Condensed benzamide derivative and inhibitor of vanilloid receptor type 1 activity (vri)

FIELD: chemistry.

SUBSTANCE: benzamide derivatives are presented by the formula [1] or its salt, where Z is -O-, -NR5-, -S-, -SO-; 1 is 0 or 1; m is 0 or 1; R1 is hydrogen atom, C1-6-alkyl group, R2 is hydrogen atom, hydroxylic group, C1-6- alkyl group, carboxyl group, C1-6-alkoxycarbonyl group or -CONR10R11, or R2 and R1 together form =O; R3 is hydrogen atom or C1-6-alkyl group; R4 is hydrogen atom or halogen atom; V is direct bond or -(CR21R22)n-; P1 and P2 rings are the same or different, and each is aromatic or saturated carbocyclic group, or 5-10-member saturated or unsaturated heterocyclic group containing 1-3 heteroatoms selected out of N, O, S.

EFFECT: obtainment of compound with excellent inhibition effect on vanilloid receptor type 1 activity, efficiency in treatment of diseases involving vanilloid receptor type 1 activity.

17 cl, 56 tbl, 8 ex

 

The present invention relates to a new condensed benzamide derivative having inhibitory action on the activity of subtype 1 receptor vanilloid (VR1), and pharmaceutical compositions comprising this compound as an active ingredient, particularly drug against pain.

Capsaicin, which is the main ingredient in Cayenne pepper is called an essential ingredient, as well as inducing pain substance. Described that many nociceptive nerves, especially semilinearly fibers have a sensitivity to capsaicin and, it is known that fibers can be selectively fall, when capsaicin is administered to the baby rodent. Also described that there are many places of action of capsaicin, distributed in the skin, cornea and mucous membrane of the mouth, and their distribution see also in muscles, joints and internal organs, especially the cardiovascular system, respiratory system and urinary bladder, and it is important for reflex beam autonomic nerve fibers. In addition, sensitivity to capsaicin see also nerves Praxiteles areas of the thalamus and expected participation in the regulation of body temperature. The depolarization and influx of Na+and CA2+the introduction of capsaicin see in nociceptive what's nerves, and this leads to the separation of glutamic acid and neuropeptides (mainly substance P peptide associated with calcitonin gene) of the lateral end of the Central attachment of the main afferent fibers of the spinal dorsal horn. Now observed that the specific binding activity of resiniferatoxin (RTX) causes of action similar to the action of capsaicin, and that capsazepine manifests itself as a competitive inhibitor, and believe that laboratorymy capsaicin acts on the receptor protein (see Szallasi, A., Blumbrg P.M. (1999) Pharmacol. Rev. 51, 159-212).

Gene capsaicin receptor cloned in 1977 (see, for example, Caterina M.J., Schumacher M.A., M. Tominaga, Posen T.A., Levine JD, Julius D. (1997) Nature 389, 816-824). On the basis of its amino acid sequence suggested that it was an ion channel with six transmembrane domains. Because capsaicin is manillow group in the structure, its generative called vanilloids along with its counterparts, such as RTX, and the cloned receptor was named subtype 1 receptor vanilloid (hereinafter referred to VR1; this VR1 can also identify TRPV1 (unstable receptor potential receptor 1 vanilloid). Then conducted electrophysiological functional analysis using the method of the patch-clamp received Xenopus laevis oocytes and isolated from the human body, kultivirovaniya for the expression of VR1 and was found what VR1 directly activated by capsaicin without the mediation of intracellular second messenger (see, for example, Caterina M.J., Schumacher M.A., M. Tominaga, Posen T.A., Levine JD, Julius D. (1997) Nature 389, 816-824) and that VR1 is a non-selective cationic ion channel having a high CA2+the permeability properties of the surface purification (see, for example, Premkumar LS, Agarwal, S., Steffen D. (2002) J. Physiol. 545, 107-117).

Although capsaicin is causing the pain substance, it is used as an analgesic agent for soothing pain in diabetic neuropathy or rheumatic neurosis (see, for example, Szallasi a, Blumberg PM (1999) Pharmacol. Rev. 51, 159-212). It is clear that such a calming pain is the result of a phenomenon by which sensitive nerve ending, subjected to the action of capsaicin, ceases to respond to the stimulus of pain, then there is desensitization. Although it is believed that the mechanism of desensitization VR1 includes CA2+-mediated regulation, regulation, depending on capacity, regulate the activity of VR1 phosphorylation and dephosphorylation etc., many provisions remain unclear.

As well as capsaicin, heat and acid also cause pain, and it is known that sensitive to capsaicin nociceptive nerves react to two or more types of stimulation. Discovered that VR1 directly activerow the Xia not only by capsaicin, but thermal stimulation at 43°C or higher (see, for example, Yang D., R.W. Gereau 4th(2002) Neurosci. 22, 6388-6393). The temperature of 43°C is mainly in accordance with a temperature limit, which causes pain in humans and animals, suggesting that VR1 is involved in susceptibility to nociceptive thermal stimulation.

Acidification occurs in the body in case of inflammation or ischemia, and, as you know, it causes or increases pain (see, for example, Bevan s, Geppetti P. (1994) Trends Neurosci. 17, 509-512). It turned out that when the pH of the outside of the cells is reduced within acidification, which occurs in the case of organ damage, VR1 can directly be activated only by acidification (education protons), and it is assumed that VR1 is an active molecule that receives the stimulation of acidification in the body, which takes place in the case of inflammation or ischemia (see, for example, Yang D., R.W. Gereau 4th(2002) J. Neurosci. 22, 6388-6393).

Immunohistological analysis using specific antibodies confirmed that the number demyelinating fibers expressing VR1, is increased in the inflamed area compared to the normal region (see, for example, Carlton, S.M., Coggeshall RE. (2001) Neurosci. Lett. 310, 53-56). The increased expression of VR1 in the plexus, located under the mucous membrane, is indeed observed in inflammatory is zabolevanii human intestine (see, for example, Yiangou y, Facer p, Dyer N.H., Chan CL, Knowles C., Williams NS, Anand P. (2001) Lancet 357, 1338-1339). Such increase in the amount of expression of VR1 causes peripheral sensitization in the fevered body and presumably contributes to the duration of inflammatory hyperalgesia.

Also described that extracellular ATP, bradykinin and growth factor nerve, which are associated with inflammation substances that increase the activity of VR1 (see, for example, Tominaga M., Wada M., Masu M. (2001) Proc. Natl. Acad. Sci. USA 98, 6951-6956; X. Shu, L.M. Mendell (1999) Neurosci. Lett. 274, 159-162; Chuang H.H., Prescott E.D., Kong H., Shields, S., Jordt SE, Basbaum AI, Chao, M.V., Julius D. (2001) Nature 411, 957-962; and Sugiura, T., Tominaga M., Katsuya h, Mizumura K. (2002) J. Neurophysiol. 88, 544-548), and States that without a doubt VR1 is involved in pain and hypervisibility pain, including pain caused by inflammation (see, for example, Numazaki M., Tominaga, M. (2003) Biochemistry 75, 359-171).

Sensitive nerve cells in VR1-deficient mice do not respond to any of the stimulation of capsaicin, protons and heat. Also described that in the analysis of actions VR1-deficient mouse does not detect painful reaction after injection of capsaicin and sensitivity to thermal stimulation and decreases inflammatory hyperalgesia was not observed (see, for example, Caterina M.J., Leffler a, Malmberg A.B., Martin WJ, Trafton j, Peterson-Zeitz K.R., Koltzenburg m, Basbaum, A.I., Julius D. (2000) Science 288, 306-313 and L.B. Davis, J. Gray, M.J. Gunthorpe et al. (2000) Nature 405, 183-187). Thus, it was confirmation is but also at the individual level of analysis VR1-deficient mouse what VR1 acts as a receptor stimulation of a wide range of pain.

In addition, concerning the relationship between subtype 1 receptor vanilloid (VR1) and disease already described that a substance that inhibits the activity of VR1, is applicable as a therapeutic agent for various diseases.

In particular, with regard to therapeutic agent against pain, there is a message that capsazepine, which is known as VR1 antagonist, showed significant analgesic activity in animal models (see, for example, Ikeda Y., Ueno, A., Naraba h, Oh-ishi, S., (2001) Life Science 69, 2911-2919) and it is supposed to be used as a new therapeutic agent against pain, has inhibiting effect on the activity of VR1.

Regarding hyperlactatemia bladder type frequent urination and urinary incontinence was confirmed that the function of bladder contractions in VR1-deficient mice is reduced, and there is a message that the connection with similar pharmacological mechanism of capsaicin, or the connection has inhibiting effect on VR1, i.e., the compound inhibiting the activity of subtype 1 receptor vanilloid (VR1), is applicable to improve the function of the bladder, for example, as a therapeutic agent for the treatment of frequent urination, incontinence, and so on (see, n is the sample, (2002) Nat. Neurosci. 5, 856-860).

In addition, in another reference describes that a substance that has an inhibitory effect on subtype 1 receptor vanilloid (VR1), especially the VR1 receptor antagonist, is effective for the prevention and treatment of diseases associated with VR1 activity, especially extreme urinary incontinence, overactive bladder, chronic pain, neuropathic pain, postoperative pain, pain, rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, nerve damage, ischemic symptom, neurodegeneration, cerebral apoplexy, incontinence, inflammatory diseases, extreme urinary incontinence (UUI), and/or conditions and diseases including overactive bladder (see, for example, JP 2003-192673).

In addition, it is also known that diseases related to activity of the receptor vanilloid may include pain, acute pain, chronic pain, neuropathic role, postoperative pain, migraine, joint pain, neuropathy, nerve damage, diabetic nerve disease, neurodegenerative disease, neurogenic violation skin, cerebral apoplexy, hypersensitivity of the bladder, irritable bowel syndrome, disorders of the respiratory organs, such as asthma and chronic obstructive pulmonary disease, stimulation of the skin, eyes, or SL is sistas shell, fever, stomach ulcer or duodenal ulcer, inflammatory bowel disease, inflammatory disease and so on (see, for example, JP 2004-506714 T2).

According to this we can say that the substance having an antagonistic activity for subtype 1 receptor vanilloid (VR1), are applicable as a therapeutic agent for conditions involving fiber With, for example, not to mention the itch, Allergy, and allergic rhinitis, and overactive bladder type frequent urination and urinary incontinence, apoplexy, irritable bowel syndrome, a respiratory ailment such as asthma and chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer, inflammatory bowel disease and so on, but also when pain, acute pain, chronic pain, neuropathic pain, postoperative pain, migraine, joint pain, neuropathy, nerve damage, diabetic nerve disease, neurodegenerative disease, pain, rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, neurogenic violation skin, apoplexy, overweight, extreme urinary incontinence, ischemic symptom, and inflammatory disease, etc.

It then describes the compounds, relative to the output with a known antagonist of subtype 1 receptor vanilloid (VR1), and the compound of the present invention.

The amide compounds of the type represented by the following General formula [A], [B] and [C], described in WO 03/068749 as compounds exhibiting antagonism to VR1.

Connection type urea represented by the following General formula [D], described in WO03/080578 as a compound exhibiting antagonism to VR1.

[D]

Hinkley-3'-yl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate described in WO 03/006019 as a compound exhibiting an inhibitory effect against capsaicin-induced extravasation of plasma protein in the bladder.

Connection type urea represented by the following General formula [E], described in WO 03/053945 as a compound exhibiting antagonism to VR1.

The connection represented by the following General formula [F], described in WO 03/099284 as a compound exhibiting binding activity for VR1.

However, these compounds differ from the compounds of the present invention according to the structure, and was not detected description, which provides the connection of the present invention.

Now mainly used analgeziruushim agent, narcotic analgesics (morphine etc), non-narcotic analgesics (NSAID (non-steroidal anti-inflammatory drug is public medium)) etc. However, the use of narcotic analgesics severely limited due to the development of resistance/dependence and other serious side effects. In addition, it is well known that during long-term administration non-narcotic analgesics is often a violation of the upper gastrointestinal tract and impaired liver, and is very desirable analgesic agent with minor side effects and higher analgesic action. In addition, with regard to induced diabetic neuropathic pain, post herpetic neuralgia and neuropathic pain such as trigeminal neuralgia, has not yet found an effective analgesic agent, and the development of such an effective analgesic agent it is also assumed.

It is believed that similar to capsaicin compounds that act on VR1, find analgesic effect based on the pharmacological mechanism entirely different from the mechanisms existing analgesic agents (desensitization sensitive to capsaicin nerves), and very it is expected that they are effective as a therapeutic agent for neuropathic pain and pain that occurs when various conditions such as rheumatoid arthritis, for which existing analgesic agents are ineffective the mi.

The fact that the ultimate target of a variety of associated with inflammation substances is VR1, suggests the possibility that an agent who acts on VR1, is effective for a variety of inflammatory pain and interstitial cystitis, and it is expected to be an effective analgesic agent, which will replace the existing analgesic agents.

Therefore, the present invention is to create a new analgesic agent based on the pharmacological mechanism entirely different from the mechanisms existing analgesic agents (desensitization sensitive to capsaicin nerves), i.e. the inhibitor activity of VR1.

As a result of intensive studies for the development of analgesic agent based on a new mechanism of action, which will replace conventional analgesic agents, such as non-narcotic analgesics, pyrazolone analgesics, nephratonia analgesics and NSAID, the authors of the present invention discovered condensed benzamide derivative, which has an excellent inhibitory effect on VR1, and completed the present invention. The present invention is described in more detail below.

1. Condensed benzamide derivative represented by the following General formula [1]or its pharmaceutically acceptable salt

[where Z is a

(1) -O-,

(2) -NR5- (where R5represents a hydrogen atom or C1-6-alkyl group),

(3) -S-,

(4) -SO - or

(5) -SO2-;

l is 0, 1 or 2;

m is 0, 1 or 2;

R1represents a

(1) a hydrogen atom, or

(2) C1-6-alkyl group which may be substituted by 1-5 substituents selected from the following group:

group a:

(a) a halogen atom,

(b) a hydroxyl group,

(C) C1-6-alkoxygroup,

(d) a carboxyl group,

(e) C1-6-alkoxycarbonyl group,

(f) -CONR6R7(where R6and R7are the same or different and each represents a hydrogen atom, C1-6-alkyl group or acyl group, the above alkyl group may be substituted by a hydroxyl group or alloctype),

(g) -NR6R7(where R6and R7have the values specified above)

(h) -NR6COR7(where R6and R7have the values specified above)

(i) -NR8CONR6R7(where R6and R7have the meanings indicated above and R8represents a hydrogen atom or C1-6-alkyl group) and

(j) -NR6SO2R9(where R6has the values given above and R9represents a C1-6-alkyl group);

R2represents a

(1) a hydrogen atom,

(2) the Hydra is xinnuo group,

(3) C1-6-alkyl group which may be substituted by 1-5 substituents selected from group a where a is the same as above)

(4) a carboxyl group,

(5) C1-6-alkoxycarbonyl group or

(6) -CONR10R11(where R10and R11are the same or different and each represents a hydrogen atom or C1-6-alkyl group);

or R2together with R1forms =On;

R3represents a

(1) a hydrogen atom, or

(2) C1-6-alkyl group;

R4represents a

(1) a hydrogen atom,

(2) a halogen atom,

(3) C1-6-alkyl group which may be substituted by 1-5 substituents selected from the following group b,

(4) C1-6-alkoxygroup, which may be substituted by 1-5 substituents selected from the following group b,

(5) cycloalkyl group which may be substituted by 1-5 substituents selected from the following group b,

(6) Uralkaliy group which may be substituted by 1-5 substituents selected from the following group b,

(7) urlcategory, which may be substituted by 1-5 substituents selected from the following group b, or

(8) cycloalkylcarbonyl, which may be substituted by 1-5 substituents selected from the following groups:

group:

(a) a halogen atom,

(b) halogen-C1-6-alkyl is owned by the group,

(C) a hydroxyl group,

(d) halogen-C1-6-alkoxygroup,

(e) C1-6-alkoxycarbonyl group,

(f) C1-6-alkoxygroup,

(g) a carboxyl group,

(h) -CONR12R13(where R12and R13are the same or different and each represents a hydrogen atom or C1-6-alkyl group);

(i) -NR12R13(where R12and R13have the values specified above)

(j) -NR12COR13(where R12and R13have the values specified above)

(k) -NR14CONR12R13(where R12and R13have the meanings indicated above and R14represents a hydrogen atom or C1-6-alkyl group),

(l) -SO2R15(where R15represents a C1-6-alkyl group) and

(m) -NR12SO2R15(where R12and R15have the values specified above);

(9) a hydroxyl group,

(10) -NR16R17(where R16and R17are the same or different and each represents a hydrogen atom or C1-6-alkyl group);

(11) -R18(where R18represents a C1-6-alkyl group, C1-6-alkoxygroup, cycloalkyl group, aracelio group, urlcategory, cycloalkylcarbonyl or hydroxyl group),

(12) -CONR16R17(where R16and R17are the same or different),

(13) -NR19CONR16, R 17(where R16and R17have the meanings indicated above and R19represents a hydrogen atom or C1-6-alkyl group),

(14) -NR16R20(where R16has the values given above and R20represents a C1-6-alkyl group or cycloalkyl group)

(15) -SR20(where R20has the values listed above)

(16) -separator R s o20(where R20has the values listed above)

(17) -SO2R20(where R20has the values listed above)

(18) -SO2NR16R17(where R16and R17have the values specified above), or

(19) -NR16R18(where R16and R18have the values specified above);

V represents

(1) a direct link or

(2) -(CR21R22)n- (where R21and R22are the same or different and each represents a hydrogen atom or C1-6-alkyl group and n is 1 or 2);

ring P1 and P2 are the same or different and each represents

(1) carbocyclic group which may be substituted by 1-5 substituents selected from the following group C, or

(2) heterocyclic group which may be substituted by 1-5 substituents selected from the following groups:

group:

(a) a halogen atom,

(b) a hydroxyl group,

(C) C1-6-alkoxygroup, which can be the ü substituted by 1-5 substituents, selected from group a,

(d) C1-6-allylthiourea,

(e) C1-6-alkyl group which may be substituted by 1-5 substituents selected from group a,

(f) -CONR23R24(where R23and R24are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group A)

(g) -NR123R124(where R123and R124are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group A)

(h) -NR223COR224(where R223and R224are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group A)

(i) -NR25COR323R324(where R323and R324are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group A)

(j) -SR26(where R26represents a C1-6-alkyl group),

(k) -SOR126(where R126represents a C1-6-alkyl group),

(l) -SO2R226(where R226represents a C1-6-alkyl group),

(m) -NR423SO2R32 (where R423represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group a, and R326represents a C1-6-alkyl group),

(n) -SO2NR523R524(where R523and R524are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group A)

(o) -R27(where R27represents a C1-6-alkyl group, C1-6-alkoxygroup, cycloalkyl group, aracelio group, urlcategory, cycloalkylcarbonyl or hydroxyl group),

(R) carbocyclic group which may be substituted by 1-5 substituents selected from (a)-(o) group,

(q) heterocyclic group which may be substituted by 1-5 substituents selected from (a)-(o) group,

(r) -O-R28(where R28represents an acyl group, a carbocyclic group which may be substituted by 1-5 substituents selected from (a)-(o) group, or a heterocyclic group which may be substituted by 1-5 substituents selected from (a)-(o) group,

(s) -O-(CR21R22)n-R28(where R21, R22n and R28have the values specified above)

(t) the nitro-group and

(u) cyano.

2. Condensed production is th benzamide or its pharmaceutically acceptable salt according to the above item 1, where Z represents-O-, -NR5-, -S - or-SO-.

3. Condensed benzamide derivative or its pharmaceutically acceptable salt according to the above item 1 or 2, where R3represents a hydrogen atom or C1-4-alkyl group.

4. Condensed benzamide derivative or its pharmaceutically acceptable salt according to the above claims 1 to 3, where the ring R1 is a saturated or unsaturated 5-membered or 6-membered heterocyclic ring containing 1-4 heteroatoms selected from a nitrogen atom, oxygen atom and sulfur atom, or a condensed ring of these heterocyclic rings or condensed heterocyclic ring specified heterocyclic ring and the carbocyclic ring selected from benzene, cyclopentane and cyclohexane, or a phenyl group (where the aforementioned heterocyclic ring may be substituted by halogen atom, hydroxyl group, C1-6-alkyl group, which may to be substituted by 1-5 substituents selected from group a, and C1-6-alkoxygroup, which may be substituted by 1-5 substituents selected from group a).

5. Condensed benzamide derivative or its pharmaceutically acceptable salt according to the above item 4, where the ring R1 is a saturated or unsaturated 5-membered or 6-membered heterocyclic ring, the soda is official at least 1-3 nitrogen atom, or a phenyl group (where the aforementioned heterocyclic ring may be substituted by C1-6-alkyl group which may be substituted by a hydroxyl group or C1-6-alkyl group, a halogen atom, a hydroxyl group and C1-6-alkoxygroup, which may be substituted by 1-5 substituents selected from group a).

6. Condensed benzamide derivative or its pharmaceutically acceptable salt according to the above item 5, where the ring R1 represents a heterocyclic group selected from peredelnoj group, personalni group and thiazolidine group, or phenyl group (where these heterocyclic groups can be substituted by C1-6-alkyl group which may be substituted by a hydroxyl group, a halogen atom, a hydroxyl group and C1-6-alkoxygroup, which may be substituted by 1-5 substituents selected from group a).

7. Condensed benzamide derivative or its pharmaceutically acceptable salt according to the above claims 1 to 3, where the ring R2 is a carbocyclic group which may be substituted by a group-Deputy selected from the

- halogen atom,

- hydroxyl group,

- C1-6-alkoxygroup (where specified alkoxygroup may be substituted by a halogen atom, -CONR623R624(where R623and R624are Odie is akovali or different and each represents a hydrogen atom or C1-6-alkyl group, which may be substituted by 1-5 substituents selected from group a), C3-8-cycloalkyl group, C1-6-alkoxygroup, a carboxyl group or C1-6-alkoxycarbonyl group)

- C1-6-alkyl group (where this alkyl group may be substituted by a halogen atom, a hydroxyl group or C1-6-alkoxygroup),

- -NR123R124(where R123and R124have the values specified above)

- -NR223R224(where R223and R224have the values specified above)

- -COR27(where R27represents a C1-6-alkyl group, C1-6-alkoxygroup, cycloalkyl group, aracelio group, urlcategory, cycloalkylcarbonyl or hydroxyl group),

- -CONR23R24(where R23and R24have the values specified above)

- heterocyclic group to form a saturated or unsaturated group-Deputy, which has 1-3 nitrogen atom as heteroatoms (where specified heterocyclic group may be substituted by a group-Deputy selected from a hydroxyl group, -CONR723R724(where R723and R724are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group a), C1-6-alkoxygroup, carboxyl group, C1-6-alkyl gr is PPI, which may be substituted by C1-6-alkoxygroup, C1-6-alkoxycarbonyl group and alloctype),

- -O-R28(where R28represents an acyl group, a carbocyclic group which may be substituted by 1-5 substituents selected from PP.(a)-(i) group, or a heterocyclic group which may be substituted by 1-5 substituents selected from PP.(a)to(l)),

- -O-(CR121R122)n-R128(where R121and R122are the same or different and each represents a hydrogen atom or C1-6-alkyl group, n is 1 or 2 and R28represents an acyl group, a carbocyclic group which may be substituted by 1-5 substituents selected from PP.(a)-(i) group, or a heterocyclic group which may be substituted by 1-5 substituents selected from PP.(a)to(l)),

- nitro and

- ceanography or

heterocyclic group which may be substituted by the Deputy, as described for carbocyclic group (where specified heterocyclic group means a saturated or unsaturated 5-membered or 6-membered heterocyclic ring which has 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, or a condensed ring of these heterocyclic rings or a condensed heterocyclic group kasanovadesertkasanova ring and the carbocyclic ring, selected from benzene, cyclopentane and cyclohexane).

8. Condensed benzamide derivative or its pharmaceutically acceptable salt according to the above item 7, where the ring P2 as carbocyclic group is a phenyl group or tsiklogeksilnogo group, or a ring P2 as the heterocyclic group is thiazolino group, pyridyloxy group, piperidino group, piperidino, pinolillo group, benzo[1,3]dictograph, 2,3-dihydrobenzo[1,4]dictograph or 1,2,3,4-tetrahydroquinoline group.

9. Condensed benzamide derivative according to the above claim 1, selected from

1) N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

2) 8-(4-tert-butylphenyl)carbarnoyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid,

3) N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

4) N-(4-tert-butylphenyl)-1-(3-chloropyridin-2-yl)-4-methyl-1,2,3,4-tetrahydroquinoxalin-5-carboxamide,

5) N-(4-tert-butylphenyl)-9-(3-chloropyridin-2-yl)-6,7,8,9 - tetrahydro-5-oxa-9-athensallowed-4-carboxamide,

6) N-(4-chlorophenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

7) 4-(3-chloropyridin-2-yl)-N-(4-isopropoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

8) N-(1-tert-butyl is piperidin-4-yl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

9) 4-(3-chloropyridin-2-yl)-N-(4-were)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

10) 4-(3-chloropyridin-2-yl)-N-(TRANS-4-methylcyclohexyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

11) 4-(3-chloropyridin-2-yl)-N-(4-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

12) N-benzyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

13) N-(4-chlorophenyl)methyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

14) N-(4-tert-butylphenyl)methyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

15) 4-(3-chloropyridin-2-yl)-N-(4-triptoreline)methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

16) N-(4-tert-butylphenyl)-4-(pyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

17) N-(4-tert-butylphenyl)-4-(3-triptorelin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

18) N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

19) N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-2-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

20) N-(4-tert-butylphenyl)-6-chloro-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

21) 4-(3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

22) 4-(3-chloropyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

23) 4-(3-what lipiridy-2-yl)-N-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

24) N-(TRANS-4-tert-butylcyclohexyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

25) 4-(3-chloropyridin-2-yl)-N-(4-chloro-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

26) 4-(3-chloropyridin-2-yl)-N-(4-forfinal)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

27) 4-(3-chloropyridin-2-yl)-N-(3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

28) 4-(3-chloropyridin-2-yl)-N-(4-cryptomaterial-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

29) 4-(3-chloropyridin-2-yl)-N-(5-triptorelin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

30) 4-(3-chloropyridin-2-yl)-N-(2-triptorelin-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

31) 4-(3-chloropyridin-2-yl)-N-(4-isopropylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

32) 4-(3-chloropyridin-2-yl)-N-(quinoline-7-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

33) 4-(3-chloropyridin-2-yl)-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

34) 4-(3-chloropyridin-2-yl)-N-(4-ethoxycarbonylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

35) 4-[4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carbonyl]aminobenzoic acid,

36) N-(4-carbamoylmethyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

37) 4-(3-chloropyridin-2-yl)-N-(4-methylcarbamoylmethyl)-3,4-dihydro-2H-benzo[1,4]oxazin--carboxamide,

38) 4-(3-chloropyridin-2-yl)-N-(4-dimethylcarbamoyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

39) N-(4-acetylphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

40) 4-(3-chloropyridin-2-yl)-N-[4-(1-hydroxy-1-methyl)ethylphenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

41) 4-(3-chloropyridin-2-yl)-N-[4-(1-hydroxy-1-methyl)propylphenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

42) 4-(3-chloropyridin-2-yl)-N-(1-isobutylpyrazine-4-yl)phenyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

43) N-(TRANS-4-tert-butoxyethoxy)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

44) 4-(3-chloropyridin-2-yl)-N-(3-isopropoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

45) 4-(3-chloropyridin-2-yl)-N-(3-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

46) N-(4-tert-butylphenyl)-4-(pyridin-4-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

47) N-(4-tert-butylphenyl)-4-(3-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

48) 4-(3-chloropyridin-2-yl)-N-(4-piperidinophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

49) 4-(3-chloropyridin-2-yl)-N-(4-dimethylaminophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

50) 4-(3-chloropyridin-2-yl)-N-(4-morpholinyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

51) 4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-isopropoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxaz the n-8-carboxamide,

52) 4-(3-chloropyridin-2-yl)-N-(2-fluoro-4-isopropoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

53) 4-(3-chloropyridin-2-yl)-N-(4-fluoro-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

54) 4-(3-chloropyridin-2-yl)-N-(4-dimethylamino-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

55) 4-(3-chloropyridin-2-yl)-N-(4-isopropoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

56) 4-(3-chloropyridin-2-yl)-N-(4-methoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

57) 4-(3-chloropyridin-2-yl)-N-(4-isobutoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

58) N-(4-tert-butylphenyl)-4-(4-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

59) N-(4-tert-butylphenyl)-4-(6-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

60) N-(4-tert-butylphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

61) N-(4-tert-butylphenyl)-4-(pyridin-3-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

62) N-(4-cyanophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

63) N-(3-amino-4-chlorophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

64) N-(3-acetamido-4-chlorophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

65) N-[4-(4-carbamoylbiphenyl-1-yl)-3-forfinal]-4-(5-metile the one-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

66) N-[3-fluoro-4-(4-methylcarbamoylmethyl-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

67) N-[4-(4-dimethylcarbamoyl-1-yl)-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

68) N-[4-(4-ethoxypyridine-1-yl)-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

69) N-[3-fluoro-4-(4-isopropoxypyridine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

70) N-[3-fluoro-4-(3-methoxypiperidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

71) N-[3-fluoro-4-(4-methoxypiperidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

72) N-[3-fluoro-4-(3-ethoxypyrrolidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

73) N-(4-isobutoxy-3-ethoxycarbonylphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

74) 2-isobutoxy-{[4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carbonyl]amino}benzoic acid,

75) N-(3-carbarnoyl-4-isobutylphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

76) N-(4-isobutoxy-3-methylcarbamoylmethyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

77) N-(3-dimethylcarbamoyl-4-isobutylphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihyd the on-2H-benzo[1,4]oxazin-8-carboxamide,

78) N-(4-acetylphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

79) N-[4-(1-hydroxy-1-methyl)ethylphenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

80) N-(3-acetyl-4-chlorophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

81) N-[4-chloro-3-(1-hydroxy-1-methyl)ethylphenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

82) N-[4-(1-methoxy-1-methyl)ethylphenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

83) N-(3-chloro-4-methoxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

84) 4-(5-methylpyridin-2-yl)-N-(4-propoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

85) N-(3-fluoro-4-propoxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

86) N-(4-ethoxy-3-forfinal)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

87) N-(3-ethoxy-4-were)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

88) N-(3-carbamoylmethyl-4-were)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

89) N-(3-methoxyethoxy-4-were)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

90) N-[3-fluoro-4-(2-methoxypiperidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

91) N-(4-chlorophenyl)-4-(-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

92) N-(3-fluoro-4-were)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

93) N-(2-chloropyridin-5-yl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

94) 4-(3-chloropyridin-2-yl)-N-(4-ethoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

95) 4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-piperidinophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

96) 4-(3-chloropyridin-2-yl)-N-(TRANS-4-Toxicological)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

97) 4-(3-chloropyridin-2-yl)-N-(TRANS-4-isopropylcyclohexane)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

98) 4-(3-chloropyridin-2-yl)-N-(TRANS-4-cyclopentylacetyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

99) 4-(3-chloropyridin-2-yl)-N-(TRANS-4-cyclohexyloxycarbonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

100) 4-(3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

101) 4-(3-chloropyridin-2-yl)-N-[3-fluoro-4-(4-methoxypiperidine-1-yl)phenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

102) 4-(3-chloropyridin-2-yl)-N-[4-(4-ethoxypyridine-1-yl)-3-forfinal]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

103) 4-(3-chloropyridin-2-yl)-N-[3-fluoro-4-(4-isopropoxypyridine-1-yl)phenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

104) 4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

105) N-(TRANS-4-Toxicological)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

106) N-(TRANS-4-isopropoxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

107) N-(TRANS-4-cyclohexylmethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

108) N-(TRANS-4-aminocyclohexane)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

109) N-(1,4-dioxaspiro[4,5]DECA-8-yl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

110) 4-(5-methylpyridin-2-yl)-N-(4-oxocyclohexyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

111) 4-(5-methylpyridin-2-yl)-N-(CIS-4-morpholinoethoxy)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

112) N-(TRANS-4-dimethylaminoethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

113) N-(TRANS-4-diethylaminoethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

114) 4-(5-methylpyridin-2-yl)-N-[CIS-4-(pyrrolidin-1-yl)cyclohexyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

115) 4-(5-methylpyridin-2-yl)-N-[TRANS-4-(pyrrolidin-1-yl)cyclohexyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

116) 4-(5-methylpyridin-2-yl)-N-(4-piperidinyloxy)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

117) 4-(5-methylpyridin-2-yl)-N-(CIS-4-morpholinoethoxy)-3,4-dihydro-2H-Ben is about[1,4]oxazin-8-carboxamide,

118) N-(TRANS-4-acetamidophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

119) N-(TRANS-4-cyclohexylmethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

120) 4-(5-chloropyridin-2-yl)-N-(4-ethoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

121) N-(4-chlorophenyl)-4-(5-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

122) 4-(5-chloropyridin-2-yl)-N-[3-fluoro-4-(4-methoxypiperidine-1-yl)phenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

123) 4-(5-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

124) 4-(5-methylpyridin-2-yl)-N-(2-phenylethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

125) N-[2-(4-chlorophenyl)ethyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

126) N-[2-(3-chlorophenyl)ethyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

127) N-[2-(2-chlorophenyl)ethyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

128) 6-[8-(4-triptoreline)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,

129) 4-[3-chloro-5-(1-hydroxy-1-methyl)ethylpyridine-2-yl]-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

130) 4-[3-chloro-5-(1-hydroxyethyl)pyridin-2-yl]-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

131) 5-chloro-6-[8-(3-fluoro-4-triptorelin is)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,

132) N-(4-tert-butylphenyl)-4-(5-methoxycarbonylmethyl-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

133) 6-[8-(4-tert-butylphenyl)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,

134) 5-chloro-6-[8-(4-triptoreline)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,

135) 5-chloro-6-[8-(4-tert-butylphenyl)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,

136) 4-(5-acetyl-3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

137) N-(4-tert-butylphenyl)-4-(5-methylcarbamoylmethyl-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

138) N-(4-tert-butylphenyl)-4-(5-carbamoylation-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

139) N-(4-tert-butylphenyl)-4-(5-diethylaminomethyl-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

140) N-(4-tert-butylphenyl)-4-(5-nitropyridine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

141) 4-(5-aminopyridine-2-yl)-N-(4-tert-butylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

142) 4-(5-acetamidophenyl-2-yl)-N-(4-tert-butylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

143) 4-(5-methoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

144) 4-(5-ethoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

145) 4-(3-chloro-5-methoxypyridine-2-yl)-N-(4-cryptomite is phenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

146) 4-(5-hydroxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

147) 4-(5-methoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

148) N-(4-tert-butylphenyl)-4-(4-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

149) 4-(5-herperidin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

150) 4-(3,5-differencein-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

151) N-(4-tert-butylphenyl)-4-(3-methoxypyridine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

152) N-(4-tert-butylpiperazine-1-yl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

153) 4-[5-(2-hydroxyethoxy)pyridine-2-yl]-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

154) 4-[3-chloro-5-(2-hydroxyethyl)pyridine-2-yl]-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

155) 4-(5-methylpyridin-2-yl)-N-(4-neopentecostal)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

156) N-(3-fluoro-4-piperidinophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

157) N-(3-fluoro-4-morpholinomethyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

158) N-(3,4-differenl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

159) N-(3-fluoro-4-methoxyphenyl)-4-(5-methylpyridin--yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

160) N-(4-ethoxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

161) N-[4-(2-oxopiperidin-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

162) 4-(5-methylpyridin-2-yl)-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

163) N-(4-dimethylamino-3-forfinal)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

164) N-{3-fluoro-4-[N-(2-methoxyethyl)isopropylamino]phenyl}-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

165) N-{4-[N-(2-acetoxyethyl)isopropylamino]-3-forfinal}-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

166) N-{3-fluoro-4-[N-(2-hydroxyethyl)isopropylamino]phenyl}-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

167) N-[4-(4-ethoxycarbonylpyrimidine-1-yl)-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

168) 1-(4-{[4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carbonyl]amino}phenyl)piperidine-4-carboxylic acid,

169) N-[3-fluoro-4-(4-methoxypiperidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

170) N-[4-(4-acetoxypiperidine-1-yl)-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

171) N-[3-fluoro-4-(4-hydroxypiperidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

172) N-(3-methoxy-4-were)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

173) N-[3-(2-hydroxyethoxy)-4-were]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

174) N-[4-(1-tert-butoxycarbonylamino-4-yl)oxy-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

175) N-[4-(piperidine-4-yl)oxy-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

176) N-(TRANS-4-ethoxycarbonylmethylene)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

177) (TRANS-4-{[4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carbonyl]amino}cyclohexyloxy)acetic acid,

178) N-(TRANS-4-carbamoylmethyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

179) N-(TRANS-4-methylcarbamoylmethyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

180) N-(TRANS-4-dimethylcyclohexyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

181) N-[TRANS-4-(2-hydroxyethoxy)cyclohexyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

182) N-(TRANS-4-methoxymethylethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

183) N-(TRANS-4-isopropoxyphenoxy)-4-(5-methylpyridin-2-yl)-3,4-d the hydro-2H-benzo[1,4]oxazin-8-carboxamide,

184) N-(CIS-4-methoxymethylethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

185) N-(CIS-4-isopropoxyphenoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

186) N-(TRANS-4-tert-butoxyethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

187) N-(TRANS-4-isobutyryloxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

188) N-(4,4-dimethylcyclohexyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

189) N-[TRANS-4-(3-methylbutoxy)cyclohexyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

190) N-(TRANS-4-benzyloxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

191) N-(TRANS-4-isopropylcyclohexane)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

192) N-(TRANS-4-propylcyclohexyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

193) N-(TRANS-4-neopentylglycol)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

194) N-(4-tert-butylphenyl)-4-(5-methoxypyridine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

195) 5-chloro-6-[8-(3-chloro-4-trifloromethyl)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,

196) 5-chloro-6-[8-(4-trifloromethyl)carbamoyl the -2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,

197) 4-(5-methylaminomethyl-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

198) 4-(5-ethoxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

199) 4-(3-chloro-5-methoxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

200) 4-[5-(2-hydroxyethoxy)pyridine-2-yl]-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

201) 4-(5-hydroxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

202) 4-(5-methoxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

203) 4-(3-cyano-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

204) 4-(3-carbamoylation-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

205) 4-(3-methylcarbamoylmethyl-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

206) 4-(3-dimethylcarbamoyl-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

207) 4-(3-benzyloxycarbonylamino-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

208) 2-[8-(4-trifloromethyl)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,

209) 4-(3-benzyloxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]ox the zine-8-carboxamide,

210) 4-(3-hydroxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

211) 4-[3-(2-hydroxyethoxy)pyridine-2-yl]-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

212) {2-[8-(4-triftormetilfullerenov)-2,3-dihydrobenzo[1,4]oxazin-4-yl]pyridine-3-yl}exucuse acid,

213) 4-(3-carbamoyloximes-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

214) 4-(3-methylcarbamoylmethyl-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

215) 4-(3-dimethylcarbamodithioato-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

216) 4-[3-(pyridin-2-yl)methoxypyridine-2-yl]-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

217) 4-[3-(pyridin-3-yl)methoxypyridine-2-yl]-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

218) 4-(5-cyano-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

219) 4-(5-acetamidomethyl-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

220) 4-(3-chloro-5-methoxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

221) 4-[5-(N-methylacetamide)methylpyridin-2-yl]-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

222) 4-(5-aminomethylpyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

223) 4-(5-dimethylaminomethylene-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

224) 4-(3-chloropyridin-2-yl)-2-methylcarbamoyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

225) 4-(6-hydroxymethyluracil-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

226) 4-(3-chloropyridin-2-yl)-2-dimethylcarbamoyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

227) 4-(5-carbarnoyl-3-chloropyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

228) (S)-3-atsetamidometil-4-(3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

229) (R)-4-(3-chloropyridin-2-yl)-8-(4-cryptomaterial)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid,

230) 4-(3-chloropyridin-2-yl)-2-methoxycarbonyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

231) 4-(3-chloropyridin-2-yl)-2-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

232) 4-(3-chloropyridin-2-yl)-8-(4-triftormetilfullerenov)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid,

233) (S)-3-carbarnoyl-4-(3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide is,

234) (S)-4-(3-chloropyridin-2-yl)-3-methylcarbamoyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

235) 2-carbarnoyl-4-(3-chloropyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

236) N-(4-chlorophenyl)-N-methyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

237) N-(benzo[1,3]dioxol-5-yl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

238) N-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

239) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

240) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3-chloro-4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

241) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

242) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3-fluoro-4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

243) 4-(5-hydroxymethyluracil-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

244) 4-(5-hydroxymethyluracil-2-yl)-N-(4-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

245) 4-(3-chloro-5-methoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

246) 4-(4-hydroxymethylpropane-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

247) 4-(3-hydroxymethylpropane-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

248) (+)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

249) (-)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

250) (+)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

251) (-)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

252) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(2-triptorelin-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

253) N-(4-bromo-3-chlorophenyl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

254) 4-[5-(1-hydroxy-1-methyl)ethylpyridine-2-yl]-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

255) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-isopropoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

256) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(2,3-dichloropyridine-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

257) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3,4,5-trichlorophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

258) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(6-fermentation-2-yl)-3,4-dihydro-2H-b is the site, located between[1,4]oxazin-8-carboxamide,

259) N-(4-bromo-3-triptoreline)-N-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

260) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(2-triftoratsetata-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

261) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3,4,5-tryptophanyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

262) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-fluoro-3-nitrophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

263) N-(3-amino-4-forfinal)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

264) N-(tert-butylphenyl)-4-(5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

265) N-(3,5-bis-triptoreline)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

266) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-[(2,2,2-triptoreline)phenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

267) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-[3-chloro-(2,2,2-triptoreline)phenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

268) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-triftormetilfosfinov)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

269) N-(TRANS-4-tert-butylcyclohexyl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

270) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3-fluoro-4-isopropoxyphenyl)-3,dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

271) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3-fluoro-4-piperidinophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

272) N-(4-tert-butylphenyl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

273) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-[4-(1-hydroxy-2,2,2-Cryptor-1-trifluoromethyl)ethylphenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

274) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(2,2,3,3-titrator-2,3-dihydrobenzo[1,4]dioxin-6-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

275) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

276) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(2,3-dichlorophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

277) N-(4-bromo-3-forfinal)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

278) N-(4-bromophenyl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

279) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3,5-dichlorophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

280) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-deformational)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

281) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-chlorophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

282) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-isopropylphenyl)-3,4-dihydro-2H-benzo[1,4]oxa is in-8-carboxamide,

283) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

284) 4-[3-chloro-5-(1-hydroxyethyl)pyridin-2-yl]-N-(3-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

285) 4-(3-chloropyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-3-oxo-2H-benzo[1,4]oxazin-8-carboxamide,

286) (R)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

287) (R)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

288) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

289) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

290) (S)-4-(5-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

291) (S)-4-(5-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

292) (S)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

293) (S)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

294) (S)-4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-isopropoxyphenyl)-3-hydroxymethyl-3,4-dihydro-2H-what Enzo[1,4]oxazin-8-carboxamide,

295) (S)-4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-trifloromethyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

296) (S)-4-(3-chloropyridin-2-yl)-N-(3-chloro-4-piperidinophenyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

297) (S)-4-(3-chloropyridin-2-yl)-N-(4-dimethylamino-3-forfinal)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

298) (S)-4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-were)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

299) (S)-N-(TRANS-4-tert-butylcyclohexyl)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

300) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(TRANS-4-neopentylglycol)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

301) (S)-N-(4-chlorophenyl)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

302) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-isopropylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

303) (S)-4-(3-chloropyridin-2-yl)-N-(4-fluoro-3-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

304) (S)-N-(4-bromo-3-chlorophenyl)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

305) (S)-4-(3-chloropyridin-2-yl)-N-(4-dimethylamino-3-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

306) (S)-4-(3-chloropyridin-2-yl)-N-(4-isoprop the C-3-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

307) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-piperidino-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

308) (S)-4-(3-chloropyridin-2-yl)-N-(4-ethoxy-3-forfinal)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

309) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-methoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

310) (S)-4-(3-chloro-5-methoxypyridine-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

311) (S)-4-(3-chloro-5-methoxypyridine-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

312) (S)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-N-(2-triptorelin-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

313) (S)-3-hydroxymethyl-N-(4-methoxy-3-triptoreline)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

314) (S)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-N-(4-piperidino-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

315) (S)-N-(3-fluoro-4-triptoreline)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

316) (S)-N-(3-chloro-4-trifloromethyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

317) (S)-N-(3,4-dichlorophenyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

318) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-isobutoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

319) (S)-4-(3-chloropyridin-2-yl)-N-(3,4-dichlorophenyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

320) (S)-4-(3-chloropyridin-2-yl)-N-(4-chloro-3-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

321) (S)-N-(4-bromo-3-forfinal)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

322) (S)-N-(4-chloro-3-triptoreline)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

323) (S)-3-hydroxymethyl-N-(4-isopropoxy-3-triptoreline)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

324) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-morpholino-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

325) (S)-N-(2-chloro-4-triptoreline)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

326) (S)-3-hydroxymethyl-4-(3-methylpyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

327) (S)-3-hydroxymethyl-4-(3-methylpyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

328) (S)-N-(4-tert-butoxy-3-forfinal)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

329) (S)-4-(3-chloropyridin-2-the l)-N-(3-fluoro-4-isobutylphenyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

330) (S)-3-hydroxymethyl-N-(4-isobutoxy-3-triptoreline)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

331) (S)-N-(3-fluoro-4-isopropoxyphenyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

332) (S)-N-(3-fluoro-4-morpholinomethyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

333) (S)-N-(4-chlorophenyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

334) (S)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-N-(2-morpholino-4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

335) (S)-N-(4-tert-butoxy-3-forfinal)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

336) (S)-N-(4-bromo-3-forfinal)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

337) 4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

338) (S)-4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

339) (S)-N-(3-fluoro-4-isobutylphenyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

340) (S)-N-(4-fluoro-3-triptoreline)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

341) 4-(3-chloropyridin-2-yl)-3-(1-g is proxetil)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

342) (R)-9-(3-chloropyridin-2-yl)-7-hydroxy-N-(4-trifloromethyl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide,

343) (R)-9-(3-chloropyridin-2-yl)-7-hydroxy-N-(4-triptoreline)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide,

344) (S)-9-(3-chloropyridin-2-yl)-7-hydroxy-N-(4-trifloromethyl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide,

345) N-(4-tert-butylphenyl)-4-(pyrazin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

346) N-(4-chlorophenyl)-4-(5-ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

347) N-(4-ethoxyphenyl)-4-(5-ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

348) 4-(6-chloropyridin-3-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

349) 4-(4-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

350) 4-(5-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

351) (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

352) (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

353) (S)-N-(3,4-dichlorophenyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

354) (S)-N-(3-fluoro-4-isopropoxyphenyl)-3-hydroxymethyl-4-(5-metilius the l-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

355) (S)-N-(3-fluoro-4-tert-butoxyphenyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

356) (S)-N-(3-fluoro-4-isobutylphenyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

357) (S)-N-(4-bromo-3-forfinal)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

358) (S)-N-(4-fluoro-3-triptoreline)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

359) (S)-N-(3-fluoro-4-morpholinomethyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

360) (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-N-(2-triptorelin-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

361) (S)-3-hydroxymethyl-4-(5-methoxazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

362) (S)-3-hydroxymethyl-4-(5-methoxazole-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

363) (S)-4-(4,5-dimethylthiazol-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

364) (S)-4-(4,5-dimethylthiazol-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

365) (S)-3-hydroxymethyl-4-(5-methyl[1,3,4]thiadiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

366) (S)-3-hydroxymethyl-4-(5-methyl[1,3,4]TIA is eazol-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

367) 4-(4,5-dimethylthiazol-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxamide,

368) 4-(4,5-dimethylthiazol-2-yl)-N-(4-trifloromethyl)-1-oxo-3,4-dihydrobenzo[1,4]thiazin-8-carboxamide,

369) N-(4-tert-butylphenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

370) N-(4-isobutylphenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

371) N-(4-chlorophenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

372) (S)-4-(2-chlorophenyl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

373) (S)-4-(2-chlorophenyl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

374) (S)-4-(2-chlorophenyl)-N-(3-fluoro-4-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

375) (S)-4-(4-chlorophenyl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

376) (S)-3-hydroxymethyl-4-(4-methoxyphenyl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

377) (S)-3-hydroxymethyl-4-(4-methoxyphenyl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,

378) (S)-4-(4-chlorophenyl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide and

379) (S)-4-(4-chlorophenyl)-N-(4-chlorophenyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide is,

or its pharmaceutically acceptable salt.

