

Getting ethyl-4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoate

In accordance with methods analogous to the methods described in Example 114, specified in the title compound is obtained from matched with the appropriate starting compound.

Example 153

Obtaining 1-[1-(1-benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 1, stage 4, receive specified in the header of the connection.

Example 154

Obtain 1-{1-[1-(3-carboxy-3-methylbutyryl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 65, indicated in the title compound is obtained from the corresponding starting compound.

Example 155

Obtain 1-{5-cyclopropyl-1-[1-(2-phenoxyacetyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 64, indicated in the title compound is obtained from the corresponding starting compound.

Example 156

Obtain 1-{1-[1-(3-chlorobenzoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 64, indicated in the title compound is obtained from the corresponding starting compound.

Example 157

Obtain 1-{1-[1-(2-chlorobenzoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with methodical is, similar to the method described in Example 64, indicated in the title compound is obtained from the corresponding starting compound.

Example 158

Obtaining 1-[5-cyclopropyl-1-(1-oxalipatin-4-yl)-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 65, indicated in the title compound is obtained from the corresponding starting compound.

Example 159

Obtain 1-{1-[1-(4-chlorobenzoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 64, indicated in the title compound is obtained from the corresponding starting compound.

Example 160

Obtaining 1-(5-cyclopropyl-1-{1-[2-(4-forfinal)acetyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 64, indicated in the title compound is obtained from the corresponding starting compound.

Example 161

Obtain 1-{5-cyclopropyl-1-[1-(3-trifloromethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 64, indicated in the title compound is obtained from the corresponding starting compound.

Example 162

Obtain 1-{5-cyclopropyl-1-[1-(3-methoxybenzoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 64, indicated in the title compound is obtained from the corresponding starting compound.

Example 163

Obtain hydrochloride of 1-{1-[1-(4-terbisil)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 94, specified in the title compound is obtained from the corresponding starting compound.

Example 164

Obtaining 1-[1-(1-benzosulfimide-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 108, specified in the title compound is obtained from the corresponding starting compound.

Example 165

Obtain 1-{1-[1-(4-carbamoylphenoxy)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 166

Obtain 1-{5-cyclopropyl-1-[1-(4-hydroxymethylene)piperidine-4-yl]-1H-pyrazole-4-Carbo is Il}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 167

Obtain 1-{1-[1-(5-carbamoylation-2-yl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 168

Obtain 1-{1-[1-(4-AMINOPHENYL)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 169

Obtaining 1-(5-cyclopropyl-1-{1-[4-(2-oxoacridine-3-yl)phenyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 170

Obtaining 1-(5-cyclopropyl-1-{1-[4-(3-metaxourgeio)phenyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 113, indicated the data in the title compound is obtained from the corresponding starting compound.

Example 171

Obtain 1-{5-cyclopropyl-1-[1-(4-methanesulfonylaminoethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 172

Obtaining 1-[1-(1-ethoxycarbonylpyrimidine-4-yl)-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 10, is indicated in the title compound is obtained from the corresponding starting compound.

Example 173

Obtaining 1-[1-(5-chloropyridin-2-yl)azetidin-3-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 174

Obtain 1-{1-[1-(5-chloropyridin-2-yl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-methoxymethyl-3-phenylpyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 175

Obtain 1-{1-[1-(5-cyano-2-yl)piperidine-4-yl]-5-Cyclops the saw-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 176

Getting hydrochloride 3-(2-acetoxyethyl)-3-(4-forfinal)-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 177

Getting hydrochloride {(3S*,4R*)-3-methyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-4-phenylpyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 178

Obtaining methyl-6-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)nicotinate

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 179

Obtaining methyl-2-{1-[5-(1-methylcyclopropyl)-1-(1-pyrimidine-2-reparacin-4-yl)-1H-pyrazole-4-carbonyl]pyrrolidin-3-yl}benzoate

In accordance with a technique similar to the method of vannoy in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 180

Getting hydrochloride 3-(2-hydroxymethylene)-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 181

Obtaining 1-[5-cyclopropyl-1-(1-pyridin-2-reparacin-4-yl)-1H-pyrazole-4-carbonyl]-3-hydroxy-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 182

Obtain 1-{1-[1-(4-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with methods analogous to the methods described in Example 114, specified in the title compound is obtained from the corresponding starting compound.

Example 183

Obtaining sodium 4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)-3-perbenzoate

In accordance with methods analogous to the methods described in Example 114, specified in the title compound is obtained from the appropriate source from the organisations.

Example 184

Obtaining 3-(2-cyanophenyl)-1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine

In accordance with a technique similar to the method described in Example 121, specified in the title compound is obtained from the corresponding starting compound.

Example 185

Obtain hydrochloride of 3-hydroxymethyl-1-{1-[1-(4-methoxypyridine-2-yl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-phenylpyrrolidine

In accordance with a technique similar to the method described in Example 127, specified in the title compound is obtained from the corresponding starting compound.

Example 186

Getting hydrochloride 3-(3,5-differenl)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine

In accordance with a technique similar to the method described in Example 127, specified in the title compound is obtained from the corresponding starting compound.

Example 187

Obtain 1-{1-[1-(3-chloropyridin-2-yl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 113, specified in the title compound is obtained from the corresponding starting compound.

Example 188

Obtain 1-{5-cyclopropyl-1-[1-(2-FPO is phenylcarbamoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(thiazol-2-yl)pyrrolidine

In accordance with a technique similar to the method described in Example 121, specified in the title compound is obtained from the corresponding starting compound.

Example 189

Obtain (S)-2-[(TRANS-4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}-cyclohexanecarbonyl)methylamino]-3-methylmalonic acid

In accordance with a technique similar to the method described in Example 130, specified in the title compound is obtained from the corresponding starting compound.

Example 190

Obtain 1-{5-(1-methylcyclopropyl)-1-[TRANS-4-(2-tortenelmebol)cyclohexyl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine

In accordance with a technique similar to the method described in Example 130, specified in the title compound is obtained from the corresponding starting compound.

Example 191

Obtain CIS-4-{5-(1-methylcyclopropyl)-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}-cyclohexanecarboxylic acid

In accordance with a technique similar to the method described in Example 130, specified in the title compound is obtained from the corresponding starting compound.

The structural formula and quantitative characteristics of the compounds in each Example are shown in tables Table 1-1 through Table 1-45)below.

Table 1-1
Ave. No.The structural formulaNMR
11H-NMR (400 MHz, CDCl3) δ: 0,63 of 0.77 (2H, m), 0,97-1,11 (2H, m), 1.70 to to 1.82 (1H, m), 1,96-to 2.67 (8H, m), 2,83-of 2.97 (2H, m), 3.33 and-of 3.53 (3H, m), 3,55-4,17 (3H, m), 4,50 with 4.64 (1H, m), 7.23 percent-to 7.32 (1H, m), of 7.48-to 7.64 (2H, m), 8,46-8,61 (2H, m,)
21H-NMR (400 MHz, DMSO-d6) δ: 0,59-of 0.75 (2H, m), 0,94-of 1.07 (2H, m), 1,86-of 2.36 (8H, m), 3.00 and-is 3.21 (2H, m), 3,30-3,93 (6H, m), 4,69-4,88 (1H, m), 7,44-to 7.64 (2H, m), 7,66 for 7.78 (3H, m), 8,83 (1H, users), which 9.22 (1H, users)
31H-NMR (400 MHz, CDCl3) δ: 0,65-0,83 (2H, m), 0,99-of 1.15 (2H, m), 1,73-of 1.84 (1H, m), 1,90-of 2.50 (6H, m), 3,02-3,20 (2H, m), 3,36-3,55 (1,5H, m), 3,56-of 3.80 (2H, m), 3,83-to 3.99 (1H, m), 4,06-4,17 (0,5H, m), 4,18 is 4.36 (2H, m), 4,54-4,71 (1H, m), of 6.71 (1H, users), 6,93-7,00 (1H, m), 7,02-7,14 (2H, m), 7.24 to to 7.32 (1H, m), 7,50 to 7.62 (2H, m), 8,02-of 8.09 (1H, m), of 8.47-8,59 (2H, m)
41H-NMR (400 MHz, CDCl3) δ: 0,69-0,84 (2H, m), of 1.03-1.14 in (2H, m), 1,54-2,47 (7H, m), 2,94-3,14 (2H, m), 3,40-4,20 (7H, m), 4,47-of 4.67 (2H, m), 7,32-7,72 (6H, m)

Table 1-2
Ave. No.The structural formulaNMR
51H-NMR (400 MHz, DMSO-d6) δ: 0,60-0,75 (2H, m), 0,92-of 1.07 (2H, m), 1,81-of 2.36 (6H, m), 3.04 from is 3.23 (2H, m), 3,44-3,93 (6H, m), 4,10-4,27 (2H, m), 4,65 of 4.83 (1H, m), 6,98-7,07 (1H, m), 7,39-to 7.61 (3H, m), 7,63-7,79 (3H, m), 7,92-8,02 (1H, m,), of 8.37-to 8.40 (1H, m), and 11.0 to 11.2 (1H, m)to 13.6 (1H, users)
61H-NMR (400 MHz, CDCl3) δ: 0,68-0,85 (2H, m), 1,01 totaling 1.14 (2H, m), 1.70 to 2,44 (7H, m), 2,72-of 2.86(1H, m), 2,97-3,13 (2H, m), 3,41-4.09 to (5H, m), 4,20 is 4.35 (2H, m), 4,51-of 4.75 (3H, m), 6,97? 7.04 baby mortality (1H, m), 7,11-7,19 (1H, m), 7,28-of 7.60 (5H, m), to 7.64-7,72 (1H, m), 7,92-7,98 (1H, m), 8,13-8,23 (1H, m)
71H-NMR (400 MHz, CDCl3) δ: 0,61-of 0.94 (6H, m), 0,98-1,17 (2H, m), 1,64 is 1.86 (3H, m), 1.93 and-of 2.23 (3H, m), 2,24-2,48 (1H, m), 2,79-to 2.99 (2H, m), 3,32-4,22 (9H, m), of 4.38-4,63 (1H, m), 5,64-by 5.87 (1H, m), 7,29-of 7.60 (4H, m), 7,60-7,71 (1H, m,)
81H-NMR (400 MHz, CDCl3) δ: 0,66-of 0.82 (2H,m), 0,99 by 1.12 (2H, m), of 1.20 to 1.34 (1H, m), 1,67-of 1.88 (4H, m), 1,95-of 2.21 (3H,m), 2,23 is 2.46 (1H, m), 2,82-to 3.02 (2H, m), 3,28-of 3.48 (3H, m), 3,52-3,99 (5H, m), 3,99-4,22 (2H, m), to 4.41-4,63 (1H, m,), 5,1-5,33 (1H, m), 7,28-7,71 (5H, m)

Table 1-3
Ave. No.The structural formulaNMR
91H-NMR (400 MHz, CDCl3) δ: of 0.64 to 0.87 (2H, m), 0,98-1,17 (2H, m)is 1.31 (3H, s), 1,32 (3H, s), 1,66 was 2.25 (6H, m), 2.26 and-2,47 (1H, m), 2,83-to 3.02 (2H, m), 3,39-4,20 (9H, m), 4,43 with 4.64 (1H, m), 4,67-4,84 (1H, m), 5,00-5,46 (1H, users), 7,32-7,40 (1H, m), 7,41-of 7.60 (3H, m), to 7.61-7,72 (1H, m)
101H-NMR (400 MHz, CDCl3) δ: 0,67-of 0.82 (2H, m), 1.00 and-1,11 (2H, m), 1.70 to to 1.83 (1H, m), 1,83-of 1.95 (3H, m), 1,99 (3H, users), 2,04-2,22 (3H, m), 2,27 is 2.43 (1H, m), 2,86-a 3.01 (2H, m), 3.33 and-of 3.43 (4H, m), 3,54-4,18 (6H, m), of 4.44-4,63 (1H, m), 5,42-of 5.53 (1H, m), 6,33-6,41 (1H, m), 7,32-7,71 (5H, m)
111H-NMR (400 MHz, DMSO-D6) δ: 0,58-0,74 (2H,m), 0,91-of 1.05 (2H, m), 1,78-2,34 (7H, m), 2,78-2,99 (5H, m), 3,22-of 3.94 (6H,m), 4,06-is 4.21 (2H, m), 4,54-4,72 (1H, m), 6,46-to 6.95 (1H,m), 7,42-to 7.77 (5H, m), 7,88-8,03 (3H,m)
121H-NMR (400 MHz, CDCl3) δ: 069-0,86 (2H, m), 1,01 is 1.16 (2H, m), 1,71 is 1.86 (1H, m), 1,89 is 2.46 (6H, m), 2.91 in is 3.15 (6H, m), 3,40-4,14 (11H, m), 4,47-of 4.67 (1H, m), 7,32-7,73 (5H, m)

Table 1-4
Ave. No.The structural formulaNMR
131H-NMR (400 MHz, DMSO-D6) δ: 0,68 is 0.86 (2H,m), and 1.00-to 1.15 (2H, m), 1,58-2,49 (15H, m), 2,84-3,03 (2H, m), 3,20-3,39 (2H,m), 3,41-4,25 (7H, m), of 4.44 with 4.65 (1H, m), 5,13-of 5.29 (1H, m), 7,31-7,73 (5H, m)
141H-NMR (400 MHz, CDCl3) δ: 0,71-of 0.82 (2H, m), 1,03-1,12 (2H, m), 1,46 is 1.60 (3H, m), 1,72-of 1.97 (5H, m), 2.00 in 2,44 (4H, m), 2,80-of 3.07 (4H, m), 3,42-4,10 (10H, m), 4,43-br4.61 (1H, m), 7,32-7,71 (5H, m)
151H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,83 (2H, m), 1,02-to 1.14 (2H, m), 1,71-2,45 (9H, m), 2,81-2,96 (2H, m), 3,42-4,22 (11H, m), 4,45-4,63 (1H, m), 7,32-7,72 (5H, m)
161H-NMR (400 MHz, CDCl3) δ: 0,66-of 0.85 (2H, m), 0,99-1,17 (2H, m), 1,71-2,45 (10H, m), 2,79-of 3.00 (2H, m), 3.27 to 4,11 (11H, m), 4,39-4,63 (2H, m), 7,32-7,73 (5H, the)

Table 1-5
Ave. No.The structural formulaNMR
171H-NMR (400 MHz, DMSO-d6) δ: of 0.58 to 0.75 (2H, m), 0,92 was 1.06 (2H, m), 1.32 to about 1.47 (1H, m), 1,63-to 1.98 (6H, m), 2,02-2,39 (2H,m), 2,78-of 3.00 (4H, m), 3,02-and 3.16 (2H, m), 3,38-of 3.54 (4H, m), 3,54-of 3.78 (3H, m), 3,80-4,55 (8H, m), 4,55-4,72 (1H, m,), 7,01-7,20 (1H, users), 7,41-of 7.60 (2H, m), 7,65 for 7.78 (3H, m), 9,99-10,16 (1H, users)
181H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,86 (2H, m), 1,01-of 1.15 (2H, m), 1,71-2,45 (11H, m), 2,83-a 3.01 (2H, m), 3.33 and-3,51 (4H, m), 3,57-4,11 (7H, m), 4,45-to 4.62 (1H, m), 7,31-7,73 (5H, m)
191H-NMR (400 MHz, CDCl3) δ: 0,68 is 0.86 (2H, m), 1,02-of 1.15 (2H, m), 1.70 to 2,46 (9H, m), 2,83-a 3.01 (2H, m), 3,41-4,12 (11H, m), 4,46 with 4.65 (1H, m), 7,31-7,73 (5H, m)
201H-NMR (400 MHz, CDCl3) δ: 0,69-0,84 (2H, m), 1.00 and is 1.16 (2H, m), 1,71-of 2.26 (6H, m), 2,27 at 2.45 (1H, m), 2,50 at 2.59 (1H, m), 2,81-of 3.00 (2H, m), 3,42-4,12 (9H, m), 4,46-and 4.68 (2H,m), 7,31-7,72 (5H, m)

Table 1-6
Ave. No.The structural formulaNMR
211H-NMR (400 MHz, CDCl3) δ: 0,68-0,84 (2H, m), 0,99-of 1.15 (2H, m), 1,71-2,44 (10H, m), 2,78-to 2.99 (2H, m), 3,26-4,12 (11H, m), 4,42-to 4.62 (2H, m), 7,31-7,72 (5H, m)
221H-NMR (400 MHz, CDCl3) δ: 0,69-0,85 (2H, m), 0,99-of 1.16 (2H, m), 1,68-2,47 (10H, m), was 2.76-to 2.99 (2H, m), 3.27 to 4,11 (11H, m), to 4.41-to 4.62 (2H, m), 7,32-7,73 (5H, m)
231H-NMR (400 MHz, CDCl3) δ: 0,65 is 0.81 (2H,m), 1,05-1,15 (2H, m), 1,71 at 2.45 (7H, m), 1,94 is 2.44 (6H, m), 2,85 was 3.05 (2H, m), 3,35-4,20 (9H, m), 4,45 with 4.65 (1H, m), 4,65-of 4.75 (1H, m), 7,30-8,30 (5H, m)
241H-NMR (400 MHz, CDCl3) δ: 0,67-0,83 (2H, m), 1,02-of 1.13 (2H, m), 1,15-of 1.32 (3H, m), 1,35 of 1.46 (1H, m), 1,63-2,45 (9H, m), 2,73 are 2.98 (4H, m), 3,40-4,12 (11H, m), 4,42-4,63 (1H, m), 7,29-7,74 (5H, m)

Table 1-7
Ave. No.The structural formulaNMR
251H-NMR (400 MHz, DMSO-D6) δ: 0,59-0,74 (2H, m), 0,91 was 1.06 (2H, m), 1,42-to 1.63 (2H, m), 1,72-2,46 (10H, m), 2,75-3,03 (4H, m), 3,43-3,96 (9H, m), 4,48-4,72 (1H, m), 7,38-7,83 (5H, m), compared to 12.1 and 12.4 (1H, m)
261H-NMR (400 MHz, CDCl3) δ: 0,66-of 0.85 (2H, m), 0,97-1,17 (2H, m), 1,68-2,46 (7H, m), 2,84-is 3.08 (2H, m), 3,36-4,13 (13H, m), of 4.44-of 4.67 (1H, m), 6,54-of 6.71 (1H, m), 7,30-7,73 (5H, m)
271H-NMR (400 MHz, CDCl3) δ: 0,67-0,84 (2H, m), and 1.00-to 1.15 (2H, m), 1,43-to 1.59 (1H, m), 1,61-2,45 (10H, m), 2,78-a 3.01 (2H, m), 3,32-4,10 (11H, m), 4,18-or 4.31 (1H, m), 4,45-4,63 (1H, m), 7,31-7,72 (5H, m)
281H-NMR (400 MHz, CDCl3) δ: 0,64-0,83 (2H, m), 0,96 is 1.16 (2H, m), 1.70 to to 2.29 (6H, m), 2,29-2,39 (1H, m), 2,67-2,69 (1H, m), 2,82-of 2.97 (2H, m), 3,38-4,18 (13H, m), to 4.41 with 4.65 (1H, m), 7,30-7,74 (5H, m)

Table 1-8
the R. No.The structural formulaNMR
291H-NMR (400 MHz, DMSO-D6) δ: 0,59-to 0.73 (2H, m), 0,94 was 1.06 (2H, m), 1,79-2,34 (7H, m), 2,74-2,82 (3H, m), 2,89-3,93 (17H, m), 4,55-4,74 (1H, m), 7,42-7,80 (5H, m), of 10.4 to 10.6 (1H, m)
301H-NMR (400 MHz, DMSO-D6) δ: 0,59-of 0.75 (2H, m), 0,92 was 1.06 (2H, m), 1,22-of 1.35 (6H, m), 1.77 in-2,46 (7H, m), 2,85-3,11 (5H, m), 3,21-3,96 (13H, m), to 4.52-4,74 (1H, m), 7,42-of 7.82 (5H, m), of 10.3 to 10.5 (1H, m)
311H-NMR (400 MHz, CDCl3) δ: 0,69-0,85 (2H, m), 1,02-of 1.16 (2H, m), 1,71-2,47 (10H, m), 2,87-3,03 (2H, m), 3,20-4,15 (15H, m), 4,45-of 4.66 (1H, m), 7,31-7,73 (5H, m)
321H-NMR (400 MHz, CDCl3) δ: 0,62-0,84 (2H, m), 0,97-of 1.15 (2H, m), 1,37-of 1.55 (1H, m), 1.55V is 1.96 (6H, m), 1,99-2,46 (5H, m), 2.77-to 3,03 (1H, m), 3,15-4,12 (12H, m), of 4.38 with 4.65 (1H, m), 7,30-7,74 (5H, m)

Table 1-9
Ave. No.The structural formula NMR
331H-NMR (400 MHz, CDCl3) δ: 0,68-0,85 (2H, m), 1,01 totaling 1.14 (2H, m), 1,62-1,99 (7H, m), 1,99-2,47 (5H, m), 2,74-of 3.00 (4H, m), 3,41-3,53 (0,6H, m), 3,56-4,11 (8,4H, m), 4,43-br4.61 (1H, m), 5,44 (1H, users), to 5.56 (1H, users), 7,32-7,38 (1H, m,), 7,39-of 7.60 (3H, m), 7,62-7,71 (1H, m)
341H-NMR (400 MHz, CDCl3) δ: 0,69-0,83 (2H, m), 0,99-of 1.15 (2H, m), 1,67 is 1.96 (3H, m), 1,98-of 2.24 (3H, m), 2,25 is 2.44 (1H, m), 2,78-of 3.00 (2H, m), 3,20-3,39 (1H, m), 3,40-3,53 (0,5H, m), 3,53-4.09 to (6,5H, m), 4,10-of 4.25 (4H, m), 4,40-4,66 (1H, m), 5,59 (1H, users), 5,77 (1H, users), 7,31-7,39 (1H, m), 7,40-of 7.60 (3H, m), 7,62-7,71 (1H, m)
351H-NMR (400 MHz, DMSO-d6) δ: 0,59-to 0.72 (2H, m), 0,94 was 1.06 (2H, m), 1,39-of 1.56 (2H, m), 1,78 is 2.01 (6H, m), 2.05 is-of 2.34 (2H, m), 2,72-a 3.01 (4H, m), 3,24-of 3.27 (1H, m), 3,43-4,01 (9H, m), 4.53-in-4,70 (1H, m), 7,43-of 7.60 (2H, m), 7,66-to 7.77 (3H, m), with 8.33 (3H, users)
361H-NMR (400 MHz, DMSO-d6) δ: 0,55-to 0.73 (2H, m), 0,89-1,08 (2H, m), 1,69-2,38 (10H, m), 2.77-to to 3.02 (2H, m), 3,12-4,15 (11H, m), to 4.52-to 4.73 (1H, m), 7,41-to 7.77 (3H, m), 8,18-to 8.40 (3H, m), 8,42-8,61 (1H, m), 9,36-9,63 (1H, m)

Table 1-10
Ave. No.The structural formulaNMR
371H-NMR (400 MHz, DMSO-d6) δ: 0,58-to 0.73 (2H, m), 0,92 of-1.04 (2H, m), 1,55-1,70 (2H, m), 1,74-to 1.98 (7H, m), 2,02-of 2.36 (2H, m), 2,73-to 3.02 (4H, m), 3,19-to 3.33 (2H, m), 3,45-4,32 (8H, m), 4.53-in-4,72 (1H, m), 6,44-6,62 (1H, m), 7,42-7,79 (5H, m), to 8.62 (1H, users), 8,72 (1H, users)
381H-NMR (400 MHz, DMSO-d6) δ: 0,58-0,74 (2H, m), 0,92 was 1.06 (2H, m), 1,47 by 1.68 (2H, m), 1,78-of 2.56 (8H, m), 2,62-3,03 (4H, m), 2,77 (6H, s), 3,24-3,94 (10H, m), 4,54-4,70 (1H, m), 7,42 to 7.62 (2H, m), 7,63-7,79 (3H, m), 10,2-or 10.4 (1H, m)
391H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,84 (2H, m), 1,02-to 1.14 (2H, m), 1,31 of 1.46 (2H, m), 1,71-2,45 (9H, m)of 1.97 (3H, s), 2,81-of 3.00 (4H, m), 3,42-4,10 (10H, m), of 4.44-br4.61 (1H, m), from 5.29-5,43 (1H, m), 7,33-7,72 (5H, m)
401H-NMR (400 MHz, CDCl3) δ: 0,69-0,83 (2H, m), 1.00 and is 1.13 (2H, m), 1,68-2,46 (13H, m), 2,81-of 3.00 (2H, m), 3,28-4,10 (10H, m), 4,36-4,63 (2H, m), 5,61-5,72 (1H, m), 7,31-of 7.70 (5H, m)