10. Pharmaceutical composition comprising a condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the above claims 1 to 9 and a pharmaceutically acceptable carrier.

11. Pharmaceutical composition for treatment and/or prevention of a disease selected from pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ischemic symptom, nerve injury, neurogenic skin damage, inflammatory disease, pruritus, allergic rhinitis, apoplexy, irritable bowel syndrome, asthma chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer and inflammatory bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and urinary incontinence, Lucaya condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the above claims 1 to 9 and a pharmaceutically acceptable carrier.

12. Pharmaceutical composition for treatment and/or prevention of pain, including condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the above claims 1 to 9 and a pharmaceutically acceptable carrier.

13. The pharmaceutical composition according to the above item 12, where the pain is acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute post herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy or neurodegenerative disease.

14. The inhibitor activity of subtype 1 receptor vanilloid (VR1), including the condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the preceding claims 1 to 9 and a pharmaceutically acceptable carrier.

15. The method of treatment and/or prevention of a disease selected from pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic postherpetic the Russian neuralgia, post-operative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ischemic symptom, nerve injury, neurogenic skin damage, inflammatory disease, pruritus, allergic rhinitis, apoplexy, irritable bowel syndrome, asthma, chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer and inflammatory bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and urinary incontinence, characterized in that it includes the introduction of a pharmacologically effective amount of the condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the preceding claims 1 to 9.

16. The method of treatment and/or prevention of pain, characterized in that it includes the introduction of a pharmacologically effective amount of the condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the preceding claims 1 to 9.

17. The method of treatment and/or prophylaxis according to the above item 16, where the pain is acute pain, chronic pain, neuropathic pain, Belpre rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute post herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy or neurodegenerative disease.

18. Packaging, including pharmaceutical composition according to any one of the above PP-13 and related to this pharmaceutical compositions written instructions indicating that the composition can be applied or should be applied for the treatment and/or prevention of a disease selected from pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ischemic symptom, nerve injury, neurogenic skin damage, inflammatory disease, pruritus, allergic rhinitis, apoplexy, irritable bowel syndrome, asthma, chronic is about obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer and inflammatory bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and urinary incontinence.

19. The use of condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the preceding claims 1 to 9 to obtain the pharmaceutical composition according to the above item 11, for the treatment and/or prevention of a disease selected from pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ischemic symptom, nerve injury, neurogenic skin damage, inflammatory disease, pruritus, allergic rhinitis, apoplexy, irritable bowel syndrome, asthma, chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcers and dwenadzatiperstnuu the second colon and inflammatory bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and urinary incontinence.

20. The use of condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the preceding claims 1 to 9 to obtain a pharmaceutical composition for the treatment and/or prevention of pain according to the above item 12.

21. The use of condensed benzamide derivative or its pharmaceutically acceptable salt according to the above claim 20, where the pain is acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute post herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy or neurodegenerative disease.

22. Drug, which includes a combination pharmaceutical composition comprising a condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the above claims 1 to 9 and a pharmaceutically acceptable carrier, one or more agents selected from the group consisting of anti-virus is Ghent, antidepressant, anti-convulsants, anti-arrhythmic drugs, local anesthetic means of anesthetic drugs, receptor antagonist N-methyl-D-aspartate, cortical steroid adrenal, means for blocking nerve, non-steroidal anti-inflammatory analgesic money, drugs, analgetika type antagonist, agonist receptor α2adrenaline, a medicine for external application, the antagonist of calcium channels and the discoverer of potassium channels.

23. The use of condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the above claims 1 to 9 for obtaining a medicinal product according to the above item 22.

24. The method of treatment or prophylaxis of a disease selected from pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ishemic the ski symptom, of nerve injury, neurogenic skin damage, inflammatory disease, pruritus, allergic rhinitis, apoplexy, irritable bowel syndrome, asthma, chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer and inflammatory bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and urinary incontinence, characterized in that one or more agents selected from the group consisting of antiviral agent, antidepressant, anti-convulsants, anti-arrhythmic drugs, local anesthetic means of anesthetic drugs, receptor antagonist N-methyl-D-aspartate, cortical steroid adrenal, means for blocking nerve, non-steroidal anti-inflammatory analgesic money, drugs, analgetika antagonist, agonist receptor α2adrenaline, a medicine for external application, the antagonist of calcium channels and the discoverer of potassium channels, used for holding it in combination with the introduction of a pharmacologically effective amount of the inhibitor activity of subtype 1 receptor vanilloid (VR1).

25. The way Le is to be placed and/or prophylaxis according to the above paragraph 24, where the inhibitor activity of subtype 1 receptor vanilloid (VR1) is a condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the above claims 1 to 9.

26. The method of treatment and/or prevention of pain, including the introduction of inhibitor activity subtype 1 receptor vanilloid (VR1) in combination with the analgesia caused by stimulation of pain selected from acupuncture, therapy stimulation transcutaneous electro-acupuncture, transcutaneous electrical stimulation therapy nerve therapy by acupuncture with the use of point of silver electrodes (SSP)therapy of peripheral nerve stimulation, electrical therapy of spinal cord stimulation, electroconvulsive therapy, laser therapy and low-frequency therapy.

27. The method of treatment and/or prophylaxis according to the above p, where the inhibitor activity of subtype 1 receptor vanilloid (VR1) is a condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the above claims 1 to 9.

28. The method of treatment and/or prevention of postoperative neuralgia, characterized in that the inhibitor activity of subtype 1 receptor vanilloid (VR1) is administered after surgical operation selected from the excision of the scar, curing nerve freezing, excision of peripheral nerve, ISSE is placed dorsal roots of the spinal cord, sympathectomy, and the destruction of the entrance area dorsal roots of the spinal cord, cordotomy and excision of the frontal lobe (brain).

29. The method of treatment and/or prophylaxis according to the above paragraph 28, where the inhibitor activity of subtype 1 receptor vanilloid (VR1) is a condensed benzamide derivative or its pharmaceutically acceptable salt according to any of the above claims 1 to 9.

Condensed benzamide derivative of the present invention effectively inhibits the activity of subtype 1 receptor vanilloid (VR1) and is therefore effective for drug treatment and/or prophylaxis of diseases such as pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute post herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ischemic symptom, nerve damage, neurogenic damage skin, inflammatory disease, pruritus, allergic rhinitis, apoplexy, irritable bowel syndrome, asthma, chronic obstructive l the gotschna disease dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer and inflammatory bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and urinary incontinence. In particular, it is effective as a therapeutic agent and a preventive agent for diseases accompanied by pain condition, such as pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute post herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy and neurodegenerative disease. In addition, it has been proposed different mechanisms of action of conventional analgesics.

The BEST WAY of carrying out the INVENTION

The definition of each term used in this description, is as follows.

"C1-6-alkyl group" represents an unbranched or branched alkyl group containing 1-6 carbon atoms, and specifically includes methyl group, ethyl group, through the group, isopropyl group, boutelou group from boutelou group, second-boutelou group, tert-boutelou group, pentelow group, isopentyl group, tert-pentelow group, hexoloy group, etc.

"C1-4-alkyl group" represents an unbranched or branched alkyl group containing 1-4 carbon atoms, and specifically includes methyl group, ethyl group, through the group, isopropyl group, boutelou group, isobutylene group, sec-boutelou group and tert-boutelou group.

Preferred "C1-6-alkyl group as R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26and R27is "C1-4-alkyl group, particularly methyl group and ethyl group. Preferred C1-6-alkyl group in the ring R1 and the ring P2, which may be substituted, is C1-4-alkyl group, particularly methyl group, ethyl group, through the group, isopropyl group, bucilina group, isobutylene group, sec-bucilina group and tert-bucilina group.

"Halogen atom" is a fluorine atom, chlorine atom, bromine atom or iodine atom, preferred are a fluorine atom and a chlorine atom.

As R4site is titanium is a chlorine atom and halogen atoms in the ring R1 and the ring P2, which may be substituted, preferred are a chlorine atom and a fluorine atom.

"Halogen-C1-6-alkyl group is C1-6-alkyl group as defined above definition, substituted by the halogen atom of the above definition, and preferably halogenated alkyl group, which alkyl group is unbranched or branched alkyl group containing 1-4 carbon atoms. Specifically, it includes pharmacylow group, deformational group, triptorelin group, bromatology group, chloromethylene group, 1,2-dichloroethylene group, 2,2-dichloroethylene group, 2,2,2-triptorelin group, etc.

"C1-6-alkoxygroup is alkoxygroup, in which the alkyl part is C1-6-alkyl group as defined above definition. Specifically, it includes a methoxy group, ethoxypropan, propoxylate, isopropoxy, butoxypropyl, isobutoxy, sec-butoxypropyl, tert-butoxypropyl, pentyloxy, isopentylamine, 2-methylbutoxy, neopentylglycol, 1-ethylpropoxy, hexyloxy, 4-methylpentylamino, 3-methylpentylamino, 2-methylpentylamino, 1-methylpentylamino, 3,3-Dimethylbutane, 2,2-Dimethylbutane, 1,1-Dimethylbutane, 1,2-dimethylbutyramide, 1,3-Dimethylbutane, 2,3-dimethy is butoxypropyl, 2-ethylbutane etc. is Preferred alkoxygroup, in which the alkyl part is unbranched or branched alkyl group containing 1-4 carbon atoms.

"Halogen-C1-6-alkoxygroup" is halogenlampe, in which C1-6-alkyl group, which is part of the C1-C6-alkoxygroup substituted by one or more identical or different halogen atoms, and specifically includes formatexpr, dipterocarp, cryptometer, bromoethoxy, chlorotoxin, 1,2-dichloromethoxy, 2,2-dichloromethoxy, 2,2,2-cryptometer etc.

"C1-6-allylthiourea" is C1-6-alkyl group mentioned above is attached to the sulfur atom, for example, unbranched or branched alkylthiophene containing 1-6 carbon atoms, such as methylthiourea, ethylthiourea, PropertyGroup, isopropylthio, butylthiourea, isobutylthiazole, second-butylthiourea, tert-butylthiourea, intelligroup, isopentype, 2-methylbutyrate, pointertype, vexillographer, 4-methylpentylamino, 3-methylpentylamino, 2-methylpentylamino, 3,3-dimethylbutylamino, 2,2-dimethylbutylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,3-dimethylbutadiene and preferably C1-allylthiourea.

"C1-6-alkoxycarbonyl group" represents an unbranched or branched C1-6-alkoxygroup attached to a carbonyl group, and specifically includes methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, isobutoxyethanol group, sec-butoxycarbonyl group, tert-butoxycarbonyl group, ventilatsioonile group, isobutylacetophenone group, 2-metilbutanoilny group, neopentylglycol group, 1-ethylpropylamine group, hexyloxymethyl group, 4-methylbenzyloxycarbonyl group, 3-methylbenzyloxycarbonyl group, 2-methylbenzyloxycarbonyl group, 1-methylbenzyloxycarbonyl group, 3,3-dimethylbutylamino group, 2,2-dimethylbutylamino group, 1,1-dimethylbutylamino group, 1,2-dimethylbutylamino group, 1,3-dimethylbutylamino group, 2,3-dimethylbutylamino group, 2-metilbutanoilny group, etc. is Preferred alkoxycarbonyl group, in which alkoxygroup it is unbranched or branched alkoxygroup containing 1-4 carbon atoms.

Preferred examples of the acyl group include a formyl group; carbox the function group; karbamoilnuyu group; thiocarbamoyl group; C1-6-alkylcarboxylic group (for example, acetyl group, propionyl group, butyryloxy group, isobutyryloxy group, valerino group, isovaleryl group, pivaloyl group and hexanoyl group); C2-7-alkenylboronic group (for example, crotonylene group; C3-8-cycloalkylcarbonyl group (for example, cyclobutanecarbonyl group, cyclopentanecarbonyl group, cyclohexanecarbonyl group and cyclopentanecarbonyl group); a C3-9-cycloalkylcarbonyl group (for example, 2-cyclohexanecarbonyl group); C6-14-arylcarbamoyl group (for example, benzoyloxy group, 1-naftolin group and 2-naftolin group); C7-14-aralkylamines group (for example, benzylcarbamoyl group, penicillinbinding group, phenylpropionyl group and phenylmethylsulphonyl group); C8-13-arylalkylamine group (for example, strykersville group); C8-13-arylalkylamine group (for example, feniletinilpireny group); an aromatic heterocyclic carbonyl group (for example, nicotinoyl group, isonicotinoyl group, fuelleborni group, taylorsville group, pyrimidinecarbonitrile group, benzofuranyl group, 1H-indotricarbocyanine group and hinolincarbonova GRU is PU); non-aromatic heterocyclic carbonyl group (for example, pyrrolidinylcarbonyl group, piperidinylcarbonyl group, morpholinomethyl group, tomorrooooooooow group, piperazinylcarbonyl group, thiazolidinediones group, hexamethylenediamine group and tetrahydroxyphenylchlorin group); C1-6-alkoxycarbonyl group (for example, methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl group and tert-butoxycarbonyl group); C6-14-aryloxyalkyl group (for example, vinyloxycarbonyl group and naphthalocyanine group); C7-14-aracelikarsaalyna group (for example, benzyloxycarbonyl group and ventilatsioonile group; mono - or di-C1-6-alkylcarboxylic group (for example, methylcarbamoyl group, ethylcarbitol group, dimethylcarbamoyl group, diethylcarbamoyl group, ethylmethylamino group, profilirovannuju group, butylcarbamoyl group, tert-butylcarbamoyl group, intelceremony group, hexylberberine group; mono - or di-C1-6-alkyldiethanolamine group (for example, methylthiocarbamate group and etiltiakarbotsianina group); C6-14-arylcarbamoyl group (for example, phenylcarbamoyloxy group); a C3-10-CEC is alkylcarboxylic group (for example, cyclopropylamino group, cyclopentanecarbonyl group and cyclohexylcarbonyl group); C7-14-aralkylamines group (for example, benzylcarbamoyl group, phenetically group and diphenylethylenediamine group); C4-13-cycloalkylcarbonyl group (for example, cyclohexyloxycarbonyloxy group); an aromatic heterocyclic karbamoilnuyu group (for example, isoxazolecarboxylic group and benzothiazolylthio group); non-aromatic heterocyclic karbamoilnuyu group (for example, pyrrolidinylcarbonyl group); C1-10-alkylsulfonyl group (for example, methylsulfinyl group and ethylsulfinyl group); C1-10-alkylsulfonyl group (for example, methylsulfonyl group and ethylsulfonyl group); C6-14-arylsulfonyl group (for example, phenylsulfonyl group); (mono - or di-C1-10-alkyl)phosphonopropyl, which may form a ring (for example, dimethylphosphino; diethylphosphonate; diisopropylphosphoramidite; dibutylphthalate; 2-oxide-1,3,2-dioxaphosphinan group; mono - or di-(C1-6-alkyl group which may be substituted by 1-3 halogen atoms)sulfamoyl group (for example, methylsulfonyl group and ethylsulfonyl group), etc.

Preferred examples of alloctype include acyloxy is with 2-13 carbon atoms, for example, C1-6-alkylcarboxylic etc. (for example, atomic charges, propionyloxy, butyryloxy, isobutyryloxy).

Preferred examples of "heterokaryosis include one 5-7-membered ring type heterokaryosis, for example 2-pyridyloxy, 3 pyridyloxy, 2-imidazolidone, 2-pyrimidinone, 1,2,4-triazole-5-yloxy etc.

"Carbocyclic group" is a saturated or unsaturated cyclic hydrocarbon group containing 3 to 14 carbon atoms, and specifically means aryl group, cycloalkyl group, cycloalkenyl group, described below, or condensed carbocyclic ring, in which these rings are condensed.

Here "aryl group" means an aromatic hydrocarbon group containing 6-14 carbon atoms, and specifically includes a phenyl group, naftalina group, biphenylene group, untilnow group, indenolol group, pentylaniline group, azulinebloo group, fluorenyl group, phenanthroline group, etc. are Preferably it represents a phenyl group, naftalina group and biphenylene group. Particularly preferred is a phenyl group.

Here cycloalkyl group" is a saturated cycloalkyl group containing 3-8 carbon atoms, and specifically includes cyclopropyl group is, cyclobutyl group, cyclopentyl group, tsiklogeksilnogo group, cycloheptyl group and cyclooctyl group.

"Cycloalkenyl group" represents cycloalkenyl group containing 3-8 carbon atoms, and preferably contains at least one, preferably one or two double bonds. Specifically, it includes cyclopropyl group, cyclobutenyl group, cyclopentenyl group, cyclopentadienyls group, cyclohexenyl group, cyclohexadienyl group, (2,4-cyclohexadiene-1-ilen group, 2,5-cyclohexadiene-1-ilen group, and so on), cycloheptenyl group, cyclooctyl group, etc.

"Condensed carbocyclic group in which the aryl group, cycloalkyl group and cycloalkenyl group are condensed specifically includes indenolol group, indenolol group, 1,4-dihydronaphthalene group, 1,2,3,4-tetrahydronaphthalene group (1,2,3,4-tetrahydro-2-naftalina group, 5,6,7,8-tetrahydro-2-naftalina group, and so on), perhydroanthracene group, etc. When the ring P2 is preferably aryl group and cycloalkyl group, more preferred are a phenyl group, biphenylene group and tsiklogeksilnogo group.

"Kalkilya group" is arylalkyl group in which the aryl part is the aryl group, as described above, specifically, phenyl group and the alkyl part is 1-6-alkyl group as defined above definition, and specifically it includes benzyl group, fenetylline group, 3-phenylpropyl group, 4-phenylbutyl group, 6-phenylhexanoic group, etc.

"Urlcategory" is arialcategory, in which the aryl part is an aryl group as described above, specifically, phenyl group, and alkoxides is C1-6-alkoxygroup the above values, specifically it includes benzyloxy, 3-phenylpropoxy, 4-phenylbutyraldehyde, 6-vanillacracker etc.

"Cycloalkylcarbonyl" is cycloalkylcarbonyl in which cycloalkyl part is cycloalkyl group above definitions and alkoxides is C1-6-alkoxygroup the above definitions, specifically it includes cyclopropylmethoxy, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethoxy etc.

"Heterocyclic group" means a saturated or unsaturated (including partially unsaturated and fully unsaturated) 5-membered or 6-membered monocyclic heterocyclic ring containing, besides carbon atoms, at least one, preferably 1-4 heteroatoms selected from a nitrogen atom, oxygen atom is and sulfur atom, or a condensed ring of these heterocyclic rings or a condensed ring of these heterocyclic rings or carbocyclic ring selected from benzene, cyclopentane and cyclohexane.

"Saturated monocyclic heterocyclic group" includes pyrrolidinyloxy group, tetrahydrofuryl group, tetrahydrocannibinol group, imidazolidinyl group, pyrazolidine group, 1,3-DIOXOLANYL group, 1,3-oxathiolanes group, oxazolidinyl group, diazolidinyl group, piperidinyl group, piperidino, piperazinilnom group, piperazinone, tetrahydropyranyloxy group, tetrahydropyranyloxy group, dioxinlike group, morpholinyl group, thiomorpholine group, 2-oxopyrrolidin group, 2-oxopiperidine group, 4-oxopiperidine group, 2,6-dioxopiperidin group, etc.

"Unsaturated monocyclic heterocyclic group" includes pyrrolidino group, follow group, thienyl group, imidazolidinyl group, 1,2-dihydro-2-Oxymetazoline group, pyrazolidine group, diazolidinyl group, oxazolidinyl group, isoxazolyl group, thiazolidine group, isothiazolinone group, 1,2,4-triazolyl group, 1,2,3-triazolyl group, tetrazolyl group, 1,3,4-oxadiazolyl group, 1,2,4-ox is diazolidinyl group, 1,3,4-thiadiazolyl group, 1,2,4-thiadiazolyl group, foratenolol group, pyridyloxy group, pyrimidinyl group, 3,4-dihydro-4-oxopyrimidine group, pyridazinyl group, personilnya group, 1,3,5-triazinyl group, imidazolidinyl group, pyrazolidine group and oxazolidinyl group (2-oxazolidinyl group, 3-oxazolidinyl group and 4-oxazolidinyl group), isooxazolyl group, thiazolidine group, isothiazolinone group, pyranyloxy group, 2-oxopyrrolo group, 2-oxo-2,5-dihydropyrrolo group, 1,1-dioxo-1H-isothiazolinone group.

"Condensed heterocyclic ring" includes indolenine group (for example, 4-indolering group, 7-indolering group, and so on), isoindolyl 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, benzothiophene group (for example, 4-benzothiophene group, 7-benzothiophene group, and so on), benzoxazolyl group (for example, 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-benzo is easilyyou group etc) and indolizinyl group, pinolillo group, izohinolinove group, 1,2-dihydro-2-oxopyridine group, chinazolinei group, khinoksalinona group, indolinyl group, talinolol group, chinaliaoning group, perilou 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]dioxolo group, 2,3-dihydrobenzo[1,4]dioxaspiro group, 3,4-methylenedioxyphenyl group, 4,5-ethylenediaminetetramethylene group, romanello group, romanello group, isopropanolol group, etc.

As for groups, not specifically shown here, the usual definition should be as follows.

In General formula [1] preferred examples and specific preferred examples of each character are the following. However, the present invention is not limited to them.

[Preferred Z]

Z preferably represents-O-, -NR5-, -S - or-SO - and R5preferably represents a hydrogen atom or C1-4-alkyl group. Preferably Z represents-O-, -S - or-SO-.

[Preferred l and m]

Preferably l is 0 or 1, and preferably m is 0 or 1. Preferably l+m is 1 or 2 and more preferably 1.

[Preferred R1 ]

R1represents preferably C1-6-alkyl group which can preferably be substituted by a hydroxyl group or a halogen atom. Particularly preferred R1represents a hydrogen atom.

[Preferred R2]

R2preferably represents a hydrogen atom, hydroxyl group, C1-6-alkyl group (preferably, C1-4-alkyl group), carboxyl group, C1-6-alkoxycarbonyl group (preferably, C1-4-alkoxycarbonyl group), C1-6-alkyl group substituted by a hydroxyl group (preferably, replacement of C1-4-alkyl group), karbamoilnuyu group (preferably, karbamoilnuyu group, mono-C1-4-alkyl substituted karbamoilnuyu group or di-C1-4-alkyl substituted karbamoilnuyu group), C1-6 is an alkyl group substituted by allmineral (preferably acylaminoalkyl C1-C4-alkyl group or R1and R2connected together, form a carbonyl group.

R2is particularly preferably a hydrogen atom or C1-4-alkyl group substituted by a hydroxy-group.

[Preferred R3]

R3represents a hydrogen atom or C1-6-alkyl group and preferably a hydrogen atom or methyl group.

[Preferred R4]

R4before the hat is preferably a hydrogen atom or a halogen atom.

[Preferred V]

V preferably represents a direct bond or -(CH2)n-where n is 1 or 2. Particularly preferably it is a direct connection.

[Preferred ring P1 and P2]

Each of the rings R1 and R2 represents a heterocyclic group (preferably 5-membered or 6-membered heterocyclic ring containing 1-4, more preferably 1-3 heteroatoms, preferably selected from nitrogen atom, oxygen atom and sulfur atom, or a condensed ring of these heterocyclic rings, which may be the same or different, or a condensed ring of these heterocyclic rings or carbocyclic ring selected from benzene, cyclopentane and cyclohexane (particularly preferably, pyridyloxy group, thiazolidine group, personilnya group, pyridazinyl group, pyrimidinyl group, more preferably pyridyloxy group) or carbocyclic group selected from C3-8-cycloalkyl groups (for example, tsiklogeksilnogo group, cyclopentyloxy group, and so on), C3-8-cycloalkenyl group (for example, cyclohexenyl group) or aryl group (e.g. phenyl group, and so on).

[Preferred ring P1]

Ring R1 preferably represents a 5-membered or 6-membered monocyclic aromatic hetero Klionsky group or aromatic carbocyclic group.

[Preferred aromatic heterocyclic group for ring P1]

Preferred aromatic heterocyclic group, the ring R1 represents a 5-membered or 6-membered monocyclic aromatic heterocyclic group containing at least one nitrogen atom and preferably the following aromatic heterocyclic group.

or

More preferably, the aromatic heterocyclic group is a group shown below.

or

[Preferred aromatic carbocyclic group for ring P1]

Preferred aromatic carbocyclic group for ring R1 is a phenyl group, biphenylene group or naftalina group and particularly preferably a phenyl group.

[Especially preferred group P1]

Peregrina group or phenyl group is particularly preferred as ring P1.

[Preferred ring ' P2']

Preferred ring as P2 is an aromatic carbocyclic group, a 5-membered or 6-membered cycloalkyl group, 5-membered or 6-membered saturated heterocyclic group or a 5-membered or 6-membered, aromati eskay heterocyclic group, more details are listed below.

[Preferred aromatic carbocyclic group in the ring ' P2']

Preferred aromatic carbocyclic group in ring R2 represents a phenyl group, biphenylene group and naftalina group, particularly preferably phenyl group. These aromatic carbocyclic group may be substituted by methylendioxyphenyl or ethylenedioxythiophene, as shown below.

[Preferred cycloalkyl group for ring P2]

Preferred 5-membered or 6-membered cycloalkyl group for ring P2 is specifically cyclopentolate group or tsiklogeksilnogo group and that group may be substituted by exography, as shown below, and can form Ethylenedioxy and spirochaeta.

[Preferred saturated heterocyclic group for ring P2]

Saturated 5-membered or 6-membered heterocyclic group, which may form the preferred condensed ring in the ring P2 can be replaced by exography, as shown below.

It preferably represents piperidino group, piperidino and tetrahydropyridine group, as shown below.

[Preferred aromatic heterocyclic group for ring P2]

5-membered or 6-membered aromatic heterocyclic group which may form the preferred condensed ring, ring ' P2 ' represents a 5-membered or 6-membered monocyclic aromatic heterocyclic group which preferably contains at least one nitrogen atom, and specifically, is the following aromatic heterocyclic group:

[Especially preferred group P2]

Especially preferred as ring P2 is a ring that is listed below.

or

[Preferred group-Deputy ring D1 and ring P2]

Heterocyclic group and the carbocyclic group, these rings P1 and P2 can be substituted by 1-3 substituents selected from the

- halogen atom,

- hydroxyl group,

- C1-6-alkoxygroup (where the C1-6-alkoxygroup may be substituted by a carboxyl group, a hydroxyl group and -- CONR6R7(where R6and R7are the same or different and each represents a hydrogen atom or C1-6-alkyl group, and alkyl group may be substituted by a hydroxyl group or alloctype)),

- C1-6-Alky Inoi group (where the C1-6-alkyl group may be substituted by 1-5, preferably 1-3 substituents selected from a halogen atom, hydroxyl group, C1-6-alkoxygroup, -CONR6R7(where R6and R7are the same or different and each represents a hydrogen atom or C1-6-alkyl group, and alkyl group may be substituted by a hydroxyl group or alloctype), -NR6COR7(where R6and R7are the same or different and each represents a hydrogen atom or C1-6-alkyl group, and alkyl group may be substituted by a hydroxyl group or alloctype)),

- -CONR23R24(where R23and R24are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from the above group (A),

- -NR123R124(where R123and R124are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group A)

- NR223COR224(where R223and R224are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group A)

- -COR27(where R27represents a C1-6-alkyl gr the PPU, C1-6-alkoxygroup, C3-8-cycloalkyl group, aracelio group, urlcategory, cycloalkylcarbonyl or hydroxyl group),

- -O-(CR121R122)n-R128(where R121and R122are the same or different and each represents a hydrogen atom or C1-6-alkyl group, n is 1 or 2 and R128represents an acyl group, a carbocyclic group which may be substituted by 1-5 substituents selected from PP.(a)-(i) group, or a heterocyclic group which may be substituted by 1-5 substituents selected from PP.(a)-(l) groups, where R128represents preferably a 5-membered or 6-membered heterocyclic group, which preferably contains 1-3 nitrogen atom and/or sulfur atom, more preferably an unsaturated monocyclic heterocyclic group such as Peregrina group, or aryl group such as phenyl group), and

- ceanography.

Ring R2 preferably represents a carbocyclic group (more preferably aryl group such as phenyl group or C3-8-cycloalkyl group, particularly preferably phenyl group or C5-6-cycloalkyl group) or a heterocyclic group (where specified heterocyclic group is a saturated or unsaturated 5-membered or 6-membered hetero is ilicakoy group, which contains 1-3 heteroatoms, preferably nitrogen atom and/or sulfur atom, particularly preferably 1-3 nitrogen atom, a group condensed rings of these heterocyclic rings or a condensed heterocyclic group, these heterocyclic rings, which may be the same or different, carbocyclic ring selected from benzene, cyclopentane and cyclohexane. Specific examples of preferred heterocyclic groups are thiazolidine group, Peregrina group, piperideine group, piperidino, kinolinna group or 1,2,3,4-tetrahydroquinoline group, benzothiazolyl group, benzimidazolyl group, pyrrolidinone etc), and carbocyclic group and heterocyclic group may be substituted by a group-Deputy, selected from the following substituents:

- halogen atom,

- hydroxyl group,

- C1-6-alkoxygroup, which may be substituted by a halogen atom, -CONR23R24(where R23and R24are the same or different and each represents a hydrogen atom or alkyl group. The alkyl group may be optionally substituted by a hydroxyl group or alloctype), C3-8-cycloalkyl group, C1-6-alkoxygroup, a carboxyl group or C1-6-alkoxycarbonyl group,

- C1-6-alkyl group is s, which may be substituted by a halogen atom, a hydroxyl group or C1-6-alkoxygroup,

- -NR123R124(where R123and R124are the same or different and each represents a hydrogen atom or C1-6-alkyl group),

- -NR223COR224(where R223and R224are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group A)

- -COR27(where R27preferably represents C1-6-alkyl group, C1-6-alkoxygroup, C3-8-cycloalkyl group, aracelio group, urlcategory, cycloalkylcarbonyl or hydroxyl group),

saturated or unsaturated heterocyclic group containing 1-3 nitrogen atom as heteroatoms (preferably, piperidinyloxy group, piperidino, 2-oxopiperidine, morpholinopropan or piperazinone, 1,3-DIOXOLANYL group (Spiro), pyrrolidinone and so on, and these heterocyclic rings may be substituted by a group-Deputy selected from a hydroxyl group, -CON23R24(where R23and R24have the values specified above), C1-6-alkoxygroup, carboxyl group, C1-6-alkyl group which may be substituted by C1-6-alkoxygroup, C1-6-alkoxycarbonyl gr is PPI and alloctype),

- -O-R28(where R28represents an acyl group, a carbocyclic group which may be substituted by 1-5 substituents selected from PP.(a)-(l) group, or a heterocyclic group which may be substituted by 1-5 substituents selected from PP.(a)to(l)),

- -O-(CR121R122)n-R128(where R121and R122are the same or different and each represents a hydrogen atom or C1-6-alkyl group, n is 1 or 2 and R128represents an acyl group, a carbocyclic group which may be substituted by 1-5 substituents selected or PP.(a)-(i) group, or a heterocyclic group which may be substituted by 1-5 substituents selected or PP.(a) (i)),

- nitro and

- ceanography.

[Group-Deputy preferred as the group of the substituent in the ring P1]

More specifically, preferred as the group of the substituent in the ring P1 is the following group-Deputy:

is a halogen atom, particularly preferably a fluorine atom, a chlorine atom,

- C1-6-alkyl group (preferably, C1-4-alkyl group),

is cyano,

- hydroxyl group,

- carboxyl group,

- C1-6-alkoxycarbonyl group (preferably, C1-4-alkoxycarbonyl group),

- -NR123R124(where R123and R24 are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group A)

- C1-6-alkoxygroup (preferably, C1-C4-alkoxygroup (where alkoxygroup may be substituted by 1-2 substituents selected from hydroxyl group, carboxyl group, -CONR23R24(where R23and R24have the above values) and 5-membered or 6-membered monocyclic aromatic heterocyclic group (preferably, peredelnoj group)

- urlcategory (preferably, benzyloxy),

- alcoxycarbenium group (preferably, benzyloxycarbonyl group),

- C1-6-alkyl group (preferably, C1-4-alkyl group substituted by 1-2 substituents chosen from hydroxyl groups, C1-4-alkoxygroup and-NR123N124(where R121and R124have the values specified above), or

- CONR23R24(where R23and R24have the values specified above).

A preferred group Deputy for aromatic carbocyclic group which forms a ring P2 is the group Deputy indicated below:

is a halogen atom,

- C1-6-alkyl group (preferably, C1-4-alkyl group, which may be branched,

- C1-6-alkoxygroup is (preferably, C1-4-alkoxygroup) (where C1-6-alkoxygroup may be substituted by a hydroxyl group, carbamoyl group or C1-6-alkoxygroup),

the nitrogroup,

is cyano,

- carboxyl group,

- halogen-C1-6-alkoxygroup (preferably, halogen-C1-4-alkoxygroup),

- halogen-C1-6-allylthiourea (preferably, halogen-C1-4-allylthiourea),

- C1-6-alkoxycarbonyl group (preferably, C1-4-alkoxycarbonyl group),

- acyl group,

- C1-6-alkyl group substituted by 1-3 substituents selected from hydroxyl group, halogen atom and C1-6-alkoxygroup (preferably, C1-4-alkoxygroup),

- -NR123R124(where R123and R124have the values specified above)

- -NR23R24(where R23and R24have the values specified above)

- saturated 5-membered or 6-membered heterocyclic ring which contains at least one nitrogen atom (preferably, piperidinium, pyrrolidinium or morpholinopropan, which may be substituted by oxopropoxy) and which may be substituted by a group-Deputy chosen from hydroxyl groups, C1-6-alkoxygroup, carboxyl group, C1-6-alkoxycarbonyl group, C1-6-alkyl group (where the C1-6-alkyl group may be substituted by a hydroxyl group or C1-6-alkoxygroup), the carbs is strong groups and alloctype, or

- piperidineacetate, which may be substituted by C1-6-alkoxycarbonyl group.

[Group-Deputy, is particularly preferred as the group of the substituent in the ring P1]

Especially preferred group Deputy as a group of the substituent in the ring R1 is a halogen atom (particularly, fluorine atom and chlorine atom), C1-4-alkyl group, C1-4-alkyl group substituted by hydroxyl group, C1-4-alkyl group, a substituted C1-4-alkyl group, C1-4-alkoxygroup, amino group, amino group, substituted C1-4-alkyl group, or amino group substituted by two identical or different C1-4-alkyl groups.

[Group-Deputy to aromatic carbocyclic groups in the ring ' P2']

is a halogen atom,

- C1-6-alkyl group (preferably, C1-C4-alkyl group, which may be branched,

- C1-6-alkoxygroup (where the C1-6-alkoxygroup may be substituted by a hydroxyl group, carbamoyl group or C1-6-alkoxygroup),

the nitrogroup,

is cyano,

- carboxyl group,

- halogen-C1-6-alkoxygroup (preferably, halogen-C1-4-alkoxygroup),

- halogen-C1-6-allylthiourea (preferably, halogen-C1-4-allylthiourea),

- C1-6-alkoxycarbonyl group (preferably, C1-4-alkoxycarbonyl group),

- acyl group,

- The 1-6-alkyl group, substituted by 1-3 substituents selected from hydroxyl group, halogen atom and C1-6-alkoxygroup (preferably, C1-4-alkoxygroup),

- -NR123R124(where R123and R124have the values specified above)

- -NR23R24(where R23and R24have the values specified above)

- saturated 5-membered or 6-membered heterocyclic ring which contains at least one nitrogen atom (preferably, piperidinium, pyrrolidinium or morpholinopropan, which may be substituted by oxopropoxy) and which may be substituted by a group-Deputy chosen from hydroxyl groups, C1-6-alkoxygroup, carboxyl group, C1-6-alkoxycarbonyl group, C1-6-alkyl group (where the C1-6-alkyl group may be substituted by a hydroxyl group or C1-6-alkoxygroup), carbamoyl group and acyl group, or

- piperidineacetate, which may be substituted by C1-6-alkoxycarbonyl group.

[Especially preferred group Deputy to aromatic carbocyclic groups in the ring ' P2']

Especially preferred substituents for the aromatic carbocyclic groups in the ring P2 are the following placeholders:

is a halogen atom,

- C1-6-alkyl group (preferably, C1-4-alkyl group, which may be branched,

- C1-6-alkoxygroup (where the C1-6-alkoxygroup may be substituted by a hydroxyl group, carbamoyl group or C1-6-alkoxygroup),

- halogen-C1-6-alkyl group (preferably, halogen-C1-4-alkyl group, particularly preferably triptorelin group),

- halogen-C1-6-alkoxygroup (preferably, halogen-C1-4-alkoxygroup),

- -NR123R124(where R123and R124have the meanings indicated above and, in particular, it can be di-C1-4-alkylamino),

- saturated 5-membered or 6-membered heterocyclic ring which contains at least one nitrogen atom (preferably, piperidinium, pyrrolidinium or morpholinopropan, which may be substituted by oxopropoxy) and which may be substituted by a group-Deputy selected from C1-6-alkoxygroup, C1-6-alkoxycarbonyl group and C1-6-alkyl group (where the C1-6-alkyl group may be substituted by C1-6-alkoxygroup), or

- piperidineacetate, which may be substituted by C1-6-alkoxycarbonyl group.

[Group-Deputy, preferred saturated hydrocarbonaceous group in the ring ' P2']

- C1-6-alkyl group (where the C1-6-alkyl group may be substituted by a hydroxyl group or C1-6-alkoxygroup),

- C1-6-alkoxygroup (where the C1-6-alkoxygroup may be substituted carboxyl the th group, C1-6-alkoxycarbonyl group, carbamoyl group)

- urlcategory,

- -NR123R124(where R123and R124have the values specified above)

- oxoprop,

- C3-6-cycloalkyl-C1-6-alkoxygroup,

- C3-6-cycloalkylation or

- saturated 5-membered or 6-membered heterocyclic ring containing at least one nitrogen atom (preferably, piperidinium, pyrrolidinium, morpholinopropan, which may be substituted by oxopropoxy),

[The substituents, particularly preferred saturated hydrocarbonaceous group in the ring ' P2']

- C1-6-alkyl group (particularly, C1-4-alkyl group),

- C1-6-alkoxygroup (especially C1-4-alkoxygroup) or

[The substituents, preferred saturated heterocyclic group in the ring ' P2']

- C1-6-alkyl group (where the C1-6-alkyl group may be substituted by a hydroxyl group or C1-6-alkoxygroup),

- C1-6-alkoxygroup,

- carnemolla group or

- acyl group.

[The substituents, preferred aromatic heterocyclic group in the ring ' P2']

is a halogen atom,

- C1-6-alkyl group, or

- halogen-C1-6-alkyl group.

"Pharmaceutically acceptable salt" may be any salt as long as it is non-toxic salt of the compound represented by the above about what her formula [1], and can be obtained by interacting, for example, inorganic acid, such as hydrochloric acid, sulfuric acid, phosphoric acid or Hydrobromic acid; organic acid 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, methylsulfonate acid or benzylmalonate acid; an inorganic base such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide or ammonium hydroxide; organic base such as methylamine diethylamine, triethylamine, triethanolamine, Ethylenediamine, Tris(hydroxymethyl)methylamine, guanidine, choline or cinchonine, or an amino acid such as lysine, arginine or alanine. Hydrated compound, hydrate and MES of each connection are also included in the present invention.

In addition, the compound represented by the above General formula [1], exists in the form of various isomers. For example, the isomers E and Z isomer exist as geometric isomers and when there is an asymmetric carbon atom, there are enantiomers and diastereoisomers as stereoisomers, there are also tautomers. Sledovatel is but all of these isomers and their mixtures are included in the range of the present invention. In addition, the present invention, among the compounds represented by the above General formula [1]includes proletarienne derivatives of these compounds and metabolic compounds as the equivalent connections.

"Prodrug" is a derivative of the compound of the present invention containing a group which can be removed by cleavage of chemical or metabolic method, after the introduction of a living organism it becomes by means of chemical transformations in the compound that has activity as a drug and has an initial pharmacological action also includes complexes and salts formed non-covalent bond.

The prodrug is used to improve the absorption by oral administration or for targeting in place-target. Residues that need to be modified for the formation of prodrugs include reactive functional groups such as hydroxyl group, carboxyl group, amino group and Tolna group in the compound of the present invention. Specific examples of the modifying group for a hydroxyl group include acetyl group, propionyl group, isobutyryl group, pivaloyl group, benzoyloxy GRU is PU, 4-methylbenzoyl group, dimethylcarbamoyl group, alphagroup etc. Specific examples of the modifying group for the carboxyl group include ethyl group, pivaloyloxymethyl group, 1-(atomic charges)ethyl group, 1-(ethoxycarbonyl)ethyl group, 1-(cyclohexyloxycarbonyloxy)ethyl group, carboxymethyl group, methyl-(5-methyl-2-oxo-1,3-dioxol-4-ilen) group, phenyl group, o-taillow group, etc. and Specific examples of the modifying group for the amino group include hexylberberine group, 3-methylthio-1-(acetylamino)propelleronline group, 1-sulfo-1-(3-ethoxy-4-hydroxyphenyl)methyl group, methyl-(5-methyl-2-oxo-1,3-dioxol-4-ilen) group, etc.

"Pharmaceutical composition" includes a combination of drugs with other drugs and so on, in addition to the so-called "composition", which includes the active ingredient as a drug and combinatorial agent, etc. Needless to specify that the pharmaceutical composition of the present invention can be used in combination with any type of other medicines, provided that it is authorized to apply in clinical practice. Therefore, we can say that this pharmaceutical composition is a pharmaceutical composition for combined application with each the mi medicines.

"Pain" means every type of pain condition, regardless of whether the state (for example, no matter whether it is a nagging pain or acute pain, chronic or acute pain, and so on), regardless of what disease causes pain (for example, no matter whether the pain is the result of rheumatic fever or pain is the result of cancer and so on). Therefore, the term "pain"as used here, includes in addition to the so-called "pain" acute pain, chronic pain, neuropathic pain, pain, rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy and neurodegenerative disease.

The inhibitor activity of subtype 1 receptor vanilloid (VR1) means a substance that inhibits the function of subtype 1 receptor vanilloid as ion channel and eliminates or reduces its activity. Specifically, it includes the antagonist subtype 1 receptor vanilloid etc. Antagonist subtype 1 receptor vanilloid means a substance that inhibits the action of the agonist, which acts on the subtype 1 is eceptor of vanilloid, thereby inhibiting the function of subtype 1 receptor vanilloid as an ion channel. The inhibitor of the present invention does not compete with the agonist, but may also inhibit the function of VR1 ion channel. Specifically, agonists that act on the subtype 1 receptor vanilloid include capsaicin, a derivative of capsaicin, acid stimulation (proton), thermal stimulation, etc., inhibitor activity subtype 1 receptor vanilloid (VR1) can be a substance that inhibits the flow into Sa2+in the cell, caused by stimulation of agonist capsaicin, acid stimulation (proton) or thermal stimulation.

The pharmaceutical composition of the present invention can enter the human and other mammals (mouse, rat, hamster, rabbit, cat, dog, cow, horse, sheep, monkey, etc). Therefore, the pharmaceutical composition of the present invention is also applicable as a drug for the animal, not to mention the man.

When the compound of the present invention used as a pharmaceutical preparation, it can be mixed with a pharmacologically acceptable carrier, usually known in itself excipient, diluent, filler, dezintegriraat agent, stabilizer, preservative, buffer, emulsifier, perfume, paint is eat, sweetening agent, a thickener, Corrigendum, auxiliary dissolving agent and other agents, especially water, vegetable oil, alcohol such as ethanol or benzyl alcohol, carbohydrates, such as polyethylene glycol, glycerol triacetate, gelatin, lactose and starch, magnesium stearate, talc, lanolin, vaseline, etc. to obtain drugs in the form, such as tablet, pill, powder, granule, suppository, agent for injection, eye drops, liquid medication, the agent in the form of capsules, toffee, aerosol agent, elixirnyi agent, suspension, emulsion and syrup, for systemic or local injection, orally or parenterally.

Although the dose varies depending on age, weight, condition, therapeutic effects, methods of administration and so on, the drug is usually administered at a dose in the range of 0.01 mg to 1 g per dose, with the introduction from 1 times to several times a day to adults in the form of oral medication or drugs for injection, such as intravenous injection, etc.

"Prevention" is the so-called prevention, and it means, for example, the delay at the beginning of neuralgia or chronic disease prevention. As for the pain, specifically included is the prophylactic delay acutely the herpetic neuralgia, start-herpetic neuralgia, conversion of acute herpetic pain post herpetic neuralgia, chronic conditions-herpetic neuralgia, early post-operative pain, chronic post-operative pain, the onset of symptoms cancer pain, chronic cancer pain, the onset of symptoms of inflammatory pain, the beginning of interstitial cystitis, chronic inflammatory pain, early post-traumatic neuralgia or chronic posttraumatic neuralgia.

"The drug, which includes a combination"means a drug, characterized in that it is a drug containing pharmaceutical composition or agent that you want to combine, drug, characterized in that it is a kit comprising a pharmaceutical composition or agent that you want to combine, drug, characterized in that the pharmaceutical composition or agent that you want to combine, administered via the same or different routes of administration, respectively.

The compound and pharmaceutical composition of the present invention can be used in combination with one or more other agents common method currently used in conventional medical PR is ctice. When used in combination drug used tool, you can enter with other agents simultaneously or separately with a time delay. Although there are various compounds that can be used in combination with the compound of the present invention, especially preferred are anti-viral agent, an antidepressant, an anticonvulsant drug, an antiarrhythmic drug, a local anesthetic agent, an anaesthetic drug, receptor antagonist N-methyl-D-aspartate, cortical steroid adrenal glands, the means for blocking nerve, non-steroidal anti-inflammatory analgesic agent, a drug, an analgetic antagonist, agonist receptor α2adrenaline, a method of analgesia stimulation, medicines for external use, the antagonist of calcium channels and the discoverer of potassium channels.

Antiviral agent specifically includes vidarabine, acyclovir, ganciclovir, zidovudine, didanosin, amantadine, idoxuridine, interferon, etc.

Antidepressant specifically includes amitriptyline, imipramine, clomipramine, trimipramine, lofepramine, dosulepin, desipramine, amoxapine, nortriptyline, fluoxetine, fluvoxamine, maprotiline, mianserin, setiptiline, trazodone etc.

Anticonvulsant drug specifically includes the t gabapentin, pregabalin, phenobarbital, primidone, phenytoin, mephenytoin, Nirvana, ethotoin, trimethadione, ethosuximide, acetylphenyl, carbamazepine, zonisamide, acetazolamide, diazepam, clonazepam, nitrazepam, diphenylhydantoin, volpaia acid, baclofen, etc.

Antiarrhythmic drug specifically include quinidine, disopyramide, procainamide, aymalin, primarium, cibenzoline, lidocaine, meksiletin, aprindine, sonicaid, phenytoin, flecainide, pilsicainide, propafenone, propranolol, amiodarone, verapamil, bepridil, etc.

Local anesthetic specifically includes lidocaine, meksiletin, cocaine, procaine, bupivacaine, mepivacaine, prilocaine, tetracaine, dibucaine, ethylaminomethyl etc.

Anaesthetic drug specifically includes the benzodiazepine, diazepam, midazolam, thiopental, thiamylal, propofol, baclofen, droperidol, Sufentanil etc. receptor Antagonist N-methyl-D-aspartate specifically includes ketamine, dextromethorphan, memantine, amantadine, etc.

Cortical steroid adrenal specifically includes cortisol, cortisone, prednisolone, triamcinolone, dexamethasone, betamethasone, paramethasone, fluoqinolona acetonide, fluocinonide, beclometasone, fludrocortisone etc.

The means for blocking nerve specifically includes means for blocking the cervical-thoracic ganglion, the remedy for blocked the epidural I ganglion, the means for blocking the ganglion of the brachial plexus, the means for blocking the nerve roots, the means for blocking the thoracic/lumbar sympathetic ganglion, the means for blocking Markovych zones, means for blocking the subarachnoid cyst, the means for blocking the trigeminal nerve, the means for blocking the sympathetic nerves, the means for blocking local infiltration, the means for blocking peripheral nerves, etc.

Non-steroidal antiinflammatory analgetic specifically include celecoxib, rofecoksib, etodolac, meloxicam, nimesulide, sodium diclofenac, mefenamico acid, zaltoprofen, sodium loxoprofen, sulindac, nabumetone, diflunisal, piroxicam, ibuprofen, naproxen, fenoprofen, acetylsalicylic acid, tolmetin, indomethacin, flurbiprofen, oxaprozin, Ketoprofen, movetalk, acetaminophen, Ketorolac, zomepirac, nitrospira, cuprofen, ampiroxicam, tiaramide, epirizole etc.

Drugs specifically include morphine, fentanyl, oxycodone, methadone, codeine, cocaine, pethidine, opium, ipecac etc.

Analgesic antagonist specifically includes Pentagon, buprenorphine, nalorfin, cyclazocine, butorphanol, etc.

Agonist receptor α2-adrenaline specifically includes clonidine, dexmedetomidine, tizanidine, guanfacine, guanabenz and so on

Medicinal product for external use specifically includes capsaicin cream, etc.

Method of analgesia stimulation specifically includes acupuncture, stimulation therapy via percutaneous needle electrodes, transcutaneous electrical stimulation therapy nerve, treatment by acupuncture with the use of point of silver electrodes (SSP), the stimulus of peripheral nerves, the electrical stimulus of the spine, electric spasm treatment, laser surgery, rare therapy, etc.

In addition, the compound of the present invention can be applied as a General method, usually conducted in this area, the introduction after surgery for the prevention or treatment of pain. Although various surgical operations can be performed in combination with the compound of the present invention, particularly preferred are the excision of the scar, hardening nerve freezing, excision of peripheral nerve excision of the dorsal roots of the spinal cord, sympathectomy, destruction entrance area dorsal roots, cordotomy and excision of the frontal lobe (brain).

Although the use of compounds of the present invention is described primarily as applied for the prevention or treatment of pain, the compound of the present invention can be used to condition the, involving fiber With, for example, itching, allergies and allergic rhinitis, and overactive bladder type frequent urination and urinary incontinence, apoplexy, irritable bowel syndrome, respiratory ailments such as asthma and chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer, inflammatory bowel disease, etc.

Then specifically describes a method of obtaining a compound represented by the General formula [1] of the present invention, without the need to specify that the present invention is not limited to these methods of obtaining. Thus, the connection of the present invention can be synthesized according to the following methods of obtaining a, b or C, but it can be obtained according to the following examples or reference to these methods. When the connection of the present invention the procedure for conducting reactions can be modified appropriately. Receiving can be performed starting from the first stage reaction or replacement parts stages, considering that it is rational. For example, the ring P2 can be entered before the introduction of the rings R1, and this order can be reversed. With regard to education heterokonta condensed with benzene ring (benzamido group), reaktsiooniline rings can be conducted with the formation of this heterokonta before the introduction of the rings R1 and/or ring P2 or alternatively, the reaction ring closure can be carried out with the formation of this heterokonta after the introduction of the rings R1 and/or ring P2. Introduction protecting and Unprotecting can be appropriately performed when there is a functional group of the reagent. To improve the efficiency of the reaction can suitably be applied reagents, other than illustrated reagents.

The following sequence of operations of the method of obtaining is a typical example of the production method, but obtaining compounds of the present invention is not specifically limited in the following way. Each connection obtained at each stage, you can select and clear the usual method, but depending on the case, the connection can be used in the next step without isolation and purification.

1. The method of receiving As:

(where R represents carboxylate group (carboxylamide group here includes, for example, methyl group, ethyl group, through the group, tert-boutelou group, benzyl group, para-methoxybenzyloxy group etc) and forms an ester which is easily transformed into a carboxylic acid by hydrolysis or catalytic hydrogenation reaction, X is a halogen atom such as chlorine atom or bromine, or sulfonyloxy the group, such as 3-nitrobenzenesulfonamide, p-toluensulfonate, benzolsulfonate, p-bromobenzosulfonyl, methysulfonylmethane or triftormetilfullerenov, and every other character has the values listed above).

The first stage

This stage is the reaction of obtaining compound (IIIA), catalyzed by palladium amination reaction type Buchwald/Hartwig of the compounds (IA) and compound (IIA).

The compound (IIIA) can be obtained by the interaction of (IA) with compound (IIA) in toluene, 1,4-dioxane, tetrahydrofuran or the like or a mixed solvent of these solvents with the use of palladium catalyst, such as a mixture of palladium acetate and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, bis(diphenylphosphino)ferienparadies(II) or Tris(dibenzylideneacetone)diplodia together with a base such as sodium carbonate, tribalistas (K3RHO4), potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate or tert-piperonyl potassium, at a temperature from 20°C to the boiling temperature under reflux, preferably from 60°C to the boiling temperature under reflux over 5 hours up to 96 hours, preferably for from 8 hours to 48 hours.

When the ring R1 is an aromatic heterokonta, such as ring oxa is Ola, of the thiazole or 1,3,4-thiadiazole, the compound (IIA) does not apply and response build aromatic heterokonta carried out in a known manner, and the connection is transferred to the second stage.

For example, when the ring R1 is 5-methoxazole, the compound (IA) is subjected to interaction with thiophosgene or 1,1-thiocarbonyldiimidazole etc. in tetrahydrofuran, ethyl acetate, toluene, water or a mixed solvent of these solvents, in the presence or in the absence of a base, such as triethylamine, sodium bicarbonate, potassium carbonate or pyridine, with the formation of isothiocyanates connection, which then allow you to interact with 1-azidoaniline and triphenylphosphine in a solvent such as dichloromethane, dichloroethane and chloroform, at temperatures from -20°C to the boiling temperature under reflux, preferably from 0°C to 50°C., for from 0.5 hour to 24 hours, preferably from 2 hours to 8 hours, to obtain compound (IIIA).

When the ring R1 is 4-methylthiazole, the compound (IA) is subjected to interaction with thiophosgene or 1,1-thiocarbonyldiimidazole etc. in tetrahydrofuran, ethyl acetate, toluene, water or a mixed solvent of these solvents in the presence or in the absence of a base, such as triethylamine, sodium bicarbonate, potassium carbonate or pyridine, with the formation of isotiocianato connection which then allow you to communicate with ammonia water, etc. to obtain a derivative of thiourea and this connection will allow you to interact with 1-chloroacetone, 1-bromoacetone, etc. in a solvent such as methanol, ethanol, tetrahydrofuran or acetone, at temperatures from -20°C to the boiling temperature under reflux, preferably from 0°C. to the boiling temperature under reflux, for from 0.5 hour to 24 hours, preferably from 1 hour to 12 hours, to obtain the compound (IIIA).

The second stage

This stage is the stage for the removal of R from the compound (IIIA) and obtain the carboxylic acid (IVA).

For example, when R represents a methyl group, ethyl group, through the group, and so that the compound (IIIA) can hydrolyze in water, methanol, ethanol, propanol, tetrahydrofuran or a mixed solvent of these solvents with the use of bases such as sodium hydroxide, potassium hydroxide, lithium hydroxide, potassium carbonate or sodium carbonate, at temperatures from -20°C to the boiling temperature under reflux, preferably from 20°C to the boiling temperature under reflux, for from 0.5 hour to 24 hours, preferably from 0.5 to 8 hours hours, to obtain compound (IVA).

For example, when R represents a tert-boutelou is the Rupp, the compound (IVA) can be obtained by the interaction of the compounds (IIIA) without solvent or in water, methanol, ethanol, propanol, tetrahydrofuran or a mixed solvent of these solvents with the use of acid, such as hydrochloric acid or triperoxonane acid, at a temperature from 0°C to the boiling temperature under reflux, preferably from 0°C to 50°C for from 0.5 hour to 24 hours, preferably from 0.5 hour to 8 hours.

When R represents a benzyl group, a para-methoxybenzyloxy group, etc. that the compound (IVA) can be obtained by the interaction of methanol, ethanol, propanol, tetrahydrofuran or a mixed solvent of these solvents in the presence of a catalyst, palladium-on-charcoal, etc. using hydrogen or ammonium formate at a temperature of from about 0°C. to the boiling temperature under reflux, preferably from about 20°C to the boiling temperature under reflux for 0.5 hour to 96 hours, preferably from 1 hour to 48 hours.

The third stage

This stage is the reaction of obtaining compound (1) by the condensation reaction of compound (IVA) and a compound (VA).

The condensation reaction can be performed using condensing agent, or by formation of a carboxylic acid, etc.

When p is the share of direct condensation is carried out with the use of condensing agent, the compound (IVA) is subjected to interaction with the compound (VA) in N,N-dimethylformamide, methylene chloride, chloroform, etc. or a mixed solvent of these solvents with the use of condensing agent, such as dicyclohexylcarbodiimide or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, at temperatures from -20°C to the boiling temperature under reflux, preferably from about 0°C to 50°C for from 1 hour to 48 hours, preferably from about 1 hour to 24 hours. In this case, it is preferable to add additives, such as hydroxybenzotriazole or imide N-hydroxyethanoic acid.

When the reaction proceeds through the formation of carboxylic acid, compound (IVA) is subjected to interaction with thionyl chloride, oxalylamino etc. in chloroform, methylene chloride, tetrahydrofuran, etc. or a mixed solvent of these solvents to obtain the carboxylic acid (IVA) and it is subjected to interaction with the compound (VA) in toluene, chloroform, tetrahydrofuran or a mixed solvent of these solvents in the presence of a base such as triethylamine or pyridine, at temperatures from -20°C to the boiling temperature under reflux, preferably from about 0°C to 40°C for 0.5 hours up to 24 hours, preferably approximately the nutrient from 0.5 hours to 12 hours, obtaining compound (1).

2. Way of getting In:

This method is an alternative method of obtaining the compound (IIIA)in which Z represents an oxygen atom in the method of obtaining A (where Z represents an oxygen atom, R represents a C1-6-alkyl group and forms an ester which is easily transformed into a carboxylic acid by hydrolysis or catalytic hydrogenation, R' represents a protective group of a phenolic hydroxyl group easily removable by hydrolysis or catalytic hydrogenation, every other character has the values listed above).

The first stage

This stage is the reaction of obtaining compound (IIB) catalyzed by palladium amination reaction type Buchwald/Hartwig of the compounds (IB) and compound (IIA).

The compound (IIB) can be obtained by the interaction (IE) with compound (IIA) in toluene, 1,4-dioxane, tetrahydrofuran or the like or a mixed solvent of these solvents with the use of palladium catalyst, such as a mixture of palladium acetate and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, bis(diphenylphosphino)ferienparadies(II) or Tris(dibenzylideneacetone)diplodia together with a base such as sodium carbonate, tribalistas (K3RHO4), potassium carbonate, carbonate C is Zia, sodium bicarbonate, bicarbonate or potassium tert-piperonyl potassium, at a temperature from 20°C to the boiling temperature under reflux, preferably from 60°C to the boiling temperature under reflux over 5 hours up to 96 hours, preferably for from 8 hours to 48 hours.

When the ring R1 is an aromatic heterokonta, such as ring oxazole, thiazole or 1,3,4-thiadiazole, the compound (IIA) is not used and the response of education aromatic heterokonta carried out by a known method, and the compound obtained is transferred to the second stage.

For example, when the ring R1 is 5-methoxazole, compound (IB) is subjected to interaction with thiophosgene or 1,1-thiocarbonyldiimidazole etc. in tetrahydrofuran, ethyl acetate, toluene, water or a mixed solvent of these solvents, in the presence or in the absence of a base, such as triethylamine, sodium bicarbonate, potassium carbonate or pyridine, with the formation of isothiocyanates connection, which then allow you to interact with 1-azidoaniline and triphenylphosphine in a solvent such as dichloromethane, dichloroethane or chloroform, at temperatures from -20°C to the boiling temperature under reflux, preferably from 0°C to 50°C., for from 0.5 hour to 24 hours, preferably from 2 hours to 8 hours, for receiving the Oia compounds (IIB).

When the ring R1 is 4-methylthiazole, compound (IB) is subjected to interaction with thiophosgene or 1,1-thiocarbonyldiimidazole etc. in tetrahydrofuran, ethyl acetate, toluene, water or a mixed solvent of these solvents in the presence or in the absence of a base, such as triethylamine, sodium bicarbonate, potassium carbonate or pyridine, with the formation of isothiocyanates connection, which then allow you to interact with ammonia water or the like to obtain a derivative of thiourea and this connection will allow you to interact with 1-chloroacetone, 1-bromoacetone, etc. in a solvent such as methanol, ethanol, tetrahydrofuran or acetone, at temperatures from -20°C to the boiling temperature under reflux, preferably from 0°C. to the boiling temperature under reflux, for from 0.5 hour to 24 hours, preferably from 1 hour to 12 hours, to obtain the compound (IIB).

The second stage

This stage is the stage for the removal of R', which is a protective group of a phenolic hydroxyl group of the compound (IIB).

For example, when R' represents methoxymethyl group, tetrahydropyranyloxy group, etc., connection (V) can be obtained by the interaction of the compounds (IIB) without solvent or in water, methanol, ethanol, isopropanol, tetrahed is furane, chloroform or a mixed solvent of these solvents with the use of acid, such as sulfuric acid, hydrochloric acid or triperoxonane acid, at a temperature from 0°C to the boiling temperature under reflux, preferably from 0°C to 50°C., for from 0.5 hour to 24 hours, preferably from 0.5 hour to 8 hours.

The third stage

This stage is the stage of obtaining cyclic compounds (IIIA) from the compound (IIIB).

For example, when l is 1, R1and R2represent hydrogen atoms, and m is 0, the compound (IIIB) is subjected to interaction with dehalogenation, such as 1,2-dibromoethane, 1,2-dichloroethane or 1-bromo-2-chlorate, chloroform, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, ethyl acetate, methanol, water or a mixed solvent of these solvents in the presence of a base such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide or triethylamine, at temperatures from 0°C to the boiling temperature under reflux, preferably from 0°to 60°C, for from 0.5 hour to 24 hours to obtain the compound (IIIA). Alternatively, after receiving it interacts with the acid chloride halogenases acid, such as acetylchloride, with the formation of cyclic lactam, compound (IIIA) can also in order to teach the conduct of reduction reaction in tetrahydrofuran using the reagent, complex, borane-tetrahydrofuran, etc. at a temperature from 0°C to the boiling temperature under reflux for 0.5 hour to 8 hours.

For example, when l is 1, R1represents hydroxymethylene group, R2represents a hydrogen atom and m is 0, a reaction similar to reaction with dehalogenation, can be performed using gildenhard, glycidylmethacrylate or glycidylether with obtaining the compound (IIIA). In this case, the formed hydroxyl group can be subjected to stage the introduction of the commonly used protective group such as acetyl group, methoxymethyl group, tetrahydropyranyl group or benzyl group, and the product can be used in subsequent stages and can be subjected to unprotect a suitable manner to obtain the compound (1).

3. The way to obtain

This method is an alternative method of obtaining the compound (1)in which Z represents an oxygen atom in the method of obtaining A.

(where R represents a C1-6-alkyl group and forms an ester which is easily transformed into a carboxylic acid by hydrolysis or catalytic hydrogenation, R” represents a protective group of amino group easily removable by hydrolysis or catalytic hydrogenation, to whom gdy other symbol has the value above).

The first stage

This stage is the stage of obtaining cyclic compounds (IIC) from compound (IC).

For example, when l is 1, R1and R2represent hydrogen atoms, and m is 0, the compound (IC) is subjected to interaction with dehalogenation, such as 1,2-dibromoethane, 1,2-dichloroethane or 1-bromo-2-chlorate, chloroform, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, ethyl acetate, methanol, water or a mixed solvent of these solvents in the presence of a base such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide or triethylamine, at temperatures from 0°C to the boiling temperature under reflux for 0.5 hour to 24 hours obtaining the compound (IIC).

For example, when l is 1, R1represents hydroxymethylene group, R2represents a hydrogen atom and m is 0, the compound (IIC) can be obtained by using the compound (IC) with glycidylether, goldencasinocom or glycidylester in reactions similar to reactions with dehalogenation. In this case, the formed hydroxyl group can be the stage for the introduction of a widely used protective group such as acetyl group, methoxymethyl group, tetrahydropyranyl group or benzyl group, and the product is you can apply in subsequent stages, and protection can appropriately be removed to obtain compound (1).

The second stage

This stage is the stage of removal of R from the compound (IIC) for connection carboxylic acid (IIIC).

For example, when R represents a methyl group, ethyl group, through the group, and so that the compound (IIIC) can be obtained by hydrolysis of compound (IIC) in water, methanol, ethanol, propanol, tetrahydrofuran, etc. or a mixed solvent of these solvents with the use of bases such as sodium hydroxide, potassium hydroxide, lithium hydroxide, potassium carbonate and sodium carbonate or aqueous them at a temperature from -20°C to the boiling temperature under reflux, preferably from 20°C to the boiling temperature under reflux, for from 0.5 hours up to 24 hours, preferably for from 0.5 hour to 8 hours.

For example, when R represents a tert-boutelou group, the compound (IIIC) can be obtained by the interaction of the compound (IIC) without solvent or in water, methanol, ethanol, propanol, or tetrahydrofuran, etc. or a mixed solvent of these solvents with the use of acid, such as hydrochloric acid or triperoxonane acid, at a temperature from 0°C to the boiling temperature under reflux, preferably from 0°C to 50°C, in accordance with the s from 0.5 hours to 24 hours, preferably from 0.5 hour to 8 hours.

When R represents a benzyl or para-methoxybenzyloxy group, etc. that the compound (IIIC) can be obtained by the interaction of methanol, ethanol, propanol, tetrahydrofuran, etc. or a mixed solvent of these solvents with the use of hydrogen or formate with ammonia in the presence of a catalyst, palladium-on-coal etc. at a temperature from about 0°C. to the boiling temperature under reflux, preferably from about 20°C. to 50°C., for from 0.5 hour to 96 hours, preferably from 1 hour to 48 hours.

The third stage

This stage is the stage in which the compound (IVC) is obtained by condensation reaction of compound (IIIC) and compound (VA). The condensation reaction can be carried out either by means of the condensing agent or by way of through the formation of carboxylic acid, etc.

When conducting the reaction of direct condensation with the use of the condensing agent, the compound (IVC) can be obtained by the interaction of the compound (IIIC) with compound (VA) in N,N-dimethylformamide, methylene chloride, chloroform, etc. or a mixed solvent of these solvents with the use of condensing agent, such as dicyclohexylcarbodiimide or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, at temperatures from -20°C to the boiling temperature is placed under reflux, preferably from about 0°C to 50°C for from 1 hour to 48 hours, preferably from 1 hour to 24 hours. In this case, it is preferable to add additives, such as hydroxybenzotriazole and imide N-hydroxyethanoic acid.

When the reaction is carried out through the formation of carboxylic acid, the compound (IIIC) is subjected to interaction with thionyl chloride, oxalylamino etc. in chloroform, methylene chloride, tetrahydrofuran, etc. or a mixed solvent of these solvents to obtain the carboxylic acid (IIIC), and this compound is subjected to interaction with the compound (VA) in toluene, chloroform or tetrahydrofuran, etc. or a mixed solvent of these solvents in the presence of a base such as triethylamine or pyridine, at temperatures from -20°C to the boiling temperature under reflux, preferably from about 0°C to 40°C for from 0.5 hour to 24 hours, preferably from 0.5 hours to 12 hours, thereby obtaining the compound (IVC).

The fourth stage

This stage is the stage of removal aminosidine group R” of compound (IVC) and receive connection (VC).

For example, when R” is acetyl group, or formyl group, the compound (VC) can be obtained by the interaction of the compound (IVC) in tetrahydrofuran, methanol, ethanol, isopr is panola, water or a mixed solvent of these solvents in the presence of a base such as sodium hydroxide, potassium hydroxide, lithium hydroxide or sodium methoxide, or in the presence of acid, such as sulfuric acid, hydrochloric acid or triperoxonane acid, at temperatures from -20°C to the boiling temperature under reflux, preferably from about 0°C. to the boiling temperature under reflux, for from 0.5 hour to 24 hours, preferably from 0.5 hour to 8 hours.

For example, when R represents a tert-butoxycarbonyl group, the compound (VC) can be obtained by the interaction of the compound (IVC) without solvent or in tetrahydrofuran, methanol, ethanol, isopropanol, chloroform, water or a mixed solvent of these solvents in the presence of acid, such as hydrochloric acid or triperoxonane acid, at a temperature from 0°C to the boiling temperature under reflux, preferably from about 0°C to 50°C., for from 0.5 hour to 24 hours, preferably from 0.5 hour to 8 hours.

When R' represents benzyloxycarbonyloxy group, benzyl group, etc., connection (VC) can be obtained by the interaction of the compound (IVC) in methanol, ethanol, propanol, tetrahydrofuran, etc. or a mixed solvent of which is shown solvents using hydrogen or ammonium formate in the presence of a catalyst, palladium-on-coal etc. at a temperature from about 0°C. to the boiling temperature under reflux, preferably from about 20°C to 50°C for from 0.5 hour to 96 hours, preferably from 1 hour to 48 hours.

Fifth stage

This stage is the reaction of obtaining compound (1) catalyzed by palladium amination reaction type Buchwald/Hartwig of connection (VC) and the compound (IIA).

The compound (1) can be obtained by the interaction (VC) with compound (IIA) in toluene, 1,4-dioxane, tetrahydrofuran or the like or a mixed solvent of these solvents with the use of palladium catalyst, such as a mixture of palladium acetate and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl, bis(diphenylphosphino)ferienparadies(II) or Tris(dibenzylideneacetone)diplodia together with a base such as sodium carbonate, tribalistas (K3RHO4), potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate or tert-piperonyl potassium, at a temperature from 20°C to the boiling temperature under reflux, preferably from 60°C to the boiling temperature under reflux over 5 hours up to 96 hours, preferably for from 8 hours to 48 hours.

When the ring R1 is an aromatic heterokonta, such as ring oxazole, thiazole or 1,3,4-thiadiazole, connect the out (IIA) does not apply and the response of education aromatic heterokonta carried out in a known manner and the connection is transferred to the second stage.

When the ring R1 is 5-methoxazole, connection (VC) is subjected to interaction with thiophosgene or 1,1-thiocarbonyldiimidazole etc. in tetrahydrofuran, ethyl acetate, toluene, water, etc. or a mixed solvent of these solvents, in the presence or in the absence of a base, such as triethylamine, sodium bicarbonate, potassium carbonate or pyridine, with the formation of isothiocyanates connection, which then allow you to interact with 1-azidoaniline and triphenylphosphine in a solvent such as dichloromethane, dichloroethane and chloroform, at temperatures from -20°C to the boiling temperature under reflux, preferably from 0°C to 50°C., for from 0.5 hour to 24 hours, preferably from 2 hours to 8 hours, thus obtaining the compound (1).

When the ring R1 is 4-methylthiazole, connection (VC) is subjected to interaction with thiophosgene or 1,1-thiocarbonyldiimidazole etc. in tetrahydrofuran, ethyl acetate, toluene, water, etc. or a mixed solvent of these solvents in the presence or in the absence of a base, such as triethylamine, sodium bicarbonate, potassium carbonate or pyridine, with the formation of isothiocyanates connection, which then allow you to interact with ammonia water, etc. to obtain a derivative of thiourea and this connection gives the capability is there to interact with 1-chloroacetone, 1-bromoacetone, etc. in a solvent such as methanol, ethanol, tetrahydrofuran or acetone, at temperatures from -20°C to the boiling temperature under reflux, preferably from 0°C. to the boiling temperature under reflux, for from 0.5 hour to 24 hours, preferably from 1 hour to 12 hours, thus obtaining the compound (1).

Example 1

Example 1-001

Obtaining N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-3-nitrosalicylic

3-Nitrosalicylic acid (7.5 g) was dissolved in methanol (75 ml), add concentrated sulfuric acid (2 ml) and the mixture refluxed for 24 hours. The reaction mixture is left to cool and the precipitated pale yellow solid is collected by filtration, washed with water and dried under vacuum, thus obtaining specified in the header connection (7,19 g).

The second stage

Obtaining methyl-3-aminosalitsilata

Methyl-3-nitrosalicylic (7,19 g)obtained in the first stage, dissolved in tetrahydrofuran (100 ml) and add ethyl acetate (50 ml), 5% palladium-on-coal (water content 50%) (0,70 g) and the mixture is stirred at room temperature for 2 hours in hydrogen atmosphere. From the reaction mixture palladium-on-coal is separated by filtration, the filtrate is concentrated and add Aut n-hexane. The precipitated white solid was separated by filtration and dried, thus obtaining specified in the header connection (5.59 in).

The third stage

Obtaining methyl-3-chlortetracycline

Methyl-3-aminosalitsilata (5,59 g)obtained in the second stage, dissolved in chloroform (100 ml), add aqueous saturated sodium bicarbonate (50 ml), then with vigorous stirring and cooling with ice add chlorocatechol (3.2 ml), the mixture is then stirred for 1.5 hours under ice cooling. The reaction mixture was kept for the separation of layers, the chloroform layer is dried over anhydrous magnesium sulfate and concentrated, thus obtaining specified in the title compound (white solid, 8,07 g).

The fourth stage

Obtaining methyl-3,4-dihydro-3-oxo-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-3-chlorotetracycline (8,07 g)obtained in the third stage, dissolved in N,N-dimethylformamide (80 ml), add potassium carbonate (9,15 g) and the mixture was stirred at 80°C for 1 hour. The reaction suspension concentrate and precipitate white solids obtained by the addition of water, separated by filtration, washed with water and dried, thus obtaining specified in the header connection (6,37 g).

Fifth stage

Obtaining methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-3,4-dihydro-3-oxo-2H-Ben is about[1,4]oxazin-8-carboxylate (2,07 g), obtained in the fourth stage, suspended in tetrahydrofuran (20 ml), under cooling with ice and stirring was added 1 M solution of the complex of borane-tetrahydrofuran in tetrahydrofuran (12 ml) and the mixture refluxed for 1 hour in a stream of argon. The reaction mixture is cooled in ice water (10 ml) and acetone (5 ml) is added in order to stop the reaction, then add 6 N. hydrochloric acid (10 ml) and the mixture is stirred for 1 hour. the pH of the reaction mixture regulate up to 8-9 by addition of 4 n sodium hydroxide and aqueous saturated sodium bicarbonate and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header connection (1,82 g) as a colourless oil.

Sixth stage

Obtaining methyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxylate

Methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (of 0.58 g)obtained in the fifth stage, dissolved in toluene (7.5 ml), add 2,3-dichloropyridine (0,44 g), Tris(dibenzylideneacetone)dipalladium (69 mg), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (93 mg) and cesium carbonate (1.47 g) in that order and the mixture is stirred at 80°C for 24 hours. Again add 2,3-dichloropyridine (0,44 g, Tris(dibenzylideneacetone)tipaldi (69 mg) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (93 mg) and additional mixing continued for 15 hours at excessive heating. After cooling, the reaction mixture is distributed between ethyl acetate and water. The obtained ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated. Thus obtained residue is distilled using chromatography with silica gel (hexane:tetrahydrofuran = 3:1), while receiving specified in the header of the oily compound orange (0,53 g).

The seventh stage

Getting 4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (of 0.53 g)obtained in the sixth stage, dissolved in methanol (5 ml), add 4 M sodium hydroxide solution and the mixture is stirred at 60°C for 1 hour under heating. After cooling, the reaction mixture is neutralized by adding 1 M hydrochloric acid (4 ml), add water (20 ml), the precipitated solid is separated by filtration and dried, thus obtaining specified in the header of a pale orange solid (0,43 g).

The eighth stage

Obtaining N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(3-X is herperidin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (0,43 g), obtained in the seventh stage, dissolved in N,N-dimethylformamide (5 ml), add 4-tert-butylaniline (0.24 g), 1-hydroxybenzotriazole (0.25 g) and the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.31 g) in that order and the mixture is stirred at room temperature for 1 hour. After adding water and a saturated solution of sodium bicarbonate, the mixture is extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated. Thus obtained residue is purified using chromatography on silica gel (hexane:ethyl acetate = 3:2), while receiving specified in the header of the amorphous solid connection (0,42 g).

1H-NMR (400 MHz, CDCl3): δ=1,33 (s, 9 H), 3,88-of 3.97 (m, 2H), 4,57 with 4.65 (m, 2H), 6,66 (DD, J=8,00, of 1.28 Hz, 1H), 6.90 to (t, J=7,88 Hz, 1H), 7,11 (DD, J=7,88, to 4.87 Hz, 1H), 7,38 (d, J=8,58 Hz, II (H), 7,60 (d, J=8,58 Hz, 2H), to 7.77-of 7.82 (m, 2H), of 8.37 (DD, J=4.75 V, of 1.28 Hz, 1H), to 9.57 (s, 1H).

Example 1-002

Getting 8-(4-tert-butylphenyl)carbarnoyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid

The first stage

Obtaining N-(4-tert-butylphenyl)-3-nitro-2-hydroxybenzamide

3-Nitrosalicylic acid (10.0 g) is dissolved in methylene chloride (100 ml), add oxalicacid (6.2 ml) and N,N-dimethylformamide (0.1 ml) and the mixture is stirred at room temperature for 2 hours. The reaction mixture conc tryout and the concentrate added to a solution of 4-tert-butylaniline (5,2 g) and triethylamine (5.1 ml) in acetonitrile (100 ml), the mixture is then stirred at room temperature for 3 hours. After concentrating the reaction mixture, the reaction mixture was partitioned between chloroform and water. The obtained chloroform layer was washed with water, dried over anhydrous sodium sulfate and then concentrated. Thus obtained residue is purified using chromatography on silica gel (hexane-ethyl acetate = 1:1), while receiving specified in the title compound (3.0 g).

The second stage

Obtain 3-amino-N-(4-tert-butylphenyl)-2-hydroxybenzamide

N-(4-tert-Butylphenyl)-3-nitro-2-hydroxybenzamide (3.0 g)obtained in the first stage, dissolved in methanol (100 ml), add the uranyl chloride iron(III) (0.27 g) and activated charcoal (0.5 g), the mixture was stirred at 80°C and added dropwise to hydrazinehydrate (2,6 ml). After stirring under heating for 1 hour the reaction mixture is cooled and the insoluble matter is separated by filtration, then the solvent is evaporated in vacuum. The residue is distributed between ethyl acetate and water. The obtained ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous magnesium sulfate and then concentrated. Thus obtained residue is dissolved in ethyl acetate, add n-hexane, the precipitated solid is separated by filtration and dried, thus obtaining specified in the header is VCE connection (1,61 g).

The third stage

Getting ethyl-8-(4-tert-butylphenyl)carbarnoyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

3-Amino-N-(4-tert-butylphenyl)-2-hydroxybenzamide (1.6 g)obtained in the second stage, dissolved in acetone (20 ml), add ethyl-2,3-dibromopropionate (2.2 g) and potassium carbonate (2.3 g) and the mixture is stirred at room temperature for 16 hours. The reaction mixture is concentrated, water is added and the precipitated solid is separated by filtration. The thus obtained solid matter suspended in a mixed solvent of ethyl acetate and n-hexane and washed with mixed solvent, is separated by filtration and dried, thus obtaining specified in the header connection (1,67 g).

The fourth stage

Getting ethyl-8-(4-tert-butylphenyl)carbarnoyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylate

Ethyl-8-(4-tert-butylphenyl)carbarnoyl-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylate (1.66 g)obtained in the third stage, dissolved in toluene (10 ml), add 2,3-dichloropyridine (0.64 g), Tris(dibenzylideneacetone)dipalladium (394 mg), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (270 mg) and cesium carbonate (3.5 g) in that order and the mixture is stirred at 80°C for 24 hours. The reaction mixture was diluted with ethyl acetate (10 ml), add activated charcoal (1 g) and the mixture is stirred and filtered through celite. Filtration is at concentrated and purified using chromatography on silica gel (gradient elution with a mixture of n-hexane-ethyl acetate), while receiving specified in the header of a light yellow solid (1,03 g).

Fifth stage

Getting 8-(4-tert-butylphenyl)carbarnoyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid

Ethyl-8-(4-tert-butylphenyl)carbarnoyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (1,03 g)obtained in the fourth stage, dissolved in tetrahydrofuran (10 ml) and ethanol (10 ml)is added 2 M sodium hydroxide (2 ml) and the mixture is stirred at room temperature for 3 hours. The reaction mixture is concentrated, water is added (20 ml), the mixture is neutralized by adding 1 n sodium hydrosulphate and the precipitated solid is separated by filtration. The thus obtained solid substance is suspended and washed with a mixed solvent of ethyl acetate and n-hexane, separated by filtration and dried, thus obtaining specified in the header connection (0,60 g).

1H-NMR (400 MHz, DMSO-d6): δ=1,29 (m, 9H), 3,62 (m, 1H), 4,18 (m, 1H), 4,70 (m, 1H), 6,47 (DD, J=8,07, to 1.47 Hz, 1H), 6,79 (t, J=7,89 Hz, 1H), 7,21-7,35 (m, 4H), 7,84-a 7.92 (m, 2H), 7,98 (DD, J=7,70, to 1.47 Hz, 1H), 8,43 (DD, J=4,99 and 1.51 Hz, 1H), 12,34 (s, 1H).

Example nearby 1-003

Obtaining N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-3-nitro-2-(2-oxopropoxy)benzoate

Methyl-3-nitrosalicylic (1,95 g)obtained in the first stage, the PR is a measure 1-001, dissolved in N,N-dimethylformamide (20 ml), add potassium carbonate (2,73 g) and bromoacetone (1.1 ml) and the mixture is stirred at room temperature over night. The reaction mixture was partitioned between water and ethyl acetate and the ethyl acetate layer is washed twice with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header brownish oily substance (2,46 g).

The second stage

Obtaining methyl-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-3-nitro-2-(2-oxopropoxy)benzoate (2,46 g)obtained in the first stage, dissolved in tetrahydrofuran (25 ml), add 10% palladium-on-coal (containing 50% water) (0.25 g) and the mixture is stirred at room temperature for 24 hours in an atmosphere of hydrogen. The catalyst separated from the reaction mixture by filtration and the filtrate concentrated. The concentrate is purified using chromatography on silica gel (n-hexane:ethyl acetate = 1:1), while receiving specified in the header of a yellowish oily substance (0.45 g).

The third stage

Obtaining methyl-4-(3-chloropyridin-2-yl)-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (of 0.62 g)obtained by the method of the second stage, is subjected to the interaction method similar to the method in the fourth stage in which the example 2, and the product was then purified using chromatography on silica gel (n-hexane:acetone = 5:1), while receiving specified in the header of a pale yellowish oily substance (0.10 g).

The fourth stage

Getting 4-(3-chloropyridin-2-yl)-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-(3-chloropyridin-2-yl)-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (0.09 g)obtained in the third stage, dissolved in tetrahydrofuran (1 ml) and added dropwise methanol (1 ml), 4 M sodium hydroxide solution (0.5 ml) and the mixture was stirred at 60°C for 1 hour. The reaction mixture is neutralized 1 M hydrochloric acid and the solvent is evaporated in vacuum. The residue is distributed between water and ethyl acetate and the ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header of a pale yellowish oily substance (75 mg).

Fifth stage

Obtaining N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(3-Chloropyridin-2-yl)-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (75 mg)obtained in the fourth stage, is subjected to the interaction method similar to the method in the eighth stage in the example 1-001, and add water and a saturated aqueous solution of sodium bicarbonate in order Precipitated pale brown solid is separated by filtration and dried, while receiving specified in the title compound (95 mg).

1H-NMR (400 MHz, DMSO-d6): δ=1,23 (d, J=of 6.49 Hz, 3H), of 1.28 (s, 9H), 4,07-to 4.15 (m, 1H), 4,22-4,32 (m, 2H), 6,38 (DD, J=8,12, of 1.62 Hz, 1H), 6,80 (t, J=7,88 Hz, 1H),? 7.04 baby mortality (DD, J=7,54 and 1.51 Hz, 1H), 7,31-7,39 (m, 3H), of 7.64-7,71 (m, 2H), 8,07 (DD, J=7,88, of 1.62 Hz, 1H), 8,45 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,10 (s, 1H).

Example 1-004

Obtaining N-(4-tert-butylphenyl)-1-(3-chloropyridin-2-yl)-4-methyl-1,2,3,4-tetrahydroquinoxalin-5-carboxamide

The first stage

Obtaining methyl-2-chloro-3-nitrobenzoate

2-Chloro-3-nitrobenzoic acid (15.0 g) is subjected to interaction by a method similar to the method in the first stage of example 1-001, while receiving specified in the header of a pale yellow compound (9.0 g).

The second stage

Obtaining methyl-2-[(ethoxycarbonylmethyl)-(N-methyl)amino]-3-nitrobenzoate

Methyl 2-chloro-3-nitrobenzoate (2.0 g)obtained in the first stage, dissolved in n-butanol (20 ml), add sodium carbonate (2,46 g) and the hydrochloride of ethyl ether complex of sarcosine (2.14 g) and the mixture is refluxed for 4.5 hours with stirring. The cooled reaction mixture is poured into a mixture of 1 M hydrochloric acid (50 ml)/ethyl acetate (50 ml) under ice cooling with stirring. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated, thus obtaining a red oily substance content is ASEE specified in the title compound, which serves to the next stage without purification.

The third stage

Obtaining methyl-4-methyl-2-oxo-1,2,3,4-tetrahydroquinoxalin-5-carboxylate

Oily substance containing methyl-2-[(ethoxycarbonylmethyl)-(N-methyl)amino]-3-nitrobenzoate obtained in the second stage, dissolved in methanol (20 ml), add 5% palladium-on-coal (0.2 g) and the mixture is stirred at room temperature for 2 hours in hydrogen atmosphere. The catalyst separated from the reaction mixture by filtration. The filtrate is concentrated and then purified using chromatography on silica gel (n-hexane:ethyl acetate = 1:3), add diethyl simple ether and the precipitated pale brown solid is separated by filtration and dried, thus obtaining specified in the header connection (0,41 g).

The fourth stage

Obtaining methyl-4-methyl-1,2,3,4-tetrahydroquinoxalin-5-carboxylate

Methyl-4-methyl-2-oxo-1,2,3,4-tetrahydroquinoxalin-5-carboxylate (0,41 g)obtained in the third stage, is subjected to the interaction method, similar to the fifth stage of example 1, thus obtaining specified in the header yellowish oily compound (203 mg).

Fifth stage

Obtaining methyl-1-(3-chloropyridin-2-yl)-4-methyl-1,2,3,4-tetrahydroquinoxalin-5-carboxylate

Methyl-4-methyl-1,2,3,4-tetrahydroquinoxalin-5-carboxylate (206 mg)obtained in the fourth stud and, subjected to interaction by a method similar to the method of the fourth stage in the example 1-002, while receiving specified in the header of a pale yellowish-brown solid compound (179 mg).

Sixth stage

Obtaining methyl-1-(3-chloropyridin-2-yl)-4-methyl-1,2,3,4-tetrahydroquinoxalin-5-carboxylic acid

Methyl-1-(3-chloropyridin-2-yl)-4-methyl-1,2,3,4-tetrahydroquinoxalin-5-carboxylate (176 mg)obtained in the fifth stage, is subjected to the interaction method, similar to the fourth stage in the nearby 1-003 example, while receiving specified in the header of a pale yellowish-brown solid compound (130 mg).

The seventh stage

Obtaining N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-4-methyl-1,2,3,4-tetrahydroquinoxalin-5-carboxamide

Methyl-1-(3-chloropyridin-2-yl)-4-methyl-1,2,3,4-tetrahydroquinoxalin-5-carboxylic acid (130 mg)obtained in the sixth stage, is subjected to the interaction method, similar to the eighth stage in the example 1-001, and the reaction mixture is partitioned between aqueous saturated solution of sodium bicarbonate and ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated. The residue is purified using chromatography on silica gel (n-hexane-ethyl acetate = 3:1), while receiving specified in the header of a pale yellow amorphous compound (00 mg).

1H-NMR (400 MHz, DMSO-d6): δ=1.28 (in s, 9H), and 2.83 (s, 3H), 3,34-3,39 (m, 2H), 3,69-3,74 (m, II (H), 6,33 (DD, J=8,12, 1,39, 1 Hz, 1H), 6,72 (t, J=to 7.77 Hz, 1H), 7,03 (DD, J=7,65, 1.39 Hz, 1H), 7,30 (DD, J=7,88, with 4.64 Hz, H), 7,33-7,38 (m, 2H,), 7,63-to 7.68 (m, 2H), 8,02 (DD, J=7,88, of 1.62 Hz, 1H), 8,44 (DD, J=4.75 V, 1,74 Hz, 1H), to 10.62 (s, 1H).

Example 1-005

Obtaining N-(4-tert-butylphenyl)-9-(3-chloropyridin-2-yl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide

The first stage

Obtaining methyl-5-chloro-3-nitrosalicylic

Methyl-5-chlorosalicylic (5.0 g) is dissolved in concentrated sulfuric acid (15 ml)with stirring under ice cooling is added dropwise a mixture of concentrated nitric acid (1.2 ml) and concentrated sulfuric acid (1.2 ml) and the mixture is additionally stirred after adding dropwise. The reaction mixture was poured into a mixture of ice-water, the precipitated solid is separated by filtration, washed with water, then dried, thus obtaining specified in the header connection (5,51 g).

The second stage

Obtaining methyl-3-amino-5-chlorosalicylic

Methyl-5-chloro-3-nitrosalicylic (9,16 g)obtained by the method of the first stage, is subjected to the interaction method similar to the method in the second stage of example 2, and purified using chromatography on silica gel (n-hexane:ethyl acetate = 1:1), while receiving specified in the header of white solid compound (4,46 g).

The third stage

Obtaining IU the Il-3-ndimethylacetamide-5-chlorosalicylic

Methyl-3-amino-5-chlorosalicylic (4,46 g)obtained in the second stage, dissolved in tetrahydrofuran (50 ml) and with stirring and cooling with ice add pyridine (2 ml) and acetylchloride (1.6 ml). After 30 minutes the reaction mixture was concentrated and partitioned between water and ethyl acetate. The ethyl acetate layer was washed with 1 M hydrochloric acid, saturated sodium chloride solution, saturated aqueous sodium bicarbonate and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header of white solid compound (a 4.86 g).

The fourth stage

Obtaining methyl-9-acetyl-2-chloro-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylate

Methyl-3-ndimethylacetamide-5-chlorosalicylic obtained in the third stage, dissolved in N,N-dimethylformamide (10 ml), add potassium carbonate (1,38 g) and 1-bromo-3-chloropropane (2.0 ml) and the mixture is stirred at room temperature for 1 hour. Then the temperature was raised to 120°C. and the mixture is stirred for 3 hours. After cooling the reaction mixture, water is added and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and then concentrated. The residue is purified by chromatography using the raffia on silica gel (n-hexane:ethyl acetate = 1:1), while receiving specified in the header of white solid compound (630 mg).

Fifth stage

Obtaining methyl-9-acetyl-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylate

Methyl-9-acetyl-2-chloro-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylate (1.9 g)obtained in the same method as in the fourth stage, dissolved in tetrahydrofuran (20 ml) and methanol (20 ml), add 5% palladium (0.2 g) and triethylamine (1.2 ml) and the mixture is stirred at room temperature for 45 hours in a hydrogen atmosphere. The catalyst from the reaction suspension allocate by filtration, the filtrate is concentrated and the concentrate partitioned between water and ethyl acetate. The ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header of a colorless oily compound (1.45 g).