Table 1-11
Ave. No.The structural formulaNMR
411H-NMR (400 MHz, DMSO-d6) δ: 0,58-of 0.71 (2H, m), 0,92-of 1.03 (2H, m), 1,76-of 2.36 (8H, m), 2.70 height is 2.80 (6H, users), 2,81-3,03 (2H, m), 3,24-3,92 (13H, m), to 4.52-4,71 (1H, m), 7,41-to 7.77 (5H, m), 10,76-10,91 (1H, users)
421H-NMR (400 MHz, DMSO-d6) δ: 0,58-0,74 (2H, m), 0,92-of 1.05 (2H, m), 1,60-2,00 (9H, m), 2,03-of 2.38 (2H, m), 2,65-3,93 (15H, m), 4.04 the-4,24 (2H, m), 4,51-to 4.73 (1H, m), 6,28-of 6.65 (1H, m), 7,41-7,81 (5H, m), 9,88 (1H, users)
431H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,83 (2H, m), 1,02-of 1.15 (2H, m), 1,22-to 1.38 (2H, m), 1.70 to 2.26 and (11H, m), 2,28 is 2.46 (1H, m), 2,67-and 2.79 (1H, m), 2,86 totaling 3.04 (2H, m), 3,10-3,24 (1H, m), 3,40-4,21 (9H, m), 4,32 is 4.45 (1H, m), 4,47 with 4.64 (2H, m,), 7,32-7,72 (5H, m)
441H-NMR (400 MHz, CDCl3) δ: 0,70-0,85 (2H, m), 1,02-of 1.18 (2H, m), 1.70 to 2.57 m (11H, m), 2.91 in-is 3.08 (2H, m), 3,38-4,13 (11H, m), 4,74-of 4.66 (1H, m), 7,32-7,76 (5H, m)

Table 1-12
Ave. No.The structural formulaNMR
451H-NMR (400 MHz, CDCl3) δ: 0,65-0,85 (2H, m), 0,96-1,17 (2H, m), 1,65-of 1.95 (3H, m), 1,96-2,22 (3H, m)to 1.99 (3H, s), 2,25-2,48 (1H, m), 2,81-to 3.02 (2H, m), 3,38-3,5 (0,6H, m), 3,54-4,14 (8,4H, m), 4,19-4,37 (2H, m), 4,43-4,72 (2H,, m), 6,24-6,40 (1H, m), 7,32-7,40 (1H, m), 7,41-to 7.61 (3H, m), 7,62-of 7.70 (1H, m)
461H-NMR (400 MHz, CDCl3) δ: 0,69-0,88 (2H, m), 1,02-1,17 (2H, m), 1,71-to 1.87 (1H, m), 1,88 at 2.45 (6H, m), 2,48-2,60 (2H, m), 2,90-of 3.06 (2H, m), 3,43-4,11 (11H, m), 4,49-of 4.66 (1H, m), 7,33-7,72 (5H, m)
471H-NMR (400 MHz, CDCl3) δ: 0,69 is 0.81 (2H, m), 1,01 by 1.12 (2H, m), 1,71-to 1.82 (1H, m), 1,83 is 1.96 (3H, m), 1,99 was 2.25 (3H, m), 2.26 and is 2.43 (1H, m), 2,93-is 3.08 (2H, m), 3,41-4,00 (6H, m), 4,00-4,20 (2H, m), 4,49 with 4.64 (1H, m), 4,85 is equal to 4.97 (1H, m,), 7,30-of 7.70 (5H, m)
481H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,86 (2H, m), 1,01-1,17 (2H, m), 1,71 at 2.45 (7H, m), 2,86-of 3.06 (2H, m), 3,42-4,12 (11H, m), 4,49-of 4.67 (1H, m), 7,31-7,73 (5H, m)

Table 1-13
Ave. No.The structural formulaNMR
491H-NMR (400 MHz, CDCl3) δ: 0,71-0,83 (2H,m), 0,92-of 1.02 (6H, m), 1,02-of 1.13 (2H, m), 1,22-of 1.33 (2H, m), 1,71-to 1.98 (4H,m), 1,99 at 2.45 (4H, m), 2,88-is 3.08 (2H, m), 3,14 of 3.28 (1H, users), 3,38-4,24 (8H, m), 4,47-to 4.73 (2H, m), 7,32-7,72 (5H, m)
501H-NMR (400 MHz, CDCl3) δ: 0,63-0,81 (2H, m), 0,96 is 1.13 (2H, m), 1.60-to is 1.81 (3H, m), 1,90-of 2.21 (3H, m), 2.26 and is 2.46 (1H, m), 2,72 are 2.98 (4H, m), 3,38-4,13 (9H, m), 4,37-4,59 (1H, m), 4,94-5,04 (1H, m), 7,16-7,73 (10H, m)
511H-NMR (400 MHz, CDCl3) δ: 0,68-of 0.82 (2H, m), 1.00 and by 1.12 (2H, m), 1,69-of 1.85 (3H, m), 1,96-2,22 (3H, m), 2,25-of 2.45 (1H, m), 2,84-a 3.01 (2H, m), 3,39-3,50 (2H, m), 3,54-4,27 (7H, m), to 4.41-br4.61 (1H, m), 4,93-5,04 (1H, m), 5,38-of 5.55 (1H, m,), 7.23 percent-7,73 (10H, m)
521H-NMR (400 MHz, CDCl3) δ: 0,68-of 0.79 (2H, m), 0,89 is 0.99 (6H, m), 1,02 by 1.12 (2H, m), 1,31 was 1.43 (2H, m), 1.60-to of 1.85 (4H, m), 2.00 in of 2.20 (3H, m), 2,25-of 2.45 (1H, m), 2,81-of 3.00 (2H, m), 3,39-4,21 (10H, m), 4,42-4,60 (1H, m), 4,79 to 4.92 (1H, m,), 7,30-7,73 (5H, m)
Table 1-14
Ave. No.The structural formulaNMR
531H-NMR (400 MHz, CDCl3) δ: 0,66-0,83 (2H, m), and 1.00-to 1.14 (2H, m), 1,67-1,90 (3H, m), 1,98-of 2.27 (3H, m), 2,27-of 2.24 (1H, m), 2,98-3,14 (2H, m), 3,42-4,11 (5H, m), 4,22-and 4.40 (2H, m), 4,50-of 4.66 (1H, m), 6,78-to 6.88 (1H, m), 6,98-7,13 (3H, m), 7,14-7,21 (1H, m), 7,34-to 7.61 (4H, m), of 7.64-7,73 (1H, m), 9,24-9,36 (1H, m)
541H-NMR (400 MHz, CDCl3) δ: 0,67-0,85 (2H, m), 0,97 is 1.16 (2H, m)and 1.51-2,46 (15H, m), 2,84-of 3.07 (2H, m), 3,42-4,19 (9H, m), 4,47 with 4.64 (1H, m), 4,65-of 4.75 (1H, m), 5,14-5,24 (1H, m), 7,31-7,73 (5H, m)
551H-NMR (400 MHz, CDCl3) δ: 0,61-0,85 (2H, m), 0,95-of 1.18 (2H, m), 1,36 was 2.25 (7H, m), 2,25 is 2.44 (1H, m), was 2.76 was 3.05 (2H, m), 3,38-3,47 (0,5H, m), 3,52-3,91 (3,5H, m), 3.95 to or 4.31 (3H, m), 4,34-4,60 (1H, m), 7,29-7,73 (8H, m), 8,00-8,13 (2H, m)
561H-NMR (400 MHz, CDCl3) δ: 0,63-0,83 (2H, m), 0,98 is 1.16 (2H, m), 1,65 is 1.91 (3H, m), 1,92-of 2.23 (3H, m), 2,24-of 2.50 (1H, m), 2,80 was 3.05 (2H, m), 3,16-to 3.34 (3H, m), 3,39-3,51 (0,6H, m), 3,52-4,13 (5,4H, m), 4,19-4,43 (2H, m), of 4.44 with 4.64 (H, m), 7,30-7,39 (1H, m), 7,41-of 7.60 (3H, m), to 7.61-of 7.70 (1H, m)

Table 1-15
Ave. No.The structural formulaNMR
571H-NMR (400 MHz, CDCl3) δ: 0,64-0,83 (2H, m), 0,98-of 1.15 (2H, m), 1,65-of 1.94 (3H, m), 1,94 was 2.25 (3H,m), 2,25-of 2.45 (1H, m), 2.77-to 3,05 (2H, m), 3,43-4,07 (8H, m), 4,11-of 4.45 (2H, m), 4,45 with 4.65 (1H, m), 7,30-7,72 (5H, m)
581H-NMR (400 MHz, DMSO-D6) δ: 0,67-0,84 (2H, m), 1,03-of 1.15 (2H, m), 1,69-2,59 (8H, m), 2,86-3,11 (2H, m), 3,38-4,13 (7H, m), 4,19-of 4.44 (4H, m), 4,48-of 4.66 (1H, m), 7,30-7,74 (5H, m)
591H-NMR (400 MHz, CDCl3) δ: of 0.64 to 0.87 (2H, m), 0,99-of 1.18 (2H, m), 1,72 is 1.86 (1H, m), 1,87 of 1.99 (2H, m), 2.06 to 2,47 (4H, m), 2,63-3,23 (10H, m), 3,26-of 3.42 (2H, m), 3.43 points is 4.13 (3H, m), 4,20-4,75 (5H, m), 7,33-7,39 (1H, m), 7,40-7,63 (3H, m), to 7.64-of 7.69 (1H, m), 12,69 (1H, users)
601H-NMR (400 MHz, CDCl3) δ: 0,72-0,83 (2H, m), 1,07 is 1.23 (2H, m), 1,35-of 1.56 (1H, m), 1,79 is 2.00 (4H, m), 2.06 to a 2.45 (6H, m), 2,68-3,20 (4H, m), 3.27 to to 3.41 (2H, m), 3,43-4,08 (9H, m), 4,22-4,48 (2H, m), 4,58-4,82 (3H, m), 7,34-7,40 (1H, m,) 7,44 is 7.50 (1H, m), 7,53-of 7.60 (1H, m), 7,65-7,72 (2H, m), 12,22 (1H, users)

Table 1-16
Ave. No.The structural formulaNMR
611H-NMR (400 MHz, CDCl3) δ: 0,69-0,88 (2H, m), 1,03-to 1.21 (2H, m), 1,79 is 2.01 (3H, m), 2,01-2,32 (7H, m), 2,33 at 2.45 (1H, m), 2,81-of 3.12 (2H, m), 3,11-4,14 (9H, m), 4,15-of 4.49 (2H, m), 4,54-of 4.75 (1H, m), 4.92 in-5,09 (1H, m), 7,33-7,41 (1H, m,), 7,44-to 7.61 (2H, m), 7,63 to 7.75 (2H, m), 9,45-9,81 (2H, m)
621H-NMR (400 MHz, CDCl3) δ: 0,68-of 0.87 (2H, m), 1.04 million-to 1.21 (2H, m), 1,78 is 2.01 (3H, m), 2,03-2,49 (7H, m), 2,50 of 2.68 (1H, m), 2,72-3,14 (7H, m), 3,23-4,07 (7H, m), 4,17-of 4.44 (2H, m), 4,57-of 4.75 (1H, m), 4,76-4,89 (0,5H, m), 5,01-5,09 (0,5H, m), 7,33-7,41 (1H, m), 7,43-7,52 (1H, m), 7,52-to 7.61 (1H, m), 7,62-7,73 (2H, m), 12,38-12,70 (1H, m)
631H-NMR (400 MHz, CDCl3) δ: 0,66-of 0.85 (2H, m), 0,99-of 1.16 (2H, m), 1,57-2,25 (13H, m), 2.26 and is 2.46 (1H, m), 2,79-3,11 (2H, m), 3.27 to 3,54 (2,6H, m), 3,55-4,12 (6,4H, m), 4,14-of 4.66 (3H, m), 4,85-5,00 (1H, m), 7,31-7,40 (1H, m), 7,41-to 7.61 (3H, m), 7,62-7,71 (1H, m)
641H-NMR (400 MHz, CDClsub> 3) δ: 0,64-0,87 (4H, m), 0,91-of 1.18 (4H, m), 1.70 to to 1.86 (2H, m), 1,88-2,48 (6H, m), 2,65-2,89 (1H, m), 3,13-3,39 (1H, m), 3,41-4,13 (5H, m), 4,27-4,89 (3H, m), 7,31-7,76 (5H, m)

Table 1-17
Ave. No.The structural formulaNMR
651H-NMR (400 MHz, CDCl3) δ: 0,68-of 0.87 (2H, m), 1,01 is 1.16 (2H, m), 1,69 is 1.86 (1H, m), 1,90-2,49 (6H, m), 2,85-to 3.02 (1H, m), 3,07-3,26 (1H, m), 3,40-4,12 (7H, m), 4,16-the 4.29 (2H, m), 4,54-4,82 (2H, m), 7,31-to 7.77 (5H, m)
661H-NMR (400 MHz, CDCl3) δ: 0,63-0,83 (2H, m), 0,98-1,10 (2H, m), 1,12-of 1.23 (2H, m), 1,38-is 1.51 (2H, m), 1,66-2,22 (6H, m), 2,27 at 2.45 (1H, m), 2,73-3,03 (2H, m), 3,37-4,11 (5H, m), 4,15-of 4.95 (3H, m), 6,94-7,73 (9H, m)
671H-NMR (400 MHz, DMSO-d6) δ: 0,60-0,74 (2H, m), 0,92 was 1.06 (2H, m), 1,15-1,20 (1H, m), 1,75-of 2.36 (4H, m), 2,78-2,87 (6H, users), 3,14-to 3.36 (1H, m), 3,40-3,92 (9H, m), 4,22-4,56 (3H, m), with 4.64-a 4.86 (1H, m), 7,40 to 7.62 (2H, m), of 7.64-to 7.77 (3H, m), being 9.61-9,74 (1H, users)
681H-NMR (400 MHz, CDCl3) δ: 0,72-0,84 (2H, m), 1.04 million-to 1.16 (2H, m), 1,7-to 1.86 (1H, m), 1,90-2,28 (8H, m), 2,28 at 2.45 (1H, m), 2,81-2,96 (1H, m), 3,15 to be 3.29 (1H, m), 3,42-3,51 (0,5H, m), to 3.58-4,21 (7,5H, m), 4,58-rate 4.79 (2H, m), 6,58 is 6.67 (1H, users), 7,33-7,42 (1H, m), 7,42 to 7.62 (3H, m), 7,63-7,72 (1H, m)

Table 1-18
Ave. No.The structural formulaNMR
691H-NMR (400 MHz, CDCl3) δ: 0,54-of 0.67 (2H, m), 0,71 is 0.86 (2H, m), 0,92-1,02 (2H, m), 1.04 million-to 1.14 (2H, m), 1,28-of 1.40 (3H, m), 1,72 is 1.86 (1H, m), 1,89-2,24 (5H, m), 2,27 is 2.46 (1H, m), 2,86-3,13 (2H, m), 3,41-4,12 (5H, m), 4,51-4,71 (3H, m), 7,32 to 7.75 (5H, m)
701H-NMR (400 MHz, CDCl3) δ: 0,69-of 0.82 (2H, m), 1,01 by 1.12 (2H, m), 1.60-to 1,71 (7H, m), 1,71-2,45 (10H, m), 2,93-of 3.12 (1H, m), 3,37-4,10 (6H, m), 4,47-4,70 (2H, m), 6,70-6,79 (1H, users), 7,28-7,71 (5H, m)
711H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,84 (2H, m), 1,02-of 1.13 (2H, m), 1,29-of 1.41 (4H, m), 1,71-of 1.84 (1H, m), 1,89 at 2.45 (7H, m), was 2.76-2,96 (2H, m), 3,16-to 3.34 (2H, m), 3,39-to 4.15 (5H, m), 4,56-rate 4.79 (2H, m), 4,85-4,99 (1H, m), 6,55 is 6.67 (1H, m,), 7,31-of 7.70 (5H, m)
721H-NMR (400 MHz, CDCl3) δ: 0,69-0,83 (2H, m), 0,84-of 1.03 (6H, m), of 1.03-1.14 in (2H, m), 1,22-of 1.34 (2H, m), 1,71-2,44 (9H, m), was 2.76 of 2.92 (1H, m), 3,17-4,79 (9H, m), 4,84-of 4.95 (1H, m), is 6.19-6,30 (1H, m), 7,31-7,71 (5H, m)

Table 1-19
Ave. No.The structural formulaNMR
731H-NMR (400 MHz, CDCl3) δ: 0,66-0,86 (2H, m), 0,99-of 1.18 (2H, m), 1,69-of 1.85 (1H, m), 1,89 at 2.45 (6H, m), 2,78-to 2.94 (1H, m), 3,19-3,39 (3H, m), 3,41-3,50 (0,6H, m), 3,56-4,10 (5,4H, m), 4,56 of 4.83 (2H, m), 7,32-7,40 (1H, m), 7,41-to 7.61 (3H, m), 7,62-7,71 (1H, m)
741H-NMR (400 MHz, CDCl3) δ: 0,67-0,85 (2H, m), 1,03-of 1.15 (2H, m), 1,69 is 1.86 (1H, m), 1.91 a-2,61 (9H, m), was 2.76-2,95 (1H, m), 3,18-4,11 (8H, m), of 4.44 of 4.83 (3H, m), USD 5.76-to 5.93 (1H, m), 7,32 to 7.75 (5H, m)
751H-NMR (400 MHz, CDCl3) δ: 0,69-of 0.82 (2H, m), 1,02-of 1.13 (2H, m), 1,69-of 1.84 (1H, m), 1.85 to a 2.01 (6H, m), 2,02-of 2.23 (2H, m), 2.26 and is 2.46 (1H, m), 2,47-2,60 (2H, m), 2.71 to 2,84 (1H, m), 3,11-3,26 (1H, m), 3,41-4,10 (8H, m), 4,54-and 4.68 (1H, m,), 4,69-4,82 (1H, m), 6,32-6,40 (1H, users), 7,31-of 7.70 (5H, m)
761H-NMR (400 MHz, CDCl3) δ: from 0.6 to 0.87 (2H, m), 1,02-of 1.18 (2H, m)is 1.31 (3H, s)of 1.33 (3H, s), 1,72-of 1.88 (1H, m), 1,90-2,48 (6H, m), 2,88-3,10 (2H, m), 3,42-4,15 (8H, m), 4,47-of 4.75 (3H, m), 7,32-7,74 (5H, m)

Table 1-20
Ave. No.The structural formulaNMR
771H-NMR (400 MHz, DMSO-d6) δ: 0,59-0,74 (2H, m), 0,93-of 1.05 (2H, m), 1,21-1,32 (1H, m), 1,72-of 2.34 (5H, m), 2,79 are 2.98 (1H,m), 3,13-to 3.34 (1H, m), 3,39-4,36 (9H, m), of 4.38-4,55 (1H, m), 4.63 to-4,84 (1H, m), 7,40-of 7.60 (2H, m), 7,63-7,74 (3H, m), 8,80-8,18 (3H, users)
781H-NMR (400 MHz, CDCl3) δ: 0.70 to 0.89 as (4H, m), 0,97 is 1.16 (4H, m), 1,71 is 1.86 (1H, m), 1,88-of 2.24 (6H, m), 2,27 is 2.46 (1H, m), 2,90-3,11 (2H, m), 3,41-4,11 (7H, m), 4,54-4,74 (3H, m), 7,33-7,74 (5H, m)
791H-NMR (400 MHz, DMSO-d6) δ: 0,60-0,74 (2H, m), 0,94-of 1.03 (2H, m), 1,50-of 1.65 (7H, m), 1,74-of 2.38 (5H, m), 2,99 of 3.28 (2H,m), 3,37-3,90 (5H, m), 3,94 with 4.65 (3H, m), 4,67-4,89 (1H, m), 7,40 for 7.78 (5H, m), 8,12-8,32 (3H, users)
801H-NMR (400 MHz, CDCl3) δ: 0,68-0,83 (2H, m), 1,02-to 1.14 (2H, m), 1.70 to of 1.85 (1H, m), 1.85 to the 2.46 (8H, m) 2,49-2,60 (2H, m), 2,69-to 2.85 (2H, m), 3,13-3,29 (1H, m), 3,41-3,50 (0,5H, m), 3,55-4,14 (7,5H, m), 4.53-in-4,70 (1H, m), 4,71-is 4.85 (1H, m), 7,31-7,40 (1H, m), 7,40-to 7.61 (3H, m), 7,62-7,73 (1H, m)

Table 1-21
Ave. No.The structural formulaNMR
811H-NMR (400 MHz, DMSO-d6) δ: 0,58-0,74 (2H, m), 0,93-1,10 (2H, m), 1.70 to 2,48 (12H, m), 2,83-3,03 (1H, m), 3,11-4,08 (9H, m), to 4.41-4,85 (2H, m), 7,42-7,53 (2H, m), 7,65 for 7.78 (3H, m), to 9.91-of 10.05 (1H, users), 10,12-10,24 (1H, users)
821H-NMR (400 MHz, DMSO-d6) δ: 0,60-0,75 (2H, m), 0,92-of 1.03 (2H, m), 1,74-2,17 (11H, m), 2,18 to 2.35 (1H, m), 2,73-2,87 (3H, m), 2,88-3,90 (10H, m), 4,43-4,56 (1H, m), 4,60-is 4.85 (1H, m), 7,41-7,76 (5H, m), at 9.53-to 9.70 (1H, users)
831H-NMR (400 MHz, DMSO-d6) δ: 0,58-to 0.72 (2H, m), 0,93 of-1.04 (2H, m), 1,69-2,02 (5H, m), 2,03-of 2.16 (1H, m), 2,17-of 2.34 (1H, m), 2,64-2,87 (3H, m), 2.91 in-of 3.07 (2H, m), 3,16-of 3.32 (1H, m), 3,42-of 3.78 (6H, m), 3,80-to 3.99 (1H, m), of 4.44-4,58 (1H, m,), 7,42-7,94 (8H, m)
841H-NMR (400 MHz, DMSO-d6) δ: 0,60-0,73 (2H, is), 0,87-1,10 (8H, m), 1,73-2,17 (8H, m), 2,18-of 2.34 (1H, m), 2,81 are 2.98 (1H, m), 3,21-3,37 (1H, m), 3,40-to 3.92 (4H, m), 4.04 the-4,19 (1H, m), 4,23-to 4.41 (1H, m), 4,46-br4.61 (1H, m), 4,66-is 4.85 (1H, m), 7,43-to 7.61 (2H, m), of 7.64-to 7.77 (3H, m), 8.07-a 8,24 (3H, m)

Table 1-22
Ave. No.The structural formulaNMR
851H-NMR (400 MHz, DMSO-d6) δ: 0,60-0,74 (2H, m), 0,92 was 1.06 (2H, m), 1,72 to 2.35 (8H, m), 2,53-2,62 (3H, m), 2,80 are 2.98 (1H, m), 3,18-to 3.34 (1H, m), 3,42-3,90 (5H, m), 3,98-to 4.23 (2H, m), 4,40-of 4.54 (1H, m), 4,66-4,82 (1H, m), 7,42 for 7.78 (5H, m), 8,77-of 9.02 (2H, m)
861H-NMR (400 MHz, DMSO-d6) δ: 0,59-to 0.72 (2H, m), 0,93-1,02 (2H, m), 1,67-of 1.84 (6H, m), 1.85 to a 2.00 (4H, m), 2,03-2,17 (1H, m), 2,18 is 2.33 (1H, m), 2,65-of 2.81 (1H, m), 2,84-is 3.08 (3H, m), 3,16-of 3.32 (4H, m), 3,52-are 3.90 (3H, m), 4,05-4,19 (1H, m,), of 4.44-of 4.57 (1H, m), 4.63 to-4,79 (1H, m), 7,40 to 7.75 (5H, m), 8,62-8,78 (1H, m), 9,04-9,16 (1H, m)
871H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,84 (2H, m), 1,03-1,12 (2H, m), 1,14-1,22 (7H, m), 1,66-of 2.24 (6H, m), 2,27-of 2.54 (2H, m), 2,79-2,96 (1H, m), 3,13-of 3.27 (1H, m), 3,39-3,50 (1H, m), 3,55-4,18 (6H, m), 4.53-in-4,79 (2H, m), 6,58-of 6.61 (1H, m,), 7,31-7,71 (5H, m)
88 1H-NMR (400 MHz, CDCl3) δ: 0,68-0,83 (4H, m), 0,92-a 1.01 (2H, m), 1,01 is 1.13 (2H, m), 1,45-and 1.54 (1H, m), 1,68 is 2.44 (8H, m), 2,80-2,95 (1H, m), 3,12-3,29 (1H, m), 3,41-3,50 (1H, m), 3,57-4,22 (6H, m), 4,56-rate 4.79 (2H, m), 6,68-6,76 (1H, m,), 7,31-of 7.70 (5H, m)