Sixth stage

Getting 6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylic acid

Water (25 ml) and concentrated sulfuric acid (5 ml) is added to methyl-9-acetyl-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylate (1,43 g)obtained in the fifth stage, and the mixture is refluxed with stirring over night. The reaction mixture is left to cool, neutralized by adding 2 M solution of g is of droxia sodium to achieve a weakly acid reaction and extracted twice with ethyl acetate. The ethyl acetate layer is washed twice with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the title compound (530 mg). The aqueous layer was extracted with tetrahydrofuran, dried over anhydrous sulfate and concentrated, while receiving additional compound (320 mg).

The seventh stage

Getting ethyl-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylate

6,7,8,9-Tetrahydro-5-oxa-9-athensallowed-4-carboxylic acid (850 mg) was dissolved in ethanol (30 ml), add concentrated sulfuric acid (2 ml) and the mixture refluxed with stirring for 2 hours. The reaction mixture is cooled, neutralized with a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The ethyl acetate layer is concentrated and thus specified in the header of the oily compound (721 mg).

The eighth stage

Getting ethyl-9-(3-chloropyridin-2-yl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylate

Ethyl-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylate (720 mg)obtained in the seventh stage, is subjected to the interaction method, similar to the fourth stage in the example 1-002, and the crude product was then purified using chromatography on silica gel (n-hexane:ethyl acetate = 3:1), while receiving specified in the agolove oily compound (154 mg).

Ninth stage

9-(3-chloropyridin-2-yl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylic acid

Ethyl-9-(3-chloropyridin-2-yl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylate (150 mg) is dissolved in tetrahydrofuran (2 ml) and add ethanol (2 ml), 2 M sodium hydroxide solution (2 ml) and the mixture was stirred at 60°C for 1.5 hours. The reaction mixture was concentrated, acidified with 1 M aqueous potassium hydrosulfate and extracted twice with ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header of the oily compound (102 mg).

The tenth stage

Obtaining N-(4-tert-butylphenyl)-9-(3-chloropyridin-2-yl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide

9-(3-Chloropyridin-2-yl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylic acid (100 mg)obtained in the ninth stage, is subjected to the interaction method similar to the method described in the ninth stage in the example 1-001, and the crude product was then purified using chromatography on silica gel (n-hexane:ethyl acetate = 2:1), add n-hexane, the precipitated white solid was separated by filtration and dried, thus obtaining specified in the title compound (35 mg).

1H-NMR (400 MHz, DMSO-d6): δ=1,25 (s, 9H), of 1.95 (m, 2H), 397 (m, 2H), 4,27 (m, 2H), is 6.61 (DD, J=8,00 and 1.51 Hz, 1H), 6,93 (t, J=to 7.77 Hz, 1H), 7,06 (DD, J=to 7.77, of 4.75 Hz, 1H), 7,26 (DD, J=7,54 and 1.51 Hz, 1H), 7,30-7,38 (m, 2H), 7,63 (DDD, J=9,04, 2,55, 2,32 Hz, 2H), 7,76 (DD, J=7,65, of 1.62 Hz, 1H), 8,31 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,15 (s, 1H).

Example 1-006

In a method similar to the method of example 1-001 corresponding carboxylic acid and amine is used to obtain the compounds of example 1-006 shown in the table below.

Example 1-007

In a method similar to the method of example 1-001 corresponding carboxylic acid and amine is used to obtain the compounds of example 1-007 shown in the table below.

Example 1-008

In a method similar to the method of example 1-001 corresponding carboxylic acid and amine is used to obtain the compounds of example 1-008 shown in the table below.

Example 1-009

In a method similar to the method of example 1-001 corresponding carboxylic acid and amine is used to obtain the compounds of example 1-009, shown in the following table.

Example 1-010

In a method similar to the method of example 1-001 corresponding carboxylic acid and amine is used to obtain the compounds of example 1-010 shown in the table below.

Example 1-011

In a method similar to the method of example 1-001 corresponding carboxylic acid and amine is used to obtain the compounds of example 1-011 shown in the table below.

Note the R 1-012

In a method similar to the method of example 1-001 corresponding carboxylic acid and amine is used to obtain the compounds of example 1-012 shown in the table below.

Example 1-013

In a method similar to the method of example 1-001 corresponding carboxylic acid and amine is used to obtain the compounds of example 1-013 shown in the table below.

Example 1-014

In a method similar to the method of example 1-001 corresponding carboxylic acid and amine is used to obtain the compounds of example 1-014 shown in the table below.

Example 1-015

In a method similar to the method of example 1-001 corresponding carboxylic acid and amine is used to obtain the compounds of example 1-015 shown in the table below.

Example 1-016

In the sixth stage of example 1-001 2-bromopyridin used instead of 2,3-dichloropyridine and this and other compounds are treated in the same method as in this example, thus obtaining the compound of example 1-016 shown in the table below.

Example 1-017

In the sixth stage in the example 1-001 2-chloro-3-triptorelin used instead of 2,3-dichloropyridine and this and other compounds are treated in the same method as in this example, thus obtaining the compound of example 1-017 shown in the table below.

Example 1-018

In the third stage of example 1-001 2 promise ethylbromide used instead of chloroacetanilide and this and other compounds are treated in the same way that in this example, thus obtaining the compound of example 1-018 shown in the table below.

Example 1-019

In the third stage of example 1-001 2-chloropropionate used instead of chloroacetanilide and this and other compounds are treated in the same method as in this example, thus obtaining the compound of example 1-019 shown in the table below.

Example 1-020

3-Amino-5-chlorosalicylic acid obtained by the method of the second stage in the example 1-005, used in the method after the third stage of example 1-001, thus obtaining the compound of example 1-020 shown in the table below.

Example 1-021

Getting 4-(3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(3-Chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (100 mg)obtained in the seventh stage in the example 1-001, dissolved in tetrahydrofuran (1 ml), add oxalicacid (0.05 ml) and N,N-dimethylformamide (0.01 ml), the mixture is stirred at room temperature for 30 minutes and the reaction mixture is concentrated, thus obtaining the acid chloride of the acid in the form of a yellowish solid. To 4-triptoreline (48 mg) was added tetrahydrofuran (1 ml) and 1 M sodium hydroxide solution, under stirring and under cooling with ice add a solution of carboxylic acid in tetrahydrofuran (1 ml) and the reaction is th the mixture is stirred at room temperature for 30 minutes. The reaction mixture is concentrated and distributed between ethyl acetate and water and the ethyl acetate layer was washed with 1 M sodium hydroxide and a saturated solution of sodium chloride in this order, dried over anhydrous sodium sulfate and then concentrated. The residue is suspended in n-hexane and the suspension is filtered and the precipitate is dried, thus obtaining specified in the title compound (72 mg).

Example 1-022

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-022 shown in the table below.

Example 1-023

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-023 shown in the table below.

Example 1-024

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-024 shown in the table below.

Example 1-025

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-025 shown in the table below.

Example 1-026

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-026 shown in nigelle the existing table.

Example 1-027

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-027 shown in the table below.

Example 1-028

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-028 shown in the table below.

Example 1-029

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-029, shown in the following table.

Example 1-030

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-030 shown in the table below.

Example 1-031

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-031 shown in the table below.

Example 1-032

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-032 shown in the table below.

Example 1-033

In a method similar to the method in example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-033 shown in n ieslegusi table.

Example 1-034

Getting 4-(3-chloropyridin-2-yl)-N-(ethoxycarbonylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Methyl-4-aminobenzoate (260 mg) used in a method similar to the method in example 1-21, to obtain specified in the title compound (515 mg).

Example 1-035

Obtain N-(4-carboxyphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(3-Chloropyridin-2-yl)-N-(ethoxycarbonylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (500 mg)obtained in example 1-034, dissolved in tetrahydrofuran (5 ml) and methanol (5 ml), add 4 M sodium hydroxide solution (1 ml) and the mixture was stirred at 60°C for 5 hours. The reaction mixture is neutralized by adding 1 M hydrochloric acid and then concentrated. The concentrate is diluted with water and stirred, WHI white solid is collected by filtration and dried, thus obtaining specified in the title compound (433 mg).

Example 1-036

Obtaining N-(carbamoylmethyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

N-(4-Carboxyphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (100 mg)obtained in example 1-035, dissolved in N,N-dimethylformamide (2 ml), add ammonium chloride (65 mg), 1-hydroxybenzotriazole (56 mg), the hydrochloride of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (70 mg) and triethylamine (0,20 ml) specified in the order and the mixture is stirred at room temperature for 10 hours. After adding water and a saturated solution of sodium bicarbonate to the reaction mixture, the mixture is distributed by the addition of ethyl acetate. After the ethyl acetate layer was washed with water, concentrated and dried concentrate is suspended in water and washed with water, the white solid is collected by filtration and dried, thus obtaining specified in the title compound (80 mg).

Example 1-037

In a method similar to the method of example 1-036, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-037 shown in the table below.

Example 1-038

In the method similar to the method of example 1-036, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-038 shown in the table below.

Example 1-039

Obtain N-(4-acetylphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4'-Aminoacetophenone (279 mg) used in a method similar to the method of example 1-021, while receiving specified in the title compound (673 mg).

Example 1-040

Getting 4-(3-chloropyridin-2-yl)-N-[4-(1-hydroxy-1-methyl)ethyl]phenyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

N-(4-Acetylphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (150 mg)obtained in example 1-039, dissolved in tetrahydrofuran (15 ml), under cooling with ice add 1 the solution methylanisole - tetrahydrofuran (1.1 ml) and the mixture is then stirred at room temperature for 30 minutes. Then additionally add a 1 M solution methylanisole - tetrahydrofuran (0,37 ml) and the mixture is stirred at room temperature for 30 minutes. The reaction mixture is cooled on ice, the reaction is stopped by the addition of saturated aqueous ammonium chloride and the mixture extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated. The residue is purified using chromatography on silica gel (n-hexane-ethyl acetate = 1:4), while receiving specified in the header of a white amorphous compound (79 mg).

Example 1-041

Getting 4-(3-chloropyridin-2-yl)-N-[4-(1-hydroxy-1-methyl)propyl]phenyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

In reactions similar to reactions of example 1-040, 2 M ethylmagnesium used to obtain specified in the header of a white amorphous substance (100 mg) of N-(4-acetylphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (150 mg).

Example 1-042

In a method similar to the method of example 1-001, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-042 shown in the table below.

Example 1-043

In a method similar to the method of example 1-001, used to meet the total carboxylic acid and amine to obtain the compound of example 1-043, shown in the following table.

Example 1-044

In a method similar to the method of example 1-001, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-044 shown in the table below.

Example 1-045

In a method similar to the method of example 1-001, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-045 shown in the table below.

Example 1-046

In the sixth stage of example 1-001 4-bromopyridin used instead of 2,3-dichloropyridine and this and other compounds are treated in the same manner as in the example, thus obtaining the compound of example 1-046 shown in the table below.

Example 1-047

In the sixth stage of example 1-001 2-bromo-3-picoline is used instead of 2,3-dichloropyridine and this and other compounds are treated in the same manner as in the example, thus obtaining the compound of example 1-047 shown in the table below.

Example 1-048

In a method similar to the method of example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-048 shown in the table below.

Example 1-049

In a method similar to the method of example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-049 shown in the table below.

When the EP 1-050

In a method similar to the method of example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-050 shown in the table below.

Example 1-051

In a method similar to the method of example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-051 shown in the table below.

Example 1-052

In a method similar to the method of example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-052 shown in the table below.

Example 1-053

In a method similar to the method of example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-053 shown in the table below.

Example 1-054

In a method similar to the method of example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-054 shown in the table below.

Example 1-055

In a method similar to the method of example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-055 shown in the table below.

Example 1-056

In a method similar to the method of example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-056 shown in the table below.

the example 1-057

In a method similar to the method of example 1-021, apply the corresponding carboxylic acid and amine to obtain the compound of example 1-057 shown in the table below.

Example 1-058

Obtaining N-(4-tert-butylphenyl)-4-(4-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Getting 4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

In the sixth stage of example 1-001 2-chloro-4-picoline (890 mg) was used instead of 2,3-dichloropyridine and this connection and others are treated in the same manner as in the seventh stage of example 1-001, while receiving specified in the title compound (690 mg).

The second stage

Obtaining N-(4-tert-butylphenyl)-4-(4-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

N-(4-tert-Butylphenyl)-4-(4-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (150 mg)obtained by the method of example 1-001, used in a method similar to the method of example 1-021, to obtain specified in the title compound (130 mg).

Example 1-059

Connection example 1-059 shown in the table below, derived from the corresponding brancolini using the method similar to the method of example 1-021.

Example 1-060

Connection example 1-060 shown in the table below, derived from the corresponding brancolini using the method similar to etodo example 1-021.

Example 1-061 - example 1-236

Connection examples 1-061 - 1-236 listed below will receive is similar to performing any of the methods described in the General methods a-C for connection and/or by the method described in examples 1-001 - 1-060 mentioned previously.

Example 2

Example 2-01

Obtaining N-(benzo[1,3]dioxol-5-yl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-4-{3-chloro-5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

3,4-Dihydro-2H-benzo[1,4]oxazin-8-carboxylate (2.0 g)obtained by the method of the fifth stage of example 1-001, dissolved in toluene (30 ml), added 2,3-dichloro-5-(tetrahydropyran-2-yl)oxymethylene (2.76 g), palladium acetate (0.25 g), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.7 g) and cesium carbonate (7.4 g) and the mixture was stirred at 90°C over night. The reaction mixture was filtered, concentrated and the resulting residue purified using column chromatography on silica gel (hexane:tetrahydrofuran = 2:1), while receiving specified in the header of the oily compound (2.48 in).

The second stage

Getting 4-{3-chloro-5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-{3-chloro-5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-carboxylate (2,48 g), obtained in the first stage, is subjected to the interaction, analogous to the interaction of the fourth stage in the nearby 1-003 example, while receiving specified in the header connection (1,33 g).

The third stage

Obtaining N-(benzo[1,3]dioxol-5-yl)-4-{3-chloro-5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-{3-Chloro-5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (0.20 g)obtained in the second stage, and a 5-aminobenzo[1,3]dioxolane (0.10 g) is subjected to interaction, similar to the interaction of the eighth stage in the example 1-001, while receiving specified in the title compound (0.21 g).

The fourth stage

Obtaining N-(benzo[1,3]dioxol-5-yl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

N-(Benzo[1,3]dioxol-5-yl)-4-{3-chloro-5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (0.21 g)obtained in the third stage, dissolved in tetrahydrofuran (3 ml), add 6 M hydrochloric acid and the mixture is stirred at room temperature over night. The reaction mixture was concentrated and the residue purified using column chromatography on silica gel, thus obtaining specified in the title compound (0.12 g).

Example 2-02

Obtaining N-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-4-(3-chlor-hydroxymethylpropane-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

In the third stage of example 2-01 6-amino-2,3-dihydrobenzo[1,4]dioxin (111 mg) was used instead of 5-aminobenzo[1,3]dioxolane and this connection and others treated the same way as in the specified way, get listed in the title compound (109 mg).

Example 2-03

Obtain N-(4-trifloromethyl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

In the third stage of example 2-01 4-cryptomaterial (87 mg) was used instead of 5-aminobenzo[1,3]dioxolane and this connection and others treated the same way as in the specified way, get listed in the title compound (101 mg).

Example 2-04

Obtaining N-(3-chloro-4-trifloromethyl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

In the third stage of example 2-01 3-chloro-4-cryptomaterial (87 mg) was used instead of 5-aminobenzo[1,3]dioxolane and this connection and others treated the same way as in the specified way, get listed in the title compound (58 mg).

Example 2-05

Obtain N-(4-triptoreline)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtain N-(4-triptoreline)-4-{3-chloro-5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8 carbox the foreign Ministry

4-{3-Chloro-5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (300 mg)obtained in the second stage of example 2-01, dissolved in pyridine (5 ml), add thionyl chloride (88 mg) and the mixture was stirred at 80°C for 1 hour. The reaction mixture is cooled to room temperature, add 4-triptorelin (80 mg) and the mixture is stirred for 1 hour. The reaction mixture was partitioned between water and ethyl acetate and the ethyl acetate layer was washed with water, dilute aqueous potassium hydrosulfate, dilute aqueous sodium hydroxide and saturated sodium chloride solution, dried over magnesium sulfate and then concentrated, thus obtaining a residue containing specified in the title compound, which serves to the next stage without purification.

The second stage

Obtain N-(4-triptoreline)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The concentrated residue obtained in the first stage, dissolved in tetrahydrofuran (3 ml), add 6 M hydrochloric acid (3 ml) and the mixture is stirred at room temperature for 1 hour. The reaction mixture was partitioned between water and ethyl acetate and the ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous magnesium sulfate and is eat concentrate. Thus obtained concentrated residue purified using chromatography on silica gel, thus obtaining specified in the title compound (71 mg).

Example 2-06

Obtaining N-(3-fluoro-4-triptoreline)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

In the first stage of example 2-05 3-fluoro-4-triptorelin (110 mg) is used instead of 4-triptorelin and this connection and others are treated in the same manner as in the specified way, get listed in the title compound (50 mg).

Example 2-07

Obtain N-(4-triptoreline)-4-(5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Getting 4-{5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-{5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (560 mg), which is produced by using 2-chloro-5-(tetrahydropyran-2-yl)oksietilpiperazina instead of 2,3-dichloro-5-(tetrahydropyran-5-yl)oksietilpiperazina in the first stage of example 2-01, dissolved in methanol (8 ml), add 4 M sodium hydroxide solution (1.1 ml) and the mixture is stirred at 60°C for 2 hours. The reaction mixture was concentrated and the concentrate is distributed by the addition of water and ethyl acetate. the pH of the aqueous layer to regulate 4 to what t hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer is dried over anhydrous sodium sulfate and then concentrated. The precipitated solid is obtained by adding diisopropyl simple ether, collected by filtration and dried, thus obtaining specified in the title compound (420 mg).

The second stage

Obtain N-(4-triptoreline)-4-{5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Interaction, similar to the interaction of the first stage of example 2-05, carried out with application of 4-{5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (200 g)obtained in the first stage of example 2-05, while receiving the concentrated residue containing specified in the header of the connection.

The third stage

Obtain hydrochloride of N-(4-triptoreline)-4-(5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The concentrated residue containing N-(4-triptoreline)-4-{5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide, dissolved in methanol (2 ml) and add tetrahydrofuran (2 ml), 6 M hydrochloric acid (1 ml) and the mixture is stirred at room temperature for 1 hour. The reaction mixture is concentrated, water is added and diethyl simple ether and then precipitated yellow solid of going to the t by filtration and dried, while receiving specified in the title compound (170 mg).

Example 2-08

Getting 4-(5-hydroxymethyluracil-2-yl)-N-(4-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Using 4-{5-(tetrahydropyran-2-yl)oxymethylene-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (200 mg)obtained in the first stage of example 2-07, and 4-isobutylketone (110 mg) and these compounds and others are subjected to interaction, analogous to the interaction of example 2-05, while receiving specified in the title compound (140 mg).

Example 2-09

Getting 4-(3-chloro-5-methoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-4-{3-chloro-5-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (1.3 g)obtained in the first stage of example 2-01, dissolved in tetrahydrofuran (5 ml), add 6 M hydrochloric acid (5 ml) and the mixture is stirred at room temperature for 2 hours. The reaction mixture is neutralized and extracted with ethyl acetate. The extract was concentrated, to thereby obtain a concentrated residue containing specified in the header of the connection.

The second stage

Obtaining methyl-4-(3-chloro-5-methoxypyridine-2-yl)-3,-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

The concentrated residue obtained in the first stage, are dissolved in N,N-dimethylformamide (5 ml), add sodium hydride (50%) (0.32 g) and the mixture is stirred at room temperature until foaming. Then add sodium iodide (1 ml) and the mixture is additionally stirred for 1 hour. The reaction mixture was partitioned between water and ethyl acetate and the ethyl acetate layer was washed with water, dried over anhydrous sodium sulfate and then concentrated. The concentrate is purified using chromatography on silica gel, thus obtaining specified in the header of the oily compound (1.20 g).

The third stage

Getting 4-(3-chloro-5-methoxypyridine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-(3-chloro-5-methoxypyridine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (1.20 g)obtained in the second stage, dissolved in tetrahydrofuran (10 ml) and add methanol (10 ml), 2 M sodium hydroxide (5 ml) and the mixture is then stirred at 60°C for 1 hour. The reaction mixture was concentrated and neutralized, filtered receive a solid black color, which is dried, thus obtaining specified in the title compound (915 mg).

The fourth stage

Getting 4-(3-chloro-5-methoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(3-Chloro-5-methoxypyridine-2-is)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (200 mg), obtained in the third stage, dissolved in chloroform (2 ml), add oxalicacid (60 μl) and N,N-dimethylformamide (one drop) and the mixture is stirred at room temperature for 1 hour. The reaction mixture was concentrated, added pyridine (2 ml) and 4-triptorelin (75 μl) and the mixture is stirred at room temperature for 1 hour. The reaction mixture was partitioned between water and ethyl acetate and the ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate and then concentrated. The precipitated solid is obtained by adding n-hexane and diethyl ether to the concentrate is collected by filtration and dried, thus obtaining specified in the title compound (64 mg).

Example 2-10

Obtain N-(4-triptoreline)-4-(4-hydroxymethylpropane-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Getting 4-{4-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-{4-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate obtained by the method in which the reaction of the first stage of example 2-01 carried out in a similar manner using 2-chloro-4-(tetrahydropyran-2-yl)oksietilpiperazina (1.52 g) instead of 2,3-dichloro-5-(tetrahydropyran-2-yl)oksietilpiperazina and the reaction mixture is filtered, concentrated and iseut using column chromatography on silica gel, dissolved in methanol (10 ml) and tetrahydrofuran (10 ml), add 4 M sodium hydroxide solution and the mixture is stirred at 60°C for 1.5 hours. The reaction mixture is neutralized and concentrated. Concentrate distribute the addition of water and ethyl acetate. The ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous magnesium sulfate and concentrated, thus obtaining specified in the header connection (913 mg).

The second stage

Obtain N-(4-triptoreline)-4-(4-hydroxymethylpropane-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-{4-(Tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (300 mg)obtained in the first stage, dissolved in pyridine (5 ml), add thionyl chloride (89 μl) and the mixture is stirred at room temperature for 2 hours. Then add 4-triptorelin (102 μl) and stirred at the same temperature throughout the night. The reaction mixture was partitioned between water and ethyl acetate. The ethyl acetate layer was washed with water and saturated sodium chloride in this order, dried over anhydrous magnesium sulfate and then concentrated. The concentrate is purified using chromatography on silica gel. To a purified concentrated substance added tetrahydrofuran (5 ml) and 6 M chlorotoluron the acid (2 ml) and stirred at room temperature for 2 hours. The reaction mixture was partitioned between water and ethyl acetate. The ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous magnesium sulfate and then concentrated. The concentrate is purified using chromatography on silica gel, thus obtaining specified in the title compound (12 mg).

Example 2-11

Obtain N-(4-trifloromethyl)-4-(3-hydroxymethylpropane-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-4-{3-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Conducting the reaction similar to the reaction in the first stage of example 2-01, using 2-chloro-3-(tetrahydropyran-2-yl)oksietilpiperazina (712 mg) instead of 2,3-dichloro-5-(tetrahydropyran-2-yl)oksietilpiperazina, while receiving specified in the title compound (536 mg).

The second stage

Getting 4-{3-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-{3-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (536 mg)obtained in the first stage, dissolved in ethanol (10 ml)is added 2 M sodium hydroxide solution (2 ml) and the mixture was stirred at 60°C for 1 hour. The reaction mixture is neutralized by adding hydrochloric acid and conc the Ute, partitioned between water and ethyl acetate. Thus obtained ethyl acetate layer is dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the title compound (493 mg).

The third stage

Obtain N-(4-trifloromethyl)-4-{3-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-{3-(Tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (266 mg)obtained in the second stage, and 4-cryptomaterial (97 μl) were interaction, similar to the interaction of the eighth stage of example 1-001, while receiving specified in the title compound (222 mg).

The fourth stage

Obtain N-(4-trifloromethyl)-4-(3-hydroxymethylpropane-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

N-(4-Trifloromethyl)-4-{3-(tetrahydropyran-2-yl)oxymethylene-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (217 mg)obtained in the third stage, dissolved in methanol (5 ml), add 6 M hydrochloric acid (0.3 ml) and the mixture is stirred at room temperature for 1 hour. The reaction mixture is diluted with water, neutralized by adding sodium hydroxide solution and extracted with ethyl acetate. The ethyl acetate layer is dried over anhydrous sodium sulfate, concentrated and purified using chromatography on what silicagel, while receiving specified in the title compound (164 mg).

Example 2-12

Obtain (+)-N-(4-triptoreline)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-3-acetamido-2-hydroxybenzoate

Methyl-3-aminosalitsilata (10 g)obtained in the second step of example 1-001, dissolved in ethyl acetate (30 ml), add water (30 ml) and sodium bicarbonate (5,54 g) under stirring and cooling with ice add acetylchloride (5 ml). After stirring at room temperature for 30 minutes, the ethyl acetate layer is dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header connection (11,47 g).

The second stage

Obtaining methyl-4-acetyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-3-ndimethylacetamide-2-hydroxybenzoate obtained in the first stage, are dissolved in N,N-dimethylformamide (42 ml), add potassium carbonate (9,67 g) and 1-bromo-2-chlorate (4,99 ml) and the mixture was stirred at 50°C over night. The reaction mixture is distributed between ethyl acetate and water and the ethyl acetate layer was washed with water, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header connection (4,32 g).

The third stage

Getting 4-acetyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

To methyl 4-acetyl-3,4-dihydro-benzo[1,4]oxazin-8-carboxylate (4,32 g), obtained in the second stage, add 2 M sodium hydroxide solution and the mixture is refluxed with stirring for 1.5 hours. The reaction mixture is cooled on ice and added dropwise a solution of tetrahydrofuran (10 ml)containing acetylchloride (2,62 ml). Additionally added 2 M sodium hydroxide and acetylchloride to complete the reaction. Thus obtained reaction mixture was acidified with aqueous citric acid solution and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated sodium chloride, dried over anhydrous sodium sulfate and then concentrated. To the concentrate is added isopropanol and the precipitated solid is collected by filtration and dried, thus obtaining specified in the title compound (2.25 g).

The fourth stage

Getting 4-acetyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-Acetyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (2,75 g)obtained by the method similar to the method of the third stage, dissolved in tetrahydrofuran (30 ml), add oxalicacid (1.3 ml) and N,N-dimethylformamide (one drop) and the mixture is stirred at room temperature for 1 hour. To the reaction mixture are added pyridine (30 ml) and 4-triptorelin (1.9 ml) and stirred at room temperature for 1 hour. The reaction mixture is distributed is between water and ethyl acetate and the ethyl acetate layer was washed with water, dried over anhydrous sodium sulfate and then concentrated. The precipitated solid is obtained by adding n-hexane and diethyl ether to the concentrate is collected by filtration and dried, thus obtaining specified in the title compound (2.70 g).

Fifth stage

Obtaining N-(triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Tetrahydrofuran (15 ml) is added to 4-acetyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (2.70 g)obtained in the fourth step, add water (15 ml) and concentrated sulfuric acid (5 ml) and the mixture refluxed for 4 hours with stirring. The reaction mixture is cooled, neutralized with sodium hydroxide solution and extracted with ethyl acetate. The layer of ethyl acetate, concentrated and purified using chromatography on silica gel, thus obtaining specified in the header connection (1,94 g).

Sixth stage

Obtaining 1-(5,6-dichloropyridine-3-yl)ethyl ester (2R)-2-phenylpropionate

2,3-Dichloro-5-(1-hydroxy)ethylpyridine (7,58 g) dissolved in tetrahydrofuran (65 ml), add (R)-2-phenylpropionate acid (5.5 ml), add diisopropylethylamine (9,5 ml) and triphenylphosphine (12,54 g) and the mixture is stirred for 1 hour under ice cooling. To the reaction mixture is added a mixed solution of hexane:ethyl acetate (9:1), precipitated the solid substance was separated by filtration, the filtrate is concentrated and purified using chromatography on silica gel, thus obtaining a more polar isomer (4,54 g) and the less polar isomer (5,38 g) specified in the connection header.

The seventh stage

Getting 4-{3-chloro-5-[1-(2R)-2-phenylpropionyl)oxyethyl]pyridine-2-yl}-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The more polar isomer of 1-(5,6-dichloropyridine-3-yl)ethyl ester (2R)-2-phenylpropionate (324 mg)obtained in the sixth stage, and N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (322 mg) is subjected to the reaction similar to the reaction of the first stage of example 2-01, while receiving specified in the title compound (80 mg).

The eighth stage

Obtain (+)-N-(4-triptoreline)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-{3-Chloro-5-[1-((2R)-2-phenylpropionyl)oxyethyl]pyridine-2-yl}-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (80 mg)obtained in the seventh stage, dissolved in methanol (0.3 ml) and add tetrahydrofuran (0.3 ml), 4 M sodium hydroxide (0.3 ml) and the mixture was stirred at 60°C for 1 hour. The reaction mixture was concentrated and the precipitated solid substance obtained by the addition of water, collected by filtration and dried, thus obtaining programalso isomer specified in the title compound (32 mg).

Example 2-13

Obtaining (-)-N-(4-triptoreline)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Apply polar isomer of 1-(5,6-dichloropyridine-3-yl)ethyl ester (2R)-2-phenylpropionate (324 mg)obtained in the sixth stage of example 2-12, and then carry out the method of obtaining the same way after the seventh stage of example 2-12, while receiving specified in the header levogyrate isomer specified in the title compound (115 mg).

Example 2-14

Obtain (+)-N-(4-trifloromethyl)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtain N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

In the fourth stage of example 2-12 4-cryptomaterial (2.25 g) is used instead of 4-triptorelin and conducting the reaction similar to the reaction of methods 4 and 5 of example 2-12, while receiving specified in the title compound (1.77 g).

The second stage

Obtain (+)-N-(4-trifloromethyl)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Apply N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (334 mg)obtained in the first stage, and the more polar isomer of 1-(5,6-dichloropyridine-3-yl)ethyl ester (2R)-2-phenylpropionate (320 mg)obtained in the sixth stage of example 2-12, and spend Rea is the information after the seventh stage of example 2-12, while receiving specified in the header programame compound (197 mg).

Example 2-15

Obtaining (-)-N-(4-trifloromethyl)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

In the second stage of example 2-14 the more polar isomer of 1-(5,6-dichloropyridine-3-yl)ethyl ester (2R)-2-phenylpropionate replace polar isomer (320 mg) and the reaction of this and other compounds performed similarly, while receiving specified in the header levogyrate compound (180 mg).

Example 2-16 example 2-48

Compounds of examples 2-16 - 2-48 shown in the following tables, get similarly carrying out any of the methods described in the General methods a-C to obtain the compounds and/or methods described in the above examples 2-01 - 2-15.

Example 3

N-(4-Trifloromethyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-3-oxo-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-2-methoxyethoxy-3-nitrobenzoate

Methyl-3-nitrosalicylic (5,91 g)obtained in the first stage of example 1-001, dissolved in N,N-dimethylformamide (60 ml), add sodium carbonate (8,29 g), with stirring under cooling with ice add methoxymethane (2,73 ml) and the mixture is stirred for 4.5 hours. The reaction mixture is concentrated and distributed between ethyl acetate and water. The ethyl acetate layer was washed with water, the tub over anhydrous sodium sulfate and concentrated, while receiving specified in the header connection (6,98 g).

The second stage

Obtaining methyl-3-amino-2-ethoxyethylacetate

Methyl-2-methoxyethoxy-3-nitrobenzoate (6,98 g)obtained in the first stage, is subjected to hydrogenation, is similar to the second step of example 1-001, while receiving specified in the title compound (6.11 g).

The third stage

Obtaining methyl-3-(3-chloropyridin-2-yl)amino-2-ethoxyethylacetate

Methyl-3-amino-2-methoxyethoxymethyl (6.11 g)obtained in the second stage, and 2,3-dichloropyridine (4,29 g) is subjected to the reaction similar to the reaction of the first stage of example 2-01, while receiving specified in the header connection (7,46 g).

The fourth stage

Obtaining methyl-3-(3-chloropyridin-2-yl)aminosalitsilata

Methyl-3-(3-chloropyridin-2-yl)amino-2-methoxyethoxymethyl (7,46 g)obtained in the third stage, dissolved in methanol (50 ml), add 6 M hydrochloric acid and the mixture is stirred at 40°C for 1 hour. The reaction mixture was concentrated. The solid is precipitated by addition of water, collected by filtration and dried, thus obtaining specified in the header connection (5,64 g).

Fifth stage

Obtaining 3-(3-chloropyridin-2-yl)aminosalicylic acid

Methyl-3-(3-chloropyridin-2-ylamino)salicylate (is 3.08 g)obtained in the fourth stage, dissolved in methanol (20 ml), add M sodium hydroxide (8,3 ml) and the mixture was stirred at 70°C for 3 hours. The reaction mixture was concentrated. To the residue add an aqueous solution of citric acid and the precipitated solid is collected by filtration and dried, thus obtaining specified in the header connection (2,73 g).

Sixth stage

Obtaining 3-(3-chloropyridin-2-yl)amino-N-(4-triptoreline)benzamide

3-(3-Chloropyridin-2-yl)aminosalicylic acid (2,73 g)obtained in the previous fifth stage, and 4-cryptomaterial (1,46 ml) is subjected to condensation, similar to the condensation of the eighth stage of example 1-001, while receiving specified in the header connection (2,90 g).

The seventh stage

Obtain 3-[(3-chloropyridin-2-yl)-(chloroacetyl)]amino-N-(4-triptoreline)benzamide

3-(3-Chloropyridin-2-yl)amino-N-(4-triptoreline)benzamide (0.84 g)obtained in the sixth stage, dissolved in tetrahydrofuran (10 ml), while cooling with ice add triethylamine (0,30 ml) and chlorocatechol (0,175 ml) in that order and the mixture is stirred for 1 hour. The reaction mixture is distributed between ethyl acetate and water. The ethyl acetate layer is washed with water, aqueous citric acid solution, aqueous sodium bicarbonate and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and concentrated, thus obtaining a residue containing specified in the header of the connection.

The eighth stage

Obtaining N-(4-trifter ethoxyphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-3-oxo-2H-benzo[1,4]oxazin-8-carboxamide

The residue obtained in the preceding stage, dissolved in N,N-dimethylformamide (10 ml), add potassium carbonate (0.55 g) and the mixture was stirred at 80°C for 1 hour. After concentrating the reaction solution, the solution is distributed between ethyl acetate and water. The ethyl acetate layer is washed with water, aqueous citric acid solution and saturated saline solution in this order, dried over anhydrous sodium sulfate and then concentrated. The concentrated residue is purified using chromatography on silica gel, thus obtaining specified in the title compound (519 mg).

Example 4

Example 4-01

Obtaining (R)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtain (S)-methyl-3-(3-chloropyridin-2-yl)amino-2-(oxiran-2-yl)methoxybenzoate

Methyl-3-(3-chloropyridin-2-yl)aminosalitsilata (between 6.08 g)obtained in the fourth stage of example 3, is dissolved in N,N-dimethylformamide (60 ml), add potassium carbonate (3,01 g) and (S)-glycidylether (6,78) and the mixture is stirred at room temperature for 13 hours. The reaction mixture was partitioned between diethyl ether and water. The ether layer is washed with water, aqueous sodium hydrogen carbonate solution and saturated sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated. OST the current purified using chromatography on silica gel, while receiving specified in the header connection (7,22 g).

The second stage

Obtaining (R)-methyl-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

(S)-Methyl-3-(3-chloropyridin-2-yl)amino-2-(oxiran-2-yl)methoxybenzoate (7,10 g)obtained in the first stage, are dissolved in N,N-dimethylformamide (70 ml), add potassium carbonate (3,66 g) and the mixture was stirred at 60°C for 2 hours. The reaction mixture was partitioned between water and ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated. The residue is purified using chromatography on silica gel, thus obtaining specified in the header of a colorless oily compound (3.42 g).

The third stage

Obtaining (R)-methyl-4-(3-chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

(R)-Methyl-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (3.33 g)obtained in the second stage, dissolved in chloroform (35 ml), add 2,3-dihydropyran (1.0 g) and chloride dihydrate tin (225 mg) and the mixture is stirred at room temperature for 17 hours. The reaction mixture was concentrated and purified using chromatography on silica gel, thus obtaining specified in the header of the oily compound (3,49 g).

Even the fourth stage

Obtaining (R)-4-(3-chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

(R)-Methyl-4-(3-chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (3,39 g)obtained in the third stage, dissolved in tetrahydrofuran (15 ml) and methanol (15 ml), add 4 M sodium hydroxide (10 ml) and the mixture was stirred at 60°C for 0.5 hour. The reaction mixture is neutralized with hydrochloric acid, concentrated and partitioned between water and ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the title compound (3.15 g).

Fifth stage

Obtaining (R)-4-(3-chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-N-(4-trifloromethyl)-3,4-dihydro-3-oxo-2H-benzo[1,4]oxazin-8-carboxamide

(R)-4-(3-Chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (1.20 g)obtained in the fourth stage, and 4-cryptomaterial (525 mg) is subjected to condensation, similar to the eighth stage of example 1-001, while receiving specified in the header of a white amorphous compound (1.40 g).

Sixth stage

Obtaining (R)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

(R)-4(3-Chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (1,33 g), obtained in the fifth stage, dissolved in tetrahydrofuran (15 ml), add 6 M hydrochloric acid (2 ml) and the mixture is stirred at room temperature for 1 hour. The reaction mixture was partitioned between water and ethyl acetate. The ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and then concentrated. The concentrated residue is purified using column chromatography on silica gel, thus obtaining specified in the title compound (930 mg).

Example 4-02

Obtaining (R)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining (R)-4-(3-chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

(R)-4-(3-Chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (1.63 g)obtained in the fourth stage of example 4-01, dissolved in pyridine (15 ml), add thionyl chloride (0,352 ml) and the mixture is stirred at room temperature for 1 hour. Add a solution of 4-triptorelin (0,973 ml) in pyridine (1 ml) and the mixture is additionally stirred for 1 hour. The reaction mixture was concentrated and partitioned between water and ethyl acetate. Obtained the way the ethyl acetate layer was washed with aqueous citric acid solution, aqueous sodium bicarbonate and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and then concentrated. Thus obtained residue is purified using column chromatography on silica gel, thus obtaining specified in the header of a white amorphous compound (2,03 g).

The second stage

Obtaining (R)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

(R)-4-(3-Chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (1,93 g)obtained in the first stage, is subjected to the reaction similar to the reaction of the sixth stage of example 4-01, while receiving specified in the title compound (1.34 in).

Example 4-03

Obtain (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtain (S)-4-(3-chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

In the first stage of example 4-01 (R)-glycidylether (6,74 g) is used instead of (S)-glycidylmethacrylate and the reaction is carried out in a similar method from the first stage to the fourth stage, while receiving specified in the title compound (3.88 g).

The second stage

Obtain (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N - (4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Use (S)-4-(3-chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (1.88 g)obtained in the first stage, and conducting the reaction similar to the reaction of the fifth stage and the sixth stage of example 4-01, while receiving specified in the header connection (1,126 g).

Example 4-04

Obtain (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Use (S)-4-(3-chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (2.0 g)obtained in the first stage of example 4-03, and conducting the reaction similar to the reaction of the method of example 4-02, while receiving specified in the header connection (0,872 g).

Example 4-05

Obtain (S)-4-(5-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-3-(5-chloropyridin-2-yl)amino-2-ethoxyethylacetate

Methyl-3-amino-2-methoxyethoxymethyl (4,2 g), obtained using the same method as in the second stage of example 3, and 2.5-dichloropyridine (3.0 g) is subjected to the reaction similar to the reaction of the first stage of example 2-01, while receiving specified in the title compound (1.0 g).

The second stage

Obtain (S)-4-(5-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-to rockslide

Methyl-3-(5-chloropyridin-2-yl)amino-2-methoxyethoxymethyl (330 mg)obtained in the first stage, and other compounds treated by a similar way of example 4-03, while receiving specified in the title compound (83 mg).

Example 4-06

Obtain (S)-4-(5-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-3-(5-chloropyridin-2-yl)amino-2-hydroxybenzoate

In the third stage of example 3 2,5-dichloropyridine (3.0 g)is used instead of 2,3-dichloropyridine, and methyl-3-amino-2-methoxyethoxymethyl (4,20 g) is subjected to the reaction similar to the reaction of the fourth stage, while receiving specified in the title compound (1.0 g).

The second stage

Obtain (S)-4-(5-chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-3-(5-chloropyridin-2-yl)amino-2-hydroxybenzoate (1.0 g)obtained in the first stage, are used in the first stage of example 4-01, except that (R)-glycidylether (1.1 g) is used instead of (S)-glycidylether and reaction of these compounds and other conduct by a method similar to the method from the first stage to the fourth stage, while receiving specified in the title compound (830 mg).

The third stage

Obtain (S)-4-(5-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-N-benzo[1,4]oxazin-8-carboxamide

The same way of example 4-02, carried out using (S)-4-(5-chloropyridin-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (500 mg)obtained in the second stage, while receiving specified in the title compound (104 mg).

Example 4-07

Obtain (S)-4-(5-picoline-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

In the example 4-05 6-chloro-3-picoline is used instead of 2,5-dichloropyridine and subjected to the reaction similar to the reaction of the method of this example, while receiving specified in the title compound (91 mg).

Example 4-08

Obtain (S)-4-(5-picoline-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

In the example 4-06 6-chloro-3-picoline is used instead of 2,5-dichloropyridine and subjected to the reaction similar to the reaction of the method of this example, while receiving specified in the title compound (167 mg).

Example 4-09 - example 4-56

Connection examples 4-09 - 4-56 shown in the tables below, receive is similar to performing any of the methods described in the General methods a-C to obtain the compounds and/or methods, described in the earlier examples 4-01 - 4-08.

Example 4-57

Obtaining (R)-9-(3-chloropyridin-2-yl)-7-hydroxy-N-(4-trifloromethyl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-Carbo is samida

The first stage

Obtaining methyl-(R)-9-(3-chloropyridin-2-yl)-7-hydro-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylate

(S)-3-(3-Chloropyridin-2-yl)amino-2-(oxiran-2-yl)methoxybenzoate (0,30 g), which is obtained using (R)-glycidylether instead of (S)-glycidylether in the method of example 4-01, dissolved in N,N-dimethylformamide (5 ml), add sodium methoxide (72 mg) and the mixture is stirred at room temperature for 1.5 hours. The reaction mixture is distributed between ethyl acetate and water. The ethyl acetate layer washed with water and dried over anhydrous sodium sulfate. The solvent is distilled, thus obtaining an oily substance containing specified in the header of the connection.

The second stage

Obtaining (R)-9-(3-chloropyridin-2-yl)-7-hydro-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylic acid

Methyl-(R)-9-(3-chloropyridin-2-yl)-7-hydro-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylate (520 mg)obtained by the method similar to the method of the preceding stage, dissolved in methanol (5 ml), add 4 n sodium hydroxide (1.6 ml) and the mixture was stirred at 65°C for 3 hours. The reaction mixture was concentrated and partitioned between water and ethyl acetate. the pH of the aqueous layer to regulate 3 Appendix 6 N. hydrochloric acid. The precipitated solid is collected by filtration, washed with water and dried, the floor is th at this is mentioned in the title compound (415 mg).

The third stage

Obtaining (R)-9-(3-chloropyridin-2-yl)-7-hydroxy-N-(4-trifloromethyl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide

(R)-9-(3-Chloropyridin-2-yl)-7-hydro-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxylic acid (321 mg)obtained in the second stage, is subjected to the condensation reaction similar to the reaction of condensation of the eighth stage of example 1-001, while receiving specified in the title compound (310 mg).

Example 4-58

Obtaining (R)-9-(3-chloropyridin-2-yl)-7-hydroxy-N-(4-triptoreline)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide

In the process for example, 4-04, when conducting the reaction similar to the reaction of the sixth stage of example 4-01 specified in the title compound in the form of a white solid is obtained as a by-product.

Example 4-59

Obtain (S)-9-(3-chloropyridin-2-yl)-7-hydroxy-N-(4-trifloromethyl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide

(S)-Glycidylether used in the same way of example 4-57, to obtain specified in the connection header.

Example 5

Example 5-01

Obtaining N-(4-tert-butylphenyl)-4-(pyrazin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-4-(pyrazin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Apply methyl-3,4-dihydro-2H-be the AOR[1,4]oxazin-8-carboxylate (1.0 g), obtained in the fifth stage of example 1-001, and chloropyrazine (0.6 g) and conducting the reaction mix, similar to the reaction of the fourth stage of example 1-002, while receiving specified in the header of the oily compound (0.84 g).

The second stage

Getting 4-(pyrazin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-(pyrazin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (0.84 g)obtained in the first stage, dissolved in tetrahydrofuran (2 ml), add methanol (2 ml) and 2 n sodium hydroxide (3 ml) and the mixture was stirred at 60°C for 3 hours. The reaction mixture was concentrated and add 1 n potassium hydrosulfate. The precipitated yellow solid is collected by filtration and dried, thus obtaining specified in the title compound (0.40 g).

The third stage

Obtaining N-(4-tert-butylphenyl)-4-(pyrazin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(Pyrazin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (150 mg)obtained in the second stage, dissolved in tetrahydrofuran (3 ml), add oxalicacid (0.05 ml) and N,N-dimethylformamide (one drop) and the mixture is stirred at room temperature for 0.5 hours. The reaction mixture was concentrated. The concentrated residue is dissolved in tetrahydrofuran (3 ml), add tert-butylaniline (74 mg) and triethylamine (0.5 ml) and the mixture is stirred at room Tempe is the atur for 0.5 hours. The reaction mixture was partitioned between water and ethyl acetate, the ethyl acetate layer is dried over anhydrous sodium sulfate and then concentrated. The residue is dissolved in methanol with heating. The solution is cooled to obtain a solid substance, which is collected by filtration and dried, thus obtaining specified in the title compound (12 mg).

Example 5-02

Obtaining N-(4-chlorophenyl)-4-(5-ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-4-(5-ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Apply methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (677 mg)obtained in the fifth stage of example 1-001, and 2-chloro-4-ethylpyrimidine (500 mg) and conducting the reaction mix, a similar reaction combination of the fourth stage of example 1-002, while receiving specified in the header yellowish oily compound (944 mg).

The second stage

Getting 4-(5-ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-(5-ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (944 mg)obtained in the first stage, is subjected to the reaction similar to the reaction of the second stage of example 5-02, while receiving specified in the header of white solid compound (820 mg).

The third stage

Obtaining N-(4-chlorophenyl)-4-(5-ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-Carbo is samida

4-(5-Ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (100 mg)obtained in the second stage, and 4-Chloroaniline (45 mg) is subjected to the condensation reaction similar to the reaction of condensation of the eighth stage of example 1-001, while receiving specified in the title compound (99 mg).

Example 5-03

Obtain N-(4-ethoxyphenyl)-4-(5-ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(5-Ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (100 mg)obtained in the second stage of example 5-02, and p-fenetidin (48 mg) is subjected to the condensation reaction similar to the reaction of condensation of the eighth stage of example 1-001, while receiving specified in the title compound (84 mg).

Example 5-04

Getting 4-(6-chloropyridin-3-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-4-(6-chloropyridin-3-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Apply methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (0.5 g)obtained in the fifth stage of example 1-001, and 3,6-dichloropyridazine (0,575 g) and conducting the reaction mix, a similar reaction combination of the fourth stage of example 1-002, while receiving specified in the title compound (0.24 g).

The second stage

Getting 4-(6-chloropyridin-3-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-(6-Harper dazin-3-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (240 mg), obtained in the first stage, is subjected to the reaction similar to the reaction of the second stage of example 5-02, while receiving specified in the header of the solid compound (145 mg).

The third stage

Getting 4-(6-chloropyridin-3-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(6-Chloropyridin-3-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (145 mg)obtained in the second stage, and 4-triptorelin (89 mg) is subjected to the condensation reaction, similar to the condensation reaction of example 5-01, and the product was then purified using chromatography on silica gel (n-hexane:ethyl acetate = 3:1), while receiving specified in the title compound (38 mg).

Example 5-05

Getting 4-(4-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-4-thiocarbamide-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (1,93 g)obtained in the first stage of example 1-001, dissolved in tetrahydrofuran (20 ml), under cooling with ice add 9-fluorenylmethoxycarbonyl (2,95 g) and the mixture is stirred for 0.5 hour. Added piperidine (5 ml) and the mixture is additionally stirred for 0.5 hour. Thus obtained reaction mixture was concentrated and the residue purified using chromatography on silica gel, n is the best at that specified in the header of the connection of 2.27 g).

The second stage

Obtaining methyl-4-(4-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-4-thiocarbamide-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (1.10 g)obtained in the first stage, dissolved in methanol (15 ml), add chloroacetone (0.4 ml) and the mixture is refluxed for 5 hours. The reaction mixture is concentrated and distributed between ethyl acetate and a saturated solution of sodium bicarbonate. The ethyl acetate layer is washed with water, aqueous citric acid and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and concentrated, thus obtaining a residue containing specified in the header of the connection.

The third stage

Getting 4-(4-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

The residue, containing methyl-4-(4-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate obtained in the second stage, dissolved in methanol (10 ml), add 4 n sodium hydroxide (3 ml) and the mixture is refluxed for 0.5 hours. The reaction mixture was concentrated. The solid is precipitated by addition of an aqueous citric acid, collected by filtration and dried, thus obtaining specified in the title compound (1.10 g).

The fourth stage

Getting 4-(4-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-b is the site, located between[1,4]oxazin-8-carboxamide

4-(4-Methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (0.55 g)obtained in the third stage, and 4-cryptomaterial (0,28 ml) was subjected to reactions similar to reactions of the eighth stage of example 1-001, and purified using chromatography on silica gel, thus obtaining specified in the header connection (0,722 g).

Example 5-06

Getting 4-(5-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

2,4,6-Tris-(1-chloroethyl)-1,3,5-trioxane (0.64 g) and montmorillonite K-10 (39 mg) is heated at 110°C for 10 minutes. Add toluene (10 ml) and methyl-4-thiocarbamide-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (1,17 g)obtained in the first stage of example 5-05, then add 2,4,6-Tris-(1-chloroethyl)-1,3,5-trioxane appropriately when heated to boiling under reflux until the end of the reaction. The reaction mixture is concentrated and distributed between ethyl acetate and a saturated solution of sodium bicarbonate. The ethyl acetate layer is concentrated and thus specified in the title compound (0.68 g).

The second stage

Getting 4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (0.68 g), receive the config in the second stage, dissolved in methanol (7 ml), add 4 n sodium hydroxide (1.77 ml) and the mixture refluxed for 20 minutes with stirring. The reaction mixture was concentrated. The solid is precipitated by addition of an aqueous citric acid, collected by filtration and dried, thus obtaining specified in the title compound (0.66 g).

The third stage

Getting 4-(5-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(5-Methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (0.66 g)obtained in the second stage, and cryptomaterial (0.28 mg) is subjected to the reaction similar to the reaction of the eighth stage of example 1-001, while receiving specified in the header of the connection (of 0.878 g).

Example 6

Example 6-01

Obtain (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-2-methoxyethoxy-3-toraibandodeta

Methyl-3-amino-2-methoxyethoxymethyl (2,11 g)obtained in the second step of example 3, was dissolved in tetrahydrofuran (20 ml) and cooled with ice add 9-fluorenylmethoxycarbonyl (3,09 g) and the mixture is stirred for 3 hours. The reaction mixture was concentrated, add N,N-dimethylformamide and piperidine (1 ml) and the mixture is additionally stirred tip is of 2 hours. Thus obtained reaction mixture is concentrated and distributed between ethyl acetate and water. The ethyl acetate layer was washed with aqueous citric acid, saturated sodium hydrogen carbonate solution and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header connection (1,91 g).

The second stage

Obtaining methyl-3-(5-methylthiazole-2-yl)aminosalitsilata

Methyl-2-methoxyethoxy-3-thoreidans (1.64 g)obtained in the first stage, is subjected to the reaction similar to the reaction of the first stage of example 5-06, while receiving specified in the header connection (734 mg).

The third stage

Obtaining methyl-(R)-3-(5-methylthiazole-2-yl)amino-2-(oxiran-2-yl)methoxybenzoate

Methyl-3-(5-methylthiazole-2-yl)aminosalitsilata (848 mg)obtained by the method similar to the method in the second stage, dissolved in N,N-dimethylformamide (8 ml), add potassium carbonate (452 mg) and (R)-glycidylether (915 mg) and the mixture is stirred at room temperature for 5 hours. The reaction mixture is distributed between ethyl acetate and water. The ethyl acetate layer was washed with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated. The residue is purified using chromatography on silica gel (n-hexane:ethyl acetate = 3:1), receiving the ri listed in the title compound (719 mg).

The fourth stage

Obtain methyl(S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-(R)-3-(5-methylthiazole-2-yl)amino-2-(oxiran-2-yl)methoxybenzoate (700 mg)obtained in the third stage, dissolved in dimethyl sulfoxide (5 ml), added 1,8-diazabicyclo[5,4,0]undecene-7-ene (166 mg) and the mixture is stirred at room temperature for 1.5 hours. The reaction mixture is distributed between ethyl acetate and water. The ethyl acetate layer was washed with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header of a colorless oily compound (695 mg).

Fifth stage

Obtain methyl(S)-4-(5-methylthiazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-(S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (695 mg)obtained in the fourth stage, dissolved in chloroform (7 ml), add 2,3-dihydropyran (700 mg) and hydrate p-toluensulfonate acid (453 mg) and the mixture is stirred at room temperature for 7 hours. The reaction mixture is concentrated and distributed between ethyl acetate and a saturated solution of sodium bicarbonate. The thus obtained ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over besttranslator sodium and then concentrated. The concentrated residue is purified using chromatography on silica gel (n-hexane:ethyl acetate = 3:1), while receiving specified in the title compound (552 mg).

Sixth stage

Obtain (S)-4-(5-methylthiazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-(S)-4-(5-methylthiazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (552 mg) was dissolved in tetrahydrofuran (2.5 ml) and methanol (2.5 ml), add 4 M sodium hydroxide (1.0 ml) and the mixture was stirred at 60°C for 1 hour. The reaction mixture was neutralized with diluted hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the title compound (563 mg).

The seventh stage

Obtain (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-N-(trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

(S)-4-(5-Methylthiazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (250 mg)obtained in the sixth stage, and 4-cryptomaterial (170 mg) is subjected to the condensation reaction similar to the reaction of condensation of the eighth stage of example 1-001, while receiving specified in the header is EDINENIE (379 mg).

The eighth stage

Obtain (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

(S)-3-Hydroxymethyl-4-(5-methylthiazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-N-(trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (379 mg)obtained in the seventh stage, dissolved in tetrahydrofuran (5 ml), add 6 N. hydrochloric acid (1 ml) and the mixture is stirred at room temperature for 1 hour. The reaction mixture was neutralized with a saturated solution of sodium bicarbonate and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated. The residue is purified using column chromatography on silica gel. To a purified substance is added n-hexane and the precipitated solid is collected by filtration and dried, thus obtaining specified in the title compound (216 mg).

Example 6-02

Obtain (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtain (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

(S)-4-(5-Methylthiazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,oxazin-8-carboxylic acid (260 mg), obtained in the sixth stage of example 6-01, dissolved in pyridine (5 ml), add thionyl chloride (0,097 ml) and the mixture is stirred at room temperature for 1 hour. Then add 4-triptorelin and the mixture is stirred over night. The reaction mixture is concentrated and distributed between ethyl acetate and 5% aqueous citric acid solution. The ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and concentrated, thus obtaining a residue containing specified in the header of the connection.

The second stage

Obtain (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The residue containing (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide obtained in the first stage, is subjected to the reaction similar to the reaction of the eighth stage of example 6-01, while receiving specified in the title compound (227 mg).

Example 6-03

Obtaining hydrochloride (S)-N-(3,4-dichlorophenyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-2-methoxyethoxy-3-(3-prop-2-inyl)thioridazine

Methyl-3-amino-2-methoxyethoxymethyl (21,12 g), obtained the second stage of example 3, dissolved in ethyl acetate (100 ml), add water (100 ml) and sodium bicarbonate (25,2 g) under stirring and ice cooling are added dropwise thiophosgene (7,62 ml). After 0.5 hours add propargylamine (7.2 ml) and the mixture is stirred at room temperature for 2 hours. The reaction mixture is distributed and the ethyl acetate layer was washed with water, dried over anhydrous sodium sulfate and concentrated, thus obtaining a brownish oily substance (36,16 g)containing specified in the header of the connection.

The second stage

Obtaining methyl-2-methoxyethoxy-3-(5-methylene-4,5-dihydrothiazolo-2-yl)aminobenzoate

Brownish oily substance (36,16 g)obtained in the first stage, dissolved in methanol (200 ml), add n-toluensulfonate acid (1.90 g) and the mixture refluxed for 2 hours with stirring. The reaction mixture is concentrated and distributed between ethyl acetate and saturated aqueous sodium bicarbonate. The ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header connection (34,42 g).

The third stage

Obtaining methyl-3-(5-methylthiazole-2-yl)aminosalitsilata

Methyl-2-methoxyethoxy-3-(5-methylene-4,5-dihydrothiazolo-2-yl)aminobenzoate (34,42 g), polucen the th in the second stage, stirred at 50°C for 30 minutes in a solution of 25% hydrogen bromide/acetic acid (60 ml). The reaction mixture is cooled, with stirring, 4 n sodium hydroxide (75 ml) and the precipitated solid is collected by filtration and dried, thus obtaining specified in the header of the connection.

The fourth stage

Obtain methyl(S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Methyl-3-(5-methylthiazole-2-yl)aminosalitsilata (3,54 g)obtained in the third stage, is subjected to the reaction similar to the reaction of the third stage and the fourth stage of example 6-01, while receiving specified in the header connection (4,29 g).

Fifth stage

Obtain (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-(S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (4,29 g)obtained in the fourth stage, dissolved in tetrahydrofuran (10 ml) and add methanol (10 ml), 4 n sodium hydroxide solution (10 ml) and the mixture was stirred at 60°C for 0.5 hour. The reaction mixture is neutralized, concentrated and distributed between ethyl acetate and water. The ethyl acetate layer was washed with a saturated solution of sodium chloride and then concentrated. To the residue is added ethyl acetate, the insoluble matter is separated by filtration and concentrate the recip what I mentioned in the title compound (3,53 g).

Sixth stage

Obtaining hydrochloride (S)-3-acetoxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

(S)-3-Hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (2,53 g)obtained in the fifth stage, dissolved in tetrahydrofuran (25 ml), add 4-(dimethylamino)pyridine (1.01 g) and the mixture is stirred at room temperature for 1 hour. Then add acetic anhydride (0,779 ml) and the mixture is additionally stirred for 0.5 hour. The reaction mixture is distributed between ethyl acetate and 5% aqueous citric acid solution. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and then concentrated. The concentrated residue is dissolved in ethyl acetate (50 ml) and add a solution of 4 n hydrogen chloride/ethyl acetate (2.5 ml). The precipitated solid is collected by filtration and dried, thus obtaining specified in the header connection (2,60 g).

The seventh stage

Obtain (S)-3-acetoxymethyl-N-(3,4-dichlorophenyl)-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Hydrochloride (S)-3-acetoxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (445 mg)obtained in the sixth stage, dissolved in pyridine (5 ml), add thionyl chloride (has 0.168 ml) and the mixture is stirred at room is the temperature for 1 hour. Add 3,4-dichloraniline (187 mg) and the mixture is additionally stirred for 0.5 hour. The reaction mixture is concentrated and distributed between ethyl acetate and 5% aqueous citric acid solution. The ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and then concentrated. The residue is purified using chromatography on silica gel (n-hexane:ethyl acetate = 2:1), while receiving specified in the title compound (398 mg).

The eighth stage

Obtaining hydrochloride (S)-N-(3,4-dichlorophenyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

(S)-3-Acetoxymethyl-N-(3,4-dichlorophenyl)-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide (398 mg)obtained in the seventh stage, dissolved in tetrahydrofuran (5 ml) and methanol (5 ml)was added 1 n sodium hydroxide (1.25 ml) and the mixture is stirred at room temperature for 0.5 hours. The reaction mixture is concentrated and distributed between ethyl acetate and water. The ethyl acetate layer was washed with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated. The residue is dissolved in diethyl ether (10 ml) and add a solution of 4 n hydrogen chloride/ethyl acetate (1 ml). The precipitated solid is collected by filtration and dried, obtaining PR is listed in the title compound (352 mg).

Example 6-04 - example 6-10

Connection examples 6-04 - 6-10 shown in the table below, receive is similar to performing any of the methods described in the General methods a-C for connection and/or the methods described in the above examples 6-01 - 6-03.

Example 6-11

Obtain (S)-3-hydroxymethyl-4-(5-methoxazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-3-isothiocyante-2-ethoxyethylacetate

Methyl-3-amino-2-methoxyethylamine (2.0 g)obtained in the second step of example 3, was dissolved in tetrahydrofuran (20 ml) and add triethylamine (4 ml) and under ice cooling and stirring, added dropwise to thiophosgene (0,76 ml). After adding water, the reaction mixture was concentrated and distributed by the addition of ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the title compound (2.4 g).

The second stage

Obtaining methyl-3-(5-methoxazole-2-yl)amino-3-ethoxyethylacetate

1-Azidation (0,94 g) dissolved in methylene chloride (10 ml), add methyl-3-isothiocyanato-2-methoxyethoxymethyl (2.4 g)obtained in the first stage, and triphenylphosphine (2.5 g) and the mixture is stirred at room temperature for 3 hours. The reaction mixture was concentrated add diethyl ether and the precipitated solid is removed by filtration. The filtrate is concentrated. The residue is purified using chromatography on silica gel (n-hexane:ethyl acetate = 5:1), while receiving specified in the header connection (1,82 g).

The third stage

Obtaining methyl-3-(5-methylisoxazol-2-yl)aminosalitsilata

Methyl-3-(5-methoxazole-2-yl)amino-3-methoxyethoxymethyl (1,77 g)obtained in the second stage, dissolved in tetrahydrofuran (20 ml), add 6 N. hydrochloric acid (3 ml) and the mixture is stirred at room temperature for 1 hour. The reaction mixture was concentrated and partitioned between water and ethyl acetate. The aqueous layer was neutralized with hydrochloric acid, the precipitated solid is collected by filtration and dried, thus obtaining specified in the title compound (1.4 g).

The fourth stage

Obtain (S)-4-(5-methoxazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-3-(5-methoxazole-2-yl)aminosalitsilata (1.4 g)obtained in the third stage, is subjected to the reaction similar to the reaction of the third stage, the sixth stage of example 6-01, while receiving specified in the title compound (760 mg).

Fifth stage

Obtain (S)-3-hydroxymethyl-4-(5-methoxazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

(S)-4-(5-Methoxazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-Digi the ro-2H-benzo[1,4]oxazin-8-carboxylic acid (200 mg), obtained in the fourth stage, is subjected to the reaction similar to the reaction of the seventh stage and the eighth stage of example 6-01, while receiving specified in the title compound (78 mg).

Example 6-12

Obtain (S)-3-hydroxymethyl-4-(5-methoxazole-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

(S)-4-(5-Methoxazole-2-yl)-3-(tetrahydropyran-2-yl)oxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (200 mg)obtained in the fourth stage of example 6-11, is subjected to the reaction similar to the reaction of the first stage and the second stage of example 6-02, while receiving specified in the title compound (80 mg).

Example 6-13

Obtain (S)-4-(4,5-dimethylthiazol-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-3-(4,5-dimethylthiazol-2-yl)amino-3-ethoxyethylacetate

Methyl-2-methoxyethoxy-3-thioridazin (2.00 g)obtained in the first stage of example 6-01, 3-bromo-2-butanone (1,34 g) and sodium bicarbonate (746 mg) in ethanol (20 ml) is refluxed for 1.5 hours with stirring. The reaction mixture was concentrated and partitioned between water and ethyl acetate. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header is connected to the e (2.65 g).

The second stage

Obtaining methyl-3-(4,5-dimethylthiazol-2-yl)aminosalitsilata

Methyl-3-(4,5-dimethylthiazol-2-yl)amino-3-methoxyethoxymethyl (2.65 g) was dissolved in tetrahydrofuran (10 ml), add 6 N. hydrochloric acid (2 ml) and the mixture was stirred at 60°C for 1 hour. The reaction mixture is neutralized by adding a saturated solution of sodium bicarbonate and then concentrated. The precipitated solid is collected by filtration and dried, thus obtaining specified in the title compound (2.00 g).

The third stage

Obtain (S)-4-(4,5-dimethylthiazol-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Methyl-3-(4,5-dimethylthiazol-2-yl)aminosalitsilata obtained in the second stage, is subjected to the reaction similar to the reaction of the method of the third stage, the eighth stage of example 6-001, while receiving specified in the header of the connection.

Example 6-14

Obtain (S)-4-(4,5-dimethylthiazol-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Methyl-3-(4,5-dimethylthiazol-2-yl)aminosalitsilata obtained in the second stage of example 6-13, is subjected to the reaction similar to the reaction of the method of the third stage, the sixth stage of example 6-01 and first stage and second stage of example 6-02, while receiving specified in the header of the connection.

Example 6-15

Receipt is (S)-3-hydroxymethyl-4-(5-methyl[1,3,4]thiazol-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-3-(acetylgalactosamine)amino-2-ethoxyethylacetate

Methyl-3-isothiocyante-2-methoxyethoxymethyl (6,12 g)obtained in the first stage of example 6-11, dissolved in tetrahydrofuran (100 ml), add acetohydrazide (2.5 g) and the mixture refluxed with stirring. The reaction mixture was partitioned between water and ethyl acetate. The ethyl acetate layer was washed with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated. The residue is purified using chromatography on silica gel (n-hexane:ethyl acetate = 1:1), while receiving specified in the header connection (equal to 4.97 g).

The second stage

Obtaining methyl-3-(5-methyl[1,3,4]thiadiazole-2-yl)aminosalitsilata

Methyl-3-(acetylgalactosamine)amino-2-methoxyethoxymethyl (equal to 4.97 g)obtained in the first stage, dissolved in ethanol (100 ml) and cooled with ice add concentrated sulfuric acid (50 ml). The mixture is additionally stirred at room temperature for 1 hour. The reaction mixture is neutralized and partitioned between water and ethyl acetate. The ethyl acetate layer was washed with water and saturated sodium chloride solution in order, dried over anhydrous sodium sulfate and then concentrated. The residue is purified using chromatography on Sealy is agile (n-hexane:ethyl acetate = 2:1), while receiving specified in the header connection (1,11 g).

The third stage

Obtain (S)-3-hydroxymethyl-4-(5-methyl[1,3,4]thiadiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Methyl-3-(5-methyl[1,3,4]thiadiazole-2-yl)aminosalitsilata obtained in the second stage, is subjected to the reaction similar to the reaction of the method of the third stage, the eighth stage of example 6-001, while receiving specified in the header of the connection.

Example 6-16

Obtain (S)-3-hydroxymethyl-4-(5-methyl[1,3,4]thiadiazole-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Methyl-3-(5-methyl[1,3,4]thiadiazole-2-yl)aminosalitsilata obtained in the second stage of example 6-15, is subjected to the reaction similar to the reaction of the method of the third stage, the sixth stage of example 6-001 and first stage and second stage of example 6-02, while receiving specified in the header of the connection.

Example 6-17

Getting 4-(4,5-dimethylthiazol-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxamide

The first stage

Obtaining methyl-2-carbomethoxybiphenyl-3-nitrobenzoate

Methyl 2-chloro-3-nitrobenzoate (11.6 g)obtained in the first stage of example 1-004, dissolved in methanol (100 ml), add sodium bicarbonate (6,83 g) and mercaptohexanol acid (2,64 ml) and the mixture refluxed with stirring for 16 hours. The reaction is ionic solution is left for cooling, poured into a mixture of 2 M hydrochloric acid (100 ml) - ethyl acetate (100 ml) with stirring under ice cooling, and distribute. The ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated. The residue is purified by chromatography on silica gel (chloroform:methanol:acetic acid = 19:0,9:0,1), while receiving specified in the header connection (4,84 g) as a pale orange solid.

The second stage

Obtaining methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxylate

Ammonium chloride (379 mg) dissolved in water (10 ml) and added reduced iron (3,66 g) when heated to 85°C. and stirring. To the mixture add a solution of methyl 2-carbomethoxybiphenyl-3-nitrobenzoate obtained in the above stage (to 4.81 g)in N,N-dimethylformamide (20 ml)for 15 minutes and the mixture is heated and stirred at 85°C. for additional one hour. The reaction solution is left to cool, add water, ethyl acetate and tetrahydrofuran. After removing the insoluble substance mixture evenly. The organic layer is dried over anhydrous sodium sulfate and concentrated. Pale grey solid precipitated diisopropyl ether, collected by filtration and dried, thus obtaining specified in the header connection (2,99 g).

The third stage

Obtaining methyl-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxylate

Methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxylate obtained in the above stage (2,99 g), is subjected to the same reaction as in the fifth stage of example 1-001, while receiving specified in the header connection (2,53 g) as a yellow solid.

The fourth stage

Obtaining methyl-4-thiocarbamide-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxylate

The same reaction as in the first stage of example 5-05, hold for methyl-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxylate obtained in the above stage, while receiving specified in the title compound (1.44 g) as a white solid.

Fifth stage

Obtaining methyl-4-(4,5-dimethylthiazol-2-yl)-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxylate

Methyl-4-thiocarbamide-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxylate (1.44 g)obtained in the above stage, 3-bromo-2-butanone (972 mg) and sodium hydrogen carbonate (541 mg) is refluxed with stirring in methanol (15 ml) and tetrahydrofuran (10 ml) for 17 hours. The reaction solution was concentrated and partitioned between water and ethyl acetate. The resulting ethyl acetate layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated, thus obtaining specified in the header connection (1,91 g).

The sixth study the Sabbath.

Getting 4-(4,5-dimethylthiazol-2-yl)-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxylic acid

Methyl-4-(4,5-dimethylthiazol-2-yl)-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxylate (1,91 g)obtained in the above stage dissolved in methanol (5 ml) and tetrahydrofuran (5 ml), add 4 n sodium hydroxide (2.0 ml) and the mixture refluxed with stirring for one hour. The reaction solution was concentrated and neutralized by adding 2 N. hydrochloric acid under ice cooling. The precipitated solid is separated by filtration and dried, thus obtaining specified in the header connection (1,41 g).

The seventh stage

Getting 4-(4,5-dimethylthiazol-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxamide

The same reaction as in the eighth stage of example 1-001, hold for 4-(4,5-dimethylthiazol-2-yl)-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxylic acid obtained in the above stage (1.40 g)and 4-triphtalocyaninine (809 mg), while receiving specified in the header of the connection (of 1.03 g) as a white solid.

Example 6-18

Getting 4-(4,5-dimethylthiazol-2-yl)-N-(4-trifloromethyl)-1-oxo-3,4-dihydrobenzo[1,4]thiazin-8-carboxamide

4-(4,5-Dimethylthiazol-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxamide obtained in example 6-17 (500 mg), suspended in chloroform (15) - Rev. l), add meta-chloroperbenzoic acid (247 mg) and the mixture is stirred at room temperature for two hours. To the reaction solution was added a saturated solution of sodium bicarbonate and the mixture evenly. The chloroform layer was washed with a saturated solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated. The residue is purified by chromatography on silica gel (chloroform:methanol = 9:1) and a white solid precipitated diisopropyl ether, separated by filtration and dried, thus obtaining specified in the title compound (290 mg).

Example 7

Example 7-01

Obtaining N-(4-tert-butylphenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate

Apply methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (1.0 g)obtained in the fifth stage of example 1-001, and 4-bromoanisole (1.0 g) and conducting the reaction mix, similar to the reaction of the fourth stage of example 1-002, while receiving specified in the header of the oily compound (0,58 g).

The second stage

Getting 4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid

Methyl-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylate (of 0.58 g)obtained in the first stage, dissolved in tetrahydrofuran (10 ml) and methanol (10 ml), dobavlaut 2 N. the sodium hydroxide solution (5 ml) and the mixture was stirred at 60°C for 1.5 hours. After concentrating the reaction mixture, a yellow solid is precipitated by addition of 1 n potassium hydrosulfate, collected by filtration and dried, thus obtaining specified in the header connection (0,552 g).

The third stage

Obtaining N-(4-tert-butylphenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(4-Methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (57 mg)obtained in the second stage, dissolved in tetrahydrofuran (5 ml), add oxalicacid (0,03 ml) and N,N-dimethylformamide (one drop) and the mixture is stirred at room temperature for 0.5 hours, then the reaction mixture was concentrated. The concentrated residue is dissolved in tetrahydrofuran (5 ml), add tert-butylaniline (30 mg) and triethylamine (0.5 ml) and the solution stirred at room temperature for 1 hour. The reaction mixture was partitioned between water and ethyl acetate. The ethyl acetate layer is dried over anhydrous sodium sulfate and then concentrated. The precipitated solid is obtained by adding hexane to the residue, collected by filtration, and dried, thus obtaining specified in the title compound (48 mg).

Example 7-02

Obtain N-(4-isobutylphenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4(4-Methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (57 mg), obtained in the second stage of example 7-01, and 4-isobutylketone (40 mg) is subjected to the reaction similar to the reaction of the third stage of example 7-01, while receiving specified in the title compound (31 mg).

Example 7-03

Obtaining N-(4-chlorophenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

4-(4-Methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid (57 mg)obtained in the second stage of example 7-01, and 4-Chloroaniline (40 mg) is subjected to interaction, analogous to the interaction of the third stage of example 7-01, while receiving specified in the title compound (29 mg).

Example 7-04

Obtain (S)-4-(2-chlorophenyl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

The first stage

Obtaining methyl-3-(2-chlorophenyl)amino-2-ethoxyethylacetate

Methyl-3-amino-2-methoxyethoxymethyl (3.5 g)obtained in the second step of example 3 and 2-iocharset (2,62 ml) was subjected to reactions similar to reactions of the first stage of example 2-01, while receiving specified in the header connection (2,33 g).

The second stage

Obtaining methyl-3-(2-chlorophenyl)aminosalitsilata

Methyl-3-(2-chlorophenyl)amino-2-methoxyethoxymethyl (2,33 g)obtained in the first stage, is subjected to the reaction similar to the reaction of the fourth stage of example 3, thus obtaining specified in the title compound (1.75 g).

p> The third stage

Obtain (S)-4-(2-chlorophenyl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide

Methyl-3-(2-chlorophenyl)aminosalitsilata obtained in the second stage, is subjected to reaction following the third stage in the example 6-01, while receiving specified in the header of the connection.

Example 7-05 - example 7-11

Connection examples 7-05 - 7-11, shown here below, get similarly carrying out any of the methods described in the General methods a-C to obtain the compounds and/or methods described in the above examples 4-01 - 4-59 and the method described in example 7-04.

Chemical structure, molecular weight and the data of the NMR spectra of the compounds obtained in examples 1-001 - 7-11 shown in table 1 - table 50.

[Table 1]
No. approx.Chemical compoundNMR
11-001(400 MHz, CHLOROFORM-D) of 1.33 (s, 9H), 3,88-of 3.97 (m, 2H), 4,57 with 4.65 (m, 2H), 6,66 (DD, J=8,00, of 1.28 Hz, 1H), 6.90 to (t, J=7,88 Hz, 1H), 7,11 (DD, J=7,88, to 4.87 Hz, 1H), 7,38 (d, J=8,58 Hz, 2H), 7,60 (d, J=8,58 Hz, 2H), to 7.77-7,82 (m, 2H), of 8.37 (DD, J=4.75 V, of 1.28 Hz, 1H), to 9.57 (s, 1H)
21-002(300 MHz, DMSO-D6) of 1.29 (m, 9H), 3,62 (m, 1H), 4,18 (m, 1H), 4,70 (m, 1H), 6,47 (DD, J=8,07, to 1.47 Hz, 1H), 6,79 (t, J=7,89 Hz, 1H), 7,21-7,35 (m, 4H), 7,84-a 7.92 (m, 2H), 7,98 (DD, J=7,70, to 1.47 Hz, 1H), 8,43 (DD, J=4,99 and 1.51 Hz, 1H), 12,34 (s, 1H)
3Nearby 1-003(400 MHz, DMSO-D6) of 1.23 (d, J=of 6.49 Hz, 3H), of 1.28 (s, 9H), 4,07-to 4.15 (m, 1H), 4,22-4,32 (m, 2H), 6,38 (DD, J=8,12, of 1.62 Hz, 1H), 6,80 (t, J=7,88 Hz, 1H),? 7.04 baby mortality (DD, J=7,54 and 1.51 Hz, 1H), 7,31-7,39 (m, 3H), of 7.64-7,71 (m, 2H), 8,07 (DD, J=7,88, of 1.62 Hz, 1H), 8,45 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,10 (s, 1H)
41-004(400 MHz, DMSO-D6) of 1.28 (s, 9H), and 2.83 (s, 3H), 3,34-3,39 (m, 2H), 3,69-3,74 (m, 2H), 6,33 (DD, J=8,12, 1.39 Hz, 1H), 6,72 (t, J=to 7.77 Hz, 1H), 7,03 (DD, J=7,65, 1.39 Hz, 1H), 7,30 (DD, J=7,88, with 4.64 Hz, 1H), 7,33-7,38 (m, 2H), 7,63-to 7.68 (m, 2H), 8,02 (DD, J=7,88, of 1.62 Hz, 1H), 8,44 (DD, J=4.75 V, 1,74 Hz, 1H), to 10.62 (s, 1H)
51-005(400 MHz, DMSO-D6) of 1.25 (s, 9H), of 1.95 (m, 2H), 3,97 (m, 2H), 4,27 (m, 2H), is 6.61 (DD, J=8,00 and 1.51 Hz, 1H), 6,93 (t, J=to 7.77 Hz, 1H), 7,06 (DD, J=to 7.77, of 4.75 Hz, 1H), 7,26 (DD, J=7,54 and 1.51 Hz, 1H), 7,30-7,38 (m, 2H), 7,63 (DDD, J=9,04, 2,55, 2,32 Hz, 2H), 7,76 (DD, J=7,65, of 1.62 Hz, 1H), 8,31 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,15 (s, 1H)
6 1-006(400 MHz, DMSO-D6) 3,76 (m, 2H), 4,37 (m, 2H), 6.48 in (DD, J=8,12, 1.39 Hz, 1H), 6.73 x-6,83 (m, 1H), 7,02 (DD, J=7,54 and 1.51 Hz, 1H), 7,28 (DD, J=7,88, with 4.64 Hz, 1H), was 7.36 (DD, J=6,80, 2.10 Hz, 1H), of 7.75 (DD, J=8,00, 1,74 Hz, 2H), 8,01 (DD, J=8,00, 1,74 Hz, 2H), 8,39 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,28 (s, 1H)
71-007(400 MHz, DMSO-D6) 1,17-of 1.26 (d, J=6,00 Hz, 6H), of 3.75 (m, 2H), 4,39 (m, 2H), 4.53-in (m, 1H), 6,46 (DD, J=8,12, 1.39 Hz, 1H), 6,76 (t, J=7,88 Hz, 1H), 6,86 (m, 2H), 7,03 (DD, J=7,54 and 1.51 Hz, 1H), 7,27 (DD, J=8,00, 4,75 Hz, 1H), 7,60 (m, 2H), 8,01 (DD, J=7,88, of 1.62 Hz, 1H), 8,39 (DD, J=with 4.64, of 1.62 Hz, 1H), 9,98(s, 1H)
81-008(400 MHz, DMSO-D6) of 1.02 (m, 9H), 1,43-and 1.54 (m, 2H), 1.77 in-to 1.87 (m, 2H), 2,12-2,17 (m, 2H), 2,86-2,95 (m, 2H), 3,69-of 3.80 (m, 3H), 4,37-4,47 (m, 2H), 6,46 (DD, J=8,12, of 1.62 Hz, 1H), 6.73 x-6,77 (m, 1H), 7,12 (DD, J=7,65, of 1.62 Hz, 1H), 7,29 (DD, J=7,88, 4,46 Hz, 1H), 7,98 (d, J=7,88 Hz, 1H), 8,02 (DD, J=7,88, of 1.62 Hz, 1H), to 8.41 (DD, J=4.75 V, 1,74 Hz, 1H)

/tr>
[Table 2]
No. approx.Chemical compoundNMR
91-009 (300 MHz, DMSO-D6) of 2.28 (s, 3H), of 3.77-a-3.84 (m, 2H), 4,40-4,48 (m, 2H), 6,50 (DD, J=8,07, to 1.47 Hz, 1H), 6,79 (t, J=of 7.70 Hz, 1H), 7,07-7,10 (m, 1H), 7,14 (d, J=8,44 Hz, 2H), 7,31 (DD, J=8,07, of 4.77 Hz, 1H), 7,63 (d, J=8,44 Hz, 2H), with 8.05 (DD, J=8,07, to 1.47 Hz, 1H), 8,43 (DD, J=4,77, to 1.47 Hz, 1H), 10,06 (s, 1H)
101-010(300 MHz, DMSO-D6) of 0.89 (d, J=6,60 Hz, 3H), 0,93-1,11 (m, 2H), 1,19-of 1.40 (m, 3H), 1,64 to 1.76 (m, 2H), 1,81-of 1.93 (m, 2H), 3,60-3,81 (m, 3H), of 4.38-of 4.44 (m, 2H), 6,45 (DD, J=7,89, 1.65 Hz, 1H), 6,72-6,77 (m, 1H), 7,10 (DD, J=7,70, to 1.47 Hz, 1H), 7,28 (DD, J=7,89, 4.59 Hz, 1H), 7,89 (d, J=of 7.70 Hz, 1H), 8,02 (DD, J=7,89, 1.65 Hz, 1H), 8,40 (DD, J=4,59, 1.65 Hz, 1H)
111-011(400 MHz, DMSO-D6) of 0.97 (d, J=16.4 Hz, 6H), for 2.01 (m, 1H), and 3.72 (d, J=of 6.49 Hz, 2H), 3,79-a-3.84 (m, 2H), 4,40-4,48 (m, 2H), 6,50 (DD, J=8,12, of 1.62 Hz, 1H), 6,80 (t, J=to 7.77 Hz, 1H), 6.87 in-to 6.95 (m, 2H), was 7.08 (DD, J=7,54, is 1.51 Hz, 1H), 7,31 (DD, J=8,00, of 4.75 Hz, 1H), 7,60-of 7.69 (m, 2H), 8,04 (DD, J=8,12, of 1.62 Hz, 1H), 8,43 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,01 (s, 1H)
121-012(300 MHz, DMSO-D6) of 3.77-3,82 (m, 2H), to 4.41 is 4.45 (m, 2H), 4,50 (d, J=6,24 Hz, 2H), of 6.49 (DD, J=8,07, to 1.47 Hz, 1H), 6,77 (t, J=7,89 Hz, 1H), 7,19 (DD, J=7,70, to 1.47 Hz, 1H), 7.23 percent and 7.36 (m, 6H), 8,03 (DD, J=7,89, 1.65 Hz, 1H), 8,42 (DD, J=4,59, 1.65 Hz, 1H), 8,71 (t, J=6,05 Hz, 1H)
131-013(300 MHz, DMSO-D6) of 3.77-a 3.83 (m, 2H), 4,43-4,58 (m, 4H), of 6.49 (DD, J=7,89, 1.65 Hz, 1H), 6,77 (t, J=7,89 Hz, 1H), 7,18 (DD, J=7,70 and 1.83 Hz, 1H), 7,30 (DD, J=8,07, of 4.77 Hz, 1H), 7,39 (m, 4H), 8,03 (DD, J=7,89, 1.65 Hz, 1H), 8,42 (DD, J=4,77, to 1.47 Hz, 1H), up 8.75 (t, J=6,05 Hz, 1H)
141-014(300 MHz, DMSO-D6) of 1.27 (s, 9H), 3,69-a-3.84 (m, 8H), to 4.41-4,48 (m, 5H), of 6.49 (DD, J=8,07 and 1.83 Hz, 1H), 6,77 (t, J=of 7.70 Hz, 1H), 7,19 (DD, J=7,70, to 1.47 Hz, 1H), 7,26-7,38 (m, 5H), 8,03 (DD, J=7,89, 1.65 Hz, 1H), 8,42 (DD, J=4,59, 1.65 Hz, 1H), 8,64-8,68 (m, 1H)
151-015(300 MHz, DMSO-D6) of 3.78-a 3.83 (m, 2H), to 4.41-4,48 (m, 2H), 4,58 (d, J=6,24 Hz, 2H), 6,50 (DD, J=8,07, to 1.47 Hz, 1H), 6,78 (t, J=7,89 Hz, 1H), 7,19 (DD, J=7,52, 1.65 Hz, 1H), 7,30 (DD, J=7,89, 4.59 Hz, 1H), 7,58 (d, J=8,07 Hz, 2H), 7,72 (d, J=8,07 Hz, 2H), 8,04 (d, J=8,07 Hz, 1H), 8,42 (DD, J=4,59, 1.65 Hz, 1H), 8,84 (t, J=6,24 Hz, 1H)
161-016(300 MHz, DMSO-D6) of 1.28 (s, 9H), a 4.03-4,10 (m, 2H), or 4.31-to 4.38 (m, 2H), 6.90 to-6,97 (m, 2H), 7,21-7,24 (m, 2H), 7,35 (d, J=8,44 Hz, 2H), 7,47-7,52 (m, 1H), 7,62-7,72 (m, 3H), 8,31 (d, J=3,30 Hz, 1H), 10,06 (s, 1H)

(300 MHz, DMSO-D6) of 1.28 (s, 9H), 3,78-a 3.83 (m, 2H), 4,39 is 4.45 (m, 2H), 6,46 (d, J=2.20 Hz, 1H),? 7.04 baby mortality (d, J=2.57 m Hz, 1H), 7,34-7,40 (m, 4H), to 7.64 (d, J=8,80 Hz, 2H), 8,10 (DD, J=8,07, to 1.47 Hz, 1H), of 8.47 (d, J=4,77 Hz, 1H), 10,16 (s, 1H)
[Table 3]
No. approx.Chemical compoundNMR
171-017(400 MHz, DMSO-D6) of 1.28 (s, 9H), 3,59 at 3.69 (m, 2H), to 4.38-4,48 (m, 2H), 6,23 (DD, J=8,12, 1.39 Hz, 1H), 6,74 (t, J=to 7.77 Hz, 1H), 7,01 (DD, J=7,65, 1.39 Hz, 1H), 7,32-7,42 (m, 2H), 7.62mm (DD, J=7,42, to 4.87 Hz, 1H), of 7.64-7,73 (m, 2H), of 8.37 (DD, J=8,00, 1,74 Hz, 1H), 8,81 (DD, J=4.75 V and 1.51 Hz, 1H), 10,08 (s, 1H)
181-018(300 MHz, DMSO-D6) of 1.28 (s, 9H), of 1.44 (s, 6H), of 3.65 (s, 2H), 6,52-of 6.61 (m, 1H), PC 6.82 (t, J=7,89 Hz, 1H), 7.23 percent (DD, J=7,70, to 1.47 Hz, 1H), 7,30 (DD, J=8,07, of 4.77 Hz, 1H), 7,37 (d, J=8,80 Hz, 2H), to 7.64 (d, J=8,44 Hz, 2H,), 8,03 (DD, J=7,89, 1.65 Hz, 1H), 8,44 (DD, J=4,77, to 1.47 Hz, 1H), 9,99 (s, 1H)
191-019DMSO-D6 of 1.28 (s, 9H), of 1.39 (d, J=6,26 Hz, 3H), 3,51 (DD, J=was 12.75, 7,88 Hz, 1H), 3,86 (DD, J=was 12.75, 2.55 Hz, 1H), 4,49-4,59 (m, 1H), 6,53 (DD, J=8,00 and 1.51 Hz, 1H), for 6.81 (t, J=7,88 Hz, 1H), 7,15 (DD, J=7,65, of 1.62 Hz, 1H), 7,30 (DD, J=7,88, with 4.64 Hz, 1H), 7,33-7,38 (m, 2H), to 7.59-to 7.68 (m, 2H), 8,04 (DD, J=8,00 and 1.51 Hz, 1H), 8,42 (DD, J=4,46, of 1.62 Hz, 1H), of 10.05 (s, 1H)
201-020
211-021(300 MHz, DMSO-D6) 3,81 (m, 2H), of 4.44 (m, 2H), 6,53 (DD, J=8,10, 1.50 Hz, 1H), PC 6.82 (t, J=of 7.90 Hz, 1H), was 7.08 (DD, J=7,30, 1,40 Hz, 1H), 7,33 (DD, J=8,10, 4,80 Hz, 1H), 7,72 (d, J=8,80 Hz, 2H), 7,98 (d, J=8,80 Hz, 2H), of 8.06 (DD, J=8,30, 1.50 Hz, 1H), 8,44 (DD, J=4,80, 1.50 Hz, 1H), 10,52 (s, 1H)
221-022(300 MHz, DMSO-D6) 3,81 (m, 2H), 4,42 (m, 2H), of 6.52 (DD, J=8,10, 1.50 Hz, 1H), 6,83 (t, J=of 7.90 Hz, 1H), was 7.08 (DD, J=7,30, 1,40 Hz, 1H), 7,33 (DD, J=4,80, 8,10 Hz, 1H), 7,35 (d, J=8,80 Hz, 2H), 7,86 (d, J=8,80 Hz, 2H), of 8.06 (DD, J=1,50, 8,30 Hz, 1H), 8,45 (DD, J=1,50, 4,80 Hz, 1H), 10,36 (s, 1H)
231-023(300 MHz, DMSO-D6) 3,74 (s, 3H), 3,80 (m, 2H), 4,43 (m, 2H), 6,51 (DD, J=8,12, 1.39 Hz, 1H), 6,80 (t, J=7,89 Hz, 1H), 6,91 (d, J=9,17 Hz, 2H), was 7.08 (DD, J=7,70, to 1.47 Hz, 1H), 7,31 (DD, J=7,89, 4.59 Hz, 1H), 7,66 (d, J=9,17 Hz, 2H), with 8.05 (DD, J=7,89, 1.65 Hz, 1H), 8,43 (DD, J=4,59, 1.65 Hz, 1H), 10,01 (s, 1H)
241-024(400 MHz, DMSO-D6) of 0.82 (s, 9H), of 0.91 to 1.00 (m, H), of 1.03 (m, 2H), 1,22 (m, 2H), 1,72 (m, 2H), 1,90 (m, 2H), 3,61 (m, 1H), 3,74 (m, 2H), 4,36 (m, 2H), 6,41 (DD, J=8,12, of 1.62 Hz, 1H), 6,70 (t, J=7,88 Hz, 1H), 7,05 (DD, J=7,54 and 1.51 Hz, 1H), 7,25 (DD, J=7,88, with 4.64 Hz, 1H), 7,87 (d, J=7,88 Hz, 1H), to 7.99 (DD, J=7,88, of 1.62 Hz, 1H), of 8.37 (DD, J=4,87, of 1.62 Hz, 1H)