Table 1-23
Ave. No.The structural formulaNMR
891H-NMR (400 MHz, CDCl3) δ: 0,71-of 0.82 (2H, m), of 1.03-1.14 in (2H, m), 1.70 to of 1.84 (1H, m), 1.85 to to 2.25 (12H, m), 2,25-to 2.42 (1H, m), of 2,75 2,95 (1H, m), 3,18-4,21 (9H, m), 4,54-4,78 (2H, m), 4,87 is equal to 4.97 (1H, m), 7,32-7,71 (5H, m)
901H-NMR (400 MHz, CDCl3) δ: 0,68-0,85 (2H, m), 1,02-of 1.16 (2H, m), 1.70 to to 1.86 (1H, m), 1,89 at 2.45 (6H, m), 2,83-2,96 (1H, m), 2,96-3,03 (3H, m), 3,16-of 3.31 (1H, m), 3,41-3,50 (0,6H, m), 3,56-4,12 (7,4H, m), 4,57-of 4.77 (2H, m), 5,35-5,44 (1H, m), 7,32-7,40 (1H, m), 7,41-to 7.61 (3H, m), 7,62-7,71 (1H, m)
911H-NMR (400 MHz, CDCl3) δ: 0,71 is 0.81 (2H, m), 1.04 million-1,12 (2H, m), 1,62-2,44 (11H, m), is 2.09 (3H, users), 2,66-2,82 (3H, m), 3,05-3,17 (1H, m), 3,18-of 3.31 (1H, m), 3,39-3,50 (1H, m), 3,55-3,99 (5H, m), 4,00-to 4.15 (1H, m), 4,51-4,70 (2H, m), 4,71-4,84 (1H, m), 7,31-of 7.70 (5H, m)
921H-NMR (400 MHz, DMSO-d6) δ: 0,59-to 0.72 (2H, m), 0,93-of 1.05 (2H, m), 1,67-2,02 (11H, m), 2,04-of 2.16 (1H, m), 2,18-of 2.34 (1H, m), 2,66 is 2.75 (3H, users), 2,86-a 3.01 (2H, m), 3,09-of 3.32 (1H, m), 3,36-3,91 (6H, m), 3,99-4,16 (1H, m), of 4.44-4,58 (2H, m,), 4,63-4,80 (1H, m), 7,43-7,76 (5H, m), of 10.21-10,33 (1H, m)

Table 1-24
Ave. No.The structural formulaNMR
931H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,84 (2H, m), 1,03-1,12 (2H, m), 1,14-1,22 (7H, m), 1,66-of 2.24 (6H, m), 2,27-of 2.54 (2H, m), 2,79-2,96 (1H, m), 3,13-of 3.27 (1H, m), 3,39-3,50 (1H, m), 3,55-4,18 (6H, m), 4.53-in-4,79 (2H, m), 6,58-of 6.61 (1H, m,), 7,31-7,71 (5H, m)
941H-NMR (400 MHz, DMSO-d6) δ: 0,57-to 0.73 (2H, m), 0,90-of 1.05 (2H, m), 1,82 of $ 2.53 (8H, m), 3,23-with 3.79 (6H, m), 3,81-4,24 (4H, m), 4.63 to-equal to 4.97 (1H, m), 7,39-to 7.77 (6H, m), 7,98-8,17 (1H, m), 9,99-10,27 (1H, m)
951H-NMR (400 MHz, DMSO-d6) δ: 0,59-of 0.75 (2H, m), 0,91-of 1.07 (2H, m), 1,82 is 2.46 (8H, m), 2,64 was 2.76 (3H, m), 3,21-3,99 (10H, m), br4.61-4,82 (1H, m), 7,41-7,79 (5H, m), 8,48-8,69 (1H, m), 9,99-10,24 (1H, m)
961H-NMR (400 MHz, CDCl3) δ: 0,61-of 0.82 (2H, m), 1,02-of 1.18 (2H, m), 1.69 in (6H, s), 1.70 to of 1.84 (1H, m), 2.05 is-of 2.23 (3H, m), 2,29 is 2.46 (1H, m), 3,03-4,07 (11H, m), 5,02 (1H, users), 5,74 (1H, users), 7,34-7,41 (1H, m), 7,44 is 7.50 (1H, m), 7,51-7,60 (2H, m), 7,65-of 7.70 (1H, m), 9,13 (1H, users), RS 11.80 (1H, users)

Table 1-25
Ave. No.The structural formulaNMR
971H-NMR (400 MHz, DMSO-d6) δ: 0,58 of 0.77 (2H, m), 0,90 was 1.06 (2H, m), 1,83-to 1.98 (1H, m), 2,04-to 2.74 (6H, m), 3,07-3,96 (13H, m), with 4.64-equal to 4.97 (1H, m), 7,20-a 7.85 (7H, m), of 10.09-10,49 (1H, m)
981H-NMR (400 MHz, DMSO-d6) δ: 0,30-0,49 (2H, m), 0.56 to 0.76 to (4H, m), from 0.88 to 1.05 (2H, m), 1,07-1,22 (1H, m), 1,81-to 1.98 (1H, m), 1,99-of 2.38 (6H, m), 2,88 totaling 3.04 (2H, m), 3,09-3,26 (2H, m), 3,41-of 3.95 (7H, m), 4,58-a 4.86 (1H, m), 7,34-a 7.85 (5H, m), 10,17-10,53 (1H, m)
991H-NMR (400 MHz, DMSO-d6) δ: 0,60-0,74 (2H, m), 0,75-0,85 (2H, m), 0,93 of-1.04 (2H, m), 1,12-of 1.23 (2H, m), 1,86-2,54 (7H, m), 2.71 to 2,82 (1H, m), 3,28-3,92 (9H, m), 4,66 of 4.83 (1H, m), 7,42-to 7.77 (5H, m), or 10.60-10,79 (1H, m)
1001H-NMR (400 MHz, DMSO-d6) δ: 0,57-of 0.75 (2H, m), 0,91-of 1.05 (2H, m), 1,82-2,53 (7H, m), 2,85-a 3.01 (6H, m), 3,18-of 4.44 (11H, m), 4,62 of 4.83 (1H, m), 7,41 for 7.78 (5H, m), 9,66-becomes 9.97 (1H, user.)

Table 1-26
Ave. No.The structural formulaNMR
1011H-NMR (400 MHz, DMSO-d6) δ: 0,59-of 0.75 (2H, m), 0,91 was 1.06 (2H, m), 1,84 is 2.00 (1H, m), 2,03 at 2.45 (6H, m), 3,15-of 3.95 (9H, m), 4,06-to 4.23 (2H, m), 4,63 of 4.83 (1H, m), 7,41-7,80 (5H, m)
1021H-NMR (400 MHz, DMSO-d6) δ: 0,59-of 0.75 (2H, m), 0,91 was 1.06 (2H, m), 1,46-of 1.62 (4H, m), 1,84-2,60 (7H, m), 3,23-3,94 (7H,m), 4,16-4,32 (1H, m), 4,51-of 5.06 (2H, m), 7,40-7,79 (6H, m), 10,11-10,42 (1H, users)
1031H-NMR (400 MHz, DMSO-d6) δ: 0,60-to 0.73 (2H, m), 0,92 of-1.04 (2H, m), 1,43-and 1.54 (3H, m), 2.00 in 2,58 (8H, m), 3,14-4,17 (9H, m), 4,68-is 4.85 (1H, m), 7,42-7,79 (6H, m), 8,08-to 8.20 (1H, m), of 10.09 (1H, users)
1041H is the Mr (400 MHz, DMSO-d6) δ: 0,61-of 0.75 (2H, m), 0,94 was 1.06 (2H, m), 1,22-to 1.38 (6H, m), 1,82-2,62 (7H, m), 3,13-3,96 (11H, m), 4,69-of 4.95 (1H, m), 7,38-of 7.82 (6H, m), 9,23-9,88 (1H, m)

Table 1-27
Ave. No.The structural formulaNMR
1051H-NMR (400 MHz, DMSO-d6) δ: 0,59-of 0.75 (2H, m), 0,93 was 1.06 (2H, m), 1,22-to 1.38 (6H, m), 1,83-to 1.98 (1H, m), 1,99-2,62 (6H, m), 3,14-3,94 (11H, m), 4,69-is 4.93 (1H, m), 7,27-7,80 (7H, m), 9,05-9,52 (1H, m)
1061H-NMR (400 MHz, DMSO-d6) δ: 0,56 of 0.77 (2H, m), 0,91-of 1.07 (2H, m), 1,15-of 1.39 (4H, m), 1,82-2,62 (7H, m), 3,13-4,03 (11H, m), 4.63 to-equal to 4.97 (1H, m), 7,06-to 7.32 (2H, m), 7,40-7,81 (5H, m), 9,76-10,08 (1H, m)
1071H-NMR (400 MHz, DMSO-d6) δ: 0,61-0,74 (2H, m), 0,93 of-1.04 (2H, m), 1,13-to 1.21 (2H, m), of 1.25 to 1.34 (2H, m), 1.85 to to 1.98 (1H, m), 2,01-of 2.54 (6H, m), is 3.08-3,92 (16H, m), with 4.64-4,84 (1H, m), 7,43 for 7.78 (6H, m), to 9.57-9,92 (1H, m)
1081H-NMR (400 MHz, CDCl3) δ: 0,67-of 0.82 (2H, m), 1,01 totaling 1.14 (2H, m), 1,66 of-1.83 (1H, m), 1,94 is 2.44 (6H, m), 3,18-to 3.49 (2H, m), 3,54-4,20 (7H, m), 4,534,70 (1H, m), 7,28-7,72 (5H, m)

Table 1-28
Ave. No.The structural formulaNMR
1091H-NMR (400 MHz, CDCl3) δ: 0,65-0,83 (2H, m), 0,99-1,11 (2H, m), 1,68 of-1.83 (1H, m), 1,91 at 2.45 (6H, m), 3.04 from-3,20 (2H, m), 3,38-4,11 (9H, m), 4,47-of 4.66 (1H, m), 7,72-8,35 (5H, m)
1101H-NMR (400 MHz, CDCl3) δ: of 0.64 to 0.88 (2H, m), 0,98-to 1.21 (2H, m), 1,66-of 1.88 (1H, m), 1,89-2,54 (9H, m), 2,94-3,17 (1H, m), 3,26-3,53 (1,5H, m), 3,54-4,21 (5,5H, m), 4,58-is 4.93 (2H, m), 7.29 trend to 7.75 (5H, m)
1111H-NMR (400 MHz, CDCl3) δ: 0,62-0,83 (2H, m), 0,97-1,17 (2H, m), 1,63-of 1.95 (3H, m), 1,96-of 2.24 (3H, m), 2,25-2,47 (1H, m), 2,97-3,19 (5H, m), 3,40-3,49 (0,5H, m), 3,55-4.26 deaths (6,5H, m), 4,46-4,69 (1H, m), 5,54-USD 5.76 (1H, m), 7,30-7,60 (4H, m), to 7.61-7,73 (1H, m)
1121H-NMR (400 MHz, CDCl3) δ: 0,60-0,81 (2H, m), 0,98 is 1.16 (2H, m), 1,62-to 1.82 (3H, m), 1.93 and was 2.25 (3H, m), 2.26 and-2,47 (1H, m), 2,90-is 3.08 (2H, m), 3,35-3,50 (0,5H, m), 3,53-4.09 to (4,5H, m), 4,17-4,34 (2H, m), 4,45 with 4.65 (1H, m), 5,94-6,14 (2H, m), 7,29-to 7.61 (4H, m), 7,62-7,74 (1H, m)

Table 1-29
Ave. No.The structural formulaNMR
1131H-NMR (400 MHz, CDCl3) δ: 0,71-of 0.87 (2H, m), 1,03-of 1.18 (2H, m), 1,71-2,47 (7H, m), 3.00 and-3,18 (2H, m), 3,42-4,17 (7H, m), 4,56-of 4.75 (1H, m), 6,85-6,97 (2H, m), 7,32-7,71 (5H, m), 7,92-of 8.00 (2H, m)
1141H-NMR (400 MHz, CDCl3) δ: 0.70 to 0.87 for (2H, m), 1,02-1,19 (2H, m), 1,74-of 2.50 (7H, m), 2,81-3,19 (2H, m), 3,44-4,14 (7H, m), 4,48-4,80 (1H, m), 7,07-a 7.85 (9H, m)
1151H-NMR (400 MHz, DMSO-D6) δ: 0,59 of 0.77 (2H, m), 0,92-1,08 (2H, m), 1,87-2,36 (7H, m), is 3.08-3,94 (9H, m), 4,60-to 4.81 (1H, m), 6,16-of 6.29 (1H, m), 7,38-7,80 (6H, m), 12,25(1H, broad singlet)
1161H-NMR (300 MHz, DMSO-D6) δ: 0,62-to 0.73 (2H, m), 0,96 of-1.04 (2H, m), 1,87 is 2.33 (7H, m), 3,18-of 3.32 (3H, m), 3,44-3,91 (4H, m), 3,97-4,10 (2H, m), 4,66-4,80 (1H, m), 7,41-of 7.60 (2H, m), 7,63 for 7.78 (4H, m), USD 12.6 (1H, users)

Table 1-30
Ave. No.The structural formulaNMR
1171H-NMR (400 MHz, DMSO-D6) δ: 0,59 of 0.77 (2H, m), 0,93-1,08(2H, m), 1,88-2,39 (10H, m), 3,21-4,12 (11H, m), with 4.64-4,84 (1H, m), 7,41-7,80 (5H, m)
1181H-NMR (400 MHz, DMSO-D6) δ: 0,60-0,75 (2H, m), 0,89-of 1.09 (6H, m), 1,86-of 2.36 (8H, m), 3,11-4,11 (11H, m), br4.61-4,82 (1H, m), 7,41-7,80 (5H, m)
1191H-NMR (400 MHz, DMSO-D6) δ: 0,60-0,76 (2H, m), 0,92 was 1.06 (2H, m), 1,88-of 2.38 (8H, m), 3,15-4,15 (10H, m), 4,42-a 4.53 (2H, m), 4.63 to-4,82 (1H, m), 7,39-7,79 (6H, m)
1201H-NMR (400 MHz, DMSO-D6) δ: 0,58 of 0.77 (2H, m), 0,92 was 1.06 (2H, m), 1.85 to 2,41 (7H, m), 3,11-4,10 (9H, m), or 4.31 is 5.07 (2H, m), 7,41-7,79 (5H, m), and 13.3 to 13.5 (1H, m)

Table 1-31
Ave. No.The structural formulaNMR
1211H-NMR (400 MHz,CDCl 3) δ: 0,72-of 0.87 (2H, m), 1,05-1,15 (2H, m), 1,49-2,48 (7H, m), 3,05-up 3.22 (2H, m), 3,40-4,14 (5H, m), 4,20 is 4.36 (2H, m), to 4.52-to 4.73 (1H, m), 6,60-of 6.71 (1H, m), 6,94-7,16 (3H, m), 7,33-7,72 (5H, m), 8,04-8,14 1H, m)
1221H-NMR (400 MHz, CDCl3) δ: 0,57-0,66 (2H, m), 0,66-0,84 (4H, m), 1,01 is 1.13 (2H, m), 1.32 to the 1.45 (3H, m), 1,55-2,48 (7H, m), 2,81-of 3.00 (2H, m), 3,41-to 4.15 (5H, m), of 4.44-4,63 (2H, m), 4,85-4,96 (1H, m), 7,33-7,71 (6H, m)
1231H-NMR (400 MHz, CDCl3) δ: 0,71-of 0.82 (2H, m), 1,02-of 1.13 (2H, m), 1,13-1,22 (6H, m),1,55-2,47 (8H, m), 2,84-a 3.01 (2H, m), 3,41-4,34 (9H, m), 4,45-4,63 (1H, m), 7,30-7,71 (6H, m)
1241H-NMR (400 MHz, CDCl3) δ: 0,72-of 0.87 (2H, m), 1.04 million-1,17 (2H, m), 1,53-2,46 (7H, m), 3,05-is 3.21 (2H, m), 3,42-4,11 (5H, m), 4,20 is 4.35 (2H, m), 4,55-4,71 (1H, m), 6,62-6,70 (1H, m), 6,93-7,16 (3H, m), 7,33-7,72 (5H, m), 8,04-to 8.14 (1H, m,)

Table 1-32
Ave. No.The structural formulaNMR
1251H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,84 (2H, m), 1,03 is 1.13 (2H, m), 1,13-to 1.21 (6H, m), 1,55-2,47 (8H, m), 2,84-,01 (2H, m), 3,41-or 4.31 (9H, m), 4,45-4,63 (1H, m), 7,33-7,72 (6H, m)
1261H-NMR (400 MHz, CDCl3) δ: 0,58-0,66 (2H, m), 0,66-0,83 (4H, m), 1,02-1,11 (2H, m), 1,36 was 1.43 (3H, m), 1,53-2,46 (7H, m), 2,83-to 2.99 (2H, m), 3,41-to 4.15 (5H, m), 4,45-br4.61 (2H, m), 4,85 to 4.92 (1H, m), 7,32-7,72 (6H, m)
1271H-NMR (400 MHz, DMSO-D6) δ: 0,56 is 0.86 (4H, m), 1,32 was 1.43 (3H, m), 1.85 to a 2.12 (6H, m), 2,28-2,39 (1H, m), 3,09-3,26 (2H, m), 3,31-4,94 (6H, m), 4,74-4,91 (3H, m), 6,30 (1H, broad singlet), 6,69 to 6.75 (1H, m), 7,07-7,37 (4H, m), 7,53 to 7.62 (1H, m), 8,40-of 8.50 (2H, m)
1281H-NMR (400 MHz, DMSO-D6) δ: 0,56-0,88 (4H, m), 1,32 is 1.48 (3H, m), 1.85 to a 2.12 (6H, m), 2,28-2,39 (1H, m), 3,09-3,24 (2H, m), 3,30-4,95 (6H, m), 4,73-is 4.93 (3H, m), of 5.81 (1H, broad singlet), 6,64-of 6.73 (1H, m), 7,06-7,40 (4H, m), 7,50-to 7.67 (1H, m), 8,39-8,49 (2H, m)

Table 1-33
Ave. No.The structural formulaNMR
1291H-NMR (400 MHz, DMSO-d6) δ: of 0.66 to 0.69 (2H, m), 0,99-1,01 (2H, m), 1,91 is 2.33 (7H, m), 3,11-3,14 (2H, m), 3.46 in-the 3.89 (5H, m), 4,49-to 4.52 (2H, is), 4,75-of 4.77 (1H, m), of 7.48-7,74 (6H, m), a 7.85-of 7.90 (1H, m), 8,17 (1H, users), 8,43-to 8.45 (1H, m)
1301H-NMR (400 MHz, CDCl3) δ: 0,65-of 0.79 (2H, m), 0,94-1,10 (2H, m), 1,63-2,44 (12H, m), 3,38-4,10 (5H, m), 4,32-4,51 (1H, m), 5,33 (1H, usher.), the 5.51 (1H, usher.), 7,27-of 7.70 (5H, m)
1311H-NMR (400 MHz, CDCl3) δ: 0,62-of 0.82 (2H, m), 0,95-1,10 (2H, m), 1,23-of 1.39 (2H, m), 1,65 at 2.45 (8H, m), 3,40-4,10 (6H, m), 4.26 deaths-4,60 (4H, m), 7,27-7,71 (6H, m)
1321H-NMR (400 MHz, CDCl3) δ: 0,67-of 0.79 (2H, m), from 0.84 to 0.92 (2H, m), 1.06 a-1,15 (2H, m), 1,22-of 1.35 (3H, m), 1,73-2,49 (8H, m), 3,05-3,19 (1H, m), 3,39-3,55 (1H, m), 3,61-4,17 (3H, m), 4,46-br4.61 (1H, m), 7,33-7,71 (5H, m)

Table 1-34
Ave. No.The structural formulaNMR
1331H-NMR (400 MHz, CDCl3) δ: 0,71-of 0.95 (4H, m), to 1.38 to 1.47 (3H, m), 1,61-of 1.88 (2H, m), 1,99-to 2.29 (3H, m), 2,34-of 2.50 (1H, m), 2,94-of 3.12 (2H, m), 3,36-4,18 (5H, m), 4,25-and 4.40 (2H, m), 4,54-4,72 (1H, m), 6,99-7,33 (2H, m), 7,44-the 7.65 (6H, m), 8,44-8,61 (2H, m)
1341H-NMR (400 MHz, CDCl3) δ: 0,89-of 1.05 (2H, m), 1,22-of 1.34 (2H, m), 1,94 is 2.44 (6H, m), 3,05-is 3.21 (2H, m), 3,28-3,39 (3H, m), 3,42-4,11 (5H, m), 4,20 is 4.35 (2H, m), 4,77-is 4.93 (1H, m), 6,62-of 6.71 (1H, m), 6,93-to 7.18 (3H, m), 7,32-7,72 (5H, m), 8,05-to 8.14 (1H, m)
1351H-NMR (400 MHz, CDCl3) δ: 0,57-of 0.95 (4H, m), 1,34-and 1.54 (3H, m), 1,83-of 2.08 (2H, m), 2,18-to 2.41 (2H, m), 2,45-2,61 (1H, m), 2,73 of 2.92 (1H, m), 3,02-3,24 (2H, m), 3,51-4,86 (7H, m), 6,60-of 6.78 (1H, m), 6,93-to 7.18 (3H, m), 7,20-7,46 (5H, m), 7,46-EUR 7.57 (1H, m), 8,01-of 8.15 (1H, m)
1361H-NMR (400 MHz, CDCl3) δ: 0,71 is 0.81 (2H, m), and 1.00-to 1.14 (2H, m), 1,71-of 1.85 (1H, m), 1.93 and is 2.43 (6H, m), 3,05-3,19 (2H, m), 3,40-4,10 (5H, m), 4,20-to 4.33 (2H, m), 4,55-4,69 (1H, m), 6.48 in-to 6.57 (1H, m), for 6.81-6,92 (2H, m), 7,17 was 7.45 (4H, m), 7,50-of 7.60 (1H, m), 7,94-8,03 (1H, m)
1371H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,83 (2H, m), 1,01 totaling 1.14 (2H, m), 1,75 is 1.86 (1H, m), 1,94-of 2.36 (6H, m), is 2.37-2.49 USD (1H, m), 3,07-3,20 (2H, m), 3,40-to 4.14 (4H, m), 4,22-4,34 (2H, m), 4,57-4,71 (1H, m), 6,61-6,70 (1H, m), 6,93-7,03 (1H, m,), 7,03-7,17 (3H, m), 7,51-of 7.70 (2H, m), 8,02-of 8.15 (1H, m), 8,28-of 8.37 (1H, users)

Table 1-35
Ave. No. The structural formulaNMR
1381H-NMR (CDCl3) δ: 0,94 (6H, s)of 1.33 (6H, s), 2,03-2,11 (4H, m), a 2.36-2,39 (2H, m), 3,07-to 3.09 (2H, m), 3,37 is 3.76 (4H, m), 3,89-of 3.96 (1H, m), 4,28-4,32 (4H, m), of 6.65 (1H, s), 7,01-was 7.08 (3H, m), 7.24 to to 7.32 (1H, m), 7,53-7,63 (2H, m), 8.07-a of 8.09 (1H, m), 8,53-to 8.57 (2H, m)
1391H-NMR (300 MHz, CDCl3) δ: of 1.25 to 1.48 (3H, m), 1,69-2,48 (13H, m), 2,85-3,19 (3H, m), 3.33 and-to 4.41 (8H, m), 6,59-6,69 (1H, m), 6.89 in-7,14 (3H, m), 7.23 percent and 7.36 (1H, m), 7,43-to 7.68 (2H, m), with 8.05 (1H, t, J = 8,1 Hz), 8,44-8,59 (2H, m)
1401H-NMR (400 MHz, CDCl3) δ: 0,67-0,83 (2H, m), 1,01-of 1.15 (2H, m), 1,72 is 1.86 (1H, m), 1,92 is 2.43 (6H, m), 3,03-3,20 (2H, m), 3,36-4,11 (5H, m), 4,20-4,34 (2H, m), 4,55-4,71 (1H, m), of 6.66 (1H, users), 6,93-7,16 (3H, m), 7,20-7,42 (4H, m), of 7.48-7,63 (1H, m), 8,03-to 8.14 (1H, m)
1411H-NMR (400 MHz, CDCl3) δ: 0,66-0,80 (2H, m), 1.00 and by 1.12 (2H, m), 1,58-to 1.82 (3H, m), 1,97-of 2.23 (3H, m), 2,27-2,47 (1H, m), 2,90-of 3.06 (2H, m), 3,40-4,11 (5H, m), 4,24-to 4.41 (2H, m), 4,46-to 4.62 (1H, m), 7,32-7,73 (10H, m)
1421H-NMR (400 MHz, DMSO-D6) δ: 0,57-0,7 (2H, m), 0,81-1,03 (8H, m), 1,79-of 2.36 (8H, m), 2,82-2,90 (8H, m), 3,44-3,92 (9H, m), 4,50-4,70 (1H, s), 7,42-7,53 (2H, m), 7,55-to 7.61 (1H, m), 7,66 for 7.78 (2H, m)

Table 1-36
Ave. No.The structural formulaNMR
1431H-NMR (400 MHz, CDCl3) δ: 0,62-0,84 (2H, m), 0,91-1,17 (2H, m), 1,67-of 1.88 (1H, m), 1,91-of 2.08 (2H, m), 2,14-2,42 (2,5H, m), 2,43-2,56 (0,5H, m), 2.57 m-2,72 (1H, m), 2,88-3,21 (5H, m), 3,45-3,61 (0,6H, m), 3,64-3,91 (2H, m), 3,98 is 4.13 (1H, m), 4,19 is 4.36 (2,4H, m), 4.53-in-4,72 (1H, m), 6,63-6,79 (1H, m), 6,89-to 7.18 (3H, m), 7,40-to 7.64 (4H, m), 7,75-to 7.93 (1H, m), 8,00-8,13 (1H, m)
1441H-NMR (400 MHz, CDCl3) δ: of 0.68 to 0.97 (2H, m), 0,97-of 1.35 (2H, m), 1.85 to figure 2.54 (6H, m), 2,87-is 3.21 (2H, m), 3,21-4,14 (7H, m), 4,16-to 4.46 (2H, m), 4,51-rate 4.79 (1H, m), 5,98 to 6.35 (1H, m), 6,56-of 6.78 (1H, m), 6,85-7,20 (3H, m), 7,20-7,79 (5H, m), 7,95-8,16 (1H, m)
1451H-NMR (400 MHz, CDCl3) δ: 0,68-0,84 (2H, m), 1,01 is 1.16 (2H, m), 1,68-of 1.85 (1H, m), 1,88 is 2.46 (6H, m), 3,02-3,19 (2H, m), 3,40-4,11 (5H, m), 4,24-to 4.41 (2H, m), 4.53-in-4,71 (1H, m), 6,82-6,91 (1H, m), 7,30-7,72 (7H, m)
146 1H-NMR (400 MHz, CDCl3) δ: 0,71-0,99 (4H, m), of 1.15 to 1.31 (6H, m), 1,35-of 1.52 (3H, m), 1,73-to 1.98 (2H, m), 1,98-2,47 (4H, m), 2,86-is 3.08 (2H, m), 3,42-4,11 (6H, m), 4,12-or 4.31 (2H, m), 4.53-in-4,72 (1H, m), 7,08-7,21 (1H, m), 7,30-7,40 (1H, m,), 7,41-to 7.61 (3H, m), to 7.61-7,74 (1H, m)
1471H-NMR (300 MHz, CDCl3) δ: 0,64 is 0.81 (2H, m), 0,96 is 1.13 (2H, m), 1,55-of 1.93 (3H, m), 1,95 is 2.44 (4H, m), 2,84-to 3.02 (2H, m), 3,36-4,22 (7H, m), 4,30-to 4.41 (2H, m), 4,43-to 4.62 (1H, m), a 4.83-4,99 (1H, m), 6,91-7,05 (2H, m), 7,17-7,71 (7H, m)

Table 1-37
Ave. No.The structural formulaNMR
1481H-NMR (400 MHz, CDCl3) δ: 0,73-0,84 (2H, m), 0,85-to 0.96 (2H, m)of 1.45 (3H, s), 1,84-of 1.97 (2H, m), 2,01-of 2.20 (1H, m), and 2.26-2.49 USD (3H, m), 2,97-of 3.12 (4H, m), 3,37-4,19 (9H, m), br4.61-of 4.75 (1H, m), 6,86-to 6.95 (1H, m), 7,08-7,22 (3H, m), 7,25-7,33 (1H, m), of 7.48-the 7.65 (2H, m), 8,46-8,63 (2H, m)
1491H-NMR (400 MHz, CDCl3) δ: 0.70 to about 0.82 (2H, m), 0,82-to 0.96 (2H, m)of 1.42 (3H, s), 1,79-of 1.97 (2H, m), 1,98-2,19 (4H, m), 2,93-is 3.08 (2H, m), 3.33 and-3,82 (5,5H, m), 3,84-4,01 (1H, m), 4.04 the-4,23 (2,5H, m), 4.26 deaths-and 4.40 (2H, m), 4,55-to 4.73 (1H, m), for 6.81-6,97 (3H, m), 7,11-7,22 (1H, m), 7.23 percent-of 7.35 (1H, m), 7,46-to 7.67 (2H, m), 8,44-to 8.62 (2H, m)
1501H-NMR (400 MHz, CDCl3) δ: 0,68-0,85 (2H, m), 1,02-of 1.18 (2H, m), 1,72-to 1.87 (1H, m), 1,94 is 2.46 (6H, m), is 3.08-3,26 (2H, m), 3,41-4,11 (5H, m), 4,18-to 4.33 (2H, m), 4,57-of 4.75 (1H, m), 6,97-7,07 (1H, m), 7.23 percent-to 7.61 (5H, m), of 7.64-7,72 (1H, m,), 8,53 at 8.60 (1H, m)
1511H-NMR (400 MHz, CDCl3) δ: 0,61-0,89 (4H, m)of 1.36 (3H, s), 1,55 of-1.83 (6H, m), 1,89-2,17 (3H, m), 2,32-2,47 (1H, m), 2,59-2,82 (4H, m), 3.33 and-4,18 (9H, m), of 4.38-to 4.52 (1H, m), 7.03 is-7,14 (2H, m), 7,16-to 7.32 (3H, m), 7,43-to 7.64 (2H, m), 8,44-8,61 (2H, m)
1521H-NMR (400 MHz, CDCl3) δ: 0,71-0,85 (2H, m), 1,03 is 1.16 (2H, m), 1,33-of 1.42 (3H, m), 1,73-of 1.88 (1H, m), 1.93 and-2,22 (3H, m), 2,25-of 2.45 (3H, m), 2,96-3,13 (2H, m), 3,41-4,11 (7H, m), 4,28-4,39 (2H, m), to 4.52-4,71 (1H, m), 6,85-of 6.96 (2H, m,), 7,32-7,40 (1H, m), 7,41-to 7.61 (3H, m), 7,63-7,71 (1H, m), 7,89-to 7.99 (2H, m)

Table 1-38
Ave. No.The structural formulaNMR
1531H-NMR (400 MHz, CDCl3) δ: 0,65-of 0.79 (2H, m), 1.00 m (PI)-1.09 (2H, m), 1.70 to of 1.97 (3H, m), 2.00 in and 2.26 (3H, m), 2,31-2,47 (1H, m), 2,86 was 3.05 (2H, m), 3,35-3,53 (1,5H, m), 3,56-of 3.77 (2H, m), 3,84-of 3.94 (1H, m),4,08-4,16 (0,5H, m), 4,25-br4.61 (3H, m), 5,14 (2H, s), 7.23 percent-7,40 (6H, m), 7,49-to 7.61 (2H, m), of 8.47-to 8.57 (2H, m)
1541H-NMR (400 MHz, CDCl3) δ: 0,61 is 0.86 (2H, m), 0,98-of 1.18 (2H, m), 1,23-of 1.41 (6H, m), 1,67 is 1.86 (1H, m), 1,87-2,47 (6H, m), 2,52-is 2.88 (3H, m), 3,06-of 3.32 (1H, m), 3,35-to 4.15 (6H, m), 4,49-4,85 (2H, m), 7,28-7,73 (5H, m)
1551H-NMR (400 MHz, CDCl3) δ: 0,62-0,83 (2H, m), 0,97-to 1.14 (2H, m), 1,66-of 2.50 (8H, m), 2,78-2,95 (1H, m), 3,16-to 3.34 (1H, m), 3,37-of 3.54 (1H, m), 3,57-with 3.79 (2H, m), 3,83-of 3.97 (1H, m), 4.09 to be 4.29 (1H, m), 4,54-4,80 (4H, m), 6.89 in? 7.04 baby mortality (3H, m), 7,21-7,38 (3H, m), of 7.48-to 7.68 (2H, m), 8,42-to 8.70 (2H, m)
1561H-NMR (400 MHz, CDCl3) δ: 0,65-of 0.82 (2H, m), 1.00 and is 1.13 (2H, m), 1,67-of 2.30 (9H, m), 2,32 is 2.51 (1H, m), 2,72-to 3.34 (2H, m), 3,36-a 4.03 (4H, m), 4,56-4,99 (1H, m), 7,20-7,46 (5H, m), 7,49-the 7.65 (2H, m), 8,42-to 8.62 (2H, m)
1571H-NMR (400 MHz, CDCl3) δ: of 0.64 to 0.85 (2H, m), 0,98 is 1.13 (2H, m), 1,57-of 1.92 (3H, m), 1,96-of 2.50 (5H, m), 2,90-of 3.54 (3H, m), 3,56-3,81 (3H, m), 3,83-3,98 (1H, m), 4.53-in-to 4.73 (1H, m), 4,85-5,04 (1H, m), 7,21-7,47 (5H, m), 7,49-the 7.65 (2H, m,), 8,45-to 8.62 (2H, m)

Table 1-39
Ave. No. The structural formulaNMR
1581H-NMR (400 MHz, CDCl3) δ: 0,62-1,19 (4H, m), 1,62-2,53 (7H, m), 2.70 height of 2.92 (1H, m), is 3.08 be 3.29 (1H, m), 3.33 and-4,21 (6H, m), 4,51-of 4.75 (2H, m), 7,31 to 7.62 (4H, m), 7,63-7,73 (1H, m)
1591H-NMR (400 MHz, CDCl3) δ: 0,64-of 0.82 (2H, m), 0,98 by 1.12 (2H, m), 1,65-2,32 (9H, m), 2,34-of 2.50 (1H, m), is 3.08 (2H, users), 3,34-4,00 (4H, m), 4,56-of 4.95 (1H, m), 7.23 percent-to 7.32 (1H, m), 7,35-7,44 (4H, m), of 7.48-the 7.65 (2H, m), 8,45-8,61 (2H, m)
1601H-NMR (400 MHz, CDCl3) δ: 0,59-0,83 (2H, m), 0,95-to 1.14 (2H, m), 1,62-of 2.20 (6H, m), 2,30-of 2.50 (1H, m), 2,69-only 2.91 (1H, m), 3,06-of 3.27 (1H, m), 3.33 and-4,20 (6H, m), of 3.73 (2H, s), 4,50-of 4.66 (1H, m), 4,71-is 4.85 (1H, m), 6,93-7,10 (2H, m), 7,15-7,34 (3H, m), 7,45-to 7.64 (2H, m), to 8.41-to 8.62 (2H, m)
1611H-NMR (400 MHz, CDCl3) δ: 0,65 is 0.81 (2H, m), 0,99-of 1.13 (2H, m), 1,72-2,50 (9H, m), 2,85-to 3.33 (2H, m), 3,35-of 3.78 (3H, m), 3,81-4,96 (3H, m), 7,22-7,33 (1H, m), 7,47-to 7.77 (6H, m), 8,44-8,63 (2H, m)
1621H-NMR (400 MHz, CDCl3) δ: 0,64-of 0.82 (2H, m), 1.00 and by 1.12 (2H, m), 1,71 of-2.32 (8H, m), 2,33 is 2.51 (1H, m), 2,85 of 3.28 (2H, m), 332-4,05 (5H, m)a 3.83 (3H, s), 4,57-4,99 (1H, m), 6.90 to? 7.04 baby mortality (3H, m), 7.24 to 7,38 (2H, m), 7,50-of 7.69 (2H, m), 8,53 (2H, users)

Table 1-40
Ave. No.The structural formulaNMR
1631H-NMR (400 MHz, DMSO-D6) δ: 0,68 is 0.86 (4H, m), 1,29-to 1.38 (3H, m), 1,99-2,17 (2H, m), 2,18-of 2.66 (5H, m), 3,14-of 3.32 (2H, m), 3,39-4,50 (8H, m), 4,68 of 4.83 (1H, m), 7,30-7,40 (2H, m), 7,43-7,53 (1H, m), 7,60-of 7.82 (6H, m), 10,55-of 10.76 (1H, m,)
1641H-NMR (400 MHz, CDCl3) δ: 0,59-0,74 (2H, m), 0,93 of-1.04 (2H, m), 1,61-of 1.73 (1H, m), 1,88-of 2.16 (3H, m), 2,25 at 2.59 (5H, m), 3,34 is 3.76 (3,5H, m), 3,83-4,01 (3H, m), 4,08-4,15 (0,5H, m), 4,27-4,39 (1H, m), 7.23 percent-7,31 (1H, m), 7,49-to 7.67 (5H, m), 7,79-to 7.84 (2H, m), 8,46-8,58 (2H, m)
1651H-NMR (400 MHz, CDCl3) δ: 0,67 is 0.86 (2H, m), 1.00 and-1,19 (2H, m), 1,73-of 1.88 (1H, m), 1,92-of 2.21 (3H, m), 2,24-2,47 (3H, m), 2,92-of 3.12 (2H, m), 3,40-4,12 (7H, m), 4,51-4,69 (1H, m), 5,74 (2H, users), 6,87-6,99 (2H, m), 7,31-7,40 (1H, m), 7,41-to 7.61 (3H, m), 7,63 for 7.78 (3H, m)
1661H-NMR (400 MHz, CDCl3) δ: 0,69-0,85 (2H, m, 1,01-of 1.16 (2H, m)and 1.51-1,67 (1H, m), 1,75-1,89 (1H, m), 1,91-of 2.23 (3H, m), and 2.26-2.49 USD (3H, m), 2,83-of 3.00 (2H, m), 3,40-4,12 (7H, m), of 4.44-and 4.68 (3H, m), 6,88? 7.04 baby mortality (2H, m), 7.23 percent-7,31 (2H, m), 7,32-7,40 (1H, m), 7,41 to 7.62 (3H, m), 7,63-7,72 (1H, m)
1671H-NMR (400 MHz, CDCl3) δ: 0,73 is 0.86 (2H, m), 1.06 a-1,12 (2H, m), 1,76-of 1.88 (1H, m), 1,94-of 2.08 (2H, m), 2,11 is 2.44 (5H, m), 3,05-3,19 (2H, m), 3,42-3,51 (0,5H, m), 3,59-4,10 (3,5H, m), 4,56-4,78 (3H, m), 5.40 to-5,94 (2H, users), 6,67-6,74 (1H, m), 7,12-7,22 (1H, m), 7,31-7,40 (1H, m), 7,41-of 7.60 (2H, m), of 7.64-7,73 (1H, m), to $ 7.91-to 7.99 (1H, m), 8,56-8,63 (1H, m)

Table 1-41
Ave. No.The structural formulaNMR
1681H-NMR (400 MHz, CDCl3) δ: 0,71-0,85 (2H, m), 1,02-to 1.14 (2H, m), 1,73-of 1.88 (1H, m), 1,90-2,22 (3H, m), 2,27 is 2.51 (3H, m), 2.71 to is 2.88 (2H, m), 3,35-4,11 (9H, m), of 4.38-4,56 (1H, m), 6,60-of 6.71 (2H, m), 6,78-6,91 (2H, m), 7,31-7,40 (1H, m,), 7,41 to 7.62 (3H, m), 7,63-7,71 (1H, m)
1691H-NMR (400 MHz, CDCl3) δ: 0.71-0.88 / l (2H, m), 1,02-of 1.16 (2H, m), 1,73-of 1.88 (1H, m), 1.91 a-2,19 (3H, m), 2,27-of 2.50 (3H, m), 2,81-of 3.00 (2H, m), 3,40-4,17 (9H, m), 4,39-4,63 (3H, m), 6,92? 7.04 baby mortality (2H, m), 7,31-7,72 (7H, m)
1701H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,86 (2H, m), 1,01 is 1.16 (2H, m), 1,72-of 1.88 (1H, m), 1,91-of 2.23 (3H, m), 2.26 and is 2.51 (3H, m), was 2.76-2,98 (2H, m), 3,42-4,11 (10H, m), 4,42-to 4.62 (1H, m), 6.89 in-7,00 (2H, m), 7,16 (1H, s), 7,31-7,73 (8H, m)
1711H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,86 (2H, m), 1.00 and is 1.16 (2H, m), 1,72-of 1.88 (1H, m), 1,92-of 2.23 (3H, m), 2.26 and-2,48 (3H, m), 2,84-to 3.02 (5H, m), 3,38-4,12 (7H, m), 4,45 with 4.65 (1H, m), 6,25-6,38 (1H, m), 6,88-6,99 (2H, m), 7,11-7,22 (2H, m,), 7,32-7,40 (1H, m), 7,41 to 7.62 (3H, m), 7,63-7,71 (1H, m)
1721H-NMR (400 MHz, CDCl3) δ: 0,69-1,01 (4H, m), of 1.16 and 1.35 (3H, m), 1,35-of 1.53 (3H, m), 1,71-of 1.97 (2H, m), 1,97-2,49 (4H, m), 2,86-to 3.09 (2H, m), 3,41-or 4.31 (9H, m), 4.53-in-the 4.75 (1H, m), 7,17-7,30 (1H, m), 7,30-7,40 (1H, m), 7,41-of 7.60 (3H, m), to 7.61-7,74 (1H, m)

Table 1-42
Ave. No.The structural formulaNMR
1731H-NMR (400 MHz, CDCl3) δ: 0,61-of 0.87 (2H, m), 1.00 and-1,19 (2H, m), 1,57-to 1.87 (1H, m), 1.93 and was 2.25 (1H, m), 2,25-2,48 (1H, m), 3,31-to 4.15 (5H, m), 4,35-4,59 (4H, m), 5,44-to 5.66 (1H, m), 6,26-6,40 (1H, m), 7,30-7,76 (6H, m), 8,02-8,17 (1H, m,)
1741H-NMR (400 MHz, CDCl3) δ: 0,69-0,93 (4H, m), 1.41 to of 1.52 (3H, m), 1,83 is 2.01 (2H, m), 2.13 and is 2.51 (4H, m), 2,97-3,11 (2H, m), 3,16-4,12 (9H, m), to 4.41-of 4.54 (2H, m), 4,65-4,78 (1H, m), 6,62-of 6.71 (1H, m), 7,12-of 7.55 (7H, m), 8,10-8,16 (1H, m,)
1751H-NMR (400 MHz, CDCl3) δ: 0,72-0,85 (2H, m), 1.04 million-to 1.16 (2H, m), 1,73-of 1.88 (1H, m), 1,94-of 2.09 (2H, m), 2,10-of 2.45 (5H, m), 3,07-up 3.22 (2H, m), 3,42-3,51 (0,5H, m), 3,57-4,10 (3,5H, m), to 4.52-4,80 (3H, m), 6,62-of 6.71 (1H, m), 7,32-7,41 (1H, m), 7,41-7,72 (5H, m), scored 8.38-to 8.45 (1H, m)
1761H-NMR (400 MHz, DMSO-D6) δ: 0,46 is 0.86 (4H, m), 1,07-1,24 (2H, m), 1,27-of 1.41 (3H, m), 1,73-2,07 (7H, m), 2,15-of 2.30 (2H, m), 3,06-4,08 (8H, m), 4.72 in-4,88 (3H, m), 6,66-6,74 (1H, m), 7,08-to 7.61 (5H, m), scored 8.38-8,48 (2H, m)
1771H-NMR (400 MHz, DMSO-D6) δ: 0.70 to 0,97 (7H, m), 1,35-of 1.42 (3H, m), 1,86-2,03 (4H, m), 2,25 is 2.46 (1H, m), 2,84-2,95 (1H, m), 3,07-3,24 (3H, m), 3,39 is 3.57 (1H, m), 3,67-of 3.77 (1H, m), 3,81-of 3.94 (1H, m), 4.75 V-4,88 (3H, m), 6,64-6,72 (1H, m,), 7,20-7,41 (5H, m), 7,53-to 7.61 (1H, m), 8,39-8,44 (2H, m)

Table 1-43
Ave. No.The structural formula NMR
1781H-NMR (400 MHz, CDCl3) δ: 0,74 is 0.86 (2H, m), 1,05-1,15 (2H, m), 1,76-of 1.88 (1H, m), 1.93 and-of 2.09 (3H, m), 2,11 is 2.46 (4H, m), 3.04 from-3,19 (2H, m), 3,43-3,51 (0,5H, m), 3,59-4.09 to (3,5H, m), 3,84-3,91 (3H, s), 4,58-4,78 (3H, m), 6,61-of 6.71 (1H, m), 7,32-to 7.61 (3,5H, m), 7,63-7,71 (1H, m), 7,98-8,08 (1,5H, m), 8,77-8,83 (1H, m)
1791H-NMR (400 MHz, CDCl3) δ: 0,77-0,98 (4H, m), 1,44-of 1.53 (3H, m), 1,86 is 2.46 (6H, m), 2,99 is 3.15 (2H, m), 3,45-4,06 (7H, m), 4,18-to 4.41 (1H, m), 4,68-is 4.85 (1H, m), 4,94-5,09 (2H, m), 6.48 in-6,55 (1H, m), 7,26-7,56 (4H, m), 7,82-a 7.92 (1H, m,), 8,31-of 8.37 (2H, m)
1801H-NMR (400 MHz, DMSO-D6) δ: 0,67-of 0.91 (4H, m), 1,29-of 1.44 (3H, m), 1,74-2,34 (7H, m), 3,02-4,18 (7H, m), 4,47-4,69 (2H, m), 4,77-4,91 (3H, m), 6,60-of 6.71 (1H, m), 7,14-of 7.69 (5H, m), 8.34 per-8,46 (2H, m)
1811H-NMR (400 MHz, CDCl3) δ: 0,68 of 0.77 (2H, m), 0,99-of 1.15 (2H, m), 1,75-1,89 (1H, m), 1,92-of 2.05 (2H, m), 2,18 of $ 2.53 (4H, m), 2,96-to 3.09 (2H, m), 3,68-of 3.85 (2H, m), a 3.87-Android 4.04 (2H, m), of 4.44-4,56 (2H, m), 4,58-4,72 (1H, m), 6,58 is 6.67 (1H, m,), 6,68-6,76 (1H, m), 7,29-7,39 (1H, m), 7,45-7,53 (2H, m), 7,75-7,88 (1H, m), 8.17-a 8,23 (1H, m), 8,54-to 8.62 (1H, m), 8,69-8,83 (1H, m)
182 1H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,83 (2H, m), 1,01-of 1.15 (2H, m), 1,69-of 1.88 (1H, m), 1,90-of 2.21 (6H, m), 2.26 and costs 2.50 (3H, m), 2.77-to of 3.00 (2H, m), 3,41-4,11 (7H, m), 4,40-to 4.62 (1H, m), 6,85-6,97 (2H, m), 7,31-7,71 (7H, m)