[Table 4]
No. approx.Chemical compoundNMR
251-025(300 MHz, DMSO-D6) 3,81 (m, 2H), of 4.44 (m, 2H), 6,53 (DD, J=8,10, 1.50 Hz, 1H), PC 6.82 (t, J=of 7.90 Hz, 1H), was 7.08 (DD, J=7,30, 1,40 Hz, 1H), 7,33 (DD, J=4,80, 8,10 Hz, 1H), of 7.70 (d, J=8,80 Hz, 2H), 8,01-8,07 (m, 2H), 8,40 (m, 1H), 10,59 (C, H)
261-026(400 MHz, DMSO-D6), 3,70 (m, 2H), 4,34 (m, 2H), 6.42 per (DD, J=8,00 and 1.51 Hz, 1H), of 6.71 (t, J=7,88 Hz, 1H), 6,97 (DD, J=7,54 and 1.51 Hz, 1H), 7,06-7,16 (m, 2H), 7,22 (DD, J=7,88, with 4.64 Hz, 1H), 7,68 (DD, J=9,04, 5,10 Hz, 2H), of 7.96 (DD, J=8,00 and 1.51 Hz, 1H), 8.34 per (DD, J=with 4.64, of 1.62 Hz, 1H), 10,13 (s, 1H)
271-027(400 MHz, DMSO-D6) of 3.78 (m, 2H), and 4.40 (m, 2H), 6,50 (DD, J=8,12, 1.39 Hz, 1H), 6,78 (t, J=7,88 Hz, 1H),? 7.04 baby mortality (DD, J=7,65, 1.39 Hz, 1H), 7,28 (DD, J=7,65, with 4.64 Hz, 1H) 7,42 (s, 1H), 7,55 (t, J=7,88 Hz, 1H), 7,92 (s, 1H), 8,02 (DD, J=7,88, of 1.62 Hz, 1H), 8,23 (s, 1H), 8,40 (DD, J=4,99 and 1.51 Hz, 1H), 10,47 (s, 1H)
281-028(300 MHz, DMSO-D6) 3,81 (m, 2H), 4,47 (m, 2H), 6,59 (DD, J=8,10, 1.50 Hz, 1H), 6,84 (t, J=of 7.90 Hz, 1H), 7,15 (DD, J=7,30, 1,40 Hz, 1H), 7,33 (DD, J=4,80, 8,10 Hz, 1H), 8,02 (s, 1H), of 8.06 (d, J=1.50 Hz, 1H), 8,45 (d, J=1.90 Hz, 1H), 12,42 (s, 1H)
291-029(300 MHz, DMSO-D6) of 3.85 (m, 2H), to 4.52 (m, 2H), 6,60 (DD, J=7,89, 1.65 Hz, 1H), 6,86 (t, J=8,07 Hz, 1H), 7,30-7,35 (m, 2H), of 8.06 (DD, J=7,89, 1.65 Hz, 1H), compared to 8.26 (DD, J=8,99, 2.38 Hz, 1H), 8,42-8,48 (m, 2H), 8,76 (s, 1H), 10,87 (s, 1H)
301-030(300 MHz, DMSO-D6) 3,82 (m, 2H), 4,45 (m, 2H), 6,55 (DD, J=7,89, to 1.47 Hz, 1H), 6,84 (t, J=7,89 Hz, 1H), 7,12 (d, J=6,60 Hz, 1H), 7,33 (DD, J=8,25, of 4.95 Hz, 1H), 7,92 (d, J=8,80 Hz, 1H), of 8.06 (d, J=of 7.70 Hz, 1H), 8,45 (TD, J=5,14 and 1.83 Hz, 1H), and 8.50 (s, 1H), 9,04 (d, J=2.20 Hz, 1H), a 10.74 (s, 1H)
311-031(400 MHz, DMSO-D6) of 1.16 (d, J=6,26 Hz, 6H), and 2.83 (m, 1H), of 3.77 (m, 2H), 4,39 (m, 2H), 6,46 (DD, J=8,12, of 1.62 Hz, 1H), 6,76 (DD, J=7,89, to 1.47 Hz, 1H),? 7.04 baby mortality (DD, J=7,65, of 1.62 Hz, 1H), 7,16 (d, J=8,58 Hz, 2H), 7,27 (DD, J=7,88, with 4.64 Hz, 1H), 7,60 (m, 2H), 8,01 (DD, J=7,88, of 1.62 Hz,1H), 8,39 (DD, J=with 4.64, of 1.62 Hz, 1H), there is a 10.03 (s, 1H)
321-032(300 MHz, DMSO-D6) 3,81-of 3.85 (m, 2H), 4,45 figure-4.49 (m, 2H), 6,55 (DD, J=8,07, to 1.47 Hz, 1H), at 6.84-6.87 in (m, 1H), 7,13 (d, J=1,47 Hz, 1H), 7,33 (DD, J=8,07, of 4.77 Hz, 1H), 7,42-7,47 (m, 1H), to $ 7.91 (d, J=1,83 Hz, 1H), 7,94-7,98 (m, 1H), of 8.06 (DD, J=8,07, to 1.47 Hz, 1H), 8,31 (d, J=8,44 Hz, 1H), 8,44 (DD, J=4,59, 1.65 Hz, 1H), at 8.60 (s, 1H), 8,87 (DD, J=4,22, 1.65 Hz, 1H), 10,54 (s, 1H)

[Table 5]
No. approx.Chemical compoundNMR
331-033(300 MHz, DMSO-D6) a 1.96 (m, 2H), 2,72 (m, 2H), 2,92 (s, 3H), of 3.28 (m, 2H), 3,81 (m, 2H), 4,43 (m, 2H), 6,51 (DD, J=8,07, to 1.47 Hz, 1H), 6,80 (t, J=7,89 Hz, 1H), 6,99 (m, 1H), was 7.08 (DD, J=7,70, to 1.47 Hz, 1H), 7,19 (m, 1H), 7,31 (DD, J=7,89, 4.59 Hz, 1H), 7,40 (m, 1H), with 8.05 (DD, J=7,89, 1.65 Hz, 1H), 8,43 (DD, J=4,77 and 1.83 Hz, 1H), 10,04 (s, 1H)
341-034(400 MHz, DMSO-D6) 3,72-a 3.83 (m, 2H), of 3.84 (s, 3H), 4,36-to 4.46 (m, 2H), 6,53 (DD, J=8,12, of 1.62 Hz, 1H), 6,76-6,84 (m, 1H), 7,07 (DD, J=7,65, of 1.62 Hz, 1H), 7,32 (DD, J=8,00, of 4.75 Hz, 1H), 7,86-of 7.97 (m, 4H), with 8.05 (DD, J=8,12, of 1.62 Hz, 1H), 8,43 (DD, J=4,4, of 1.62 Hz, 1H), 10,53 (s, 1H)
351-035(400 MHz, DMSO-D6) 3,76-a 3.87 (m, 2H), 4,37-4,48 (m, 2H), 6,53 (DD, J=8,12, 1.39 Hz, 1H), 6,80-6,83 (m, 1H), 7,07 (DD, J=7,65, of 1.62 Hz, 1H), 7,32 (DD, J=8,12, with 4.64 Hz, 1H), 7,85-to 7.95 (m, 4H), with 8.05 (DD, J=7,88, of 1.62 Hz, 1H), 8,43 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,48 (s, 1H), was 12.75 (users, 1H)
361-036(400 MHz, DMSO-D6) 3,75-of 3.85 (m, 2H), to 4.38-4,48 (m, 2H), of 6.52 (DD, J=8,00 and 1.51 Hz, 1H), 6,77-6,85 (m, 1H), was 7.08 (DD, J=7,65, of 1.62 Hz, 1H), 7,26 (users, 2H), 7,32 (DD, J=7,88, with 4.64 Hz, 1H), 7,79-of 7.90 (m, 4H), with 8.05 (DD, J=8,00, 1,74 Hz, 1H), 8,43 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,38 (s, 1H)
371-037(400 MHz, DMSO-D6) 2,78 (d, J=with 4.64 Hz, 3H), 3,76-3,86 (m, 2H), of 4.38 figure-4.49 (m, 2H), of 6.52 (DD, J=8,00 and 1.51 Hz, 1H), for 6.81 (t, J=7,88 Hz, 1H), was 7.08 (DD, J=7,54 and 1.51 Hz, 1H), 7,32 (DD, J=7,88, with 4.64 Hz, 1H), 7,82 (s, 4H), 8,05 (DD, J=8,12, of 1.62 Hz, 1H), 8,31-of 8.37 (m, 1H), 8,43 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,38 (s, 1H)
381-038(400 MHz, DMSO-D6) of 2.97 (s, 6H), 3,76-3,86 (m, 2H), 4,39-4,50 (m, 2H), of 6.52 (DD, J=8,12, of 1.62 Hz, 1H), 6,79-6,83 (m, 1H), 7,06 (DD, J=7,54 and 1.51 Hz, 1H), 7,32 (DD, J=8,12, with 4.64 Hz, 1H), 7,37-7,49 (m, 2H), 7,78-a 7.85 (m, 2H,), with 8.05 (DD, J=7,88, of 1.62 Hz, 1H), 8,43 (DD, J=with 4.64, 162 Hz, 1H), 10,34 (s, 1H)
391-039(400 MHz, DMSO-D6) to 2.55 (s, 3H), 3,74-of 3.85 (m, 2H), 4,37-4,47 (m, 2H), 6,53 (DD, J=8,12, of 1.62 Hz, 1H), PC 6.82 (t, J=to 7.77 Hz, 1H), was 7.08 (DD, J=7,65, of 1.62 Hz, 1H), 7,32 (DD, J=7,88, with 4.64 Hz, 1H), 7,83-to 7.93 (m, 2H), 7,93-8,00 (m, 2H), with 8.05 (DD, J=7,88, of 1.62 Hz, 1H), 8,43 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,51 (s, 1H)
401-040(400 MHz, DMSO-D6) of 1.42 (s, 6H), 3,76-3,86 (m, 2H), 4,37-4,48 (m, 2H), 4,96 (s, 1H), of 6.49-of 6.52 (m, 1H), 6,78-PC 6.82 (m, 1H), 7,07-to 7.09 (m, 1H), 7,30-7,33 (m, 1H), 7,37-7,46 (m, 2H), 7,60-7,71 (m, 2H), 8,04-of 8.06 (m, 1H), 8,42-8,44 (m, 1H), 10,08 (s, 1H)

[Table 6]
No. approx.Chemical compoundNMR
411-041(400 MHz, DMSO-D6) of 0.68 (t, J=7,42 Hz, 3H), of 1.40 (s, 3H), 1,63-of 1.73 (m, 2H), 3.75 to of 3.85 (m, 2H), to 4.38-4,48 (m, 2H), amounts to 4.76 (s, 1H), 6,50 (DD, J=8,12, of 1.62 Hz, 1H), 6,80 (t, J=7,88 Hz, 1H), 7,07 (DD, J=7,65, of 1.62 Hz, 1H), 7,29-7,39 (m, 3H), 7,62-to 7.68 (m, 2H), with 8.05 (DD, J=8,12, of 1.62 Hz, 1H), 8,42-8,44 (m, 1H), 10,08 (s, 1H)
421-042 (400 MHz, DMSO-D6) 0,94-of 1.03 (m, 6H), 1.30 and of 1.52 (m, 2H), 1.77 in-of 1.93 (m, 2H), 2,74-2,82 (m, 1H), 2,84-of 2.93 (m, 1H), 3,13 is 3.23 (m, 1H), 3.72 points-is 3.82 (m, 2H), a 3.87-of 3.96 (m, 1H), 3,97-4,08 (m, 1H), 4,23-or 4.31 (m, 1H), 4,33-of 4.44 (m, 2H), 6,46 (DD, J=8,12, of 1.62 Hz, 1H), to 6.88 (t, J=7,88 Hz, 1H), 7,10 (DD, J=7,65, 1.39 Hz, 1H), 7,29 (DD, J=8,12, of 4.75 Hz, 1H), 8,02 (DD, J=7,88, of 1.62 Hz, 1H), 8,07 (d, J=7,65 Hz, 1H), to 8.41 (DD, J=with 4.64, of 1.62 Hz, 1H)
431-043(400 MHz, DMSO-D6) of 1.13 (s, 9H), 1,21-of 1.44 (m, 4H), 1,71-to 1.79 (m, 2H), 1,82-1,90 (m, 2H), 3,37-of 3.46 (m, 1H), 3,62-to 3.73 (m, 1H), 3.75 to of 3.80 (m, 2H), 4,33-of 4.44 (m, 2H), 6,45 (DD, J=8,00 and 1.51 Hz, 1H), 6,74 (t, J=7,88 Hz, 1H), to 7.09 (DD, J=7,65, of 1.62 Hz, 1H), 7,28 (DD, J=7,88, with 4.64 Hz, 1H), 7,92 (d, J=7,65 Hz, 1H), 8,02 (DD, J=8,12, of 1.62 Hz, 1H), 8,40 (DD, J=with 4.64, of 1.62 Hz, 1H)
441-044(400 MHz, DMSO-D6) of 1.28 (d, J=6,03 Hz, 6H), 3,76-3,86 (m, 2H), of 4.38 figure-4.49 (m, 3H), 4,56 (m, 1H), 6,51 (DD, J=8,00 and 1.51 Hz, 1H), 6,62-of 6.71 (m, 1H), 6,80 (t, J=to 7.77 Hz, 1H), 7,06 (DD, J=7,54 and 1.51 Hz, 1H), 7,20 (t, J=8,12 Hz, 1H), 7,25-7,35 (m, 2H), 7,43 (t, J=2.20 Hz, 1H), with 8.05 (DD, J=7,88, of 1.62 Hz, 1H), 8,43 (DD, J=4,87, of 1.62 Hz, 1H), 10,11 (s, 1H)
451-045(400 MHz, DMSO-D6) 0,99 (d, J=of 6.49 Hz, 6H), 1,97-of 2.08 (m, 1H), of 3.73 (d, J=of 6.49 Hz, 2H), of 3.77-3,86 (m, 2H), of 4.38 figure-4.49 (m, 2H), 6,50 (DD, J=8,00 and 1.51 Hz, 1H), 6,63 of 6.68 (m, 1H), 6,80 (t, J=To 7.77 G is, 1H), 7,06 (DD, J=7,65, of 1.62 Hz, 1H), 7,21 (t, J=8,00 Hz, 1H), 7.24 to 7,29 (m, 1H), 7,31 (DD, J=8,00, of 4.75 Hz, 1H), of 7.48 (t, J=2,09 Hz, 1H), with 8.05 (DD, J=7,88, of 1.62 Hz, 1H), 8,43 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,12 (s, 1H)
461-046(400 MHz, DMSO-D6) of 1.28 (s, 9H), 3,82-to 3.92 (m, 2H), 4,27-to 4.38 (m, 2H), 6,88-6,98 (m, 1H), 7,16 (DD, J=4,87, of 1.62 Hz, 2H), 7,24 (DD, J=7,65, of 1.62 Hz, 1H), 7,29-7,39 (m, 3H), 7,56-to 7.67 (m, 2H), 8,31 is 8.38 (m, 2H), 10,06 (, 1H)
471-047(400 MHz, DMSO-D6) 1,24-of 1.32 (s, 9H), to 2.13 (s, 3H), 3,79-3,90 (m, 2H), 4,46-4,56 (m, 2H), 6,40 (DD, J=8,00 and 1.51 Hz, 1H), 6,80 (t, J=7,88 Hz, 1H), was 7.08 (DD, J=7,65, 1.39 Hz, 1H), 7,33 was 7.45 (m, 3H), 7,63-7,73 (m, 2H), 7,98 (d, J=6,26 Hz, 1H), to 8.41 (DD, J=5,10, of 1.62 Hz, 1H), 10,08 (s, 1H)

[Table 7]
No. approx.Chemical compoundNMR
481-048(400 MHz, DMSO-D6) of 1.56 (m, 2H), of 1.88 (m, 2H), 1,96 (m, 2H), 3,44 (m, 2H), 3,68 (m, 2H), 3.75 to with 3.79 (m, 2H), 4,34 was 4.42 (m, 2H), of 6.49 (DD, J=8,12, of 1.62 Hz, 1H), 6,72-PC 6.82 (m, 1H), 7,03 (DD, J=7,65, of 1.62 Hz, 1H), 7,29 (DD, J=7,88, with 4.64 Hz, 1H), 7,66 (m, 2H), 7,83 (m, 2H), 8,02 (DD, J=7,88, of 1.62 Hz, 1H), to 8.40 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,34 (s, 1H)
491-049(400 MHz, DMSO-D6) is 3.08 (s, 6H), of 3.78 (m, 2H), and 4.40 (m, 2H), of 6.49 (DD, J=8,12, 1.39 Hz, 1H), 6,79 (m, 1H), 7,03 (DD, J=7,54 and 1.51 Hz, 1H), 7,28 (DD, J=7,88, with 4.64 Hz, 1H), 7,68 (m, 1H), a 7.85 (d, J=8,81 Hz, 2H), 8,02 (DD, J=7,88, of 1.62 Hz, 1H), 8,40 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,35 (s, 1H)
501-050(400 MHz, DMSO-D6) 2,97-of 3.07 (m, 4H), 3,65-3,74 (m, 4H), 3,74-3,82 (m, 2H), 4,35 is 4.45 (m, 2H), 6,46 (DD, J=8,12, of 1.62 Hz, 1H), 6,76 (t, J=to 7.77 Hz, 1H), 6.89 in (d, J=9,04 Hz, 2H), 7,05 (DD, J=7,65, of 1.62 Hz, 1H), 7,28 (DD, J=7,88, with 4.64 Hz, 1H), 7,55-7,66 (m, 2H), 8,01 (DD, J=7,88, of 1.62 Hz, 1H), 8,39 (DD, J=with 4.64, of 1.62 Hz, 1H), 9,92 (s, 1H)
511-051(400 MHz, DMSO-D6) of 1.26 (d, J=6,02 Hz, 6H), 3,71-3,81 (m, 2H), 4,35 was 4.42 (m, 2H), of 4.44 (dt, J=12,00, of 6.02 Hz, 1H), 6,47 (DD, J=8,12, of 1.62 Hz, 1H), of 6.71-for 6.81 (m, 1H), 7,02 (DD, J=7,65, 1.39 Hz, 1H), 7,11 (t, J=9,39 Hz, 1H), 7,28 (DD, J=7,88, with 4.64 Hz, 1H), 7,38 (DDD, J=8,99, 2,38, 1.39 Hz, 1H), of 7.70 (DD, J=13,57, 2,43 Hz, 1H), 8,01 (DD, J=7,88, of 1.62 Hz, 1H), 8,39 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,15 (s, 1H)
521-052(400 MHz, DMSO-D6) of 1.26 (d, J=5,94 Hz, 6H), of 3.77-3,86 (m, 2H), 4,43-to 4.52 (m, 2H), 4,59 (dt, J=12,00, 5,94 Hz, 1H), 6,5 (DD, J=8,00 and 1.51 Hz, 1H), 6.73 x-6,84 (m, 2H), 6.89 in (DD, J=was 12.75, 2,78 Hz, 1H), 7,26 and 7.36 (m, 2H), 7,79 (t, J=9,04 Hz, 1H), 8,01 (DD, J=7,88, of 1.62 Hz, 1H), 8,39 (DD, J=with 4.64, of 1.62 Hz, 1H), 9,84 (s, 1H)
531-053(300 MHz, DMSO-D6) 3,81 (m, 2H), of 4.44 (m, 2H), 6,53 (DD, J=8,10, 1.50 Hz, 1H), PC 6.82 (t, J=of 7.90 Hz, 1H), was 7.08 (DD, J=7,30, 1,40 Hz, 1H), 7,33 (DD, J=4,80, 8,10 Hz, 1H), of 7.70 (d, J=8,80 Hz, 2H), 8,01-8,07 (m, 2H), compared to 8.26 (m, 1H), 8,40 (m, 1H), 10,50 (s, 1H)
541-054(300 MHz, DMSO-D6) 2,62 (s, 6H), 3,81 (m, 2H), 4,43 (m, 2H), 6,53 (DD, J=8,10, 1.50 Hz, 1H), PC 6.82 (t, J=of 7.90 Hz, 1H), was 7.08 (DD, J=7,30, 1,40 Hz, 1H), 7,33 (DD, J=4,80, 8,10 Hz, 1H), 7,94-to 8.14 (m, 3H), 8,40 (m, 1H), 10,34 (s, 1H)
551-055(300 MHz, DMSO-D6) of 1.28 (d, J=5,86 Hz, 6H), 3,81 (m, 2H), 4,43 (m, 2H), 4,78 (dt, J=12,00, 5,86 Hz, 1H), 6,50 (DD, J=8,10, 1.50 Hz, 1H), 6,80 (t, J=of 7.90 Hz, 1H), was 7.08 (DD, J=7,30, 1,40 Hz, 1H), 7,30 (DD, J=4,80, 8,10 Hz, 1H), 7,88 (d, J=8,80 Hz, 2H), 8,03-of 8.09 (m, 2H), compared to 8.26 (m, 1H), 8,44 (m, 1H), 10,50 (s, 1H)

[Table 8]
No. approx.Chemical compoundNMR
561-056(300 MHz, DMSO-D6) 3,29 (s, 3H), 3,81 (m, 2H), 4,43 (m, 2H), 4,78 (dt, J=12,00, 5,86 Hz, 1H), 6,50 (DD, J=8,10, 1.50 Hz, 1H), 6,80 (t, J=of 7.90 Hz, 1H), was 7.08 (DD, J=7,30, 1,40 Hz, 1H), 7,30 (DD, J=4,80, 8,10 Hz, 1H), 7,88 (d, J=8,80 Hz, 2H), 8,03-of 8.09 (m, 2H), compared to 8.26 (m, 1H), 8,44 (m, 1H), of 10.25 (s, 1H)
571-057(400 MHz, DMSO-D6) of 0.93 to 1.00 (d, J=PC 6.82 Hz, 6H), for 2.01 (DDD, J=13,33, 6,61, of 6.49 Hz, 1H), 3.72 points-3,81 (m, 2H), 3,84 (d, J=6,26 Hz, 2H), 4,34 is 4.45 (m, 2H), 6.48 in (DD, J=8,12, 1.39 Hz, 1H), 6,77 (t, J=7,88 Hz, 1H), 7,05 (DD, J=7,54 and 1.51 Hz, 1H), 7,20 (d, J=9,04 Hz, 1H), 7,28 (DD, J=8,00, of 4.75 Hz, 1H), 7,88 (DD, J=9,04, 2.55 Hz, 1H), 8,02 (DD, J=7,88, of 1.62 Hz, 1H), 8,08 (d, J=2,78 Hz, 1H), 8,40 (DD, J=with 4.64, of 1.62 Hz, 1H), 10,22 (s, 1H)
581-058(400 MHz, DMSO-D6) of 1.20 (s, 9H), to 2.29 (s, 3H), 3.96 points-4,08 (m, 2H), 4,29-to 4.38 (m, 2H), 6,93 (t, J=7,88 Hz, 2H), 7,13 (s, 1H), 7,21-7,28 (m, 1H), 7,29-7,35 (m, 2H), 7,46 (DD, J=8,12, 1.39 Hz, 1H), 7,56-7,66 (m, 2H), is 8.16 (d, J=5,33 Hz, 1H), there is a 10.03 (s, 1H)
591-059(400 MHz, DMSO-D6) of 1.24 (s, 9H), is 2.37 (s, 3H), 3,97-4,07 (m, 2H), 4,24-4,34 (m, 2H), 6,76 (d, J=7,42 Hz, 1H), 6.87 in-6,93 (m, 1H), 6,97 (d, J=8.35 Hz, 1H), 7,17 (DD, J=7,42, of 1.62 Hz, 1H), 7,28-7,35 (m, 2H), 7,43 (DD, J=8,12, of 1.62 Hz, 1H), 7,53 (DD, J=8,35, 7,42 Hz, 1H) 7,58-the 7.65 (m, 2H), there is a 10.03 (s, 1H)
601-060(300 MHz, DMSO-D6) of 1.27 (s, 9H), 2,22 (s, 3H), 3,97-4,01 (m, 2H), 4,30-4,34 (m, 2H), 6.87 in-6,93 (m, 1H), 7,11-7,20 (m, 2H), 7,34 (d, J=7,89 Hz, 2H), 7,41 (DD, J=8,23, to 1.47 Hz, 1H), 7,52 (DD, J=8,79, 2.20 Hz, 1H), to 7.64 (d, J=8,79 Hz, 2H), 8,15 (d, J=2,56 Hz, 1H), 10,04 (s, 1H)
611-061(300 MHz, DMSO-d6) δ: 1.28 (in s, 9H), 3,80 (t, J=4.4 Hz, 2H), 4,39 (t, J=4.4 Hz, 2H), 6,83 (t, J=7.9 Hz, 1H), 6,93 (DD, J=8,1, 1.5 Hz, 1H), 7,07 (DD, J=7,5, 1.7 Hz, 1H), 7,35 (d, J=4,2 Hz, 2H), 7,42 (dt, J=9,8 and 2.5 Hz, 1H), 7,63-7,71 (m, 3H), 8,32 (DD, J=4,8, 1.5 Hz, 1H), 8,55 (d, J=2.6 Hz, 1H), 10,04 (s, 1H)
621-062(400 MHz, DMSO-D6) of 2.23 (s, 3H), of 3.97 (t, J=4.4 Hz, 2H), or 4.31 (t, J=4.4 Hz, 2H), 6,92 (t, J=8 Hz, 1H), 7,15 (m, 2H), 7,44 (DD, J=8 and 1.4 Hz, 1H), 7,53 (DD, J=8,8, 2.2 Hz, 1H), 7,80 (d, J=8,8 Hz, 2H), 7,92 (d, J=8,8 Hz, 2H), 8,15 (d, J=2,56 Hz, 1H), of 10.58 (s, 1H)
[Table 9]
No. approx.Chemical compoundNMR
631-063 (300 MHz, DMSO-d6) δ: of 2.25 (s, 3H), 3,99 (t, J=4.6 Hz, 2H), or 4.31 (t, J=4.4 Hz, 2H), 5,34 (user. s, 2H), for 6.81-6,92 (m, 2H), 7,11-7,14 (m, 3H), 7,39 (TD, J=7,7, 1.7 Hz, 2H), 7,52 (dt, J=9,5, 1.3 Hz, 1H), 8,15 (t, J=1.1 Hz, 1H), becomes 9.97 (s, 1H)
641-064(300 MHz, DMSO-d6) δ: of 2.08 (s, 3H), of 2.23 (s, 3H), 3,98 (t, J=4.4 Hz, 2H), or 4.31 (t, J=4.4 Hz, 2H), 6.90 to (t, J=7.7 Hz, 1H), 7,13-7,16 (m, 2H), 7,42 (DD, J=8,3, 1.7 Hz, 2H), 7,53-to 7.59 (m, 2H), 8,09-of 8.15 (m, 2H), 9,50 (s, 1H), 10,27 (s, 1H)
651-065(300 MHz, DMSO-d6) δ: 1.70 to at 1.73 (m, 2H), 1.93 and-of 1.97 (m, 2H), 2,24 (s, 3H), 2.71 to to 2.74 (m, 1H), 3,24 of 3.28 (m, 2H), 3,99 (t, J=4,2 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 6,91 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (t, J=10.0 Hz, 1H), 7,17-to 7.18 (m, 2H), 7,38-7,44 (m, 2H), EUR 7.57-of 7.69 (m, 2H), 8,16 (s, 1H), 10,14 (s, 1H)
661-066(300 MHz, DMSO-d6) δ: 1,75-of 1.78 (m, 4H), 2,22 was 2.25 (m, 4H), 2,58 (d, J=4.4 Hz, 3H), 2,70-of 2.72 (m, 2H), 3,31-to 3.35 (m, 2H), 4.00 points (t, J=4,2 Hz, 2H), 4,34 (t, J=4,2 Hz, 2H), 6,92 (t, J=7.9 Hz, 1H), 7,07 (t, J=and 9.2 Hz, 1H), 7,20 (d, J=7.7 Hz, 2H), 7,39-7,44 (m, 2H), 7,63-7,72 (m, 3H), 8,14-8,18 (m, 1H), 10,15 (s, 1H)
671-067(300 MHz, DMSO-d6) δ: at 1.73 (s, 6H), 2,24 was 2.25 (m, 3H), 2,80-and 2.83 (m, 4H), 3.04 from was 3.05 (m, 3H), 3,35 is-3.45 (m, 2H), 4,01 (who, J=3,7 Hz, 2H), 4,34 (t, J=4,2 Hz, 2H), 6,93 (t, J=7.9 Hz, 2H), 7,09 for 7.12 (m, 1H), 7,19-7,21 (m, 2H), 7,42 was 7.45 (m, 3H), 7,66 (t, J=a 13.9 Hz, 1H), 8,15-8,17 (m, 1H), 10,18 (s, 1H)
681-068(300 MHz, DMSO-d6) δ: 1,13 (t, J=7.0 Hz, 3H), 1.56 to to 1.60 (m, 2H), 1.93 and is 1.96 (m, 2H), of 2.23 (s, 3H), 2.71 to and 2.79 (m, 2H), 3,17-3,20 (m, 2H), 3,40-3,51 (m, 3H), 3,99 (t, J=4.4 Hz, 2H), 4,32 (t, J=4,2 Hz, 2H), 6.90 to (t, J=7.7 Hz, 1H), 7,00 (sq, J=8,4 Hz, 1H), 7,15 (dt, J=10,1, 4.5 Hz, 2H), 7,40 (dt, J=13,1, 4,8 Hz, 2H), 7,52 (DD, J=8,6, 2.0 Hz, 1H), 7,65 (DD, J=15,0, 2.2 Hz, 1H), 8,15 (d, J=2.6 Hz, 1H), 10,12 (s, 1H)
691-069(300 MHz, DMSO-d6) δ: 1,09 (d, J=6.2 Hz, 6H), 1,52 is 1.58 (m, 2H), 1,88 is 1.91 (m, 2H), of 2.23 (s, 3H), 2,74-2,77 (m, 2H), 3,17-3,19 (m, 2H), 3,47-of 3.53 (m, 1H), 3,59-3,61 (m, 1H), 3,70-and 3.72 (m, 1H), 3,98 (t, J=4.4 Hz, 2H), 4,32 (t, J=4.4 Hz, 2H), 6.90 to (t, J=7.9 Hz, 1H), 7,01 (t, J=9.5 Hz, 1H), 7,15 (dt, J=10,1, 4.5 Hz, 2H), 7,40 (dt, J=13,6, 5.0 Hz, 2H), 7,52 (DD, J=8,4, 1.8 Hz, 1H), to 7.64 (DD, J=14,9, 2.4 Hz, 1H), 8,15 (d, J=2.2 Hz, 1H), 10,11 (s, 1H)

[Table 10]
No. approx.Chemical compoundNMR
701-070 (300 MN, DMSO-d6) δ: 1,21-of 1.30 (m, 1H), 1,51-to 1.63 (m, 1H), 1,78-to 1.79 (m, 1H), 1,96-2,02 (m, 1H), of 2.23 (s, 3H), 2,53 of 2.68 (m, 1H), is 3.08-of 3.12 (m, 1H), 3,32-to 3.38 (m, 6H), to 3.99 (t, J=4.4 Hz, 2H), 4,32 (t, J=4,2 Hz, 2H), 6.90 to (t, J=7.9 Hz, 1H), 7,02 (t, J=9.4 Hz, 1H), 7,15 (dt, J=10,1, 4.5 Hz, 2H), 7,40 (dt, J=12,3, 4.5 Hz, 2H), 7,52 (DD, J=8,4, and 2.6 Hz, 1H), 7,65 (DD, J=15,0, 2.2 Hz, 1H), 8,15 (d, J=2.6 Hz, 1H), 10,12 (s, 1H)
711-071(300 MHz, DMSO-d6) δ: 1,31-of 1.36 (m, 2H), 1.70 to at 1.73 (m, 2H), of 2.23 (s, 3H), 2,60 2.63 in (m, 2H), 3,23-3,24 (m, 5H), 3,98 (t, J=4.4 Hz, 2H), 4,32 (t, J=4,2 Hz, 2H), 6.90 to (t, J=7.9 Hz, 1H), 7,01 (t, J=9,2 Hz, 1H), 7,14 (t, J=9,2 Hz, 2H), 7,40 (DD, J=13,4, 5.0 Hz, 2H), 7,52 (DD, J=8,6, and 2.4 Hz, 1H), to 7.64 (DD, J=15,0, 2.2 Hz, 1H), 8,14 (s, 1H), 10,11 (s, 1H)
721-072(400 MHz, DMSO-d6) δ: 1,93-2,04 (m, 2H), 2,24 (s, 3H), 3,24-of 3.31 (m, 5H), 3,51 (DQC., J=10,8, and 2.6 Hz, 1H), was 4.02 (DD, J=7,7, a 4.9 Hz, 2H), 4,36 (t, J=4.4 Hz, 2H), 6.73 x (t, J=9.7 Hz, 1H), 6,93 (t, J=7.9 Hz, 1H), 7,26-7,31 (m, 3H), 7,42 (DD, J=8,1, 1,6 Hz, 1H), 7,60 to 7.62 (m, 1H), 7,74 to 7.75 (m, 1H), 8,17 (s, 1H), there is a 10.03 (s, 1H)
731-073(400 MHz, DMSO-d6) of 1.00 (d, J=7,0 Hz, 6H), 1,95-of 2.08 (m, 1H), of 2.23 (s, 3H), of 3.77-3,82 (m, 5H), 3,97-was 4.02 (m, 2H), 4,30 is 4.35 (m, 2H), 6,91 (t, J=7.9 Hz, 1H), 7,09-7,20 (m, 3H), 7,42 (d, J=7.9 Hz, 1H), 7,53 (d, J=8,8 Hz, 1H), 7,80-to 7.84 (m, 1H), 8.07-a 8,10 (m, 1H), 8,15 (users, 1H), 10,13 (s, 1H)
741-074(400 MHz, DMSO-d6) and 0.98 (t, J=8,1 Hz, 6H), 1,98-2,05 (m, 1H), of 2.23 (s, 3H), 3,79 (d, J=6,5 Hz, 2H), 3,99 (t, J=4.4 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 6,91 (t, J=7.9 Hz, 1H), was 7.08 (d, J=9,3 Hz, 1H), 7,14 (d, J=8,3 Hz, 1H), 7,19 (DD, J=7,9, and 1.4 Hz, 1H), 7,42 (DD, J=7,9, and 1.4 Hz, 1H), 7,53 (DD, J=8,3, 2.3 Hz, 1H), 7,81 (DD, J=8,8, 2.8 Hz, 1H), 8,02 (d, J=2,8 Hz, 1H), 8,15 (users, 1H), to 10.09 (s, 1H), 12,59 (s, 1H)
751-075(400 MHz, DMSO-d6) of 1.01 (d, J=6.6 Hz, 6H), 2.06 to to 2.15 (m, 1H), of 2.23 (s, 3H), 3,90 (d, J=6.6 Hz, 2H), 3,99 (t, J=4.4 Hz, 2H), 4,33 (t, J=4,2 Hz, 2H), 6,91 (t, J=7.9 Hz, 1H), 7,12-7,13 (m, 2H), 7,19 (DD, J=7,7, 3,9 Hz, 1H), 7,41 (DD, J=8,3, 1.7 Hz, 1H), 7,52 (DD, J=8,8, 2.2 Hz, 1H), 7,58 (user. s, 1H), 7,60 (user. s, 1H), a 7.85 (DD, J=9,0, 2.8 Hz, 1H), 8,13 (d, J=2,9 Hz, 1H), 8,15 (user. s, 1H), 10,08 (s, 1H)
761-076(300 MHz, DMSO-d6) of 1.00 (d, J=6.6 Hz, 6H), 2.06 to and 2.14 (m, 1H), of 2.23 (s, 3H), 2,82 (d, J=4,8 Hz, 3H), a 3.87 (d, J=6.6 Hz, 2H), 3,99 (t, J=4,2 Hz, 2H), 4,32 (t, J=4,2 Hz, 2H), 6.90 to (t, J=7.9 Hz, 1H), 7,09-7,20 (m, 3H), 7,41 (d, J=4.0 Hz, 1H), 7,52 (DD, J=8,4, and 2.6 Hz, 1H), 7,83 (DD, J=9,0, 2.8 Hz, 1H), 8,00-8,07 (m, 2H), 8,15 (user. s, 1H), 10,08 (s, 1H)
771-077(300 MHz, DMSO-d6) of 0.95 (d, J=6.6 Hz, 6H), 1,90-2,04 (who, 1H), of 2.23 (s, 3H), and 2.79 (s, 3H), 2,98 (s, 3H), 3,76 (d, J=6.2 Hz, 2H), 3,99 (t, J=4,2 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 6.90 to (t, J=7.7 Hz, 1H), 7,03 (d, J=8,8 Hz, 1H), 7,13 (d, J=8,8 Hz, 1H), 7,18 (DD, J=7,3, 1.5 Hz, 1H), 7,41 (DD, J=8,1, 1.5 Hz, 1H), 7,52 (DD, J=8,6, 2.0 Hz, 1H), EUR 7.57 (d, J=2.6 Hz, 1H), 7,69 (DD, J=9,0, 2.8 Hz, 1H), 8,15 (d, J=2.6 Hz, 1H), 10,06 (s, 1H)

td align="left"> (400 MHz, CHLOROFORM-d) was 1.04 (t, J=7.4 Hz, 3H), 1,79 of-1.83 (m, 2H), and 2.27 (s, 3H), 3,92 (t, J=6,7 Hz, 2H), 4,17 (t, J=4.4 Hz, 2H), 4,49 (t, J=4.4 Hz, 2H), make 6.90 (d, J=9,3 Hz, 2H), 6,97 (t, J=8,1 Hz, 1H), 7,10 (d, J=8,3 Hz, 1H), 7,37 (DD, J=8,3, 2.3 Hz, 1H), 7,42 (DD, J=8,1, 1.2 Hz, 1H), EUR 7.57 (d, J=8,8 Hz, 2H), of 7.90 (DD, J=7,9, and 1.4 Hz, 1H), 8,16 (s, 1H), 9,52 (s, 1H)
[Table 11]
No. approx.Chemical compoundNMR
781-078(400 MHZ, DMSO-d6) of 2.23 (s, 3H), by 2.55 (s, 3H), 3,99 (t, J=4.4 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 6,92 (t, J=7.9 Hz, 1H), 7,14 (d, J=8,8 Hz, 1H), 7,18 (DD, J=7,9, and 1.4 Hz, 1H), 7,44 (DD, J=8,1, 1,6 Hz, 1H), 7,53 (DD, J=8,6, and 2.6 Hz, 1H), 7,87 (d, J=8,8 Hz, 2H), of 7.96 (d, J=8,8 Hz, 2H), 8,15 (s, 1H), 10,48 (s, 1H)
791-079(300 MHz, DMSO-d6) of 1.42 (s, 6H), of 2.23 (s, 3H), 4.00 points (t, J=4.4 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), is 4.93 (s, 1H), 6,91 (t, J=7.9 Hz, 1H), 7,13 (d, J=8,4 Hz, 1H), 7,19 (DD, J=7,7, 1.5 Hz, 1H), 7,39-the 7.43 (m, 3H), 7,52 (DD, J=9,0, 2.4 Hz, 1H), to 7.64 (d, J=8,4 Hz, 2H), 8,15 (s, 1H), 10,04 (s, 1H)
801-080(400 MHz, DMSO-d6) of 2.23 (s, 3H), 2,5 (, 3H), 3,99 (t, J=4.4 Hz, 2H), 4,32 (t, J=4.4 Hz, 2H), 6,92 (t, J=7.9 Hz, 1H), 7,14 (d, J=8,3 Hz, 1H), 7,18 (DD, J=7,7, and 1.6 Hz, 1H), 7,44 (DD, J=8,1, 1,6 Hz, 1H), 7,50-of 7.55 (m, 2H), 7,87 (DD, J=8,8, 2.3 Hz, 1H), 8,07 (d, J=2.3 Hz, 1H), 8,15 (s, 1H), 10,42 (s, 1H)
811-081(400 MHz, DMSO-d6) of 1.59 (s, 6H), of 2.23 (s, 3H), 3,99 (t, J=4.4 Hz, 2H), or 4.31 (t, J=4.4 Hz, 2H), 5,28 (s, 1H), 6,91 (t, J=7.9 Hz, 1H), 7,11-7,17 (m, 2H), 7,32 (d, J=8,3 Hz, 1H), 7,42 (DD, J=8,3, and 1.4 Hz, 1H), 7,53 (DD, J=8,6, and 2.6 Hz, 1H), of 7.70 (DD, J=8,8, 2.8 Hz, 1H), 8,13-8,18 (m, 2H), 10,24 (s, 1H)
821-082(300 MHz, DMSO-d6) of 1.44 (s, 6H), of 2.23 (s, 3H), 2,96 (s, 3H), 3,99 (t, J=4.4 Hz, 2H), 4,32 (t, J=4.4 Hz, 2H), 6,91 (t, J=7.9 Hz, 1H), 7,14 (d, J=8,4 Hz, 1H), 7,18 (DD, J=7,7, 1.5 Hz, 1H), 7,33 (d, J=8,8 Hz, 2H), 7,42 (DD, J=8,3, 1.7 Hz, 1H), 7,52 (DD, J=8,8, 2.2 Hz, 1H), of 7.70 (d, J=8,8 Hz, 2H), 8,15 (d, J=2.6 Hz, 1H), 10,11 (s, 1H)
831-083(300 MHz, CHLOROFORM-d) of 2.28 (s, 3H), of 3.97 (s, 3H), 4,17 (t, J=4.4 Hz, 2H), to 4.52 (t, J=4.6 Hz, 2H), at 6.84 (DD, J=8,6, and 2.4 Hz, 1H), 6,99 (t, J=8,1 Hz, 1H), 7,10 (d, J=8,4 Hz, 1H), 7,29 (d, J=8,8 Hz, 1H), 7,38 (DD, J=an 8.4 and 2.2 Hz, 1H), 7,44 (DD, J=8,1, 1.5 Hz, 1H), 7,88 (DD, J=5,9, 2,2 Hz, 2H), 8,17 (d, J=1.8 Hz, 1H), 9,71 (s, 1H)
841-084
851-085(400 MHz, CHLOROFORM-d) 1,04 was 1.06 (m, 3H), 1,82 is 1.86 (m, 2H), 2,28 (s, 3H), 3,99-4,00 (m, 2H), 4,16-4,17 (m, 2H), 4,50-4,51 (m, 2H), 6,92-7,00 (m, 2H), 7,10 (DD, J=8,3, 2.3 Hz, 1H), 7,27-7,30 (m, 1H), of 7.36 was 7.45 (m, 2H), EUR 7.57-of 7.60 (m, 1H), 7,87-to $ 7.91 (m, 1H), 8,17 (s, 1H), to 9.57 (s, 1H)

[Table 12]
No. approx.Chemical compoundNMR
861-086(400 MHz, CHLOROFORM-d) of 1.44-of 1.45 (m, 3H), 2,28 (d, J=3.2 Hz, 3H), 4,10-4,17 (m, 4H), 4,50-4,51 (m, 2H), 6,93-6,98 (m, 2H), 7,09-7,11 (m, 1H), 7,27-7,29 (m, 1H), of 7.36 was 7.45 (m, 2H), EUR 7.57-of 7.60 (m, 1H), 7,88-of 7.90 (m, 1H), 8,17 (s, 1H), to 9.57 (s, 1H)
871-087(400 MHz, CHLOROFORM-d) of 1.44 (t, J=7.0 Hz, 3H), of 2.20 (s, 3H), of 2.28 (s, 3H), 4,11 (kV, J=7,0 Hz, 2H), 4,17 (t, J=44 Hz, 2H), 4,50 (t, J=4.4 Hz, 2H), PC 6.82 (DD, J=7,9, 1.9 Hz, 1H), 6,97 (t, J=8,1 Hz, 1H), to 7.09 (DD, J=12,8, 8,1 Hz, 2H), 7,37 (DD, J=8,3, 2,3 Hz, 2H), 7,42 (DD, J=8,1, 1,6 Hz, 2H), 7.62mm (d, J=2.3 Hz, 1H), 7,89 (DD, J=to 7.9 and 1.4 Hz, 1H), 8,17 (s, 1H), 9,60 (s, 1H)
881-088(400 MHz, DMSO-d6) 2,19 (s, 3H), of 2.23 (s, 3H), 3,99 (t, J=3,9 Hz, 2H), 4,32 (t, J=4.6 Hz, 2H), and 4.40 (s, 2H), 6.90 to (t, J=7.9 Hz, 1H), 7,08-7,17 (m, 3H), from 7.24 (d, J=7.9 Hz, 1H), 7,38-7,41 (m, 4H), 7,53 (DD, J=to 8.8, 2.3 Hz, 1H), 8,15 (s, 1H), 10,07 (s, 1H)
891-089(400 MHz, DMSO-d6) a 2.12 (s, 3H), of 2.28 (s, 3H), 3,70 (t, J=4.6 Hz, 2H), 4,03-4,08 (m, 4H), to 4.38 (t, J=4,2 Hz, 2H), 6,95 (t, J=7.9 Hz, 1H), was 7.08 (d, J=7.9 Hz, 1H), 7,20 (DD, J=8,1, 1,6 Hz, 1H), 7,29 (DD, J=14,8, 8,3 Hz, 2H), 7,44 (d, J=11,1 Hz, 2H), 7,76 (d, J=8,8 Hz, 1H), 8,19 (s, 1H), 10,06 (s, 1H)
901-090(400 MHz, DMSO-d6) 1,64 (user. s, 1H), 1,79 (t, J=10.0 Hz, 2H), 1.91 a (s, 3H), of 2.30 (s, 3H), of 3.27 (d, J=7,4 Hz, 1H), 3.45 points (d, J=10.0 Hz, 3H), 3,81-a-3.84 (m, 1H), was 4.02-4,06 (m, 3H), 4,39 (user. s, 2H), 6,98 (t, J=7.7 Hz, 1H), 7,26 and 7.36 (m, 2H), of 7.48 (d, J=7.9 Hz, 1H), 7,58 (d, J=7,4 Hz, 1H), 7,86-a 7.92 (m, 3H), 8,21 (s, 1H), 10,63 (s, 1H)
911-091(300 MHz, DMSO-d6) 2,22 (s, 3H), 3.96 points (kV =6,8 Hz, 2H), 4,29 (kV, J=6,6 Hz, 2H), 6.90 to (t, J=7.9 Hz, 1H), 7,12-to 7.15 (m, 2H), 7,35-the 7.43 (m, 3H), 7,52 (DD, J=9,3, 2.3 Hz, 1H), to 7.77 (d, J=19,0 Hz, 2H), 8,14 (d, J=2.3 Hz, 1H), 10,27 (s, 1H)
921-092(300 MHz, DMSO-d6) of 2.20 (d, J=1.1 Hz, 3H), of 2.23 (s, 3H), 3,99 (t, J=4,2 Hz, 2H), 4,32 (t, J=4.4 Hz, 2H), 6,91 (t, J=7.7 Hz, 1H), 7,17-7,20 (m, 3H), 7,38-7,42 (m, 2H), 7,53 (DD, J=8,4, 2.2 Hz, 1H), to 7.67 (DD, J=12,1, 1.8 Hz, 1H), 8,15 (d, J=2.2 Hz, 1H), 10,23 (s, 1H)
931-093(300 MHz, DMSO-d6) of 2.23 (s, 3H), 3,99 (t, J=4.4 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 6,92 (t, J=7.9 Hz, 1H), 7,14-7,19 (m, 2H), 7,44-of 7.55 (m, 3H), 8,15 (kV, J=0.7 Hz, 1H), 8,23 (DD, J=8,8, 2.6 Hz, 1H), up 8.75 (d, J=2,6 Hz, 1H), 10,48 (s, 1H)
941-094(400 MHz, DMSO-d6) of 1.31 (t, J=7.2 Hz, 3H), 3,79 (t, J=4.4 Hz, 2H), 3,99 (kV, J=7,0 Hz, 2H), 4,42 (t, J=4.4 Hz, 2H), 6.48 in (DD, J=8,1, 1,6 Hz, 1H), 6,78 (t, J=7.9 Hz, 1H), to 6.88 (d, J=9,3 Hz, 2H), 7,07 (DD, J=of 7.9 and 1.4 Hz, 1H), 7,30 (DD, J=7,6, and 4.4 Hz, 1H), to 7.64 (d, J=8,8 Hz, 2H), 8,03 (DD, J=7,9, 1.9 Hz, 1H), to 8.41 (DD, J=4,4, 1,6 Hz, 1H), 9,99 (s, 1H)