Table 1-44
Ave. No.The structural formulaNMR
1831H-NMR (400 MHz, DMSO-D6) δ: 0,60-0,75 (2H, m), 0,94 was 1.06 (2H, m), 1,88-2,34 (7H, m), 2,79 are 2.98 (2H,m), 3,44-3,93 (7H, m), 4,50-and 4.68 (1H, m), 6.89 in-7,03 (1H, m), 7,43-7,80 (7H, m)
1841H-NMR (400 MHz, CDCl3) δ: 0.70 to 0,86 (2H, m), of 1.05 to 1.16 (2H, m), 1.77 in-a 1.88 (1H, m), 1,94 of $ 2.53 (6H, m), 3,06-up 3.22 (2H, m), 3,45-4,16 (5H, m), 4,21 is 4.35 (2H, m), 4,57-to 4.73 (1H, m), to 6.67 (1H, s), 6,95-7,17 (3H, m), 7,35-7,73 (5H, m), 8,05-8,13 (1H, m)
1851H-NMR (400 MHz, DMSO-D6) δ: 0,58-0,88 (4H, m), 1,29-of 1.44 (3H, m), 1,94-of 2.21 (5H, m), 2,28-to 2.41 (1H, m), 3.27 to 3,93 (8H, m), 3.95 to of 4.05 (3H, m), 4,58 is equal to 4.97 (3H, m), 5,42-of 6.26 (1H, m), 6,37-6,50 (1H, m), 7,14-7,41 (5H, m), 7,53-to 7.68 (1H, m,), 8,11-8,23 (1H, m)
1861H-NMR (400 MHz, DMSO-D6 ) δ: 0,55-0,85 (4H, m), 1.32 to 1.41 for (3H, m), 1,84-to 2.40 (7H, m), 3,06 is 3.23 (2H, m), 3,29-3,90 (5H, m), 4.72 in-4,88 (3H, m), 4,89 to 5.35 (2H, m), 6,66-6,72 (1H, m), 6,91-to 7.64 (4H, m), 8,39-8,44 (2H, m)
1871H-NMR (400 MHz, CDCl3) δ: 0,68-0,85 (2H, m), 1,01 is 1.13 (2H, m), 1,57-of 1.88 (2H, m), 1.93 and-of 2.20 (1H, m), 2,33-of 2.56 (3H, m), 2,94-of 3.07 (2H, m), 3,35-3,82 (4H, m), 3,86-is 4.21 (4H, m), to 4.52-of 4.66 (1H, m), 6,82-to 6.88 (1H, m), 7.24 to 32 (3H, m), 7,55-to 7.64 (3H, m), 8,15 is 8.22 (1H, m), of 8.47-8,61 (1H, m)

Table 1-45
Ave. No.The structural formulaNMR
1881H-NMR (400 MHz, CDCl3) δ: 0,67-0,78 (2H, m), 0,96-1,11 (2H, m), 1,71-of 1.85 (1H, m), 1,92-of 2.09 (3H, m), 2,16-to 2.57 (4H, m), 3.04 from-is 3.21 (2H, m), 3,55-4,00 (4H, m), 4,19-4,34 (2H, m), 4,54-and 4.68 (1H, m), 6,61-6,70 (1H, m), 6,91-to 7.15 (3H, m), 7.23 percent-7,31 (1H, m), 7,51-7,58 (1H, m), to 7.67-7,76 (1H, m), 8,03-to 8.12 (1H, m)
1891H-NMR (400 MHz, DMSO-D6) δ: of 0.53 to 0.69 (2H, m), 0.71-0.88 / l (2H, m), 0,91-1,11 (6H, m), USD 1.43-2,39 (10H, m), 2,62-2,82 (2H, m), 2,92-of 3.06 (3H, m), 3,42-to 3.92 (6H, m), 4,10-4,74 (2H, m), 7,39-to 7.59 (2H, m), 7,63-7,81 (2H, m)
190 1H-NMR (400 MHz, CDCl3) δ: 0,73-0,97 (4H, m), 1,36-is 1.51 (3H, m), 1.77 in-1,95 (2H, m), 1,97-of 2.26 (7H, m), 2,29-2,49 (2H, m), 3,47-4,11 (5H, m), 4,46 with 4.64 (1H, m), 7,00-7,20 (3H, m), 7,32-7,72 (6H, m), 8,29-8,42 (1H, m)
1911H-NMR (400 MHz, CDCl3) δ: 0,73-0,97 (4H, m), 1,38-1,49 (3H, m), 1,60 to 1.76 (1H, m), 1.77 in-1,90 (2H, m), 1.93 and-to 2.18 (2H, m), 2,19-of 2.56 (5H, m), 2,70-of 2.81 (1H, m), 3,47-4.09 to (5H, m), 4,42-br4.61 (1H, m), 7,31-7,72 (5H, m)

The present invention further specifically disclosed in the examples, the compounds listed below, which do not serve to limit.

The composition of example 1 (receiving capsules)
1) Connection example 130 mg
2) crystalline cellulose10 mg
3) lactose19 mg
4) magnesium stearate1 mg

Components 1), 2), 3) and 4) are mixed and placed in gelatin capsules.

td align="justify"> 2) lactose
The composition according to example 2 (production of tablets)
1) Connection example 130 mg
50 g
3) corn starch15 g
4)carboxymethylcellulose calcium44 g
5) magnesium stearate1 mg

All number of components 1), 2), 3) and 30 g of component 4) is mixed with water, and dried under reduced pressure, and pulverized. The crushed powder is mixed with 14 g of component 4) and 1 g of the component 5) and tabletirujut using tabletiruemogo device. So, get 1000 tablets containing 30 mg of compound of example 1 on the pill.

In the same manner as in the above example 1 drug or example of preparation 2, the compounds of examples 2-191 can also be issued in the form of capsules or tablets.

Experimental example 1the expression inhibitory activityin vitroregarding HSD-1 (hydroxysteroiddehydrogenase 1) the Expression of inhibitory activity against HSD-1 is determined by quantifying the inhibition of the conversion of cortisone to cortisol by the SPA system (analysis with proximal scintillation) and using as source of the enzyme human HSD-1 (hereinafter recombinant HSD-1), expressed using a system of baculoviruses. P the assets (100 μl) is added to 96-well plate (96 well Opti-plates TM-96 (Packard)) to the final concentrations shown below, and conducting the reaction at room temperature for 90-120 minutes. As the reaction mixture 5-100 ng/well of recombinant HSD-1, 500 μm NADPH and 10 nm3H-cortisone (American Radiolabeled Chemicals Inc., 50 Ci/mmol) dissolved in PBS containing 0.1% BSA (Sigma), and the test substance is 2 μl of a solution of the compound (dissolved in DMSO). After the reaction went, 50 μl of PBS (containing 0.1% BSA (Sigma))containing 0.2 μg of the monoclonal antibody against mouse cortisol (East Coast Biologics), 500 µg artemisinin antibodies associated with granules PVT SPA (Amersham Biosciences), and 133 μm carbenoxolone (Sigma) are added to the reaction mixture to stop the reaction. After completion of the reaction, the mixture is incubated at room temperature for at least 2 hours and measure the radioactivity by means of a counter Topcount (Packard). The control uses the value in the hole, in which is added 2 μl of DMSO instead of test substance (0% inhibition) and as a positive control the size of the hole in which add karbenoksolon (final concentration 100 μm) instead of the test substance (100% inhibition). Inhibition (%) test compound is calculated by the following formula: ((value in the control - value : test substance)/( size of the control - value positive control)) x 100(%). Level IC50under citybeat by the values of the inhibition of two points in 50% inhibition. The results obtained are shown in the following tables with Table 2-1 to Table 2-3.

Table 2-1
Ave. No.hHSD1(IC50(nM))Ave. No.hHSD1(IC50(nM))
2++41++
3++42++
4++43++
6++44++
7++45++
8++47++
9++48++
10++49++
11++50++
12++51++
13++52++
14++53++
15++54++
16++55++
17++56++
18++57++
19++58++
20++59++
21++60++
22++61++
23++63++
24++64++
25++65++
26++66++
27++67++
28++68++
29++69++
30++71++
31++72++
32++73++
33++74++
34++75++
35++76++
36++77++
37++78++
39++79++
40++80++

/tr>
Table 2-2
Ave. No.hHSD1(IC50(nM))Ave. No.hHSD1(IC50(nM))
83++130++
84++131++
85++132++
87++133++
88++134++
89++135++
90++136++
91++137++
93++138++
94++139++
95++140++
96++141++
97++142 ++
99++145++
100++146++
103++147++
105++148++
106++149++
107++150++
108++151++
109++154++
110++155++
111++156++
112++157 ++
113++158++
114++165++
115++166++
116++167++
117++168++
118++169++
119++170++
120++171++
124++172++
125++173++
126++174 ++
128++175++
129++176++

Table 2-3
Ave. No.hHSD1(IC50(nM))Ave. No.hHSD1(IC50(nM))
177++185++
178++186++
179++187++
180++189++
182++190++
183++191++
184++

In the above tables, ++ means that the value of the IC50is not more than 30 nm.

Industrial applicability

Heterocyclic compound of the present invention has excellent inhibitory activity against HSD1 and is suitable as an agent for the prevention and treatment of metabolic diseases such as diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, fatty infiltration of the liver etc., etc.

This application is based on patent applications Nos. 2005-168901, 2006-027097 and 2006-138252, an existing in Japan and the applications Nos. 60/692039 and 60/772734, an existing in the United States, the content of which is included in its entirety as a reference.

1. The compound of the formula [1']

where ring a is a
(1) containing nitrogen, monocyclic, saturated, 4-6-membered heterocyclic group, or
(2) 3-6-membered cycloalkyl group, the said ring a is optionally substituted by one or more identical or different substituents R1,
specified substituent R1represents a
1) a hydrogen atom,
2) -CONR5R6where R5and R6are the same or different and each represents a
(a) the ATO is hydrogen,
(b) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) a carboxyl group,
d)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:
(i) halogen atom, (ii) hydroxyl groups, and (iii) C1-6alkoxygroup) and
e) C1-6alkoxygroup),
(c) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different C1-6alkyl groups (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup)),
(d) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) phenyl group (this phenyl group is not battelino substituted by one or more identical or different substituents, selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) no (iv):
(i) halogen atom,
(ii) a hydroxyl group,
(iii) the carbonyl group and
(iv)1-6alkoxygroup),
(e) -S(=O)2-R9where R9represents a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or C1- alkyl group,
(f) nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(e) C1-6alkoxygroup or
(h) thiazolidine or pyridyloxy group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms)
or
(i) R5and R6optional form together with the nitrogen atom to which they relate, 4-6-membered containing nitrogen and optionally a sulfur atom, saturated, monocyclic, heterocyclic group, or containing nitrogen and optionally an oxygen atom, a 5-7-membered heterocyclic group condensed with benzene ring (both of these heterocyclic groups are optionally substituted by one or more, same or different substituents selected from the following a) to i):
a) a halogen atom,
b) a hydroxyl group,
c) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, identical or different is cnyh substituents, selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii) C1-6alkoxygroup),
d) a carboxyl group,
(e) -CO-C1-6alkyl group,
f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
g) the carbonyl group,
h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, and
i) C1-6alkoxygroup),
3) -COOR10where R10represents a
(a) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) through d):
a) a hydroxyl group,
b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group,
c1-6alkoxygroup and
d) phenyl group), or
(b) piperidino group, substituted Deputy, selected from EBUSY a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
4) -COR11where R11represents a
(a)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to h):
a) a halogen atom,
b) a hydroxyl group,
c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,
d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,
e) C1-6alkoxygroup,
f) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii) C1-6alkoxygroup and (iv) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
g) a carboxyl group, and
(h) fenoxaprop),
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):
a) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and
b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup)),
(C) nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(d) phenyl group (this phenyl group is obazatelno substituted by one or more identical or different substituents, selected from the following (1) through (3):
(1) halogen atom, (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3) C1-6alkoxygroup), or
(e) a carboxyl group,
5) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (d):
(a) carboxyl group,
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom, to the which they are associated, nitrogen-containing, saturated, monocyclic, heterocyclic group, and
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),
6) 3-6-membered cycloalkyl group,
7) -S(=O)2-R12where R12represents a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)or phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
8) -C(=NCN)-R13where R13represents a C1-6alkyl group,
9) -C(=NCN)NR14R15where R14and R15are the same or different and each represents the volume of hydrogen or C 1-6alkyl group,
10) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (f):
(a) carboxyl group,
(b) halogen atom,
(c) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) hydroxyl group, (b) halogen atom and (C) C1-6alkoxygroup),
(d) -NR38R39where R38and R39are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-NR40R41where R40and R41are the same or different and each represents a hydrogen atom, a C1-6alkyl group or a C1-6alkoxygroup, or-S(=O)2-R42where R42represents a C1-6alkyl group, or R38and R39optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more oxoprop),
(e) -CO-NR43R44where R43 and R44are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
(f) -COO-C1-6alkyl group) or
11) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atoms, oxygen and sulfur (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) to (h):
(a) carboxyl group,
(b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) a halogen atom,
b) a hydroxyl group and
c1-6alkoxygroup),
(C) cycloalkyl group,
(a) halogen atom,
(e) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
(f) -COO-C1-6alkyl group,
(g) ceanography and
(h)1-6alkoxygroup);
-X - represents a
(1) -N(R1)-, where R1is as defined above, or
(2) -CCR7R8)-, where R7and R8are the same or different and each not only is no other
1) a hydrogen atom,
2) -NR16R17where R16and R17are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-NR36R37where R36and R37are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
3) -CONR18R19where R18and R19are the same or different and each represents a hydrogen atom, a C1-6alkyl group (specified With1-6alkyl group is optionally substituted one or more carboxyl groups) or phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) halogen atom and (b) C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
4) tetrazolyl group, or
5) a carboxyl group;
R2represents a
(1) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:
1) C1-6 alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) a hydroxyl group and (b) C1-6alkoxygroup), and 2) C1-6alkoxygroup); and
R3and R4are the same or different and each represents a
(1) a hydrogen atom,
(2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: 1) halogen atom,
2) a hydroxyl group, 3)1-6alkoxygroup and 4) -OCO-C1-6alkyl group),
(3) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following 1) to 6):
1) halogen atom,
2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) halogen atom, (b) hydroxyl groups, and (C) C1-6alkoxygroup),
3)1-6alkoxygroup (specified C1-6alkoxygroup is optionally substituted one or more quantity the STV identical or different halogen atoms),
4) carboxyl group
5) -COO-C1-6alkyl groups and
6) ceanography),
(4) pyridyloxy or thiazolidine group (this heterocyclic group is optionally substituted by halogen atom),
(5) a hydroxyl group, or
(6) C1-6alkoxygroup,
or its pharmaceutically acceptable salt.

2. The compound of the formula [1]

where-X - is a
(1) -N(R1)-, where R1represents a
1) a hydrogen atom,
2) -CONR5R6where R5and R6are the same or different and each represents a
(a) a hydrogen atom,
(b) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following groups:
(a) a hydroxyl group,
(b) halogen atom,
c) a carboxyl group,
d)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii) C1-6alkoxygroup) and
e) C1-6alkoxygroup),
(c) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted one or the largest share of the PTO same or different C 1-6alkyl groups (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup)),
(d) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2); (1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is a long is the super substituted by one or more identical or different substituents, selected from the following (i) no (iv):
(i) halogen atom,
(ii) a hydroxyl group,
(iii) the carbonyl group and
(iv)1-6alkoxygroup),
(e) -S(=O)2-R9where R9represents a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or C1-6alkyl group,
(f) nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(g)1-6alkoxygroup or
(h) thiazolidine or pyridyloxy group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms),
or
(i) R5and R6optional form together with the nitrogen atom to which they are attached, a 4 to 6 membered, saturated, monocyclic, is heterocyclics group, containing a nitrogen atom and optionally a sulfur atom, or a 5-7-membered heterocyclic group containing a nitrogen atom and optionally an oxygen atom, condensed with benzene ring (both of these heterocyclic groups are optionally substituted by one or more, same or different substituents selected from the following a) to i):
a) a halogen atom,
b) a hydroxyl group,
c1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii) C1-6alkoxygroup),
d) a carboxyl group,
(e) -CO-C1-6alkyl group,
f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
g) the carbonyl group,
h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, and
i) C1-6alkoxygroup),
3) -COOR10where R10represents a
(a) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted od is them or more identical or different substituents, selected from the following a) through d):
a) a hydroxyl group,
b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group,
c) C1-6alkoxygroup and
d) phenyl group), or
(b) piperidino group, substituted Deputy, selected from the following (a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
4) -COR11where R11represents a
(a)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to h):
a) a halogen atom,
b) a hydroxyl group,
c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,
d) -CO-NR30R31where R30and R31are the same or different and each represents an atom bodoro is a or C 1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,
e) C1-6alkoxygroup,
f) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii) C1-6alkoxygroup and (iv) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
g) a carboxyl group, and
(h) fenoxaprop),
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):
a) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and
(b) (C1-6 alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),
(C) nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3):(1) halogen atom, (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3) C1-6alkoxygroup), or
(e) a carboxyl group,
5) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (d):
(a) carboxyl group,
(b) 3-6-membered cycloalkene the group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR 32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, and
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),
6) 3-6-membered cycloalkyl group,
7) -S(=O)2-R12where R12represents a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)or phenyl group (this phenyl group is optionally substituted one or more kolichestvoparkov or different substituents, selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
8) -C(=NCN)-R13where R13represents a C1-6alkyl group,
9) -C(=NCN)NR14R15where R14and R15are the same or different, and each represents a hydrogen atom or a C1-6alkyl group,
10) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (f):
(a) carboxyl group,
(b) halogen atom,
(c)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) hydroxyl group, (b) halogen atom and (C) C1-6alkoxygroup),
(d) -NR38R39where R38and R39are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-NR40R41where R40and R41are the same or different and each represents a hydrogen atom, a C1-6lilou group or a C 1-6alkoxygroup, -S(=O)2-R42where R42represents a C1-6alkyl group, or R38and R39optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more oxoprop),
(e) -CO-NR43R44where R43and R44are the same or different and each represents a hydrogen atom or a C1-6alkyl group, and
(f) -COO-C1-6alkyl group) or
11) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom, oxygen and sulfur (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) to (h):
(a) carboxyl group,
(b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) a halogen atom,
b) a hydroxyl group and
c) C1-6alkoxygroup),
(c) cycloalkyl group,
(d) halogen atom,
(e) -CO-NR45R46 where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
(f) -COO-C1-6alkyl group,
(g) ceanography and (h) C1-6alkoxygroup)), or
(2) -(R7R8)-, where R7and R8are the same or different and each represents a
1) a hydrogen atom,
2) -NR16R17where R16and R17are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-NR36R37where R36and R37are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
3) -CONR18R19where R18and R19are the same or different and each represents a hydrogen atom, a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted one or more carboxyl groups) or phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more identical or R is slichnih halogen atoms)),
4) tetrazolyl group or
5) a carboxyl group;
R2represents a
(1) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:
1) With the1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (a) a hydroxyl group and (b) C1-6alkoxygroup), and 2) C1-6alkoxygroup); and
R3and R4are the same or different and each represents a
(1) a hydrogen atom,
(2)1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: 1) halogen atom, 2) a hydroxyl group, 3)1-6alkoxygroup and 4) -OCO-C1-6alkyl group),
(3) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following 1) to 6):
1) halogen atom,
2)1-6alkyl group (specified With1-6an alkyl group is not necessarily alsenoy one or more identical or different substituents, selected from the following group: (a) halogen atom, (b) hydroxyl groups, and (C) with1-6alkoxygroup),
3)1-6alkoxygroup (specified With1-6alkoxygroup is optionally substituted by one or more, same or different halogen atoms),
4) carboxyl group
5) -COO-C1-6alkyl groups and
6) ceanography),
(4) pyridyloxy or thiazole group (this heterocyclic group is optionally substituted by halogen atom),
(5) a hydroxyl group, or
(6)1-6alkoxygroup,
or its pharmaceutically acceptable salt.

3. The compound according to claim 1, where-X - is-C(R7R8)-, where R7and R8are those as defined in claim 1, or its pharmaceutically acceptable salt.

4. The compound according to claim 2, where-X - is-C(R7R8)-, where R7and R8are those as defined in claim 1 or its pharmaceutically acceptable salt.

5. The compound according to claim 3, where R8represents a
1) -NR16R17where R16and R17are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
2) -CONR18R19where R18and R19are the same or different and each represents a hydrogen atom or a C1-6alkyl group, Il the
3) tetrazolyl group,
or its pharmaceutically acceptable salt.

6. The compound according to claim 4, where R8represents a
1) -NR16R17where R16and R17are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
2) -CONR18R19where R18and R19are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or
3) tetrazolyl group,
or its pharmaceutically acceptable salt.

7. The compound according to claim 1, where-X - represents-N(R1)-, where R1is as defined in claim 1, or its pharmaceutically acceptable salt.

8. The compound according to claim 2, where-X - represents-N(R1)-, where R1is as defined in claim 1, or its pharmaceutically acceptable salt.

9. The connection according to claim 7, where R1represents a
1) a hydrogen atom,
2) -CONR5R6where R5and R6are the same or different and each represents a
(a) a hydrogen atom,
(b) a phenyl group (this phenyl group is substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) a carboxyl group,
d)1-6alkyl groups (indicated what data C 1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii) C1-6alkoxygroup) and
e) C1-6alkoxygroup),
(c) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different C1-6alkyl groups (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:
(i) a hydroxyl group and (ii) C1-6alkoxygroup)),
(d) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) no (iv):
(i) halogen atom,
(ii) a hydroxyl group,
(iii) the carbonyl group and
(iv) C1-6alkoxygroup),
(e) -S(=O)2-R9where R9represents a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or C1-6alkyl group, or
(f) nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, identical is whether different substituents, selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group), or
(g) thiazolidine or pyridyloxy group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms),
or
(h) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group containing a nitrogen atom and optionally a sulfur atom (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):
a) a halogen atom,
b) a hydroxyl group,
c1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
(a) carboxyl group,
(e) -CO-C1-6alkyl group,
f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
g) the carbonyl group,
h) -NR24R25where R24and R25 are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, and
i)1-6alkoxygroup) (provided that R5and R6are not
simultaneously hydrogen atoms),
3) -COOR10where R10represents a
(a)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) through d):
a) a hydroxyl group,
b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group,
c1-6alkoxygroup and
d) phenyl group), or
(b) piperidino group, optionally substituted Deputy
selected from the following (a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
4) -COR11where R11represents a
(a)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, dinakovyh or different substituents, selected from the following a) to h):
a) a halogen atom,
b) a hydroxyl group,
c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,
d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,
e) C1-6alkoxygroup,
f) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii) C1-6alkoxygroup and (iv) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
g) a carboxyl group, and
(h) fenoxaprop),
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted one or more quantity the STV identical or different substituents, selected from the following a) and b):
a) a phenyl group (this phenyl group is optionally substituted by one or more, same go different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and
(b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or
(C) nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
(C) the carbonyl group),
(d) phenyl group (this phenyl group is substituted by one or more, same or different substituents selected from the following (1) through (3):(1) halogen atom, (2) C1-6alkyl group (the specified C1-6an alkyl group is optional is substituted on one or more, same or different halogen atoms), and (3) C1-6alkoxygroup), or
(e) a carboxyl group,
5) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (d):
(a) carboxyl group,
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different, and each represents a hydrogen atom, a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, and
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6an alkyl group is not necessarily Thames is authorized by one or more, same or different halogen atoms))),
6) 3-6-membered cycloalkyl group,
7) -S(=O)2-R12where R12represents a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)or phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
8) -C(=NCN)-R13where R13represents a C1-6alkyl group,
9) -C(=NCN)-NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
10) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (f):
(a) carboxyl group,
(b) halogen atom,
(c) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents is selected from the following group: a) a hydroxyl group, (b) halogen atom and (C) C1-6alkoxygroup),
(d) -NR38R39where R38and R39are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-NR40R41where R40and R41are the same or different and each represents a hydrogen atom, a C1-6alkyl group or a C1-6alkoxygroup, or-S(=O)2-R42where R42represents a C1-6alkyl group, or R38and R39optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more oxoprop),
(e) -CO-NR43R44where R43and R44are the same or different and each represents a hydrogen atom or a C1-6alkyl group, and
(f) -COO-C1-6alkyl group) or
11) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom, oxygen and sulfur (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following is (a) to (h):
(a) carboxyl group,
(b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) a halogen atom,
b) a hydroxyl group and
c) C1-6alkoxygroup),
(c) cycloalkyl group and
(d) halogen atom,
(e) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
(f) -COO-C1-6alkyl group,
(g) ceanography and
(h)1-6alkoxygroup),
or its pharmaceutically acceptable salt.