[Table 13]
No. approx.Chemical compound NMR
951-095(400 MHz, DMSO-d6) 1,49-and 1.54 (m, 2H), 1,61-to 1.67 (m, 4H), only 2.91 (t, J=5.1 Hz, 4H), 3,79 (t, J=4.4 Hz, 2H), 4,42 (t, J=4.4 Hz, 2H), of 6.49 (DD, J=8,1, 1,6 Hz, 1H), 6,79 (t, J=7.9 Hz, 1H), 6,99 (t, J=9,3 Hz, 1H), 7,05 (DD, J=7,4, and 1.4 Hz, 1H), 7,30 (DD, J=8.0 a, 4,4 Hz, 1H), 7,39 (DD, J=8,6, and 2.1 Hz, 1H), to 7.64 (DD, J=14,8, 2.3 Hz, 1H), 8,03 (DD, J=7,9, 1.9 Hz, 1H), 8,42 (DD, J=4,6, and 1.4 Hz, 1H), 10,13 (s, 1H)
961-096(400 MHz, DMSO-d6) of 1.08 (t, J=7.0 Hz, 3H), of 1.18 to 1.37 (m, 4H), 1.85 to to 1.98 (m, 4H), 3,17-3,24 (m, 1H), 3.43 points (kV, J=7,0 Hz, 2H), 3,67-to 3.73 (m, 1H), 3,76 (t, J=4.4 Hz, 2H), to 4.38 (t, J=4.4 Hz, 2H), 6,44 (DD, J=7,9, the 1.4 Hz, 1H), 6.73 x (t, J=7.9 Hz, 1H), 7,07 (DD, J=7,7, and 1.6 Hz, 1H), 7,27 (DD, J=8.0 a, 4,8 Hz, 1H), 7,92 (d, J=7,4 Hz, 1H), 8,01 (DD, J=7,9, 1.9 Hz, 1H), 8,39 (DD, J=4,8, 2.0 Hz, 1H)
971-097(400 MHz, DMSO-d6) of 1.05 (d, J=6.0 Hz, 6H), 1,15-to 1.38 (m, 4H), 1,85-1,90 (m, 4H), 3.27 to and 3.31 (m, 1H), 3,63-to 3.73 (m, 2H), 3,76 (t, J=4.6 Hz, 2H), to 4.38 (t, J=4.6 Hz, 2H), 6,44 (DD, J=7,9, and 1.4 Hz, 1H), 6.73 x (t, J=7.9 Hz, 1H), 7,07 (DD, J=7,7, and 1.6 Hz, 1H), 7,27 (DD, J=8.0 a, 4,8 Hz, 1H), to $ 7.91 (d, J=7.9 Hz, 1H), 8,01 (DD, J=7,9, 1.9 Hz, 1H), 8,39 (DD, J=4,6, and 1.4 Hz, 1H)
981-098(400 MHz, DMSO-d6) 1,1 is 1.70 (m, 12H), 1,84-of 1.94 (m, 4H), 3,20-of 3.25 (m, 1H), 3,66-and 3.72 (m, 1H), 3,76 (t, J=4.4 Hz, 2H), 3,98-4,01 (m, 1H), to 4.38 (t, J=4.4 Hz, 2H), 6,44 (DD, J=8,1, 1,6 Hz, 1H), 6,72 (t, J=7.9 Hz, 1H), 7,07 (DD, J=7,4, and 1.4 Hz, 1H), 7,27 (DD, J=8,1, 4.9 Hz, 1H), to $ 7.91 (d, J=7.9 Hz, 1H), 8,01 (DD, J=7,9, and 1.4 Hz, 1H), 8,39 (DD, J=4,9, and 1.6 Hz, 1H)
991-099(400 MHz, DMSO-d6) of 1.12 to 1.47 (m, 10H), 1,62-of 1.66 (m, 2H), 1,74-of 1.78 (m, 2H), 1.85 to 1.91 a (m, 4H), 3,32-to 3.36 (m, 2H), 3,66-and 3.72 (m, 1H), 3,76 (t, J=4.6 Hz, 2H), to 4.38 (t, J=4.4 Hz, 2H), to 6.43 (DD, J=8,1, 1,6 Hz, 1H), 6,72 (t, J=7.9 Hz, 1H), 7,07 (DD, J=7,9, and 1.4 Hz, 1H), 7,27 (DD, J=8.0 a, 4,8 Hz, 1H), to $ 7.91 (d, J=7.9 Hz, 1H), 8,01 (DD, J=7,9, 1.9 Hz, 1H), 8,39 (DD, J=4,8, 2.0 Hz, 1H)
1001-100(300 MHz, DMSO-d6) δ: 3,81 (t, J=4.4 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 6,53 (DD, J=8,1, 1.5 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), 7,07 (DD, J=7,5, 1.7 Hz, 1H), 7,32 (DD, J=7,9, 4.6 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), of 7.97 (d, J=8,8 Hz, 2H), with 8.05 (DD, J=8,1, 1.5 Hz, 1H), 8,43 (DD, J=2,1, 1.0 Hz, 1H), 10,52 (s, 1H)
1011-101(300 MHz, DMSO-d6) δ: 1.56 to to 1.61 (m, 2H), 1,95 of 1.99 (m, 2H), 2,74-and 2.79 (m, 2H), 3,17-3,19 (m, 2H), 3,29-to 3.33 (m, 4H), 3,80 (t, J=4.4 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 6,50 (DD, J=8,1, 1.5 Hz, 1H), 6,80 (t, J=7,9 Hz, 1H), 7,01-7,06 (m, 2H), 7,31 (DD, J=7,7, 4.8 Hz, 1H), 7,40 (DD, J=5,3, 2.7 Hz, 1H), 7,66 (DD, J=15,0, 2.2 Hz, 1H), 8,04 (DD, J=7,9, 1.7 Hz, 1H), 8,43 (DD, J=2,1, 1.0 Hz, 1H), 10,13 (s, 1H)
1021-102(300 MHz, DMSO-d6) δ: 1,13 (t, J=7.0 Hz, 3H), 1,52-to 1.63 (m, 2H), 1,95-of 1.97 (m, 2H), 2,74-2,77 (m, 2H), 3,18-3,20 (m, 2H), 3,42-to 3.49 (m, 3H), 3,80 (t, J=4.4 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 6,50 (DD, J=8,1, 1,5 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,01-7,06 (m, 2H), 7,31 (DD, J=7,9, 4.6 Hz, 1H), 7,40 (DD, J=8,8, 1.5 Hz, 1H), 7,66 (DD, J=14,9, 2.4 Hz, 1H), 8,04 (DD, J=7,9, 1.7 Hz, 1H), 8,43 (DD, J=2,2, 1,1 Hz, 1H), 10,13 (s, 1H)

[Table 14]
No. approx.Chemical compoundNMR
1031-103(300 MHz, DMSO-d6) δ: 1,10 (d, J=5,9 Hz, 6H), 1,64-to 1.67 (m, 2H), 1,95-2,04 (m, 2H), 2,92-2,95 (m, 2H), 3,26-3,30 (m, 2H), 3,55-3,59 (m, 1H), 3.72 points-with 3.79 (m, 3H), 4,43 (t, J=4.4 Hz, 2H), 6,51 (DD, J=8,1, 1.8 Hz, 1H), to 6.80 (t, J=7.7 Hz, 1H), 7,06 (DD, J=7,7, 1.5 Hz, 1H), 7,30-7,33 (m, 2H), 7,45 (d, J=8,4 Hz, 1H), 7,73 (d, J=14,7 Hz, 1H), 8,04 (DD, J=8,1, 1.8 Hz, 1H), 8,43 (DD, J=4,8, 1.5 Hz, 1H), 10,24 (s, 1H)
1041-104(400 MHz, CHLOROFORM-d) of 1.03 (s, 3H), of 1.05 (s, 3H), 2,09-of 2.15 (m, 1H), 3,79 (d, J=7,0 Hz, 2H), 3,95 (t, J=4.4 Hz, 2H), 4,63 (t, J=4.6 Hz, 2H), to 6.67 (DD, J=8,1, 1,6 Hz, 1H), 6.90 to-6,94 (m, 2H), 7,12 (kV, J=4,2 Hz, 1H), 7,30 (t, J=5.3 Hz, 1H), 7,58 (DD, J=13,0, 2.8 Hz, 1H), 7,79-7,80 (m, 2H), scored 8.38 (DD, J=4,6, and 1.4 Hz, 1H), 9,58 (s, 1H)
1051-105(400 MHz, DMSO-d6) of 1.08 (t, J=6.8 Hz, 3H), of 1.20 and 1.33 (m, 4H), 1.85 to of 1.97 (m, 4H), of 2.20 (s, 3H), 3,14-3,24 (m, 1H), 3.43 points (kV, J=6,8 Hz, 2H), 3,66 is 3.76 (m, 1H), 3,95 (t, J=4.4 Hz, 2H), 4,27 (t, J=4.4 Hz, 2H), 6,84 (DD, J=8.0 a, 7,6 Hz, 1H), 7,17 (d, J=8,8 Hz, 1H), 7,17 (DD, J=8,0, 2.0 Hz, 1H), 7,33 (DD, J=8,0, 1.2 Hz, 1H), of 7.48 (DD, J=8,4, 2.4 Hz, 1H), of 7.90 (d, J=8.0 Hz, 1H), 8,11 (d, J=2.4 Hz, 1H)
1061-106(400 MHz, DMSO-d6) was 1.04 (d, J=6.0 Hz, 6H), of 1.16 to 1.37 (m, 4H), 1,81 is 1.91 (m, 4H), of 2.20 (s, 3H), 3,23-to 3.33 (m, 1H), 3,62-to 3.73 (m, 1H), 3,95 (t, J=4.4 Hz, 2H), 4,27 (t, J=4.4 Hz, 2H), at 6.84 (DD, J=8,4, 7.2 Hz, 1H), 7,07 (d, J=8,4 Hz, 1H), 7,18 (DD, J=8,0, 2.0 Hz, 1H), 7,33 (DD, J=8,0, 2.0 Hz, 1H), of 7.48 (DD, J=8,0, 2.0 Hz, 1H), 7,89 (d, J=8.0 Hz, 1H), 8,11 (d, J=1.6 Hz, 1H)
1071-107(400 MHz, DMSO-d6) of 1.05 to 1.36 (m, 9H), 1,40-of 1.92 (m, 9H), of 2.20 (s, 3H), 3,26-to 3.36 (m, 1H), 3,64-3,74 (m, 1H), 3,95 (t, J=4.4 Hz, 2H), 4,27 (t, J=4.4 Hz, 2H), at 6.84 (DD, J=8,0, 8.0 Hz, 1H), 7,07 (d, J=8.5 Hz, 1H), 7,17 (DD, J=7,4, and 1.4 Hz, 1H), 7,33 (DD, J=8.0 a, and 1.4 Hz, 1H), of 7.48 (DD, J=8,5, and 2.6 Hz, 1H), of 7.90 (d, J=8.0 Hz, 1H), 8,12 (d, J=1.2 Hz, 1H)
1081-108 (400 MHz, DMSO-d6) was 1.04 to 1.34 (m, 4H), 1,72-to 1.87 (m, 4H), of 2.20 (s, 3H), 2,48-of 2.58 (m, 1H), 3,30 (users, 3H), 3,59-3,71 (m, 1H), 3,95 (t, J=4.4 Hz, 2H), 4,27 (t, J=4.4 Hz, 2H), at 6.84 (DD, J=8,0, 8.0 Hz, 1H), 7,07 (d, J=8.5 Hz, 1H), 7,19 (DD, J=8,0, 1.5 Hz, 1H), 7,33 (DD, J=8,0, 1.5 Hz, 1H), of 7.48 (DD, J=8,5, and 2.6 Hz, 1H), 7,86 (d, J=8.0 Hz, 1H), 8,12 (d, J=2.0 Hz, 1H)
1091-109(400 MHz, DMSO-d6) 1,48-of 1.84 (m, 8H), of 2.20 (s, 3H), 3,78-3,88 (m, 5H), of 3.95 (t, J=4.4 Hz, 2H), 4,28 (t, J=4.4 Hz, 2H), at 6.84 (DD, J=8,0, 8.0 Hz, 1H), was 7.08 (d, J=8.5 Hz, 1H), 7,18 (DD, J=8,0, 1.5 Hz, 1H), 7,34 (DD, J=8,0, 1.5 Hz, 1H), of 7.48 (DD, J=8,5, 2.5 Hz, 1H), of 7.97 (d, J=8.0 Hz, 1H), 8,12 (d, J=2.5 Hz, 1H)
1101-110(400 MHz, DMSO-d6) 1,74-of 1.84 (m, 2H), 2.05 is-is 2.09 (m, 2H), measuring 2.20 (s, 3H), 2.26 and is 2.33 (m, 2H), 2,41 is 2.46 (m, 2H), 3,95 (t, J=4.4 Hz, 2H), 4,21-to 4.28 (m, 3H), 6,85 (t, J=7.9 Hz, 1H), was 7.08 (d, J=8,8 Hz, 1H), 7,18 (DD, J=7,7, and 1.6 Hz, 1H), 7,35 (DD, J=8,1, 1,6 Hz, 1H), 7,49 (DD, J=8,8, 2.3 Hz, 1H), 8,11-8,13 (m, 2H)

[Table 15]
No. approx.Chemical compoundNMR
1111-111(400 MHz, DMSO-d) 1,49-of 1.78 (m, 8H), 2,16-of 2.20 (m, 4H), 2,43 at 2.45 (m, 4H), 3,55 (t, J=4.6 Hz, 4H), 3,98 (t, J=4.4 Hz, 3H), or 4.31 (t, J=4.6 Hz, 2H), 6,86 (t, J=7.9 Hz, 1H), was 7.08 (d, J=8,3 Hz, 1H), 7,25 (DD, J=7,7, and 1.6 Hz, 1H), 7,35 (DD, J=8,1, 1,6 Hz, 1H), 7,49 (DD, J=8,3, 2.3 Hz, 1H), 8,02 (d, J=7,4 Hz, 1H), 8,12 (s, 1H)
1121-112(400 MHz, DMSO-d6) 1,20-of 1.32 (m, 4H), 1,80 (users, 2H), 1,90 (users, 2H) 2.06 to of 2.16 (m, 7H), of 2.20 (s, 3H), 3,63-3,68 (m, 1H), 3,95 (users, 2H), 4,27 (users, 2H), 6,83 (t, J=7.9 Hz, 1H), 7,07 (d, J=8,8 Hz, 1H), 7,18 (d, J=7,9 Hz, 1H), 7,33 (DD, J=8,1, 1,6 Hz, 1H), of 7.48 (DD, J=8,6, and 1.6 Hz, 1H), 7,88 (d, J=7.9 Hz, 1H), 8,12 (s, 1H)
1131-113(400 MHz, DMSO-d6) of 0.94 (t, J=7.0 Hz, 6H), 1.26 in-1,32 (m, 4H), 1.70 to (users, 2H), 1.91 a (users, 2H), measuring 2.20 (s, 3H), 2,43 is 2.46 (m, 5H), 3,63-3,68 (m, 1H), 3,95 (t, J=4.4 Hz, 2H), 4,27 (t, J=4.4 Hz, 2H), 6,84 (t, J=7.9 Hz, 1H), 7,07 (d, J=8,3 Hz, 1H), 7,19 (DD, J=7,7, and 1.6 Hz, 1H), 7,33 (DD, J=8,1, 1,6 Hz, 1H), of 7.48 (DD, J=8,3, 2.3 Hz, 1H), 7,87 (d, J=7.9 Hz, 1H), 8,12 (d, J=2.3 Hz, 1H)
1141-114(400 MHz, DMSO-d6) of 1.55 was 1.69 (m, 12H), 2,17-of 2.24 (m, 4H), 2,45 of $ 2.53 (m, 4H), 3,88-3,90 (m, 1H), 3,97 (t, J=4.4 Hz, 2H), or 4.31 (t, J=4,2 Hz, 2H), 6,85 (t, J=7.9 Hz, 1H), was 7.08 (d, J=8,8 Hz, 1H), 7,24 (DD, J=7,9, the 1.4 Hz, 1H), 7,34 (d, J=7.9 Hz, 1H), of 7.48 (DD, J=8,6, and 2.1 Hz, 1H), of 7.97 (d, J=7,0 Hz, 1H), 8,12 (users, 1H)
115 1-115(400 MHz, DMSO-d6) of 1.18 to 1.34 (m, 4H), 1,64 (users, 4H), 1,86-of 1.95 (m, 5H), of 2.20 (s, 3H), 3,65-3,70 (m, 1H), 3,95 (t, J=4.4 Hz, 2H), 4,27 (t, J=4.4 Hz, 2H), 6,84 (t, J=7.9 Hz, 1H), 7,07 (d, J=8,8 Hz, 1H), 7,18 (DD, J=7,9, and 1.4 Hz, 1H), 7,33 (DD, J=7,9, and 1.4 Hz, 1H), of 7.48 (DD, J=8,8, 2.3 Hz, 1H), 7,89 (d, J=7.9 Hz, 1H), 8,11 (s, 1H)
1161-116(400 MHz, DMSO-d6) 1,33-of 2.16 (m, 14H), and 2.27 (s, 3H), 2,86-to 2.94 (m, 2H), 3,03-3,17 (m, 1H), 3,30-to 3.33 (m, 2H), 3,68-4,11 (m, 3H), 4,32 is 4.45 (m, 2H), 6.87 in-6,94 (m, 1H), 7.24 to 7,41 (m, 3H), 7,79 (d, J=8,3 Hz, 1H), 7,99-to 8.12 (m, 1H), 8,17 (s, 1H), 10,43-10,53 (m, 1H)
1171-117(400 MHz, DMSO-d6) 1,29-of 1.40 (m, 2H), 1.56 to of 1.65 (m, 2H), 1,94 is 2.01 (m, 2H), 2,16-2,19 (m, 2H), 2,24 (s, 3H), 3,01 is 3.15 (m, 3H), 3.33 and-to 3.38 (m, 2H), 3,44-4,01 (m, 7H), or 4.31 (t, J=4.4 Hz, 2H), to 6.88 (t, J=7.9 Hz, 1H), 7,21 (d, J=7.9 Hz, 2H), was 7.36 (DD, J=8,3, and 1.4 Hz, 1H), to 7.67 (d, J=8,3 Hz, 1H), 8,00 (d, J=7.9 Hz, 1H), 8,15 (s, 1H), 11,13 (s, 1H)
1181-118(400 MHz, DMSO-d6) 1,21-to 1.38 (m, 4H), 1,76-of 1.88 (m, 7H), of 2.20 (s, 3H), 3,44-to 3.49 (m, 1H), 3,66-and 3.72 (m, 1H), 3,95 (t, J=4,2 Hz, 2H), 4,27 (t, J=4.4 Hz, 2H), 6,84 (t, J=7.9 Hz, 1H), was 7.08 (d, J=8,3 Hz, 1H), 7.18 in (DD, J=7,9, and 1.4 Hz, 1H), 7,33 (DD, J=8,3, and 1.4 Hz, 1H), of 7.48 (DD, J=8,8, 2.3 Hz, 1H), 7,72 (d, J=7.9 Hz, 1H), 7,92 (d, J=7.9 Hz, 1H), 8,12 (d, J=1.9 Hz, 1)

[Table 16]
No. approx.Chemical compoundNMR
1191-119(400 MHz, DMSO-d6) of 0.83 to 0.92 (m, 2H), of 1.09 to 1.47 (m, 8H), 1,59 was 1.69 (m, 5H), 1,84-of 1.95 (m, 4H), of 2.20 (s, 3H), 3,13-to 3.33 (m, 3H), 3,69-3,74 (m, 1H), 3,95 (t, J=4.4 Hz, 2H), 4,27 (t, J=4.4 Hz, 2H), 6,84 (t, J=7,9 Hz, 1H), 7,07 (d, J=8,3 Hz, 1H), 7,18 (DD, J=7,7, and 1.6 Hz, 1H), 7,33 (DD, J=7,9, and 1.4 Hz, 1H), of 7.48 (DD, J=8,3, 2.3 Hz, 1H), of 7.90 (d, J=7.9 Hz, 1H), 8,12 (d, J=2.3 Hz, 1H)
1201-120(400 MHz, DMSO-d6) of 1.30 (t, J=7.0 Hz, 3H), of 3.97 (q, J=7,0 Hz, 2H), was 4.02 (t, J=4.6 Hz, 2H), 4,33 (t, J=4.6 Hz, 2H), to 6.88 (d, J=9,3 Hz, 2H), 6,93 (t, J=7.9 Hz, 1H), 7,21-7,24 (m, 2H), 7,47 (DD, J=8,1, 1,6 Hz, 1H), to 7.61 (d, J=9,3 Hz, 2H), 7,74 (DD, J=9,0, 2.6 Hz, 1H), 8,30 (d, J=2,8 Hz, 1H), 9,98 (s, 1H)
1211-121(400 MHz, DMSO-d6) was 4.02 (t, J=4.5 Hz, 3H), 4,32 (t, J=4.5 Hz, 2H), 6,94 (t, J=7.9 Hz, 1H), 7,21-of 7.23 (m, 2H), 7,38 (d, J=8,8 Hz, 2H), 7,49 (DD, J=7,9, and 1.4 Hz, 1H), 7,73-to 7.77 (m, 4H), 8,30 (d, J=2,8 Hz, 1H), 10,27 (s, 1H)
1221-12 (300 MHz, DMSO-d6) δ: 1,54-to 1.63 (m, 2H), 1,96 is 2.01 (m, 2H), 2,74-2,77 (m, 2H), 3,16-3,18 (m, 2H), 3,29-to 3.33 (m, 4H), a 4.03 (t, J=4,2 Hz, 2H), 4,34 (t, J=4.4 Hz, 2H), 6,95-7,02 (m, 2H), 7.23 percent (d, J=9,2 Hz, 2H), 7,38 (d, J=8,4 Hz, 1H), 7,50 (DD, J=8,1, 0.7 Hz, 1H), to 7.64 (DD, J=15,0, 2.2 Hz, 1H), 7,76 (DD, J=9,0, 2.8 Hz, 1H), 8,32 (d, J=2.6 Hz, 1H), 10,12 (s, 1H)
1231-123(300 MHz, DMSO-d6) δ: Android 4.04 (t, J=4.4 Hz, 2H), 4,35 (t, J=4.4 Hz, 2H), of 6.96 (t, J=7.9 Hz, 1H), 7.23 percent-7,26 (m, 2H), 7,53 (DD, J=8,3, 1.7 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), to 7.77 (DD, J=9,0, 2.8 Hz, 1H), 7,95 (d, J=8,4 Hz, 2H), 8,32 (d, J=2.6 Hz, 1H), 10,49 (s, 1H)
1241-124(400 MHz, DMSO-d6) of 2.25 (s, 3H), 2,84 (t, J=7.2 Hz, 2H), 3,50 (kV, J=6,6 Hz, 2H), 3,98 (t, J=4.4 Hz, 2H), 4,28 (t, J=4.6 Hz, 2H), 6.89 in (t, J=7.9 Hz, 1H), 7.24 to 7,35 (m, 8H), the 7.65 (d, J=8,8 Hz, 1H), 8,15-8,20 (m, 2H)
1251-125(400 MHz, CHLOROFORM-d) and 2.26 (s, 3H), only 2.91 (t, J=7,0 Hz, 2H), of 3.73 (q, J=6.5 Hz, 2H), 4,07 (t, J=4.6 Hz, 2H), 4,21 (t, J=4.4 Hz, 2H), 6,92 (t, J=7.9 Hz, 1H), 7,06 (d, J=8,3 Hz, 1H), 7,20-7,21 (m, 2H), 7,27-7,30 (m, 2H), was 7.36 (DD, J=7,9, 1.9 Hz, 2H), 7,74 (s, 1H), 7,82 (DD, J=7,9, and 1.4 Hz, 1H), 8,14 (s, 1H)
1261-126 (400 MHz, CHLOROFORM-d) and 2.26 (s, 3H), only 2.91 (t, J=6,7 Hz, 2H), 3,74 (kV, J=6,5 Hz, 2H), 4,08 (s, 2H), 4,24 (t, J=4.4 Hz, 2H), 7,76 (s, 1H), 7,83 (d, J=6,5 Hz, 1H), 8,14 (s, 1H)

[Table 17]
No. approx.Chemical compoundNMR
1271-127(400 MHz, DMSO-d6) of 2.26 (s, 3H), 2,98 (t, J=7.2 Hz, 2H), 3,53 (kV, J=6,6 Hz, 2H), 3,99 (t, J=4.4 Hz, 2H), 6.90 to (t, J=7.9 Hz, 1H), 7.23 percent-7,33 (m, 4H), 7,38-7,40 (m, 2H), 7,44 (DD, J=7,7, and 1.6 Hz, 1H), 7,69 (d, J=8,8 Hz, 1H), 8,16 (s, 1H), 8,23 (t, J=5.3 Hz, 1H)
1281-128(300 MHz, DMSO-d6) δ: 4,16 (t, J=4.4 Hz, 2H), 4,37 (t, J=4,2 Hz, 2H), 6,99 (t, J=7.9 Hz, 1H), 7.24 to 7,28 (m, 2H), 7,60 (DD, J=8,3, 1.7 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), 7,95 (d, J=8,4 Hz, 2H), 8,08 (DD, J=8,8 and 2.2 Hz, 1H), 8,77 (d, J=2.6 Hz, 1H), 10,51 (s, 1H)
1291-129(300 MHz, DMSO-d6) δ: rate of 1.51 (s, 6H), of 3.78 (t, J=4,2 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 5,33 (s, 1H), 6,46-of 6.52 (m, 1H), 6,83 (t, J=16,7 Hz, 1H), 7,05 (DD, J=7,7, 1.5 Hz, 1H), 7.68 per-7,71 (m, 2H), 7,94-of 7.97 (m, 2H), of 8.04 (d, J=2.2 Hz, 1H), 8,51 (d, J=2.2 Hz, 1H), 1050 (s, 1H)
1301-130(300 MHz, DMSO-d6) δ: 1,40 (d, J=6.6 Hz, 3H), 3,76-of 3.80 (m, 2H), to 4.41-of 4.44 (m, 2H), 4,82-4,84 (m, 1H), 5,43 (d, J=4,8 Hz, 1H), 6,47 (DD, J=8,1, 1.5 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,05 (d, J=3,9 Hz, 1H), 7,70 (d, J=8,8 Hz, 2H), 7,95-of 7.96 (m, 4H), 8,40-to 8.40 (m, 1H), 10,50 (s, 1H)
1311-131(300 MHz, DMSO-d6) δ: 3,90-to 3.92 (m, 2H), 4,42-4,43 (m, 2H), 6,77 (d, J=4.0 Hz, 1H), 6.87 in (d, J=7.7 Hz, 1H), 7,16-7,17 (m, 1H), 7,73 (d, J=9,2 Hz, 2H), of 7.96 (d, J=14,3 Hz, 1H), 8,30 (d, J=1.8 Hz, 1H), 8,83 (d, J=1.8 Hz, 1H), of 10.72 (s, 1H)
1321-132(400 MHz, CHLOROFORM-d) of 1.33 (s, 9H), to 3.92 (s, 3H), 4,36 (t, J=4.6 Hz, 2H), 4,55 (t, J=4.6 Hz, 2H), 7,06 (t, J=7.9 Hz, 1H), 7,21 (d, J=8,8 Hz, 1H), 7,38 (t, J=4.4 Hz, 2H), 7,52 (DD, J=8,1, 1,6 Hz, 3H), 7,58 (DD, J=6,7, a 4.9 Hz, 3H), 8,02 (DD, J=7,9, and 1.4 Hz, 2H), 8,08 (DD, J=8,8, 2,3 Hz, 2H), 8,93 (d, J=2.3 Hz, 1H), 9,48 (s, 1H)
1331-133(400 MHz, CHLOROFORM-d) of 1.28 (s, 9H), to 4.16 (t, J=4,2 Hz, 2H), 4,37 (t, J=4,2 Hz, 2H), 6,98 (t, J=7.9 Hz, 1H), 7,26 (DD, J=20.4, the 8,3 Hz, 2H), 7,35 (d, J=8,8 Hz, 2H), EUR 7.57 (d, J=8,3 Hz, 1H), to 7.64 (d, J=8,8 Hz, 2H), 8,07 (DD, J=8,8, 1.9 Hz, 1H), 8,77 (d, J=2.3 Hz, 1H), 10,07 (s, 1H)

[Table 18]
No. approx.Chemical compoundNMR
1341-134(300 MHz,DMSO-d6) to 3.92 (t, J=4,2 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 6,76 (DD, J=8,1, 1.5 Hz, 1H), 6,86 (t, J=7.9 Hz, 1H), 7,17 (DD, J=7,5, 1.7 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), of 7.97 (d, J=8,4 Hz, 2H), 8,31 (d, J=2.2 Hz, 1H), 8,83 (d, J=2.2 Hz, 1H), 10,53 (s, 1H)
1351-135(300 MHz,DMSO-d6) of 1.28 (s, 9H), to 3.92 (t, J=4,2 Hz, 2H), of 4.44 (t, J=4,2 Hz, 2H), 6.73 x (DD, J=8,1, 1.5 Hz, 1H), 6,84 (t, J=7.9 Hz, 1H), 7,18 (DD, J=7,5, 1.7 Hz, 1H), 7,35 (d, J=8,8 Hz, 2H), 7,65 (d, J=8,8 Hz, 2H), 8,30 (d, J=2.2 Hz, 1H), 8,83 (d, J=2.2 Hz, 1H), 10,07 (s, 1H)
1361-136(300 MHz, DMSO-d6) δ: 2,62 (s, 3H), of 3.94 (t, J=4.6 Hz, 2H), of 4.44 (t, J=4.4 Hz, 2H), 6,76 (DD, J=8,1, 1.8 Hz, 1H), 6.87 in (t, J=7.9 Hz, 1H), 7,19 (DD, J=7,3, 1.5 Hz, 1H), 7,71 (d, J=8,4 Hz, 3H), of 7.97 (d, J=8.4 and Hz, 3H), scored 8.38 (d, J=2.2 Hz, 1H), 8,91 (d, J=1.8 Hz, 1H), 10,52 (s, 1H)
1371-137(400 MHz, DMSO-d6) of 1.27 (s, 9H), 2,78(d, J=4,6 Hz, 3H), 4,14 (t, J=4,2 Hz, 2H), 4,36 (t, J=4.6 Hz, 2H), 6,98 (t, J=7.9 Hz, 1H), 7,26 (kV, J=7,4 Hz, 2H), 7,35 (d, J=8,8 Hz, 2H), 7,56 (d, J=8,3 Hz, 1H), to 7.64 (d, J=8,8 Hz, 2H), with 8.05 (DD, J=8,8, 2.3 Hz, 1H), 8,39 (d, J=5.6 Hz, 1H), 8,73 (d, J=2.3 Hz, 1H), 10,06 (s, 1H)
1381-138(400 MHz, DMSO-d6) of 1.28 (s, 9H), is 4.15 (t, J=4.4 Hz, 2H), 4,36 (t, J=4.4 Hz, 2H), 6,98 (t, J=7.9 Hz, 1H), 7,25-7,33 (m, 5H), 7,56 (d, J=8,3 Hz, 1H), to 7.64 (d, J=8,8 Hz, 2H), to 7.93 (s, 1H), 8,09 (DD, J=8,8, 2,8 Hz, 1H), 8,78 (d, J=2.3 Hz, 1H), 10,07 (s, 1H)
1391-139(400 MHz, DMSO-d6) of 1.08 (t, J=7.0 Hz, 6H), of 1.27 (s, 9H), 3,31 is 3.40 (m, 4H), 3,82 (t, J=4.4 Hz, 2H), 4,34 (t, J=4.4 Hz, 2H), for 6.81 (t, J=7.9 Hz, 1H), 7,02-7,16 (m, 4H), 7,34 (d, J=8,8 Hz, 2H), to 7.64 (d, J=8,3 Hz, 2H), a 7.85 (d, J=3.2 Hz, 1H), 10,02 (s, 1H)
1401-140(400 MHz, CHLOROFORM-d) of 1.33 (s, 9H), of 4.44 (DD, J=6,0, 3.2 Hz, 2H), 4,59 (t, J=4.9 Hz, 2H), 7,10 for 7.12 (m, 1H), 7,25-7,26 (m, 1H), 7,39 (DD, J=8,6, and 1.6 Hz, 2H), 7,52-rate of 7.54 (m, 1H), 7,58 (DD, J=8,6, and 1.6 Hz, 2H), 8,09-8,11 (m, 1H), compared to 8.26-of 8.28 (m, 1H), 9,17 (t, J=1.9 Hz, 1H), 9,40 (s, 1H)

[Table 19]
No. approx.Chemical soy is inane NMR
1411-141(400 MHz, CHLOROFORM-d) to 1.32 (s, 9H), of 3.54 (s, 2H), was 4.02 (t, J=4.4 Hz, 2H), 4,49 (t, J=4.4 Hz, 2H), 6,92 (t, J=8,1 Hz, 1H), 7,00-7,03 (m, 2H), 7,22-7,26 (m, 1H), 7,37 (t, J=4.4 Hz, 2H), to 7.59 (d, J=8,3 Hz, 2H), 7,80 (DD, J=7,9, and 1.4 Hz, 1H), to $ 7.91 (d, J=2,8 Hz, 1H), 9,59 (s, 1H)
1421-142(400 MHz, DMSO-d6) of 1.28 (s, 9H), was 2.05 (s, 3H), 3,98 (t, J=4,2 Hz, 2H), 4,33 (t, J=4,2 Hz, 2H), 6,91 (t, J=7.9 Hz, 1H), 7,19 (DD, J=13,0, 8,3 Hz, 2H), 7,33 (DD, J=12,3, 6,7 Hz, 2H), 7,40 (d, J=8,3 Hz, 1H), to 7.64 (d, J=8,3 Hz, 2H), 7,92 (t, J=5.8 Hz, 1H), 8,49 (s, 1H), of 10.05 (s, 2H)
1431-143(400 MHz, DMSO-d6) 3,29 (s, 3H), 4,06 (t, J=4.4 Hz, 2H), 4,34 (t, J=4.6 Hz, 2H), 4,36 (s, 2H), 6,95 (t, J=7.9 Hz, 1H), 7,22 (d, J=8,3 Hz, 2H), 7,52 (DD, J=8,1, 1,6 Hz, 1H), 7,65 (DD, J=8,6, and 2.6 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), 7,95 (d, J=8,8 Hz, 2H), compared to 8.26 (d, J=1.9 Hz, 1H), 10,50 (s, 1H)
1441-144(300 MHz, DMSO-d6) δ: of 1.34 (t, J=7.0 Hz, 3H), 3,91 (t, J=4.4 Hz, 2H), 4,08 (kV, J=7,1 Hz, 2H), 4,33 (t, J=4,2 Hz, 2H), to 6.88 (t, J=7.9 Hz, 1H), 7,12-7,17 (m, 2H), 7,28-7,41 (m, 4H), a 7.85 (d, J=9,2 Hz, 2H), of 8.06 (d, J=3.3 Hz, 1H), 10,31 (s, 1H)
1451-145(400 MHz, DMSO-d6) 3,71 (t, J=4.4 Hz, 2H), 3,90 (s, 3H), of 4.44 (t, J=4.4 Hz, 2H), 6,36 (DD, J=7,9, and 1.4 Hz, 1H), 6,78 (t, J=7.9 Hz, 1H), 6,99 (DD, J=7,9, and 1.4 Hz, 1H), 7,71 (d, J=8,3 Hz, 2H), to 7.77 (d, J=2,8 Hz, 1H), of 7.97 (d, J=8,3 Hz, 2H), by 8.22 (d, J=2,8 Hz, 1H), 10,50 (s, 1H)
1461-146(400 MHz, DMSO-d6) 3,86 (t, J=4.4 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 6,86 (t, J=7.9 Hz, 1H), 7,07-7,10 (m, 2H), 7.18 in-of 7.23 (m, 2H), of 7.70 (d, J=8,3 Hz, 2H), 7,94-to 7.95 (m, 3H), 9,72 (users, 1H), 10,48 (s, 1H)
1471-147(400 MHz, DMSO-d6) 3,81 (s, 3H), 3,92 (t, J=4.4 Hz, 2H), 4,34 (t, J=4.4 Hz, 2H), 6.89 in (t, J=7.9 Hz, 1H), 7,12 (DD, J=7,9, and 1.6 Hz, 1H), 7,20 (d, J=9,3 Hz, 1H), 7,31 (DD, J=7,9, and 1.6 Hz, 1H), 7,41 (DD, J=9,3, 3,2 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), of 7.96 (d, J=8,8 Hz, 2H), 8,08 (d, J=3.2 Hz, 1H), 10,50 (s, 1H)
1481-148(300 MHz, DMSO-d6)of 1.28 (s, 9H), 4,08 (t, J=4.4 Hz, 2H), 4,34 (t, J=4.4 Hz, 2H), 6,97 (t, J=7.9 Hz, 1H), 7,02 (DD, J=5,3, 1.7 Hz, 1H), 7,20 (d, J=1.5 Hz, 1H), 7,28 (DD, J=7,7, 1.5 Hz, 1H), 7,35 (d, J=8,8 Hz, 2H), 7,56 (DD, J=8,4, 1.5 Hz, 1H), to 7.64 (d, J=8,8 Hz, 2H), of 8.27 (d, J=5,1 Hz, 1H), 10,04 (s, 1H)

[Table 20]
No. approx.Chemical compoundNMR
1491-149(300 MHz, DMSO-d6) to 3.99 (t, J=4.4 Hz, 2H), 4,35 (t, J=4,2 Hz, 2H), 6,94 (t, J=7.7 Hz, 1H), 7,19-7,28 (m, 2H), 7,22 (s, 2H), 7,45 (d, J=4.0 Hz, 1H), 7,65 (DD, J=8,6, 3.1 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), of 7.96 (d, J=8,8 Hz, 2H), 8,31 (d, J=2,9 Hz, 1H), 10,49 (s, 1H)
1501-150(300 MHz, DMSO-d6) a 3.83 (t, J=4,2 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 6,74-6,77 (m, 1H), 6,85 (t, J=7.9 Hz, 1H), to 7.09 (DD, J=7,3, 1.5 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), of 7.96 (d, J=8,4 Hz, 2H), 8,00-8,07 (m, 1H), 8,35 (d, J=2.2 Hz, 1H), 10,51 (s, 1H)
1511-151(300 MHz, CHLOROFORM-d) to 1.32 (s, 9H), 3,82 (s, 3H), 3,93 (t, J=4.4 Hz, 2H), 4,58 (t, J=4.4 Hz, 2H), of 6.68 (DD, J=8,1, 1.5 Hz, 1H), 6,85 (t, J=7.9 Hz, 1H), 7,10 (DD, J=8,1, 4.8 Hz, 1H), 7,24 (DD, J=8,1, 1.1 Hz, 1H), 7,37 (d, J=8,8 Hz, 2H), 7,60 (d, J=8,4 Hz, 2H), of 7.75 (DD, J=7,9, 1.7 Hz, 1H), 8,03 (DD, J=4,6, 1.3 Hz, 1H), 9,63 (s, 1H)
1521-152(300 MHz, DMSO-d6) δ: 0,86 (s, 9H), 0,96-1,00 (m, 1H), 1,27-of 1.39 (m, 2H),1,64 (d, J=13,2 Hz, 2H), 2,22 (s, 3H), 2,58 (d, J=10,6 Hz, 2H), of 3.07 (d, J=10.3 Hz, 2H), 3.96 points (t, J=4,2 Hz, 2H), 4,27 (t, J=4.4 Hz, 2H), 6,84 (t, J=7.7 Hz, 1H), 7,05-7,10 (m, 2H), 7,34 (DD, J=8,1, 1.5 Hz, 1H), 7,50 (DD, J=8,6, 2.0 Hz, 1H), 8,13 (d, J=2.2 Hz, 1H), 8,88 (s, 1H)
1531-153(400 MHz, DMSO-d6) and 3.72 (q, J=5,1 Hz, 2H), 3,92 (t, J=4,2 Hz, 2H), Android 4.04 (t, J=5,1 Hz, 2H), 4,34 (t, J=4,2 Hz, 2H), 4,89 (t, J=5,1 Hz, 1H), 6.89 in (t, J=7.9 Hz, 1H), 7,12-7,13 (m, 1H), 7,19 (d, J=8,8 Hz, 1H), 7,31-7,32 (m, 1H), 7,42 (DD, J=8,8, 3.2 Hz, 1H), 7,71 (d, J=8,3 Hz, 2H), of 7.96 (d, J=8,3 Hz, 2H), 8,08 (d, J=2,8 Hz, 1H), 10,49 (s, 1H)
1541-154(300 MHz, DMSO-d6) 2,77 (t, J=6.4 Hz, 2H), 3,67 (kV, J=5,9 Hz, 2H), of 3.77 (t, J=4.4 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4.72 in (t, J=5,1 Hz, 1H), 6,47 (DD, J=8,1, 1.8 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=the 7.7, 1.5 Hz, 1H), 7,69-7,72 (m, 3H), of 7.96 (DD, J=9,9, 5,1 Hz, 3H), 8,30 (d, J=1.8 Hz, 1H), 10,50 (s, 1H)
1551-155(400 MHz, DMSO-d6) δ: 1,20 (s, 6H), 2,31(s, 3H), of 3.65 (s, 2H), Android 4.04 (t, J=4.4 Hz, 2H), 4,37 (t, J=4.4 Hz, 2H), 6,72 (m, 3H), 7,28 (m, 2H), 7,30 (DD, J=8,1, 1.8 Hz, 1H), 7,63 (DD, J=9,0, 2.4 Hz, 1H), 7,72 (DD, J=9, 2.4 Hz, 2H), 8,18 (d, J=2.6 Hz, 1H), 10,00 (s, 1H)
1561-156 (400 MHz, DMSO-d6) δ: 1,50-is 1.51 (m, 2H), 1.60-to of 1.66 (m, 4H), of 2.21 (s, 3H), 2,89-2,90 (m, 4H), of 3.97 (t, J=4.4 Hz, 2H), 4,30 (t, J=4.4 Hz, 2H), 6.89 in (t, J=7.9 Hz, 1H), 6,99 (t, J=9.5 Hz, 1H), 7,12-7,14 (m, 2H), 7,38 (DDD, J=13,6, and 8.2, 1.7 Hz, 2H), 7,51 (DD, J=8,8, 2.3 Hz, 1H), 7,63 (DD, J=14,8, 2.3 Hz, 1H), 8,13-to 8.14 (m, 1H), 10,11 (s, 1H)

[Table 21]
No. approx.Chemical compoundNMR
1571-157(400 MHz, DMSO-d6) δ: of 2.21 (s, 3H), 2,90-2,96 (m, 4H), 3,71-and 3.72 (m, 4H), of 3.96 (t, J=20.4 Hz, 2H), 4,30 (t, J=4,2 Hz, 2H), 6.89 in (DD, J=5,3, and 2.6 Hz, 1H), 7,00 (t, J=9.5 Hz, 1H), 7,11-7,14 (m, 2H), 7,39-7,41 (m, 2H), 7,51 (TD, J=4.2, and 2.0 Hz, 1H), 7,66 (DD, J=15,1, and 2.1 Hz, 1H), 8,13-to 8.14 (m, 1H), 10,15 (s, 1H)
1581-158(400 MHz, DMSO-d6) δ: of 2.21 (s, 3H), of 3.97 (t, J=4.4 Hz, 2H), 4,30 (t, J=4.4 Hz, 2H), 6.90 to (DD, J=11,1, 4.6 Hz, 1H), 7,13 (TD, J=6,0, 4,3 Hz, 2H), was 7.36-7,53 (m, 4H), 7,89-a 7.92 (m, 1H), 8,13-to 8.14 (m, 1H), 10,35 (s, 1H)
1591-159(400 MHz, DMSO-d6) δ: of 2.21 (s, 3H), of 3.80 (s, 3H), of 3.97 (t, J=4.4 Hz, 2H), 4,30 (t, J=4.4 Hz, 2H), 6.89 in (t, J=7.9 Hz, 1H), 7,11-7,16 (m, 3H), 7,41(kV, J=4,6 Hz, 2H), 7,51 (DD, J=8,3, 2.3 Hz, 1H), of 7.70 (DD, J=13,7, 2.6 Hz, 1H), 8,13 (s, 1H), 10,14 (s, 1H)
1601-160(400 MHz, DMSO-d6) δ: 1,32 (t, J=7.0 Hz, 3H), of 2.25 (d, J=10,6 Hz, 3H), 3.96 points-a 4.03 (m, 4H), 4,32 (t, J=4.4 Hz, 2H), 6,88-6,93 (m, 3H), 7,16 (TD, J=9,4, 3.8 Hz, 2H), 7,41 (DD, J=8,1, 1.8 Hz, 1H), 7,52 (DD, J=9,0, the 2.4 Hz, 1H), 7,63 (dt, J=9,9, 2,8 Hz, 2H), 8,15 (d, J=2.6 Hz, 1H), 9,98 (s, 1H)
1611-161(300 MHz, DMSO-d6) δ: 1,83-to 1.86 (m, 4H), of 2.23 (s, 3H), 2,36-2,39 (m, 1H), 3,56-of 3.60 (m, 2H), 3,98-4,01 (m, 2H), or 4.31-4,34 (m, 2H), 6,91-6,94 (m, 1H), 7,12-of 7.23 (m, 4H), 7,47 (DD, J=31,2, and 7.7 Hz, 2H), 7,72 (d, J=8.1 Hz, 2H), 8,15 (s, 1H), 10,16 (s, 1H)
1621-162(300 MHz, DMSO-d6) δ: 1,83 is 1.91 (m, 2H), of 2.23 (s, 3H), 2,63-to 2.65 (m, 2H), 2,80 (s, 3H), 3,16-3,18 (m, 2H), 3,99 (t, J=4.4 Hz, 2H), 4,32 (t, J=4,2 Hz, 2H), for 6.81 (d, J=8,1 Hz, 1H), 6.90 to (DD, J=9,2, and 6.6 Hz, 2H), 7,02-7,06 (m, 1H), 7,14-7,17 (m, 2H), 7,40 (d, J=8,4 Hz, 1H), 7,52 (d, J=8,4 Hz, 1H), 8,14-of 8.15 (m, 1H), 9,83 (s, 1H)
1631-163(300 MHz, DMSO-d6) δ: of 2.23 (s, 3H), by 2.73 (s, 6H), to 3.99 (t, J=4,2 Hz, 2H), 4,32 (t, J=4.4 Hz, 2H), 6.90 to-to 6.95 (m, 2H), 7,13-7,17 (m, 2H), was 7.36-the 7.43 (m, 2H), 7,52 (DD, J=8,4, 2.2 Hz, 1H), 7,63 (DD, J=15,4, 2.2 Hz, 1H), 8,15 (d, J=1.8 Hz, 1H), 10,08 (s, 1H)
1641-164(300 MHz, DMSO-d6) δ: 1,09-of 1.18 (m, 7H), of 2.28 (s, 3H), 3,11 (s, 3H), 3,38-to 3.41 (m, 2H), 3,56-3,59 (m, 1H), 4,01-of 4.05 (m, 2H), 4,37-to 4.38 (m, 2H), of 6.96 (t, J=7.9 Hz, 1H), 7,27 (DD, J=18,5, 7.9 Hz, 2H), 7,46 (d, J=8,1 Hz, 1H), 7,54-7,58 (m, 1H), of 7.75 (d, J=8,8 Hz, 1H), 7,88 (d, J=13,2 Hz, 1H), 8.17-a 8,21 (m, 1H), 10,52 (s, 1H)
1651-165(300 MHz, DMSO-d6) δ: 1,05-of 1.07 (m, 6H), and 2.26 (s, 3H), and 2.26 (s, 3H), and 3.31 (s, 1H), 3.95 to 4.00 points (m, 3H), 4,27 was 4.42 (m, 2H), 6,93 (t, J=7.9 Hz, 1H), 7,19-of 7.23 (m, 2H), 7,39-7,44 (m, 2H), 7,63-of 7.69 (m, 2H), 8.17-a 8,19 (m, 1H), of 10.21 (s, 1H)