10. Compound 8, where R1represents a
1) a hydrogen atom,
2) -CONR5R6where R5and R6are the same or different and each represents (a) hydrogen atom,
(b) a phenyl group (this phenyl group is substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) a carboxyl group,
d)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following groups shall: (i) halogen atom, (ii) a hydroxyl group, and (iii) C1-6alkoxygroup) and
e) C1-6alkoxygroup),
(c) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different C1-6alkyl groups (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup)),
(d) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl is to Rupp, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) no (iv):
(i) halogen atom,
(ii) a hydroxyl group,
(iii) the carbonyl group and
(iv) C1-6alkoxygroup),
(e) -S(=O)2-R9where R9represents a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or C1-6alkyl group, or
(f) nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group), or
(g) thiazolidine or pyridyloxy g is the SCP (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms),
or
(h) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):
a) a halogen atom,
b) a hydroxyl group,
c1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
d) a carboxyl group,
(e) -CO-C1-6alkyl group,
f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
g) the carbonyl group,
h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, and
i) C1-6alkoxygroup) (provided that R5and R6are not
simultaneously hydrogen atoms),
3) -COOR10where R10represents a
(a) C1-6alkyl group (the specified C1-6and Celina group is optionally substituted by one or more identical or different substituents, selected from the following a) through d):
a) a hydroxyl group,
b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group,
c1-6alkoxygroup and
d) phenyl group), or
(b) piperidino group, optionally substituted Deputy, selected from the following (a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
4) -COR11where R11represents a
(a)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following a) to h):
a) a halogen atom,
b) a hydroxyl group,
c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,
d) -CO-NR30R31where R30and R31are the same or different and each represents the nd atom of hydrogen or C 1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,
e)1-6alkoxygroup,
f) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii)1-6alkoxygroup and (iv)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
g) a carboxyl group, and
(h) fenoxaprop),
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):
a) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and
(b) (C1-6/sub> alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup)), or
(C) nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(d) phenyl group (this phenyl group is substituted by one or more, same or different substituents selected from the following (1) through (3):(1) halogen atom, (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3) C1-6alkoxygroup), or
(e) a carboxyl group,
5)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (d):
(a) carboxyl group,
(b) 3-6-membered cycloalkyl group (indicated what data cycloalkyl group is optionally substituted by one or more, same or different-CO-NR 32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, and
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),
6) 3-6-membered cycloalkyl group,
7) -S(=O)2-R12where R12represents a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)or phenyl group (this phenyl group is optionally substituted by one or more, dinakovyh or different substituents, selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
8) -C(=NCN)-R13where R13represents a C1-6alkyl group,
9) -C(=NCN)NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
10) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (f):
(a) carboxyl group,
(b) halogen atom,
(c) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) hydroxyl group, (b) halogen atom and (C) C1-6alkoxygroup),
(d) -NR38R39where R38and R39are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-NR40R41where R40and R41are the same or different and each represents a hydrogen atom, a C1-6and kilou group or a C 1-6alkoxygroup, or-S(=O)2-R42where R42represents a C1-6alkyl group, or R38and R39optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group is optionally substituted one or more oxoprop),
(e) -CO-NR43R44where R43and R44are the same or different and each represents a hydrogen atom or a C1-6alkyl group, and
(f) -COO-C1-6alkyl group) or
11) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom, oxygen and sulfur (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) to (h):
(a) carboxyl group,
(b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) a halogen atom,
b) a hydroxyl group and
c) C1-6alkoxygroup),
(c) cycloalkyl group and
(d) halogen atom,
(e) -CO-NR45R 46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
(f) -COO-C1-6alkyl group,
(g) ceanography and
(h)1-6alkoxygroup),
or its pharmaceutically acceptable salt.

11. The connection according to claim 7 wherein R' represents 1) -CONR5R6where R5and R6are the same or different and each represents a
(a) a hydrogen atom,
(b) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group;
a) a hydroxyl group,
(b) halogen atom,
c) a carboxyl group,
d) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii) C1-6alkoxygroup) and
e) C1-6alkoxygroup),
(c) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different C1-6alkyl groups (the specified C1-6alkyl group is optionally substituted one or more quantity the STV identical or different substituents, selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup)),
(d) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2): (1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) no (iv):
(i) halogen atom,
(ii) hydroxyl groups is,
(iii) the carbonyl group and
(iv) C1-6alkoxygroup),
(e) -S(=O)2-R9where R9represents a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or C1-6alkyl group, or
(f) nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(g) C1-6alkoxygroup or
(h) thiazolidine or pyridyloxy group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms)
or
(i) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, 4-7-membered monocyclic, heterocyclic group (this heterocyclic group, t is aetsa optionally substituted by one or more identical or different substituents, selected from the following a) to i):
a) a halogen atom,
b) a hydroxyl group,
c1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
d) a carboxyl group,
(e) -CO-C1-6alkyl group,
f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
g) the carbonyl group,
h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or - CO-C1-6alkyl group, and
1) C1-6alkoxygroup) (provided that R5and R6are not any combination of substituents selected from the following group: (i) a hydrogen atom and (ii) unsubstituted C1-6alkyl group),
2) -COOR10where R10represents a
(a) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) through d):
a) a hydroxyl group,
b) -NR26R27where R26and R27are Odinak is new or different and each represents a hydrogen atom or a C 1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group,
c1-6alkoxygroup and
d) phenyl group), or
(b) piperidino group, substituted Deputy, selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
3) -COR11where R11represents a
(a)1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to h):
a) a halogen atom,
b) a hydroxyl group,
c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,
d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,
e) C1-6/sub> alkoxygroup,
f) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii) C1-6alkoxygroup and (iv) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
g) a carboxyl group, and
(h) fenoxaprop),
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):
a) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and
(b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) the Hydra is Xylenol group and (ii) C 1-6alkoxygroup)), or
(C) nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3) C1-6alkoxygroup), or
(e) a carboxyl group,
4) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) to (d):
(a) carboxyl group,
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents the Wallpaper hydrogen atom, C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, and
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),
5) 3-6-membered cycloalkyl group,
6) -S(=O)2-R12where R12represents a C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different halogen atoms)or phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C-6 alkyl group is optionally substituted by one or more, same or different halogen atoms)),
7) -C(=NCN)-R13where R13represents a C1-6alkyl group,
8) -C(=NCN) NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
9) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom, oxygen and sulfur (this heterocyclic group is substituted by one or more, same or different substituents selected from the following (a) to (g):
(a)1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) through (C):
a) a halogen atom,
b) a hydroxyl group and
c) C1-6alkoxygroup),
(b) cycloalkyl group,
(c) halogen atom,
(d) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
(e) -COO-C1-6alkyl group,
(f) ceanography and
(g) C1-6alkoxygroup),
or its pharmaceutically acceptable salt.

<> 12. The connection of claim 8, where R1represents a
1) -CONR5R6where R5and R6are the same or different and each represents a
(a) a hydrogen atom,
(b) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) a carboxyl group,
d) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii) C1-6alkoxygroup) and
e)1-6alkoxygroup),
(c) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different C1-6alkyl groups (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),
(d) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted one or more measure the ohms are the same or different substituents, selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) no (iv):
(i) halogen atom,
(ii) a hydroxyl group,
(iii) the carbonyl group and
(iv) C1-6alkoxygroup),
(e) -S(=O)2-R9where R9represents a phenyl group (this phenyl group is optionally substituted by one or more identical or different substituents, the curse of the following (1) and (2):(1) halogen atom and (2) C 1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or C1-6alkyl group, or
(f) nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(g) C1-6alkoxygroup, or
(h) thiazolidine or pyridyloxy group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms)
or
(i) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):
a) a halogen atom,
b) a hydroxyl group,
c) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted one or more quantity the STV identical or different substituents, selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
(a) carboxyl group,
(e) -CO-C1-6alkyl group,
f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
g) the carbonyl group,
h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, and
1) C1-6alkoxygroup) (provided that R5and R6are not any combination of substituents selected from the following group: (i) a hydrogen atom and (ii) unsubstituted C1-6alkyl group),
2) -COOR10where R10represents a
(a)1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) through d):
a) a hydroxyl group,
b) -NR26R27where R26and R27are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 5-6-membered, heterotic the practical group,
c) C1-6alkoxygroup and
d) phenyl group), or
(b) piperidino group, substituted Deputy, selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
3) -COR11where R11represents a
(a)1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to h):
a) a halogen atom,
b) a hydroxyl group,
c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,
d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,
e)1-6alkoxygroup,
f) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following g PPI: (i) halogen atom, (ii) hydroxyl group, (iii) C1-6alkoxygroup and (iv) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
g) a carboxyl group, and
(h) fenoxaprop),
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):
a) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and
(b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup)), or
(C) nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or is a large number of the same or of different substituents, selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3) C1-6alkoxygroup), or
(e) a carboxyl group,
4) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) to (d):
(a) carboxyl group,
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6 alkoxygroup),
(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, and
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),
5) 3-6-membered cycloalkyl group,
6) -S(=O)2-R12where R12represents a C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different halogen atoms)or phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
7) -C(=NCN)-R13where R13represents a C1-6alkyl group,
8) -C(=NCN) NR14R15, where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or
9) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom, oxygen and sulfur (this heterocyclic group is substituted by one or more, same or different substituents selected from the following (a) to (g):
(a)1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) through (C):
a) a halogen atom,
b) a hydroxyl group and
c) C1-6alkoxygroup),
(b) cycloalkyl group,
(c) halogen atom,
(d) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
(e) -COO-C1-6alkyl group,
(f) ceanography and
(g) C1-6alkoxygroup),
or its pharmaceutically acceptable salt.

13. The connection according to claim 7, where R1represents a
1) -CONR5R6where R5and R6are the same or different and each represents a
(a) a hydrogen atom,
(b) a phenyl group (this phenyl gr is the PAP is substituted by one or more identical or different substituents, selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) a carboxyl group,
d) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii) C1-6alkoxygroup) and
e) C1-6alkoxygroup),
(c) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different C1-6alkyl groups (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup)),
(d) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the shown C 1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) no (iv):
(i) halogen atom,
(ii) a hydroxyl group,
(iii) the carbonyl group and
(iv) C1-6alkoxygroup),
(e) -S(=O)2-R9where R9represents a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or C1-6alkyl group, or
(f) nitrogen-containing, saturated, monocyclic, 4-6-membered Goethe is acyclically group (this heterocyclic group is optionally substituted by one or more identical or different substituents, selected from the following (a) through (C):
a)1-6alkyl groups and
b) -CO-C1-6alkyl groups and
c) the carbonyl group), or
(g) thiazolidine or pyridyloxy group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms), or
(h) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):
a) a halogen atom,
b) a hydroxyl group,
c) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
d) a carboxyl group,
(e) -CO-C1-6alkyl group,
f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
g) the carbonyl group,
h) -NR24R25where R24and R25are the same or different and each prex is represents a hydrogen atom, C1-6alkyl group or-CO-C1-6alkyl group, and
1) With the1-6alkoxygroup) (provided that R5and R6are not simultaneously hydrogen atoms),
2) -COOR10where R10represents a
(a) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) through d):
a) a hydroxyl group,
b) -NR26R27where R26and R27are the same or different and
each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group,
c) C1-6alkoxygroup and
d) phenyl group), or
(b) piperidino group, substituted Deputy, selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
3) -COR11where R11represents (a) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to h):
a) a halogen atom,
b) a hydroxyl group,
c) -NR28, R 29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,
d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,
e)1-6alkoxygroup,
f) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii) C1-6alkoxygroup and (iv) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
g) a carboxyl group, and
(h) fenoxaprop),
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):
a) phenyl groups is (this phenyl group is optionally substituted by one or more identical or different substituents, selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and
b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (1) a hydroxyl group and (ii)1-6alkoxygroup)), or
(C) nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3) C1-6alkoxygroup), or
(e) a carboxyl group,
4) C1-6alkylen the St group (specified C 1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) to (d):
(a) carboxyl group,
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R34and R35optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,and
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (the specified C1-6Ala is supplemented flax group is optionally substituted by one or more, same or different halogen atoms))),
5) 3-6-membered cycloalkyl group,
6) -S(=O)2-R12where R12represents a C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different halogen atoms)or phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
7) -C(=NCN)-R13where R13represents a C1-6alkyl group,
8) -C(=NCN) NR14R15where R14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or
9) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom, oxygen and sulfur (this heterocyclic group is substituted by one or more, same or different substituents selected from the following (a) to (g):
(a) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or b is a great number of the same or of different substituents, selected from the following (a) through (C):
a) a halogen atom,
b) a hydroxyl group and
c1-6alkoxygroup),
(b) cycloalkyl group,
(c) halogen atom,
(d) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
(e) -COO-C1-6alkyl group,
(f) ceanography and
(g) C1-6alkoxygroup),
or its pharmaceutically acceptable salt.

14. The connection of claim 8, where R1represents 1) -CONR5R6where R5and R6are the same or different and each represents a
(a) a hydrogen atom,
(b) a phenyl group (this phenyl group is substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) a carboxyl group,
d) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii) C1-6alkoxygroup) and
e) C1-6alkoxygroup),
(C) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted one and the and a large number of the same or different C 1-6alkyl groups (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)),
(d)1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally samisen the second one or more identical or different substituents, selected from the following (i) no (iv):
(i) halogen atom,
(ii) a hydroxyl group,
(iii) the carbonyl group and
(iv) C1-6alkoxygroup),
(e) -S(=O)2-R9where R9represents a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (specified With1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or C1-6alkyl group, or
(f) nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) C1-6alkyl groups and
b) -CO-C1-6alkyl groups and
c) the carbonyl group), or
(g) thiazolidine or pyridyloxy group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms), or
(h) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered, heterocycle is a mini-group (this heterocyclic group is optionally substituted by one or more identical or different substituents, selected from the following a) to i):
a) a halogen atom,
b) a hydroxyl group,
c) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup),
d) a carboxyl group,
(e) -CO-C1-6alkyl group,
f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
g) the carbonyl group,
h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, and
1) C1-6alkoxygroup) (provided that R5and R6are not simultaneously hydrogen atoms),
2) -COOR10where R10represents a
(a) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) through d):
a) a hydroxyl group,
b) -NR26R27where R26and R27are the same or different and
each represents a hydrogen atom or a C1-6alkyl groups is, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group,
c1-6alkoxygroup and
d) phenyl group), or
(b) piperidino group, substituted Deputy, selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
3) -COR11where R11represents a
(a) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to h):
a) a halogen atom,
b) a hydroxyl group,
c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,
d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,
e)1-6alkoxygroup,
f)phenyl group (this phenyl group is optionally substituted by one or more identical or different substituents, selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii)1-6alkoxygroup and (iv)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
g) a carboxyl group, and
(h) fenoxaprop),
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):
a) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and
(b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii)1-6alkoxygroup)), or
(C) nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group (specified heterocyclic g is the SCP is optionally substituted by one or more identical or different substituents, selected from the following (a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3) C1-6alkoxygroup), or
(e) a carboxyl group,
4) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) to (d):
(a) carboxyl group,
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6/sub> alkoxygroup),
(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, and
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),
5) 3-6-membered cycloalkyl group,
6) -S(=O)2-R12where R12represents a C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different halogen atoms)or phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
7) -C(=NCN)-R13where R13represents a C1-6alkyl group,
8) -C(=NCN)NR14R15where R 14and R15are the same or different, and each represents a hydrogen atom or a C1-6alkyl group,
9) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom, oxygen and sulfur (this heterocyclic group is substituted by one or more, same or different substituents selected from the following (a) to (g):
(a) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) through (C):
a) a halogen atom,
b) a hydroxyl group and
c) C1-6alkoxygroup),
(b) cycloalkyl group,
(c) halogen atom,
(d) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
(e) -COO-C1-6alkyl group,
(f) ceanography and
(g)1-6alkoxygroup),
or its pharmaceutically acceptable salt.

15. The compound according to claim 1, where R2represents cyclopropyl group or 1-methylcyclopropyl group, or its pharmaceutically acceptable salt.

16. The compound according to claim 2, where R2represents cyclopropyl group or 1-met is cyclopropyl group, or its pharmaceutically acceptable salt.

17. The compound according to claim 1, where R3and R4are the same or different and each represents a
(1) a hydrogen atom,
(2)1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following group: 1) halogen atom and (2) -CCA-C1-6alkyl group),
(3) a phenyl group (this phenyl group is substituted by one or more, same or different substituents selected from the following 1) to 5):
1) With the1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following group: (a) halogen atom and (b) a hydroxyl group),
2)1-6alkoxygroup (specified C1-6alkoxygroup is substituted by one or more, same or different halogen atoms),
3) carboxyl group,
4) -COO-C1-6alkyl groups and
5) ceanography) or
(4) pyridyloxy or thiazolidine group (this heterocyclic group is substituted by a halogen atom),
(provided that R3and R4are not simultaneously hydrogen atoms),
or its pharmaceutically acceptable the AI Sol.

18. The compound according to claim 2, where R3and R4are the same or different and each represents a
(1) a hydrogen atom,
(2)1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following group: 1) halogen atom and (2) -CCA-C1-6alkyl group),
(3) a phenyl group (this phenyl group is substituted by one or more, same or different substituents selected from the following 1) to 5):
1) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following group: (a) halogen atom and (b) a hydroxyl group),
2)1-6alkoxygroup (specified C1-6alkoxygroup is substituted by one or more, same or different halogen atoms),
3) carboxyl group,
4) -COO-C1-6alkyl groups and
5) ceanography) or
(4) pyridyloxy or thiazolidine group (specified heterocyclic
group is substituted by a halogen atom),
(provided that R3and R4are not simultaneously hydrogen atoms),
or its pharmaceutically acceptable salt.

19. The compound according to claim 1, where R1/sup> represents a
1) -CONR5R6where R5and R6are the same or different and each represents a
(a) a hydrogen atom,
(b) a phenyl group (this phenyl group is substituted by one or more, same or different substituents selected from the following groups:
a) a hydroxyl group,
(b) halogen atom,
c) a carboxyl group,
d)1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii)1-6alkoxygroup) and
e) C1-6alkoxygroup),
(c) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different C1-6alkyl groups (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup)),
(d) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the trail is ment group;
a) a hydroxyl group,
(b) halogen atom,
c) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
d) -NR20R21where R20and R21are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, or R20and R21optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (i) no (iv):
(i) halogen atom,
(ii) a hydroxyl group,
(iii) the carbonyl group and
(iv) C1-6alkoxygroup),
(e) -S(=O)2-R9where R9represents a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1)halogen atom and (2) C 1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), or C1-6alkyl group, or
(f) nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(g) C1-6alkoxygroup or
(h) thiazolidine or pyridyloxy group (this heterocyclic group is optionally substituted by one or more, same or different halogen atoms), or
(i) R5and R6optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 4-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more, same or different substituents selected from the following a) to i):
a) a halogen atom,
b) a hydroxyl group,
c1-6alkyl group (specified With1-6alkyl group is optionally substituted one or more numbers is the your identical or different substituents, selected from the following group: (i) halogen atom, (ii) hydroxyl groups, and (iii) C1-6alkoxygroup),
d) a carboxyl group,
(e) -CO-C1-6alkyl group,
f) -CO-NR22R23where R22and R23are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
g) the carbonyl group,
h) -NR24R25where R24and R25are the same or different and each represents a hydrogen atom, a C1-6alkyl group or-CO-C1-6alkyl group, and
1) C1-6alkoxygroup) (provided that R5and R6are not simultaneously hydrogen atoms),
2) -COOR10where R10represents a
(a) C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) through d):
(a) a hydroxyl group,
b) -NR26R27where R26and R27are the same or different and
each represents a hydrogen atom or a C1-6alkyl group, or R26and R27optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group,
c1-6alkoxygroup and
d) phenyl group), br/> (b) piperidino group, substituted Deputy, selected from the following (a) through (C):
a)1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
3) -COR11where R11represents a
(a)1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following a) to h):
a) a halogen atom,
b) a hydroxyl group,
c) -NR28R29where R28and R29are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-cycloalkyl group, or-S(=O)2-C1-6alkyl group,
d) -CO-NR30R31where R30and R31are the same or different and each represents a hydrogen atom or a C1-6alkyl group, or R30and R31optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group,
e) C1-6alkoxygroup,
f) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) halogen atom, (ii) hydroxyl group, (iii) C1-6 alkoxygroup and (iv) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
g) a carboxyl group, and
(h) fenoxaprop),
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different substituents selected from the following a) and b):
a) a phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) and (2):(1) halogen atom and (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)), and
(b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1-6alkoxygroup)), or
(C) nitrogen-containing, saturated, monocyclic, 5-6-membered heterocyclic group (this heterocyclic group is optionally substituted by one or more identical or R is slichnih substituents, selected from the following (a) through (C):
a) C1-6alkyl group,
b) -CO-C1-6alkyl groups and
c) the carbonyl group),
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (1) through (3): (1) halogen atom, (2) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms), and (3) C1-6alkoxygroup), or
(e) a carboxyl group,
4)1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different substituents selected from the following (a) (a):
(a) carboxyl group,
(b) 3-6-membered cycloalkyl group (specified cycloalkyl group is optionally substituted by one or more, same or different-CO-NR32R33where R32and R33are the same or different and each represents a hydrogen atom, a C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: (i) a hydroxyl group and (ii) C1- alkoxygroup),
(c) -CO-NR34R35where R34and R35are the same or different and each represents a hydrogen atom or a C1-6alkyl group, and
(d) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms))),
5) 3-6-membered cycloalkyl group,
6) -S(=O)2-R12where R12represents a C1-6alkyl group (the specified C1-6an alkyl group is substituted by one or more, same or different halogen atoms)or phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) halogen atom and (b) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different halogen atoms)),
7) -C(=NCN)-R13where R13represents a C1-6alkyl group,
8) -C(=NCN) NR14R15where R 14and R15are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
9) phenyl group (this phenyl group is optionally substituted by one or more, same or different substituents selected from the following (a) to (f):
(a) carboxyl group,
(b) halogen atom,
(c) C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following group: a) hydroxyl group, (b) halogen atom and (C) C1-6alkoxygroup),
(d) -NR38R39where R38and R39are the same or different and each represents a hydrogen atom, a C1-6alkyl group, -CO-C1-6alkyl group, -CO-NR40R41where R40and R41are the same or different and each represents a hydrogen atom,
With1-6alkyl group or a C1-6alkoxygroup, or-S(=O)2-R42where R42represents a C1-6alkyl group), or R38and R39optional form together with the nitrogen atom to which they are linked, nitrogen-containing, saturated, monocyclic, heterocyclic group (this heterocyclic group C is optionally substituted one or more oxoprop),
(e) -CO-NR43R44where R43and R44are the same or different, and each represents a hydrogen atom or a C1-6alkyl group, and
(f) -COO-C1-6alkyl group) or
10) a 5-membered or 6-membered unsaturated, monocyclic, heterocyclic group containing 1 to 4 heteroatoms selected from nitrogen atom, oxygen and sulfur (this heterocyclic group is substituted by one or more, same or different substituents selected from the following (a) to (h):
(a) carboxyl group,
(b) (C1-6alkyl group (the specified C1-6alkyl group is optionally substituted by one or more, same or different substituents selected from the following (a) through (C):
a) a halogen atom,
b) a hydroxyl group and
c) C1-6alkoxygroup),
(c) cycloalkyl group,
(d) halogen atom,
(e) -CO-NR45R46where R45and R46are the same or different and each represents a hydrogen atom or a C1-6alkyl group,
(f) -COO-C1-6alkyl group,
(g) ceanography and
(h) C1-6alkoxygroup),
or its pharmaceutically acceptable salt.

20. The compound according to claim 1 or its pharmaceutically acceptable salt which is selected from the following compounds:
(1) 1-[5-cyclopropyl-1-(PI is uridin-4-yl)-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine,
(2) of the hydrochloride of 1-[5-cyclopropyl-1-(piperidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(3) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(4) 1-[1-(1-carbamoylbiphenyl-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(5) 1-{1-[1-(2-carboxyphenylazo)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(6) 1-{5-cyclopropyl-1-[1-(2-hydroxymethyluracil)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(7) 1-{5-cyclopropyl-1-[1-(1-hydroxymethylpropane)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(8) 1-{5-cyclopropyl-1-[1-(2-hydrooximethylcarbamil)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(9) 1-{5-cyclopropyl-1-[1-(2-hydroxy-1,1-dimethylthiocarbamyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(10) 1-{1-[1-(2-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(11) of the hydrochloride of 1-{1-[1-(2-aminoethylamino)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(12) 1-{5-cyclopropyl-1-[1-(1,1-diocletianopolis-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carb the Nile}-[(S)-3-(2-triptoreline)]pyrrolidine,
(13) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoethanol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(14) 1-{5-cyclopropyl-1-[1-(4-hydroxypiperidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(15) 1-{1-[1-(azetidin-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(16) 1-{5-cyclopropyl-1-[1-(3-hydroxypyrrolidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(17) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-piperidine-1-iletileri)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(18) 1-{5-cyclopropyl-1-[1-(4,4-deformability-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(19) 1-{5-cyclopropyl-1-[1-(3,3-debtorprovidian-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(20) 1-{5-cyclopropyl-1-[1-(3-hydroxyazetidine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(21) 1-(5-cyclopropyl-1-{1-[(R)-3-hydroxypyrrolidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(22) 1-(5-cyclopropyl-1-{1-[(S)-3-hydroxypyrrolidine-1-carbonyl] piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(23 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxy-1-methylethylketon]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(24) 1-{5-cyclopropyl-1-[1-(4-hydroxyethylpiperazine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(25) 1-{1-[1-(4-carboxypeptidase-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(26) 1-{5-cyclopropyl-1-[1-(3-oxopiperidin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(27) 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxyethylpyrrolidine-1-carbonyl] piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(28) 1-{5-cyclopropyl-1-[1-(3-hydroxymethylation-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(29) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(4-methylpiperazin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(30) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(4-isopropylpiperazine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(31) 1-{1-[1-(4-acetylpiperidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(32) 1-(5-cyclopropyl-1-{1-[(R)-3-hydroxypiperidine-1-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(33) 1-{1-[1-(4-carbamoylbiphenyl-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline who yl)]pyrrolidine,
(34) 1-{1-[1-(3-carbamoylation-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(35) of the hydrochloride of 1-{1-[1-(4-aminopiperidin-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(36) of the hydrochloride of 1-{1-[1-(3-aminopyrrolidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(37) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-yl-carbarnoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(38) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(4-dimethylaminopyridine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(39) 1-{1-[1-(4-acetylaminophenol-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(40) 1-{1-[1-(3-acetylpyrrolidine-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(41) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(3-dimethylaminopropan-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(42) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-yl-carbarnoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(43) 1-{1-[1-(1-acetylpiperidine-4-yl-carbarnoyl)piperidine-4-yl]-5-cyclo is ropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(44) 1-{5-cyclopropyl-1-[1-(4-oxopiperidin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(45) 1-{1-[1-(3-acetylaminoacetylenes-1-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(46) 1-{5-cyclopropyl-1-[1-(3-oxopyrrolidin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(47) 1-{5-cyclopropyl-1-[1-(2,2,2-triptoreline)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(48) 1-{5-cyclopropyl-1-[1-(3,3,4,4-tetrafluoropyridine-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(49) 1-(5-cyclopropyl-1-{1-[(S)-1-hydroxymethyl-2-methylpropionyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(50) 1-(1-{1-[(S)-1-benzyl-2-hydrooximethylcarbamil]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(51) 1-(5-cyclopropyl-1-{1-[(S)-2-hydroxy-1-phenylethanol]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(52) 1-(5-cyclopropyl-1-{1-[(S)-1-hydroxymethyl-3-methylbutanoyl] piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(53) 1-{5-cyclopropyl-1-[1-(2-hydroxyphenylarsonic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(54)1-{5-cyclopropyl-1-[1-(1-hydroxymethylglutaryl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(55) 1-[1-(1-pensacolanewsjournal.com-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(56)1-[5-cyclopropyl-1-(1-methanesulfonylaminoethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(57) 1-[5-cyclopropyl-1-(1-ethoxycarbonylpyrimidine-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(58) 1-{5-cyclopropyl-1-[1-(2-hydroxyethoxyethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(59) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoethoxide)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(60) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-piperidine-1-yl-etoxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(61) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-yl-oxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(62) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-yl-oxycarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(63) 1-{1-[1-(1-acetylpiperidine-4-yl-oxycarbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(64) 1-[1-(1-cyclopropanecarbonitrile-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrole is on,
(65) 1-{5-cyclopropyl-1-[1-(2-hydroxyacyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(66) 1-(5-cyclopropyl-1-{1-[1-(4-forfinal)cyclopropanecarbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(67) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-dimethylaminoacetyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(68) 1-{1-[1-(2-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(69) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(70) 1-{1-[1-(2-acetylamino-2-methylpropionyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(71) 1-(1-{1-[(S)-2-acetylaminophenol]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(72) 1-(1-{1-[(S)-2-acetylamino-3-methylbutyryl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(73) 1-{5-cyclopropyl-1-[1-(3,3,3-triptocaine)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(74) 1-(5-cyclopropyl-1-{1-[(S)-5-oxopyrrolidin-2-carbonyl] piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(75) 1-{1-[1-(3-acetylaminophenol)piperidine-4-yl]-5-Cyclops the peel-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(76) 1-{5-cyclopropyl-1-[1-(3-hydroxy-2,2-dimethylpropionic)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(77) of the hydrochloride of 1-{1-[1-(2-aminoacetyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(78) 1-{5-cyclopropyl-1-[1-(1-hydroxymethylpropane)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(79) of the hydrochloride of 1-{1-[1-(2-amino-2-methylpropionyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(80) 1-{5-cyclopropyl-1-[1-(4-hydroxybutyryl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(81) of the hydrochloride of 1-(5-cyclopropyl-1-{1-[(S)-pyrrolidin-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(82) of the hydrochloride of 1-(5-cyclopropyl-1-{1-[(S)-1-methylpyrrolidine-2-carbonyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(83) of the hydrochloride of 1-{1-[1-(3-aminopropyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(84) hydrochloride 1-(1-{1-[(S)-2-amino-3-methylbutyryl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(85) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(2-methylaminomethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidin is a,
(86) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(piperidine-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(87) 1-{5-cyclopropyl-1-[1-(2-isobutylamino)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(88) 1-{1-[1-(2-cyclopropanecarboxylate)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(89) 1-(1-{1-[(S)-1-acetylpyrrolidine-2-carbonyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(90) 1-{5-cyclopropyl-1-[1-(2-methanesulfonylaminoethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(91) 1-{1-[1-(1-acetylpiperidine-4-carbonyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(92) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(1-methylpiperidin-4-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(93) 1-{1-[1-(3-carbamoylbiphenyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(94) of the hydrochloride of 1-[1-(1-carbamoylmethyl-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(95) of the hydrochloride of 1-[5-cyclopropyl-1-(1-methylcarbamoylmethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(96) of the hydrochloride of 1-{1-[1(1-carbarnoyl-1-methylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(97) of the hydrochloride of 1-{1-[1-(2-carbamoylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(98) of the hydrochloride of 1-[5-cyclopropyl-1-(1-cyclopropylmethyl-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(99) of the hydrochloride of 1-[5-cyclopropyl-1-(1-cyclopropylidene-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(100) of the hydrochloride of 1-[5-cyclopropyl-1-(1-dimethylcarbamodithioato-4-yl)-1H-pyrazole-4-carbonyl-[(S)-3-(2-triptoreline)]pyrrolidine,
(101) of the hydrochloride of 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(102) of the hydrochloride of 1-[1-(1-carboxyethylidene-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(103) of the hydrochloride of 1-{1-[1-(1-carbamoylethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(104) of the hydrochloride of 1-{1-[1-(2-carboxy-2-methylpropyl " piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(105) of the hydrochloride of 1-{1-[1-(2-carbarnoyl-2-methylpropyl " piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(106) of the hydrochloride of 1-{1-[1-(1-carbamoylmethyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(07) hydrochloride 1-(5-cyclopropyl-1-{1-[1-(2-hydrooximethylcarbamil)cyclopropylmethyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(108)1-[5-cyclopropyl-1-(1-triftormetilfullerenov-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(109) 1-{5-cyclopropyl-1-[1-(2,2,2-cryptogramophone)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(110) 1-{1-[1-(1-cyanoimino)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(111) 1-(1-{1-[cyanoimino(methylamino)methyl]piperidine-4-yl}-5-cyclopropyl-1H-pyrazole-4-carbonyl)-[(S)-3-(2-triptoreline)]pyrrolidine,
(112) 1-{1-[1-(N-cyanocarbonimidate)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(113) 4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid
(114) 3-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoic acid
(115) 5-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiophene-2-carboxylic acid,
(116) 2-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)thiazole-4-carboxylic acid,
(117) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-methyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(118) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-cyclopropyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-piraso the-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(119) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-hydroxymethyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(120) of the hydrochloride of 1-{5-cyclopropyl-1-[1-(5-trifluoromethyl-4H-[1,2,4]triazole-3-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(121) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine,
(122) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine,
(123) 1-{5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(R)-3-(2-triptoreline)]pyrrolidine,
(124) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(125) 1-{5-cyclopropyl-1-[1-(1-isopropylcarbamate)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(126) 1-{5-cyclopropyl-1-[1-(1-methylcyclopropene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(127) of the hydrochloride of (-)-3-(4-forfinal)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,
(128) of the hydrochloride of (+)-3-(4-forfinal)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl)pyrrolidine,
(12) of the hydrochloride of 1-[5-cyclopropyl-1-(1-pyrazin-2-reparacin-4-yl)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(130) 1-[1-(TRANS-4-carbamoylmethyl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(131) 1-[5-cyclopropyl-1-(TRANS-4-reidiculously)-1H-pyrazole-4-carbonyl]-[(S)-3-(2-triptoreline)]pyrrolidine,
(132) 1-{5-cyclopropyl-1-[TRANS-4-(1H-tetrazol-5-yl)cyclohexyl]-1H-pyrazole-4-carbonyl}-[(S)-3-(2-triptoreline)]pyrrolidine,
(133) 1-{5-(1-methylcyclopropyl)-1-[1-(4-cryptomaterial)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(134) 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(1-methoxycyclohexyl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(135) 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-phenyl-3-triftormetilfullerenov,
(136) 3-(2-chlorophenyl)-1-{5-cyclopropyl-1-[1-(2,4-differencemaker)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,
(137) 3-(2-chloropyridin-3-yl)-1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,
(138) 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(2,2,3,3-tetramethylcyclopropane)-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(139) 1-{5-cyclohexyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(140) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-trifloromethyl)pyrrolidine,
(141) 1-{5-cycloprop the l-1-[1-(4-cryptomaterial)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(142) 1-(5-cyclopropyl-1-{1-[((S)-1-carboxy-2-methylpropyl)methylcarbamoyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(2-triptoreline)pyrrolidine,
(143) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-methoxy-3-(2-triptoreline)pyrrolidine,
(144) 1-{1-[1-(2-tortenelmebol)piperidine-4-yl]-5-(1-hydroxymethylglutaryl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(145) 1-{5-cyclopropyl-1-[1-(thiazol-2-ylcarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(146) 1-{1-[1-(isopropoxycarbonyl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(147) 1-{5-cyclopropyl-1-[1-(4-verbesserbar)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(148) 1-{1-[1-(2,3-dihydroindol-1-carbonyl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(149) 1-{1-[1-(2,3-dihydro[1,4]oxazin-4-carbonyl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(150) 1-{5-cyclopropyl-1-[1-(2,6-dichloropyridine-3-ylcarbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(151) 1-{5-(1-methylcyclopropyl)-1-[1-(2,3,4,5-tetrahydrobenzo[b]azepin-1-carbonyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(152) ethyl-4-(4-{5-cyclopropyl-4-[3-(2-trifloromethyl the Nile)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)benzoate,
(153) 1-[1-(1-benzyloxycarbonylamino-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine,
(154) 1-{1-[1-(3-carboxy-3-methylbutyryl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(155) 1-{5-cyclopropyl-1-[1-(2-phenoxyacetyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(156) 1-{1-[1-(3-chlorobenzoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(157) 1-{1-[1-(2-chlorobenzoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(158) 1-[5-cyclopropyl-1-(1-oxalipatin-4-yl)-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidine,
(159) 1-{1-[1-(4-chlorobenzoyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(160) 1-(5-cyclopropyl-1-{1-[2-(4-forfinal)acetyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(pyridin-3-yl)pyrrolidine,
(161) 1-{5-cyclopropyl-1-[1-(3-trifloromethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(162) 1-{5-cyclopropyl-1-[1-(3-methoxybenzoyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)pyrrolidine,
(163) of the hydrochloride of 1-{1-[1-(4-terbisil)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(164) 1-[1-(1-benzosulfimide-4-yl)-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(pyridin-3-yl)pyrrolidine,
(165) 1-{1-[1-(4-carbarnoyl enyl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(166) 1-{5-cyclopropyl-1-[1-(4-hydroxymethylene)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(167) 1-{1-[1-(5-carbamoylation-2-yl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(168) 1-{1-[1-(4-AMINOPHENYL)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(169) 1-(5-cyclopropyl-1-{1-[4-(2-oxoacridine-3-yl)phenyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(2-triptoreline)pyrrolidine,
(170) 1-(5-cyclopropyl-1-{1-[4-(3-metaxourgeio)phenyl]piperidine-4-yl}-1H-pyrazole-4-carbonyl)-3-(2-triptoreline)pyrrolidine,
(171)1-{5-cyclopropyl-1-[1-(4-methanesulfonylaminoethyl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(172) 1-[1-(1-ethoxycarbonylpyrimidine-4-yl)-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidine,
(173) 1-[1-(5-chloropyridin-2-yl)azetidin-3-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl]-3-(2-triptoreline)pyrrolidine,
(174) 1-{1-[1-(5-chloropyridin-2-yl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-methoxymethyl-3-phenylpyrrolidine,
(175) 1-{1-[1-(5-cyano-2-yl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(176) of the hydrochloride of 3-(2-acetoxyethyl)-3-(4-forfinal)-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine, (177) hydrochloride {(3S*,4R*)-3-methyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-4-phenylpyrrolidine,
(178) methyl-6-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)nicotinate,
(179) methyl-2-{1-[5-(1-methylcyclopropyl)-1-(1-pyrimidine-2-reparacin-4-yl)-1H-pyrazole-4-carbonyl]pyrrolidin-3-yl}benzoate,
(180) of the hydrochloride of 3-(2-hydroxymethylene)-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,
(181) 1-[5-cyclopropyl-1-(1-pyridin-2-reparacin-4-yl)-1H-pyrazole-4-carbonyl]-3-hydroxy-3-(pyridin-3-yl)pyrrolidine,
(182) 1-{1-[1-(4-acetylaminophenol)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine,
(183) 4-(4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}piperidine-1-yl)-3-perbenzoate sodium
(184) 3-(2-cyanophenyl)-1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,
(185) of the hydrochloride of 3-hydroxymethyl-1-{1-[1-(4-methoxypyridine-2-yl)piperidine-4-yl]-5-(1-methylcyclopropyl)-1H-pyrazole-4-carbonyl}-3-phenylpyrrolidine,
(186) of the hydrochloride of 3-(3,5-differenl)-3-hydroxymethyl-1-{5-(1-methylcyclopropyl)-1-[1-(pyrimidine-2-yl)piperidine-4-yl]-1H-pyrazole-4-carbonyl}pyrrolidine,
(187) 1-{1-[1-(3-chloropyridin-2-yl)piperidine-4-yl]-5-cyclopropyl-1H-pyrazole-4-carbonyl}-3-(pyridin-3-yl)p is rolidone,
(188) 1-{5-cyclopropyl-1-[1-(2-tortenelmebol)piperidine-4-yl]-1H-pyrazole-4-carbonyl}-3-(thiazol-2-yl)pyrrolidine,
(189) (S)-2-[(TRANS-4-{5-cyclopropyl-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl}-cyclohexanecarbonyl)methylamine]-3-methylmalonic acid,
(190) 1-{5-(1-methylcyclopropyl)-1-[TRANS-4-(2-tortenelmebol)cyclohexyl]-1H-pyrazole-4-carbonyl}-3-(2-triptoreline)pyrrolidine and
(191) CIS-4-{5-(1-methylcyclopropyl)-4-[3-(2-triptoreline)pyrrolidin-1-carbonyl]pyrazole-1-yl)-cyclohexanecarboxylic acid.

21. Pharmaceutical composition having inhibitory activity against 11βHSD1 containing compound according to any one of claims 1 to 20, or its pharmaceutically acceptable salt.

22. 11βHSD1 inhibitor containing the compound according to any one of claims 1 to 20, or its pharmaceutically acceptable salt.

23. Agent for treatment or prevention of disorders associated with glucocorticoid-containing compound according to any one of claims 1 to 20, or its pharmaceutically acceptable salt.

24. The agent according to item 23, where the pathology associated with glucocorticoids, is:
(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,
(2) metabolic syndrome,
(3) a fatal vascular event, including myocardial infarction or apoplexies,
(4) hyperorexia,
(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, emotional disorders, schizophrenia or stimulation of appetite,
(6) a disease associated with reduced immune function,
(7) glaucoma, or
(8) osteoporosis.

25. The method of inhibition of 11βHSD1, including the introduction of a pharmaceutically effective amount of a compound according to any one of claims 1 to 20, or its pharmaceutically acceptable salt.

26. The method of treatment or prophylaxis of a pathology associated with glucocorticoids, including the introduction of a pharmaceutically effective amount of a compound according to any one of claims 1 to 20, or its pharmaceutically acceptable salt.

27. The method according to p, where the pathology associated with glucocorticoids, is one of the following:
(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,
(2) metabolic syndrome,
(3) a fatal vascular event, including myocardial infarction or stroke,
(4) hyperorexia,
(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, emotional disorders, schizophrenia or stimulation of appetite,
(6) a disease associated with the reduction of the military's immune function,
(7) glaucoma, or
(8) osteoporosis.

28. The use of compounds according to any one of claims 1 to 20, or its pharmaceutically acceptable salt to obtain 11βHSD1 inhibitor.

29. The use of compounds according to any one of claims 1 to 20, or its pharmaceutically acceptable salt to obtain an agent for treatment or prevention of disorders associated with glucocorticoids.

30. The application of clause 29, where the pathology associated with glucocorticoid is one of the following:
(1) metabolic disease, including diabetes, insulin resistance, complications of diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,
(2) metabolic syndrome,
(3) a fatal vascular event, including myocardial infarction or stroke,
(4) hyperorexia,
(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, emotional disorders, schizophrenia or stimulation of appetite,
(6) a disease associated with reduced immune function,
(7) glaucoma, or
(8) osteoporosis.

31. Commercial pack that includes a written statement stating that the pharmaceutical composition according to item 21 can or should be used for the treatment or prevention of a disease selected from the following:
(1) metabolic disease, including diabetes, insulinresistance is th complications in diabetes, obesity, hyperlipidemia, hypertension, or fatty infiltration of the liver,
(2) metabolic syndrome,
(3) a fatal vascular event, including myocardial infarction or stroke,
(4) hyperorexia,
(5) disease with impaired nerve function, including impaired cognitive abilities, neurodegenerative diseases, emotional disorders, schizophrenia or stimulation of appetite,
(6) a disease associated with reduced immune function,
(7) glaucoma, or
(8) osteoporosis.

32. The application of clause 29 to suppress the increase of the level of glucocorticoids in the blood by use in combination with a pharmaceutical agent that increases the level of glucocorticoids in the blood.

33. Dimethyl-2-[(S)-2-nitro-1-(2-triptoreline)ethyl]malonate.

34. Methyl-(S)-2-oxo-4-(2-triptoreline)pyrrolidin-3-carboxylate.

35. (S)-4-(2-Triptoreline)pyrrolidin-2-it.

36. (S)-3-(2-Triptoreline)pyrrolidine or its salt.

37. A method of producing dimethyl-2-[(S)-2-nitro-1-(2-triptoreline)ethyl]malonate, including the interaction of 1-((E)-2-nitrovinyl)-2-cryptomelane with diethylmalonate in the presence of 1-(3,5-bis-triptoreline)-3-((1S,2S)-2-dimetilaminometil)thiourea.

38. The way to obtain methyl(S)-2-oxo-4-(2-triptoreline)pyrrolidin-3-carboxylate, which includes the restoration and semakan the e ring dimethyl-2-[(S)-2-nitro-1-(2-triptoreline)ethyl]malonate.

39. The method of obtaining (S)-4-(2-triptoreline)pyrrolidin-2-it, including hydrolysis and decarboxylation of methyl-(S)-2-oxo-4-(2-triptoreline)pyrrolidin-3-carboxylate.

40. The method of obtaining salt (3)-3-(2-triptoreline)pyrrolidine, including the recovery of (S)-4-(2-triptoreline)pyrrolidin-2-she and processing of the compounds obtained by the acid with the formation of salts.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula and their pharmaceutically acceptable salts and esters. The disclosed compounds have cdk4 inhibition properties. In formula (I) n equals 0 or 1; R1 and R2 are each independently selected from a group consisting of H, lower alkyl, CO2R5, SO2R6 and COR6; or alternatively, R1 and R2 can form a ring containing 5-6 atoms in the ring, where the said ring contains carbon atoms, where the said carbon atoms are optionally substituted with oxygen, and the said atoms in the ring are optionally substituted with OR6; R3 is selected from a group consisting of H, lower alkyl, O-lower alkyl, halogen, OH, CN, NO2 and COOH; R4 is selected from a group consisting of H, lower alkyl, C3-C6-cycloalkyl, O-lower alkyl, halogen, NO2, S-lower alkyl, NR5R6, CONR7R8, OH and CN; or alternatively R3 and R4, together with two carbon atoms and the bond between them from the benzene ring, to which R3 and R4 are bonded, can form a ring containing 5-7 atoms, where the said 5-7-member ring contains carbon atoms, where the said carbon atoms are optionally substituted with one or two heteroatoms selected from O and N, and the said atoms in the ring are optionally substituted with CO2R6; R4 represents H or halogen; R5 and R6 are each independently selected from a group consisting of H and lower alkyl; R7 and R8 each represents H. The invention also relates to a pharmaceutical composition for treating or controlling diseases progression of which can be enhanced by inhibiting cdk4, containing an effective amount of the disclosed compound as an active ingredient, to use of disclosed compounds for preparing medicinal agents and method of producing said compounds.

EFFECT: more effective treatment.

30 cl, 1 tbl, 142 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: where A,Y,R and R2 assume values given in the description. The invention also relates to methods of producing compounds of formula I and their intermediate compounds, pharmaceutical compositions and methods of using the compounds and their pharmaceutical compositions for inhibiting caspase.

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

SUBSTANCE: crystalline monohydrate has X-ray powder pattern which includes four or more values 2θ, selected from a group consisting of: 18.0 ± 0.2, 18.4 ± 0.2, 19.2 ± 0.2, 19.6 ± 0.2, 21.2 ± 0.2, 24.5 ± 0.2, 25.9 ± 0.2 and 28.0 ± 0.2. The invention also relates to a method of producing crystalline monohydrate, to a pharmaceutical composition for treating disorders caused by protein tyrosine kinase containing crystalline monohydrate, to a crystalline butanol solvate of formula and to a crystalline ethanol solvate compound of formula (IV).

EFFECT: increased effectiveness of using said compounds.

8 cl, 1 tbl, 6 dwg, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (1) and their pharmaceutically acceptable salts as chemokine receptor CCR3 activity modulators, a pharmaceutical composition based on the said compounds, to synthesis method and use thereof. Said compounds can be used for treating and preventing diseases mediated by chemokine receptor CCR3 activity, such as inflammatory and allergic diseases etc. In general formula , R1 represents phenyl, [1,2,4]triazolo[4,3-a]pyridinyl, thiazolo [5,4-b]pyridinyl, benzothiazolyl, benzoxazolyl, pyridinyl, where each of the said phenyl or heterocycles can be substituted with one, two or three radicals R2; R2 each independently represents (C1-C6)halogenalkyl, halogen, COOR3; CONR3R4; R3 represents H or (C1-C6)alkyl; R4 represents H or (C1-C6)alkyl, R5 represents (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl; R6 each independently represents (C1-C6)alkoxy, (C1-C6)halogenalkyl, halogen, OR3, CN, CONR3R4; A represents C(CH3)2-CH2-CH2-, CH2-CH2-CH2- or B represents phenyl; D-E represents CH-CH2- or C=CH-, X-W-V represents N-C=CR7 or C=C-NR7; R7 represents H or (C1-C6)alkyl; Y represents NR4, O, S(O)n; i, j, m each equals 1, n equals 0 or 2.

EFFECT: increased effectiveness of using said compounds.

13 cl, 37 ex

FIELD: chemistry.

SUBSTANCE: invention relates to benzothiazole derivatives with general formula (I) and their pharmaceutically acceptable acid addition salts, optically pure enantiomers, racemates and diastereomer mixtures as adenosine receptor ligands and to a pharmaceutical preparation based on said compounds. In general formula (I), R1 represents C3-7cycloalkyl substituted with a OR group, or 2-(7-oxa-bicyclo[2.2.1]hept-1-yl)-ethyl; R represents hydrogen or C(O)-lower alkyl; X represents -CHR'-; and R' represents hydrogen or lower alkyl.

EFFECT: compounds can be used for treating or preventing diseases mediated by adenosine A2A receptors, for example Alzheimer's disease, certain depressive conditions, toxicomania and Parkinson's disease.

8 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to piperidine-amino-benzidazoles having formula (I) and to addition salts or stereochemically isomeric forms, where Q is C1-6alkyl optionally substituted with one or two substitutes, each independently selected from a group consisting of trifluoromethyl, C3-7cycloalkyl, Ar2, hydroxyl, Ar2 - oxy-, hydroxycarbonyl, aminocarbonyl, C1-4alkylcarbonyl, aminocarbonyloxy, C1-4alkoxycarbonyl, Ar2(CH2)ncarbonyloxy, C1-4alkoxycarbonyl-(CH2)noxy, mono- or di(C1-4alkyl)aminocarbonyl, aminosulfonyl, mono(C1-4alkyl)aminosulfonyl, or heterocycle selected from a group consisting of pyrrolidinyl, dihydropyrrolyl, imidazolyl, triazolyl, homopiperidinyl, pyridyl and tetrahydropyridyl; or where Q is C1-6alkyl substituted with two substitutes, where substitute is an amino group and the other is C1-6alkyloxycarbonyl; G is -CH2-; R1 is pyridyl optionally substituted with two substitutes selected from a group consisting of hydroxyl, C1-6alkyl; each n equals 1; one of R2a and R3a is C1-6alkyl and the other is hydrogen; when R2a is not hydrogen, R2b is C1-6alkyl and R3b is alkyl; and R3a, R2a, R2b all represent hydrogen; or R5 is hydrogen; t equals 2; Ar2 is phenyl or phenyl substituted with one or more, for example 2 substitutes selected from halogen, C1-6alkyloxy, aminosulfonyl and C1-4alkoxycarbonyl. The invention also relates to a pharmaceutical composition based on compound of formula I and use of the said compounds in making medicinal agents.

EFFECT: novel piperadine-amino-benzimidazoles are obtained, having inhibitory effect on respiratory syncytial virus replication.

10 cl, 3 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to 2-cycloalkylamino-5-thienyl-1,2,3-thiadiazines hydrobromides with antiaggregant activity , where R=H; CH3; Br, = morpholino-; thiomorpholino-; pyrrolidino-; 2,6-dimethylmorpholino-; hexamethylenimino-.

EFFECT: obtaining novel compounds which can be used in medicine for treating and preventing such diseases as myocardial infarcation, stroke, rejection of transplanted organs and tissue, and can also prevent embolism and thrombosis formation.

1 cl, 5 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to compounds of formula I or formula II, to their pharmaceutically acceptable salts, enantiomers and diastereoisomers as metalloprotease inhibitors, and also to a pharmaceutical composition based thereon and to versions of application thereof. Said compounds can find application in treatment of the diseases mediated by activity of metalloproteases, Her-2 SHEDDASE, ADAM-10 and ADAM-17, such as arthritis, cancer, cardiovascular disorders, skin diseases, inflammatory and allergic conditions, etc. In general formula I or II: A represents CWNHOH; B represents CH2; G represents CH2; D represents oxygen; X represents CH2NRb; Y represents CH2; M represents C; U is absent or represents NRb; V is absent or represents phenyl, or 4-10-members heterocyclyl containing 1-2 heteroatoms chosen from N and S, substituted with 0-5 groups Re; U' is absent or represents C1-10alkylene, O or combinations thereof; V' represents H, C1-8alkyl, NRbRc, C6-10carbocyclyl substituted with 0-3 groups Re, or 5-14-members heterocyclyl containing 1-3 heteroatoms chosen from N, O and C substituted with 0-4 groups Re; Ra and Re, independently represents H, T, C1-8alkylene-T, C(O)NRa'(CRb'Rc')r-T, (CRb'Rc')r-O-(CRb'Rc')r-T, OH, Cl, F, CN, NO2, NRIRII, COORIV, ORIV, CONRIRII, C1-8halogenalkyl, C3-13carbocyclyl; Rb and Rc independently represents H, T, C1-6alkylene-T, C(O)O(CRb'Rc')r-T, C(O)(CRb'Rc')r-T, S(O)p(CRb'Rc')r-T; T represents H, C1-10alkyl substituted with 0-1 groups Rb'; C3-6carbocyclyl, 5-6-members heterocyclyl containing one oxygen atom; Ra' Rb' and Rc' independently represents H, ORIV or phenyl; R1 represents hydrogen; R2 represents hydrogen; R3 represents: (i) C1-10alkyl; (ii) 4-14-members heterocyclyl containing 1-3 nitrogen atoms optionally substituted with one or two substitutes chosen from C1-6alkyl, OR13, 5-10-members heterocyclyl containing 1-3 heteroatoms chosen from N O and C, or phenyl; (iii) NR16R17; R4 represents H; R4' represents H; R5' represents H; W represents oxygen; R13 represents C1-C6alkyl; R16 and R17 independently represents C1-C10alkyl or phenyl where each is optionally substituted with one C1-4alkyl; RI and RIIindependently represents H or C1-6alkyl; RIV represents C1-6alkyl; i is equal to 0; p is equal to 1 or 2 and r is equal to 0, 1 or 2; provided that a) a spiro ring represents a stable chemical base unit and b) NR8 and NRb do not contain neither N-N, nor N-O bonds.

EFFECT: higher efficiency of the composition and method of treatment.

54 cl, 1 tbl, 9 dwg, 284 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing new 3,4-dithienyl-substituted maleic anhydrides or maleimides of general formula I: , where X=O, or NR1; R1 and R2=alkyl C1-C4; R3=alkyl C1-C4, or nitrogen- and/or sulphur-containing heterocyclic substitute. The method involves reacting the corresponding 2,5-disubstituted 3-thienyl-acetic acid with the corresponding 2,5-disubstituted 3-halogen acetythiophenes while heating in the presence of a base in a medium of inert organic solvent in atmospheric oxygen with subsequent separation of the end product of general formula I, where X=O, or, if necessary, the latter is converted to a compound of general formula I, where X=NR1, where R1 assumes values given above, by treating it with the corresponding amine. These compounds can be used as photochromes, which are widely used as optical switches in high-capacity data carriers used for recording, processing and storing data.

EFFECT: versatility of the method, ie possibility of obtaining compounds with and without equivalent heterocyclic substitutes using readily available thienyl-acetic acid and halogen ketones of the thiophene family, which considerably widens the assortment of organic photochromic dithienylethenes.

4 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula , where X, R1, R2, R3, R4 and R5 assume values given in the description and paragraphs of the formula of invention, and their pharmaceutically acceptable salts.

EFFECT: compounds have antagonistic activity on histamine receptor 3 (H3).

25 cl, 3 tbl, 215 ex

Pyrazoles // 2381217

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), where one of R1 and R2 is hydrogen or alkyl, and the other is (CH2)PY, where p=0 or 1, Y is a saturated mono-, bi- or tricyclic 5-10-member cycloalkyl ring optionally substituted with alkyl, or R1 and R2 together with N form a 7-10-member saturated bicyclic ring Z, optionally substituted with halogen, or a 5-7-member monocyclic ring Z, optionally substituted with alkyl, phenyl, phenylalkyl or pyridinyl; R3 is [2,2']bithiophenyl, 1-methylindole, 2,3-dihydrobenzo[1,4]dioxin, benzo[1,3]dioxole, benzothiophene, dibenzofuran, furan, naphthalene, quinoline, thianthrene, thiophene or pyrrole, or biphenyl substituted with halogen, or phenyl optionally substituted with one or more amino, cyano, formyls, halogens, hydroxyl, hydroxymethyls, acyls, acylamino, alkoxy, nitro, trifluoromethoxy, trifluoromethyls, phenoxy or benzyloxy, or R3 is a group, where Ar is phenyl substituted with halogen; and R4 is alkyl; and pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition with inhibitory activity towards the 11β-hydroxysteroid dehydrogenase1 (11(β-HSD1) enzyme.

EFFECT: pyrazole composition is disclosed.

22 cl, 1 tbl, 116 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrolidine-3,4-dicarboxamide derivatives of formula (I): , where: X is N or C-R6; R1 is C1-7alkyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-7alkyl, fluoro-C1-7alkyl, hydroxy-C1-7alkyl, CN-C1-7alkyl, R10C(O), R10OC(O)-, N(R11,R12)C(O)-; R10OC(O)C1-7alkyl, N(R11,R12)C(O)-C1-7alkyl, R10SO2, R10-SO2-C1-7alkyl, N(R11, R12)-SO2, N(R11,R12)-SO2-C1-7alkyl, aryl-C1-7alkyl, 5-member monocyclic heteroaryl containing a nitrogen atom, where the ring carbon atom can be substituted with a carbonyl group, heteroaryl-C1-7alkyl, where the term "heteroaryl" represents an aromatic -member monocyclic ring with 1 S atom or a 6-member monocyclic ring with 1 N atom, C1-7alkoxy-C1-7alkyl, C1-7alkoxycarbonyl-C3-10cycloalkyl-C1-7alkyl or halogen substituted 4-member heterocyclyl-C1-7alkyl with one O atom; R2 is H, C1-7alkyl; R3 is aryl, aryl-C1-7alkyl, heteroaryl, heteroaryl-C1-7alkyl, where the term "heteroaryl" represents a 5-member monocyclic ring with 1 S atom, a 6-member monocyclic ring with 1 or 2 N atoms, 9-, 10-member bicyclic system with 1 or 2 N atoms in one ring; R4 is H, C1-7alkyl, OH; R5, R6, R7, R8 are independently selected from a group consisting of H, halogen, C1-7alkyl, C1-7alkoxy, flouro-C1-7alkyl, fluoro-C1-7alkyloxy; R9 is aryl, heterocyclyl, heteroaryl, heterocyclyl-C(O)-; R10 is H, C1-7alkyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-7alkyl, fluro-C1-7alkyl, heteroaryl, heteroaryl-C1-7alkyl, where the term "heteroaryl" represents a 5-member monocyclic ring with 4 N atoms, a 5-member heterocyclyl with 1 N atom; R11, R12 are independently selected from a group consisting of H, C1-7alkyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-7 alkyl; and pharmaceutically acceptable salts thereof; where the term "aryl" represents a phenyl group which can be optionally substituted with 1 to 5 substitutes which are independently selected from a group consisting of the following: halogen, CF3, NH2, C1-7alkylsulphonyl, C1-7alkoxy, fluoro-C1-7alkyl, fluoro-C1-7 alkoxy; the term "heterocyclyl" represents a nonaromatic monocyclic 5-, 6-member heterocyclic group with 1, 2 N atoms, or with 1 N atom and 1 O atom, where the heterocyclyl group can be substituted as indicated with respect to the term "aryl", and one carbon atom of the ring system of the heterocyclyl group can be substituted with a carbonyl group; the term "heteraryl" represents an aromatic 5- or 6-member monocyclic ring system which can have 1, 2, 3 N atoms, or 1 N atom and 1 S atom, where the heteroaryl group can be substituted as indicated with respect to the term "aryl", and one carbon atom of the ring system of the heteroaryl group can be substituted with a carbonyl group. Formula I compounds have inhibitory activity towards coagulation factor Xa.

EFFECT: possibility of using said compounds in a pharmaceutical composition and for preparing a medicinal agent.

27 cl, 90 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing new 3,4-dithienyl-substituted maleic anhydrides or maleimides of general formula I: , where X=O, or NR1; R1 and R2=alkyl C1-C4; R3=alkyl C1-C4, or nitrogen- and/or sulphur-containing heterocyclic substitute. The method involves reacting the corresponding 2,5-disubstituted 3-thienyl-acetic acid with the corresponding 2,5-disubstituted 3-halogen acetythiophenes while heating in the presence of a base in a medium of inert organic solvent in atmospheric oxygen with subsequent separation of the end product of general formula I, where X=O, or, if necessary, the latter is converted to a compound of general formula I, where X=NR1, where R1 assumes values given above, by treating it with the corresponding amine. These compounds can be used as photochromes, which are widely used as optical switches in high-capacity data carriers used for recording, processing and storing data.

EFFECT: versatility of the method, ie possibility of obtaining compounds with and without equivalent heterocyclic substitutes using readily available thienyl-acetic acid and halogen ketones of the thiophene family, which considerably widens the assortment of organic photochromic dithienylethenes.

4 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention is related to compound represented by formula (1) , in formula A represents nitrogen-containing saturated ring; m represents integer number, equal to 0, 1 or 2; n represents integer number, equal to 1, 2, 3 or 4; G1 represents atom of hydrogen, hydroxyl group or alkoxygroup; G2 represents atom of halogen, hydroxyl group, cyanogroup, alkyl group, alkenyl group, alkinyl group, which may be substituted with hydroxyalkyl group, alkoxygroup, alkyl thiogroup, aminogroup or aryl group; G3 represents atom of hydrogen; G4 represents hydroxyl group or -N(R1)(R2) (R1 and R2 may be identical or different, and independently represent atom of hydrogen, alkyl group, aralkyl group, alkenyl group or saturated heterocyclic group); and G5 represents substituent at carbonic atom, which constitutes nitrogen-containing saturated ring, represented with A, and represents atom of hydrogen, to medicinal agent on the basis of this compound for treatment and prophylaxis of glaucoma, to inhibitor of phosphorylation of regulatory light chain of myosin and inhibitor of kinase Rho/Rho path, and also to method of therapeutical and/or prophylactic treatment of glaucoma.

EFFECT: new compounds have been produced and described, which efficiently inhibit phosphorylation of regulatory light chain of myosin.

32 cl, 42 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: invention is related to compound of formula (I) , where

R1 -C1-8alkyl; R2 - pyridynyl, unnecessarily substituted with C1-8alkyl, quinolyl or isoquinolyl; R3 - hydrogen or C1-8alkylcarbonyl; R4 means group of formula G-L1-(CRR')n-, in which n is integer number from 0 to 3; R and R' are independently selected from group that includes atoms of hydrogen and lower alkyl groups; L1 means connection group, selected from group, which includes direct connection, groups -O-, -CO-, -NR"-, -O(CO)O-, -O-(CO)-, -(CO)O- and -NR"-(CO)-, where R" is lower alkyl; G is selected from group, including atoms of hydrogen, C1-8alkyl, C2-8alkenyl, C3-7dicloalkyl, phenylC1-8alkyl, pyridinyl, thiophenyl or residue of indan, and also phenyl, unnecessarily substituted with atom of halogen, C1-8alkoxy, cyano- or C1-8alkyl, which, in its turn, unnecessarily contains one or more atoms of halogen. Specified compounds are active and selective inhibitors of phosphodiesterase 4 (FDE4), therefore, they are applicable for treatment, prevention or suppression of pathological conditions, diseases or disorders, for which it is known that their behavior is relieved by inhibition of FDE4, such as asthma, chronic obstructive lung disease, rheumatoid arthritis, atopic dermatitis, psoriasis or syndrome of sore large gut. Invention is related also to pharmaceutical compositions on the basis of mentioned compounds, application of compounds, method for treatment of subject, when efficient amount of specified compounds is introduced to them. Besides invention is related to combined product for treatment or prevention of pathological condition or disease, behavior of which is relieved by inhibition of phosphodiesterase 4, including specified compound and another compound, selected from the group that includes (a) steroids, (b) immunosuppressive agents, (c) blockers of T-cells receptors, (d) anti-inflammatory medicinal agents, (e) β2-adrenergic agonists and (f) antagonists of muscarine receptors M3, for single-time, separate or serial use.

EFFECT: improved efficiency of compounds use.

11 cl, 2 tbl, 77 ex

FIELD: medicine.

SUBSTANCE: invention refers to imidazole derivatives of formula (1a): and/or to stereoisomeric forms of compound of formula (1a) and/or to physiologically acceptable salt of compound of formula (1a), and U means 1) hydrogen atom; X means the remaining formula (II): -(A1)m-A2 (II), where m means an integer 1; A1 means 1) -(CH2)n- where n means an integer 1; A2 means 1) aminopyridyl; Y means 1) the remaining formula (III): A3-(A4)o-(A5)p (III), and A3 means (C3-C8)-cycloalkyl or (C2-C6)-alkinylene wherein cycloalkyl or alkinylene is unsubstituted or independently one-, two- or three-substituted with R1, A4 is absent, A5 is absent; b) A3 means -(C3-C8)-cycloalkyl wherein cycloalkyl is unsubstituted or independently one-, two- or three-substituted with R1, A4 means -N(R2)- and A5 means a)1) -C(O)-R3; a)2) -C(O)-N(R4)-R5; a)3) -(SO2)-R6; O stands for an integer 1, and p stands for an integer 1; A3 means cyclic amine with 3-8 atoms in cycle where cyclic amine is unsubstituted, A4 is absent; and A5 has value specified in cl. b), and A5 is connected with N-atom A3, o means an integer zero and p means an integer zero or 1; or d) A3 means -(CH2)q-phenyl wherein phenyl is unsubstituted or independently one-, two- or three-substituted with R1, A4 is absent; and A5 has value specified in cl. b), p means an integer 1 and q means integer zero or 1;) A3 means -(CH2)rHet wherein Het stands for benzothiophene or piperidine which is unsubstituted or independently one-, two- or three-substituted by =0 or R1, A4 is absent; and A5 has value specified cl. b), p means an integer 1 and r means an integer 1 or 2; f) A3 means -(CH2)q-phenyl wherein phenyl is unsubstituted, A4 means -O- A5 means phenyl wherein phenyl is unsubstituted or independently one-, two- or three-substituted by R1, o and p mean an integer 1, and q means an integer zero, 1; g) -CH(-phenyl)-phenyl; and R1 means phenyl, and phenyl is unsubstituted or independently one-, two- or three-substituted by -(C1-C6)alkyl, b) triazolyl,) c) - (C1-C6)-alkyl, d) - (C0-C4)-alkyl - (C3-C8) a-cycloalkyl, e) -O-CF3 or g) halogen; and R2 means: a) hydrogen atom; and R3 and R6 are identical or different and independently mean: a) -(C1-C6)-alkyl wherein alkyl is unsubstituted or independently one-, two- or three-substituted by R1, b) -phenyl wherein phenyl is unsubstituted or independently one-, two- or three-substituted by R1, while R4 and R5 are identical or different and independently mean: a) -(C1-C6)-alkyl or -(C2-C10)-alkenyl wherein alkyl or alkenyl is unsubstituted, b) -phenyl wherein phenyl is unsubstituted, c) hydrogen atom; Y means 2) the remaining formula (IV): , and R8 means a) -phenyl where phenyl is unsubstituted; Z means 1) hydrogen atom, 2) -(C1-C6)-alkyl, 3) -(C1-C6)-alkyl, 4) -(C0-C4)-alkyl-(C3-C6)-cycloalkyl, 5) -(C1-C10)-alkyl-O-C(O)-O-R1. Besides the invention concerns the method for making the compound of formula (1a) and the based medicinal agent for inhibition of TAFIa enzyme.

EFFECT: production of new compounds and the based medicinal agent to be used in medicine to prevent and treat the conditions accompanied with thromboses, embolism, hypercoagulation or fibrotic changes.

8 cl, 1 tbl, 47 ex

Amide derivatives // 2375352

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula I, to its pharmaceutically acceptable salts exhibiting properties of inhibitors of cytokine production, such as TNF (tumour necrosis factor) and various members of interleukins (IL) family, and properties of kinase inhibitors, particularly p38α kinase. The invention also concerns methods for producing; pharmaceutical compositions and application thereof for making the medicines for treating diseases affected by the compound of the invention with specified activity. In formula I , m represents 0, 1 or 2; R1 represents halogeno, hydroxy, (1-6C) alkyl, (1-6C)alkoxy, (2-6C)alkenyl, (2-6C) alkinyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, amino-(2-6C) alkoxy, (1-6C)alkylamino-(2-6C)alkoxy, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, N-(1-6C)alkylcarbamoyl - (1-6C)alkoxy, di[(1-6C) alkyl]amino-(1-6C)alkyl, hydroxy-(2-6C)alkylamino, heteroaryl-(1-6C)alkoxy, heterocyclyl, heterocyclyloxy and heterocyclyl-(1-6C)alkoxy and wherein any heteroaryl or heterocyclyl group in substitute representing R1, can probably have 1 or 2 substitutes chosen from hydroxy, halogeno, (1-6C) alkyl, (2-6C)alkinyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxycarbonyl, (2-6C) alkanoyl, halogen-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, carboxy- (1-6C)alkyl and methylsulphonyl and wherein any said substitute representing R1 which contains group CH2 attached to 2 carbon atoms, or group CH3 attached to carbon or nitrogen atom, can probably have with each specified group CH2 or CH3, one or two substitutes chosen from halogeno, hydroxy, amino, triflouromethyl, oxo, carboxy, acetamido, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkyamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, halogen-(1-6C)alkyl, (1-6C)alkoxycarbonyl, carbamoyl, N, N-di-[(1-6)alkyl]carbamoyl, (1-6C)alkylsulphonyl, heteroaryl, heteroaryl-(1-6)alkyl and heterocyclyloxy and wherein any heterocyclyl group in substitute representing R1, can probably have 1 oxo-subsitute; R2 represents trifluoromethyl or (1-6C)alkyl; R3 represents hydrogen or (1-6C)alkyl; and R4 represents (3-6C)cycloalkyl, and R4 can be optionally substituted with one or more substitutes chosen from (1-6C)alkyl; and wherein heteroaryl represents aromatic 5- or 6-merous monocyclic ring containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur; heterocyclyl represents saturated 3-10-merous monocyclic or bicyclic ring, each containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur.

EFFECT: improved efficiency.

24 cl, 16 tbl, 66 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treatment and prevention of diseases associated with activity of specified enzyme, such as diabetes, obesity, diseases associated with food intake, dyslipidemia and hypertension. In general formula (I) , R1 represents methyl, ethyl, cyclopropyl, cyclobutyl, isopropyl, tert-butyl, methoxymethyl, cyclopropyl methoxymethyl, 2-methyl thiazolyl, morpholinyl methyl or phenyl; R2 represents hydrogen, C1-4alkyl or phenyl; R3 represents hydrogen, C1-4alkyl or phenyl; R4 represents phenyl, naphthyl, thiophenyl, quinolyl or piperidyl where phenyl, naphthyl, thiophenyl, quinolyl and piperidyl are optionally substituted with one to three substitutes independently chosen of C1-4alkyl, halogen, C1-4alkoxy, cyano, trifluoromethyl, phenyl, phenyls C1-4alkyl, phenyloxy, oxasolyl and pyridinyl; R5 represents hydrogen, C1-4alkyl, phenyl-C1-4alkyl, C3-6dicloalkyl-C1-4alkyl or aminocarbonylC1-4alkyl.

EFFECT: higher clinical effectiveness.

17 cl, 2 dwg, 72 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula , where X, R1, R2, R3, R4 and R5 assume values given in the description and paragraphs of the formula of invention, and their pharmaceutically acceptable salts.

EFFECT: compounds have antagonistic activity on histamine receptor 3 (H3).

25 cl, 3 tbl, 215 ex

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