[Table 22]
No. approx.Chemical compoundNMR
1661-166(300 MHz, DMSO-d6) δ: 1,17-of 1.20 (m, 6H), and 2.26 (s, 3H), 3.45 points-to 3.50 (m, 4H), of 3.77-of 3.80 (m, 1H), 3,99-Android 4.04 (m, 2H), 4,35 (t, J=4.4 Hz, 2H), 6,95 (t, J=7.9 Hz, 1H), 7,22 (dt, J=10.5V, the 4.7 Hz, 2H), 7,46 (DD, J=8,1, 1,5 Hz, 1H), EUR 7.57-7,66 (m, 3H), 7,89 (d, J=a 13.9 Hz, 1H), 8,18 (d, J=1.1 Hz, 1H), 10,52 (s, 1H)
1671-167 (400 MHz, DMSO-d6) δ: 1,20 (t, J=5,1 Hz, 3H), 1,66-to 1.79 (m, 2H), 1,91 of 1.99 (m, 2H, in), 2.25 (s, 3H), 2,69-of 2.72 (m, 2H), 3,24-to 3.33 (m, 1H), 3,99 (t, J=4,8 Hz, 2H), 4.09 to (kV, J=26,4 Hz, 2H), 4,32 (t, J=4.4 Hz, 2H), make 6.90 (t, J=7.9 Hz, 1H), 7,01 (t, J=9.4 Hz, 1H), 7,13-7,16 (m, 2H), 7,40 (TD, J=8,1, 4.0 Hz, 2H), 7,52 (dt, J=8,4, 1.3 Hz, 1H), 7,65 (DD, J=14,9, 2.4 Hz, 1H), 8,15 (t, J=1.3 Hz, 1H), 10,12 (s, 1H)
1681-168(300 MHz, DMSO-d6) δ: 1,67-of 1.75 (m, 2H), 1,91-of 1.94 (m, 2H), of 2.23 (s, 3H), 2,33-of 2.38 (m, 1H), 2,67-a 2.71 (m, 2H), 3,19-of 3.25 (m, 2H), 3,99 (t, J=4,2 Hz, 2H), 4,32 (t, J=4.4 Hz, 2H), 6.90 to (t, J=7.9 Hz, 1H), 7,01 (t, J=9.5 Hz, 1H), 7,13-7,17 (m, 2H), 7,40 (TD, J=8,4, 1.7 Hz, 2H), 7,52 (dt, J=9,5, 1.3 Hz, 1H), 7,65 (DD, J=14,9, 2.4 Hz, 1H), 8,15 (t, J=1.3 Hz, 1H), 10,12 (s, 1H)
1691-169(400 MHz, DMSO-d6) δ: 1.55V is 1.58 (m, 2H), 1.93 and-of 1.95 (m, 1H), measuring 2.20 (s, 3H), 2,74 (dt, J=15,0, a 5.4 Hz, 2H), 3,13-3,18 (m, 2H), and 3.31 (s, 3H), of 3.97 (t, J=4.4 Hz, 2H), 4,30 (t, J=4.4 Hz, 2H), 6.89 in (t, J=7.9 Hz, 1H), 7,00 (t, J=9.5 Hz, 1H), 7,13 (dt, J=11,3, 5.0 Hz, 2H), 7,38 (DDD, J=13,9, to 8.3, 1.9 Hz, 2H), 7,51 (DD, J=8,3, 2.3 Hz, 1H), 7,63 (DD, J=14,8, 2.3 Hz, 1H), 8,14 (d, J=2.3 Hz, 1H), 10,12 (s, 1H)
1701-170(400 MHz, DMSO-d6) δ: 1,69-of 1.73 (m, 2H), 1.93 and-to 1.98 (m, 2H), 2,02 (s, 3H), 2,22 (s, 3H), 2,82-is 2.88 (m, 2H), 3,13-3,19 (m, 2H), 3,97 (t, J=4.4 Hz, 2H), 4,30 (t, J=44 Hz, 2H), 4,77-to 4.81 (m, 1H), 6.89 in (t, J=7.9 Hz, 1H), 7,03 (t, J=9,3 Hz, 1H), 7,13 (dt, J=11,1, a 4.9 Hz, 2H), 7,39 (dt, J=13,0, a 4.9 Hz, 2H), 7,51 (DD, J=8,3, 2.3 Hz, 1H), 7,65 (DD, J=14,8, 2.3 Hz, 1H), 8,14 (d, J=1.2 Hz, 1H), 10,13 (s, 1H)
1711-171(300 MHz, DMSO-d6) δ: 1,50-of 1.57 (m, 2H), 1,84-of 1.85 (m, 2H, in), 2.25 (s, 3H), 2,70-to 2.74 (m, 2H), 3,18-3,20 (m, 2H), 3,59-3,62 (m, 1H), 3,99 (t, J=4,2 Hz, 2H), 4,32 (t, J=4.4 Hz, 2H), of 4.66 (d, J=4.4 Hz, 1H), 6.90 to (t, J=7.9 Hz, 1H), 7,01 (t, J=9.4 Hz, 1H), 7,13-7,16 (m, 2H), was 7.36-the 7.43 (m, 2H), 7,52 (DD, J=8,4, and 2.6 Hz, 1H), to 7.64 (DD, J=15,0, 2.2 Hz, 1H), 8,15 (d, J=2.6 Hz, 1H), 10,11 (s, 1H)
1721-172(400 MHz, DMSO-d6) 2,11 (s, 3H), of 2.23 (s, 3H), 3,99 (t, J=4,2 Hz, 2H), 4,32 (t, J=4,2 Hz, 2H), 6,91 (t, J=7.9 Hz, 1H), 7,06 (d, J=7.9 Hz, 1H), 7,14 (d, J=8,3 Hz, 1H), 7,17-7,20 (m, 3H), 7,41 (d, J=7.9 Hz, 1H), of 7.48 (s, 1H), 7,53 (DD, J=8,3, 2.3 Hz, 1H), 8,15 (s, 1H), 10,06 (s, 1H)
1731-173(400 MHz, DMSO-d6) of 2.13 (s, 3H), of 2.23 (s, 3H), 3,75 (kV, J=5.3 Hz, 2H), 3,97 (dt, J=15,3, 4.6 Hz, 4H), to 4.33 (t, J=4.4 Hz, 2H), a 4.83 (t, J=5.6 Hz, 1H), 6,91 (t, J=7.9 Hz, 1H), 7,06 (d, J=8,3 Hz, 1H), 7,16 (DD, J=18,6, 7,9 Hz, 3H), 7,43 (t, J=9.0 Hz, 2H), 7,53 (DD, J=8,8, 1.9 Hz, 1H), 8,15 (s, 1H), there is a 10.03 (s, 1H)

[Table 23]
No. approx.Chemical compoundNMR
1741-174(400 MHz, DMSO-d6) 1,55 (user. s, 2H), 1,87-1,90 (m, 2H), of 2.23 (s, 3H), of 2.54 (s, 6H), 3,17-3,19 (m, 2H), 3,63 (user. s, 2H), 3,99 (t, J=4.4 Hz, 2H), or 4.31 (t, J=4.4 Hz, 2H), 4,47 (s, 1H), 6,91 (t, J=7.9 Hz, 1H), 7,15-7,21 (m, 3H), 7,40-the 7.43 (m, 2H), 7,51-rate of 7.54 (m, 1H), 7,73 (DD, J=13,2, and 2.1 Hz, 1H), 8,15 (d, J=1.9 Hz, 1H), 10,18 (s, 1H)
1751-175(400 MHz, DMSO-d6) 1,86 is 1.91 (m, 3H), of 2.08 and 2.13 (m, 2H), to 2.29 (s, 3H), 3,06 (user. s, 2H), 3,20 (user. s, 2H), 4,06 (t, J=4,2 Hz, 2H), to 4.38 (t, J=4,2 Hz, 2H), 4,55-4,59 (m, 1H), of 6.96 (t, J=7.9 Hz, 1H), 7,25 (DD, J=12,3, 5.8 Hz, 2H), 7,33 (d, J=8,8 Hz, 1H), 7,45 (DD, J=10,7, and 3.7 Hz, 2H), 7,75-7,80 (m, 2H), 8,20 (s, 1H), 9,12 (d, J=32,5 Hz, 2H), of 10.25 (s, 1H)
1761-176(400 MHz, DMSO-d6) to 1.19 (t, J=7.2 Hz, 3H), of 1.25 to 1.31 (m, 4H), 1.85 to 1,99 (m, 4H), of 2.20 (s, 3H), 3,28-to 3.34 (m, 1H), 3,70-to 3.73 (m, 1H), 3,95 (t, J=4.4 Hz, 2H), 4,07 is 4.13 (m, 4H), 4,27 (t, J=4.4 Hz, 2H), 6,84 (t, J=7.9 Hz, 1H), 7,07 (d, J=8,3 Hz, 1H), 7,17 (DD, J=7,9, and 1.4 Hz, 1H), 7,33 (DD, J=8,1, 1,6 Hz, 1H), of 7.48 (DD, J=8,3, 1.9 Hz, 1H), of 7.90 (d, J=7.9 Hz, 1H), 8,12 (d, J=2.3 Hz, 1H)
1771-177 (400 MHz, DMSO-d6) of 1.21 and 1.35 (m, 4H), 1.85 to 1,99 (m, 4H), of 2.20 (s, 3H), 3,22-to 3.38 (m, 1H), 3,69-3,74 (m, 1H), 3,95 (t, J=4,2 Hz, 2H), 4.00 points (s, 2H), 4,27 (t, J=4,2 Hz, 2H), 6,84 (t, J=7.9 Hz, 1H), 7,07 (d, J=8,3 Hz, 1H), 7,18 (d, J=7,4 Hz, 1H), 7,33 (DD, J=8,1, 1,6 Hz, 1H), of 7.48 (d, J=8,8 Hz, 1H), of 7.90 (d, J=7,4 Hz, 1H), 8,12 (s, 1H), 12,46 (users, 1H)
1781-178(400 MHz, DMSO-d6) 1,26-of 1.36 (m, 4H), 1,88 (users, 2H), 1,99 (users, 2H), measuring 2.20 (s, 3H), 3,26-3,30 (m, 1H), 3,70-3,74 (m, 1H), 3,79 (s, 2H), 3,95 (users, 2H), 4,27 (users, 2H), 6,84 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (users, 1H), 7,07 (d, J=8,3 Hz, 1H), 7,17 (d, J=7,4 Hz, 1H), 7,22 (users, 1H), 7,33 (d, J=8,3 Hz, 1H), of 7.48 (d, J=8,3 Hz, 1H), to $ 7.91 (d, J=7.9 Hz, 1H), 8,12 (s, 1H)
1791-179(400 MHz, DMSO-d6) of 1.28 and 1.33 (m, 4H), 1,88 (users, 2H), 1,99 (users, 2H), measuring 2.20 (s, 3H), 2,61 (d, J=4,6 Hz, 3H), 3,26-3,29 (m, 1H), 3,71-3,74 (m, 1H), 3,84 (s, 2H), 3,95 (t, J=4.4 Hz, 2H), 4,27 (t, J=4.4 Hz, 2H), 6,84 (t, J=7.9 Hz, 1H), 7,07 (d, J=8,8 Hz, 1H), 7,17 (DD, J=7,7, and 1.6 Hz, 1H), 7,33 (DD, J=8,1, 1,6 Hz, 1H), of 7.48 (DD, J=8,3, 2.3 Hz, 1H), 7,53 (users, 1H), 7,92 (d, J=7.9 Hz, 1H), 8,12 (d, J=2.3 Hz, 1H)
1801-180(400 MHz, DMSO-d6) of 1.25 to 1.31 (m, 4H), 1,86 is 2.00 (m, 4H), of 2.20 (s, 3H), and 2.79 (s, 3H), of 2.92 (s, 3H), 3,26-3,29 (m, 1H), 3,70-3,74 (m, 1H), 3,95 (t, J=4.4 Hz, 2H), 4,10 (s, 2H), 4,27 (t, J=4.4 Hz, 2H), 6,84 (t, J=7.9 Hz, H), 7,07 (d, J=8,3 Hz, 1H), 7,17 (DD, J=7,4, and 1.4 Hz, 1H), 7,33 (DD, J=8,3, and 1.4 Hz, 1H), of 7.48 (DD, J=8,8, 2.3 Hz, 1H), to $ 7.91 (d, J=7,4 Hz, 1H), 8,11 (s, 1H)
1811-181(400 MHz, DMSO-d6) of 1.14 to 1.31 (m, 4H), 1,81-of 1.93 (m, 4H), of 2.16 (s, 3H), 3,16-is 3.21 (m, 1H), 3,35-of 3.42 (m, 4H), 3,65-3,68 (m, 1H), 3,91 (t, J=4.0 Hz, 2H), 4,23 (t, J=4.0 Hz, 2H), 4,47 (t, J=5.3 Hz, 1H), 6,79 (t, J=7.9 Hz, 1H), 7,03 (d, J=8,8 Hz, 1H), 7,13 (d, J=7.9 Hz, 1H), 7,29 (d, J=7.9 Hz, 1H), 7,44 (d, J=8,3 Hz, 1H), 7,86 (d, J=7.9 Hz, 1H), 8,07 (s, 1H)
[Table 24]
No. approx.Chemical compoundNMR
1821-182(400 MHz, DMSO-d6) of 0.96 was 1.06 (m, 2H), 1,20-1,30 (m, 2H), 1,45-of 1.52 (m, 1H), 1,72 is 1.75 (m, 2H), 1,86 is 1.91 (m, 2H), of 2.21 (s, 3H), 3,14 (d, J=6,5 Hz, 2H), 3,21 (s, 3H), 3,63-3,71 (m, 1H), 3.96 points (t, J=4.4 Hz, 2H), to 4.28 (t, J=4.4 Hz, 2H), 6,84 (t, J=7.9 Hz, 1H), was 7.08 (d, J=8,8 Hz, 1H), 7,19 (DD, J=7,7, and 1.6 Hz, 1H), 7,34 (DD, J=7,9, and 1.4 Hz, 1H), 7,49 (DD, J=8,8, 2.3 Hz, 1H), of 7.90 (d, J=7.9 Hz, 1H), 8,12 (d, J=1.9 Hz, 1H)
1831-183(400 MHz, DMSO-d6) 0,94-of 1.03 (m, 2H), of 1.06 (d, J=6.5 Hz, 6H), 1,19-of 1.30 (m, 2H), 1,38 was 1.43 (m, 1H), 1,75-of 1.78 (m, 2H), 1,86 is 1.91 (m, 2H), of 2.21 (s, 3H), and 3.16 (d, J=6.5 Hz, 2H, 3,44-to 3.50 (m, 1H), 3,63-and 3.72 (m, 1H), 3.96 points (t, J=4.4 Hz, 2H), 4,28 (t, J=4.4 Hz, 2H), 6,84 (t, J=7.9 Hz, 1H), was 7.08 (d, J=8,3 Hz, 1H), 7,20 (DD, J=7,7, and 1.6 Hz, 1H), 7,34 (DD, J=8,1, 1,6 Hz, 1H), 7,49 (DD, J=of 8.3, 2.3 Hz, 1H), 7,88 (d, J=7.9 Hz, 1H), 8,12 (d, J=2.3 Hz, 1H)
1841-184(400 MHz, DMSO-d6) 1,27-of 1.36 (m, 2H), 1,50-1,70 (m, 7H), of 2.23 (s, 3H), 3,20 (d, J=6,5 Hz, 2H), up 3.22 (s, 3H), 3,99-Android 4.04 (m, 3H), 4,35 (t, J=4.4 Hz, 2H), to 6.88 (t, J=7.9 Hz, 1H), 7,16 (d, J=8,8 Hz, 1H), 7,32 (DD, J=7,7, and 1.6 Hz, 1H), 7,37 (DD, J=8,1, 1,6 Hz, 1H), to 7.59 (d, J=7,4 Hz, 1H), 8,01 (d, J=7.9 Hz, 1H), 8,14 (s, 1H)
1851-185(400 MHz, DMSO-d6) of 1.06 (d, J=6.0 Hz, 6H), of 1.29 and 1.35 (m, 2H), 1,50-1,70 (m, 7H), 2,24 (s, 3H), 3,23 (d, J=6,5 Hz, 2H), 3,45-3,51 (m, 1H), 4,01 (t, J=4,2 Hz, 3H), 4,36 (t, J=4.4 Hz, 2H), 6.89 in (t, J=7.9 Hz, 1H), 7,21 (d, J=8,3 Hz, 1H), 7,34 (d, J=7,4 Hz, 1H), 7,38 (d, J=8,3 Hz, 1H), 7,65 (d, J=8,3 Hz, 1H), 8,01 (d, J=7,4 Hz, 1H), 8,14 (s, 1H)
1861-186(400 MHz, DMSO-d6) of 0.94 to 1.37 (m, 14H), 1,75 is 1.91 (m, 4H), of 2.21 (s, 3H), 3,11 (d, J=6,5 Hz, 2H), 3,63-and 3.72 (m, 1H), 3.96 points (t, J=4.4 Hz, 2H), 4,28 (t, J=4.4 Hz, 2H), 6,84 (t, J=7.9 Hz, 1H), was 7.08 (d, J=8,3 Hz, 1H), 7,20 (DD, J=7,7, and 1.6 Hz, 1H), 7,34 (DD, J=8,1, 1,6 Hz, 1H), 7,49 (DD, J=8,3, 2.3 Hz, 1H), 7,88 (d, J=7.9 Hz, 1H), 8,12 (d, J=2.3 Hz, 1H)
1871-187 (400 MHz, DMSO-d6) 0,86 (d, J=8,4 Hz, 6H), of 1.23 to 1.34 (m, 4H), 1,86-of 1.97 (m, 4H), 2,22 (s, 3H), and 3.16 (m, 3H), of 3.96 (t, J=4.4 Hz, 2H), 4,29 (t, J=4.4 Hz, 2H), 6,85 (t, J=8 Hz, 1H), to 7.09 (d, J=8,4 Hz, 1H), 7,19 (d, J=8 Hz, 1H), 7,49 (d, J=8,4 Hz, 1H), to $ 7.91 (d, J=8 Hz, 1H), 8,12 (s, 1H)
1881-188(400 MHz, DMSO-d6) of 0.92 (s, 6H), of 1.17 to 1.47 (m, 6H), 1,62-1,72 (m, 2H), and 2.27 (s, 3H), of 3.73 (m, 3H), was 4.02 (t, J=4.4 Hz, 2H), 4,37 (t, J=4.4 Hz, 2H), 6,91 (t, J=8 Hz, 1H), 7,28 (m, 2H), 7,38 (d, J=8 Hz, 1H), 7,76 (d, J=8 Hz, 1H), 7,94 (d, J=8 Hz, 1H), 8,17 (s, 1H)
1891-189(400 MHz, DMSO-d6) of 0.83 (d, J=8,4 Hz, 6H), 1,2-1,4 (m, 6H), 1,8-2,0 (m, 4H), of 2.20 (s, 3H), 3,20 (m, 1H), 3,41 (d, J=8 Hz, 2H), and 3.72 (m, 1H), 3,97 (t, J=4.4 Hz, 2H), 4,29 (t, J=4.4 Hz, 2H), 6,85 (t, J=8 Hz, 1H), to 7.09 (d, J=8 Hz, 1H), 7,19 (d, J=8 Hz, 1H), 7,34 (d, J=8 Hz, 1H), 7,49 (d, J=8 Hz, 1H), to $ 7.91 (d, J=8 Hz, 1H), 8,12 (s, 1H)

[Table 25]
No. approx.Chemical compoundNMR
1901-190(400 MHz, DMSO-d6) to 1.3-1.4 (m, 4H),1.85 to 1,95 (m, 2H), 2,0-2,1 (m, 2H), 2,22 (s, 3H), 3,34 (m, 1H), 3,76 (m, 1H), 3.96 points (t, J=4.6 Hz, 2H), 4,29 (t, J=4.6 Hz, 2H), 4,55 (s, 2H), 6,85 (t, J=8 Hz, 1H), 7,10 (d, J=8 Hz, 1H), 7,19 (d, J=8 Hz, 1H), 7,22 to 7.4 (m, 6H), 7,50 (d, J=8 Hz, 1H), 7,94 (d, J=8 Hz, 1H), 8,13 (s, 1H)
1911-191(400 MHz, DMSO-d6) of 0.85 (d, J=6.4 Hz, 6H), from 1.0 to 1.15 (m, 3H), 1.2 to about 1.35 (m, 2H), 1,35-1,5 (m, 1H), 1,6-of 1.75 (m, 2H), 1.85 to 1,95 (m, 2H), 2,22 (s, 3H), 3,66 (m, 1H), 3,97 (t, J=4 Hz, 2H), 4,29 (t, J=4 Hz, 2H), 6,85 (t, J=8 Hz, 1H), to 7.09 (d, J=8 Hz, 1H), 7,20 (d, J=8 Hz, 1H), 7,34 (d, J=8 Hz, 1H), 7,49 (d, J=8 Hz, 1H), 7,88 (d, J=8 Hz, 1H), 8,13 (s, 1H)
1921-192(400 MHz, DMSO-d6) 0,86 (t, J=7.2 Hz, 3H), of 0.8-1.0 (m, 2H), 1.1 to about 1.35 (m, 6H), a 1.7-1.8 (m, 2H), 1,8-1,9 (m, 2H), 2,22 (s, 3H), and 3.7 (m, 1H), 3.96 points (t, J=4.4 Hz, 2H), 4,29 (t, J=4.4 Hz, 2H), 6,85 (t, J=8 Hz, 1H), was 7.08 (d, J=8 Hz, 1H), 7,33 (d, J=8 Hz, 1H), of 7.48 (d, J=8 Hz, 1H), 7,88 (d, J=8 Hz, 1H), 8,13 (s, 1H)
1931-193(400 MHz, DMSO-d6) 0,86 (s, 9H), 1,2-1,4 (m, 4H), 1,8-2,0 (m, 4H), 2,22 (s, 3H), of 3.07 (s, 2H), 3,17 (m, 1H), to 3.73 (m, 1H), 3.96 points (t, J=4 Hz, 2H), 4,29 (t, J=4 Hz, 2H), 6,85 (t, J=8 Hz, 1H), 7,09 (d, J=8 Hz, 1H), 7,18 (d, J=8 Hz, 1H), was 7.36 (DD, J=8, 2.4 Hz, 1H), 7,50 (DD, J=8, 2.4 Hz), 7,92 (d, J=8 Hz, 1H), 8,13 (s, 1H)
1941-194 (300 MHz, DMSO-d6) of 1.28 (s, 9H), 3,29 (s, 3H), 4,06 (t, J=4.4 Hz, 2H), or 4.31 is 4.36 (m, 4H), 6,93 (t, J=7.9 Hz, 1H), 7.18 in-7,25 (m, 2H), 7,34 (d, J=8,8 Hz, 2H), of 7.48 (DD, J=8,1, 1.5 Hz, 1H), 7,60-to 7.68 (m, 3H), 8,25 (d, J=2.2 Hz, 1H), of 10.05 (s, 1H)
1951-195(400 MHz, DMSO-d6) to 3.92 (t, J=4,2 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 6,76 (DD, J=8,3, and 1.4 Hz, 1H), 6,86 (t, J=7.9 Hz, 1H), 7,17 (DD, J=7,4, and 1.4 Hz, 1H), 7,56 (d, J=7.9 Hz, 1H), 7,78 (DD, J=9,0, 2.6 Hz, 1H), 8,14 (d, J=2,8 Hz, 1H), 8,30 (d, J=1.9 Hz, 1H), 8,83 (d, J=1.9 Hz, 1H), 10,51 (s, 1H), 13,47 (users, 1H)
1961-196(300 MHz, DMSO-d6) to 3.92 (t, J=4,2 Hz, 2H), 4,43 (t, J=4.0 Hz, 2H), 6,74 (DD, J=8,1, 1.5 Hz, 1H), 6,85 (t, J=7.9 Hz, 1H), 7,17 (DD, J=7,7, 1.5 Hz, 1H), 7,35 (d, J=8,8 Hz, 2H), 7,86 (d, J=8,8 Hz, 2H), 8,30 (d, J=2.2 Hz, 1H), 8,83 (d, J=2.2 Hz, 1H), 10,35 (s, 1H), 13,46 (users, 1H)
1971-197(400 MHz, DMSO-d6) 2,70 (d, J=5,1 Hz, 3H), of 3.78 (t, J=4,2 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 5,69 (kV, J=5,1 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 6,97-7,06 (m, 4H), 7,34 (d, J=8,8 Hz, 2H), of 7.75 (d, J=2,8 Hz, 1H), to 7.84 (d, J=8,8 Hz, 2H), 10,30 (s, 1H)
[Table 26]
No. approx.Chemical compounds NMR
1981-198(300 MHz, DMSO-d6) δ: of 1.34 (t, J=7.0 Hz, 3H), 3,91 (t, J=4.4 Hz, 2H), 4,08 (kV, J=7,1 Hz, 2H), 4,33 (t, J=4,2 Hz, 2H), to 6.88 (t, J=7.9 Hz, 1H), 7,12-7,17 (m, 2H), 7,28-7,41 (m, 4H), a 7.85 (d, J=9,2 Hz, 2H), of 8.06 (d, J=3.3 Hz, 1H), 10,31 (s, 1H)
1991-199(400 MHz, DMSO-d6) 3,71 (t, J=4.4 Hz, 2H), with 3.89 (s, 3H), 4,43 (t, J=4.4 Hz, 2H), 6.35mm (DD, J=7,9, and 1.4 Hz, 1H), 6,77 (t, J=7.9 Hz, 1H), 6,98 (DD, J=7,7, and 1.6 Hz, 1H), 7,35 (d, J=8,8 Hz, 2H), to 7.77 (d, J=3.2 Hz, 1H), 7,86 (d, J=8,8 Hz, 2H), by 8.22 (d, J=2,8 Hz, 1H), 10,33 (s, 1H)
2001-200(400 MHz, DMSO-d6) and 3.72 (q, J=5,1 Hz, 2H), 3,91 (t, J=4.4 Hz, 2H), Android 4.04 (t, J=5,1 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 4,89 (t, J=5,1 Hz, 1H), to 6.88 (t, J=7.9 Hz, 1H), 7,11 (DD, J=7,9, and 1.6 Hz, 1H), 7,18 (d, J=8,8 Hz, 1H), 7,31 (DD, J=7,9, and 1.6 Hz, 1H), 7,35 (d, J=8,8 Hz, 2H), 7,41 (DD, J=8,8, 3.0 Hz, 1H), a 7.85 (d, J=8,8 Hz, 2H), 8,08 (d, J=3.0 Hz, 1H), 10,32 (s, 1H)
2011-201(300 MHz, DMSO-d6) 3,86 (t, J=4,2 Hz, 2H), 4,33 (t, J=4,2 Hz, 2H), 6,85 (t, J=7.9 Hz, 1H), 7,07-7,10 (m, 2H), 7,20-7,21 (m, 2H), 7,34 (d, J=8,8 Hz, 2H), a 7.85 (d, J=9,2 Hz, 2H), to 7.93 (d, J=2,9 Hz, 1H), 10.30 a.m. (s, 1H)
2021-202(300 MHz, DMSO-d6) 3,81 (s, 3H), 3,91 (t, J=4.0 Hz, 2H), 4,33 (t, J=4,2 Hz, 2H), to 6.88 (t, J=7.9 Hz, 1H), 7,12 (DD, J=7,7, 1.5 Hz, 1H), 7,19 (d, J=8,8 Hz, 1H), 7,28-the 7.43 (m, 4H), a 7.85 (d, J=9,2 Hz, 2H), 8,08 (d, J=3.3 Hz, 1H), 10,31 (s, 1H)
2031-203(400 MHz, DMSO-d6) of 3.95 (t, J=4,2 Hz, 2H), 4,39 (t, J=4.4 Hz, 2H), 6,86 (t, J=7.9 Hz, 1H), 7,05 (DD, J=7,9, and 1.4 Hz, 1H), 7,18 (DD, J=7,7, and 1.6 Hz, 1H), 7,27 (DD, J=7,9, 5,1 Hz, 1H), 7,34 (d, J=8,8 Hz, 2H), 7,84 (d, J=8,8 Hz, 2H), 8,29 (DD, J=7,9, 1.9 Hz, 1H), 8,59 (DD, J=4,4, 2.0 Hz, 1H), 10,34 (s, 1H)
2041-204(400 MHz, DMSO-d6) of 3.78 (t, J=4,2 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 6,74 (t, J=7.9 Hz, 1H), for 6.81 (DD, J=8,1, 1,6 Hz, 1H), 7,05 (DD, J=7,4, 1.9 Hz, 1H), 7,24 (DD, J=7,7, a 4.9 Hz, 1H), 7,34 (d, J=8,8 Hz, 2H), 7,43 (s, 1H), to 7.84 (t, J=8,1 Hz, 3H), 7,92 (DD, J=7,4, 1.9 Hz, 1H), 8,45 (DD, J=4,4, 2.0 Hz, 1H), 10.30 a.m. (s, 1H)
2051-205(400 MHz, DMSO-d6) to 2.55 (d, J=4,6 Hz, 3H), of 3.78 (t, J=4,2 Hz, 2H), to 4.41 (t, J=4,2 Hz, 2H), 6,74 (t, J=7.9 Hz, 1H), 6,83 (DD, J=8,1, 1,6 Hz, 1H), to 7.09 (DD, J=7,7, and 1.6 Hz, 1H), 7,20 (DD, J=7,4, 4.6 Hz, 1H), 7,34 (d, J=8,8 Hz, 2H), 7,83-7,87 (m, 3H), 8,27-8,30 (m, 1H), 8,43 (DD, J=4,8, 2.0 Hz, 1H), 10,27 (s, 1H)

[Table 27]
No. approx.Chemical compoundNMR
2061-206(400 MHz, DMSO-d6) of 2.81 (s, 3H), of 2.86 (s, 3H), 3,71 (s, 2H), 4,34 (s, 2H), 6,80 (t, J=7.9 Hz, 1H), 6,91 (DD, J=8,1, 1,6 Hz, 1H), 7,11 (DD, J=7,4, and 1.4 Hz, 1H), 7,21 (DD, J=7,4, 4.6 Hz, 1H), 7,34 (d, J=8,3 Hz, 2H,), 7,76 (DD, J=7,4, 1.9 Hz, 1H), a 7.85 (d, J=9,3 Hz, 2H), to 8.41 (DD, J=5,2, 2.0 Hz, 1H), 10,28 (s, 1H)
2071-207(400 MHz, DMSO-d6) of 3.84 (t, J=4,2 Hz, 2H), 4,25 (t, J=4,2 Hz, 2H), is 4.93 (s, 2H), 6,77 (t, J=7.9 Hz, 1H), 6.87 in (DD, J=8,1, 1,6 Hz, 1H), 7,16 (DD, J=7,4, and 1.4 Hz, 1H), 7,21 (DD, J=8.0 a, 4,8 Hz, 1H), 7,28-7,37 (m, 7H), 7,86 (d, J=8,8 Hz, 2H), 8,12 (DD, J=7,9, 1.9 Hz, 1H), 8,53 (DD, J=5,2, 2.4 Hz, 1H), 10,26 (s, 1H)
2081-208(400 MHz, DMSO-d6) 3,82 (t, J=4,2 Hz, 2H), 4,39 (t, J=4,2 Hz, 2H), 6,77 (t, J=7.9 Hz, 1H), 6.87 in (DD, J=8,3, and 1.4 Hz, 1H), was 7.08 (DD, J=7,7, and 1.6 Hz, 1H), 7,20 (DD, J=7,4, 4.6 Hz, 1H), 7,34 (d, J=8,3 Hz, 2H), 7,86 (d, J=9,3 Hz, 2H), 8,10 (DD, J=7,9, 1.9 Hz, 1H), 8,49 (DD, J=4,4, 2.0 Hz, 1H), 10,29 (s, 1H), 13,28 (d, J=155,4 Hz, 1H)
2091-209 (400 MHz, DMSO-d6) 3,79 (t, J=4,2 Hz, 2H), to 4.38 (t, J=4.4 Hz, 2H), by 5.18 (s, 2H), is 6.61 (DD, J=8,3, and 1.4 Hz, 1H), 6,78 (t, J=7.9 Hz, 1H), 7,03 (DD, J=7,4, and 1.4 Hz, 1H), 7,21 (DD, J=8.0 a, 4,8 Hz, 1H), 7,27-7,35 (m, 7H), to 7.61 (DD, J=7,9, and 1.4 Hz, 1H), a 7.85 (d, J=8,8 Hz, 2H), 8,00 (DD, J=4,9, and 1.6 Hz, 1H), 10,29 (s, 1H), 10,29 (s, 1H)
2101-210(400 MHz, DMSO-d6) of 3.75 (t, J=4.4 Hz, 2H), to 4.41 (t, J=4,2 Hz, 2H), 6,50 (t, J=3,9 Hz, 1H), 6,76 (t, J=7.9 Hz, 1H), 6,97 (d, J=6,5 Hz, 1H), 7,10 (DD, J=8.0 a, 4,8 Hz, 1H), 7,29 (DD, J=7,9, and 1.4 Hz, 1H), 7,34 (d, J=8,8 Hz, 2H), a 7.85 (d, J=8,8 Hz, 2H), of 7.90 (DD, J=4,4, 1.2 Hz 1H), becomes 9.97 (s, 1H), 10,31 (s, 1H)
2111-211(400 MHz, CHLOROFORM-d) 3,70 (users, 2H), 4,15 (users, 2H), 4,33 (users, 2H)and 4.65 (users, 2H), 6.73 x (d, J=7,4 Hz, 1H), 6,94 (t, J=7,4 Hz, 1H), 7,22 (d, J=8,3 Hz, 2H), 7,34 (users, 1H), to 7.64 (d, J=6.0 Hz, 1H), 7,73 (d, J=8,8 Hz, 2H), 7,87 (d, J=7,4 Hz, 1H), 8,12 (users, 1H), of 9.56 (s, 1H)
2121-212(400 MHz, DMSO-d6) 3,81 (t, J=4.4 Hz, 2H), 4,39 (t, J=4,2 Hz, 2H), 4,79 (s, 2H), 6,70-6,77 (m, 2H), 7,00 (DD, J=7,2, 2.1 Hz, 1H), 7,18 (DD, J=8.0 a, 4,8 Hz, 1H), 7,34 (d, J=8,3 Hz, 2H), 7,42 (DD, J=8,3, and 1.4 Hz, 1H), a 7.85 (d, J=9,3 Hz, 2H), to 7.99 (DD, J=4,6, and 1.4 Hz, 1H), 10,32 (s, 1H), 13,12 (s, 1H)
[Tables which 28]
No. approx.Chemical compoundNMR
2131-213(400 MHz, DMSO-d6) 3,82 (t, J=4,2 Hz, 2H), 4,39 (t, J=4,2 Hz, 2H), of 4.54 (s, 2H), of 6.68 (DD, J=8,1, 1,6 Hz, 1H), 6,76 (t, J=7.9 Hz, 1H), 7,02 (DD, J=7,4, and 1.4 Hz, 1H), to 7.09 (s, 1H), 7,18 (DD, J=8.0 a, 4,8 Hz, 1H), 7,32-7,42 (m, 4H), a 7.85 (d, J=9,3 Hz, 2H), to 7.99 (DD, J=4,6, and 1.4 Hz, 1H), 10,29 (s, 1H)
2141-214(400 MHz, DMSO-d6) of 2.58 (d, J=4,6 Hz, 3H), 3,83 (t, J=4,2 Hz, 2H), 4,39 (t, J=4,2 Hz, 2H), 4,56 (s, 2H), 6,69 (DD, J=8,1, 1,6 Hz, 1H), 6,77 (t, J=7.9 Hz, 1H), 7,03 (DD, J=7,4, and 1.4 Hz, 1H), 7,17 (DD, J=8,4, 4,8 Hz, 1H), 7,33 (d, J=8,8 Hz, 2H), 7,40-7,46 (m, 2H), a 7.85 (d, J=9,3 Hz, 2H), 8,00 (DD, J=4,6, and 1.4 Hz, 1H), 10,31 (s, 1H)
2151-215(400 MHz, DMSO-d6) 2,82 (s, 3H), 2.95 and (s, 3H), 3,83 (s, 2H), 4,36 (s, 2H), 4,96 (s, 2H), of 6.71-6,79 (m, 2H), 6,97-7,00 (m, 1H), 7,12-7,16 (m, 1H), 7,32-7,37 (m, 3H), to 7.84 (d, J=8,8 Hz, 2H), 7,93-to 7.95 (m, 1H), 10,30 (s, 1H)
2161-216(400 MHz, DMSO-d6) of 3.84 (t, J=4,1 Hz, 2H), and 4.40 (t, J=4,1 Hz, 2H), 5,31 (s, 2H), 6,65 (DD, J=8,1, 1, Hz, 1H), 6.75 in (t, J=7.7 Hz, 1H), 7,02 (DD, J=7,4, 1.5 Hz, 1H), 7,22 (DD, J=8.0 a, 4,8 Hz, 1H), 7,33 (t, J=8,3 Hz, 2H), 7,42-7,46 (m, 1H), to 7.64 (DD, J=8,0, 1.5 Hz, 1H), 7,84-to $ 7.91 (m, 3H), 8,03 (DD, J=4,6, and 1.4 Hz, 1H), at 8.60 (d, J=5,1 Hz, 1H), 10,31 (s, 1H)
2171-217(400 MHz, DMSO-d6) of 3.78 (t, J=4.3 Hz, 2H), 4,37 (t, J=4.3 Hz, 2H), 5,23 (s, 2H), 6,60 (DD, J=8,3, 1.5 Hz, 1H), 6,77 (t, J=7.9 Hz, 1H), 7,02 (DD, J=7,7, 1.5 Hz, 1H), 7.23 percent (DD, J=8.0 a, 4,8 Hz, 1H), 7,32 and 7.36 (m, 3H), to 7.64-of 7.69 (m, 2H), a 7.85 (d, J=9,3 Hz, 2H), 8,02 (DD, J=4,8, 1.2 Hz, 1H), and 8.50 (DD, J=4,8, 2.0 Hz, 1H), 8,54 (d, J=2.0 Hz, 1H), 10,28 (s, 1H)
2181-218(400 MHz, DMSO-d6)1H-NMR (DMSO-d6) δ: 4,16 (t, J=4.5 Hz, 2H), 4,37 (t, J=4.5 Hz, 2H), 6,99 (t, J=8.0 Hz, 1H), 7,28-7,35 (m, 4H), to 7.61 (DD, J=8.0 a, and 1.6 Hz, 1H), 7,82 (d, J=9,3 Hz, 2H), 8,02 (DD, J=8,8, 2.3 Hz, 1H), 8,69 (d, J=2.3 Hz, 1H), 10,33 (s, 1H)
2191-219(300 MHz, DMSO-d6) δ: 1,85 (s, 3H), was 4.02 (t, J=4.4 Hz, 2H), 4,19 (d, J=5,9 Hz, 2H), 4,32 (t, J=4.6 Hz, 2H), 6,93 (t, J=7.9 Hz, 1H), 7,17-7,21 (m, 2H), 7,34 (d, J=8,4 Hz, 2H), 7,46 (DD, J=8,3, 1.7 Hz, 1H), 7,58 (DD, J=8,6, and 2.4 Hz, 1H), to 7.84 (d, J=9,2 Hz, 2H), to 8.20 (d, J=2.2 Hz, 1H), 8,30 (t, J=6,1 Hz, 1H), 10,32 (s, 1H)
[Table 29]
No. approx. Chemical compoundNMR
2201-220(300 MHz, DMSO-d6) δ: 3,34 (s, 3H), 3,80 (t, J=4,2 Hz, 2H), 4,42 (t, J=4,2 Hz, 2H), 4,47 (s, 2H), 6,51 (DD, J=8,1, 1.5 Hz, 1H), 6,80 (t, J=7.7 Hz, 1H), 7,06 (DD, J=7,7, 1.5 Hz, 1H), 7,35 (d, J=8,4 Hz, 2H), 7,86 (d, J=8,8 Hz, 2H), 7,98 (d, J=1.8 Hz, 1H), scored 8.38 (d, J=1.8 Hz, 1H), 10,33 (s, 1H)
2211-221(300 MHz, DMSO-d6) δ: 2,05 (s, 2H, keto), 2,10 (s, 1H, enol), 2,78 (s, 1H, enol), to 2.94 (s, 2H, keto), a 4.03-Android 4.04 (m, 2H), 4,32 is 4.35 (m, 2H), 4,43 (s, 1,3H, keto), 4,50 (s, 0,6H, enol), 6,91-6,94 (m, 1H), 7.18 in-7,25 (m, 2H), 7,34 (d, J=8,8 Hz, 2H), 7,50-of 7.55 (m, 2H), a 7.85 (d, J=9,2 Hz, 2H), 8,18 is 8.22 (m, 1H), 10,32 (s, 1H)
2221-222(400 MHz, DMSO-d6) δ: 3,66 (s, 2H), 4,01 (t, J=4,2 Hz, 2H), 4,32 (t, J=4.4 Hz, 2H), 6,92 (t, J=7.9 Hz, 1H), 7,17 (d, J=8,8 Hz, 2H), 7,34 (d, J=8,3 Hz, 2H), 7,44 (DD, J=8,3, and 1.4 Hz, 1H), 7,66 (DD, J=8,3, 2,3 Hz, 1H), to 7.84 (d, J=9,3 Hz, 2H), 8,23 (d, J=1.9 Hz, 1H), 10,33 (s, 1H)
2231-223(300 MHz, DMSO-d6) δ: 2.13 in (s, 6H), to 3.33 (s, 2H), a 4.03 (t, J=4.4 Hz, 2H), 4,34 (t, J=4.4 Hz, 2H), 6,91 (kV, J=8.7 Hz, 1H), 7,19 (d, J=3,9 Hz, 2H), 7,35 (d, J=8,4 Hz, 2H), 7,49 (DD, J=8,1, 1.5 G is, 1H), 7,60 (DD, J=8,4, 2.2 Hz, 1H), a 7.85 (d, J=9,2 Hz, 2H), 8,18 (d, J=1.8 Hz, 1H), 10,32 (s, 1H)
2241-224(400 MHz, DMSO-d6) to 2.65 (d, J=4,6 Hz, 3H), 3,91-4,00 (m, 2H), 5,12 (t, J=4.6 Hz, 1H), is 6.54 (DD, J=8,1, 1.5 Hz, 1H), 6.89 in (t, J=7.9 Hz, 1H), 7,24 (DD, J=7,7, 1.5 Hz, 1H), 7,30 (DD, J=7,7, 4.6 Hz, 1H), 7,38 (d, J=8.5 Hz, 2H), 7,88 (d, J=8.5 Hz, 2H), 8,01 (DD, J=7,9, 1.5 Hz, 1H), 8,15 (kV, J=4,6 Hz, 1H), 8,43 (DD, J=4,6, 2.0 Hz, 1H), 10,66 (s, 1H)
2251-225(400 MHz, DMSO-d6) of 4.05 (t, J=4.4 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 4,48 (d, J=5.6 Hz, 2H), 5,33 (t, J=5.6 Hz, 1H), 6,94 (t, J=7.9 Hz, 1H), 7,02 (d, J=7.9 Hz, 1H), 7,07 (d, J=7.9 Hz, 1H), 7,21 (DD, J=7,7, the 1.6 Hz, 1H), 7,51 (DD, J=7,7, and 1.6 Hz, 1H), to 7.67 (d, J=7.7 Hz, 1H), 7,71 (d, J=8,3 Hz, 2H), 7,95 (d, J=8,3 Hz, 2H), 10,51 (s, 1H)
2261-226(400 MHz, DMSO-d6) is 2.88 (s, 3H), 3,05 (s, 3H), to 3.58 (DD, J=13,0, 8,8 Hz, 1H), 4,20 (DD, J=13,0, 4.0 Hz, 1H), 5,54 (DD, J=8,8, 4.0 Hz, 1H), 6,56 (DD, J=8.0 a, and 1.4 Hz, 1H), 6.89 in (t, J=7.9 Hz, 1H), 7,24 (DD, J=7,9, 1,4 Hz, 1H), 7,31 (DD, J=8.0 a, 4,8 Hz, 1H), 7,37 (d, J=8,3 Hz, 2H), 7,88 (d, J=8,3 Hz, 2H), 8,03 (DD, J=8.0 a, and 1.4 Hz, 1H), 8,44 (DD, J=4,8, and 1.4 Hz, 1H), 10,80 (s, 1H)
2271-227(400 MHz, DMSO-d6) of 3.8 (t, J=4,2 Hz, 2H), 4,42 (t, J=4,2 Hz, 2H), of 6.68 (DD, J=7,9, and 1.6 Hz, 1H), 6,84 (t, J=7.9 Hz, 1H), 7,13 (DD, J=7,9, and 1.6 Hz, 1H), was 7.36 (d, J=8,3 Hz, 2H), 7,66 (s, 1H), 7,87 (d, J=8,3 Hz, 2H), 8,17 (s, 1H), scored 8.38 (d, J=2.3 Hz, 1H), 8,82 (d, J=2.3 Hz, 1H), 10,38 (s, 1H)

[Table 30]
No. approx.Chemical compoundNMR
2281-228(400 MHz, DMSO-d6) of 1.80 (s, 3H), 3,23-3,29 (m, 1H), 3,45-3,51 (m, 1H), 4,06-4.09 to (m, 1H), 4,17 (d, J=10.5 Hz, 1H), 4,47 (d, J=10.5 Hz, 1H), 6.48 in (DD, J=8,0, 1.2 Hz, 1H), 6,84 (t, J=7.7 Hz, 1H), 7,07 (DD, J=7,7, 1.2 Hz, 1H), was 7.36 (DD, J=8.0 a, 4,8 Hz, 1H), 7,72 (d, J=8,3 Hz, 2H), 8,00 (d, J=8,3 Hz, 2H), 8,08 (DD, J=8,0, 1.2 Hz, 1H), 8,16 (t, J=5.6 Hz, 1H), 8,46 (DD, J=4,8, 1.2 Hz, 1H), 10,46 (s, 1H)
2291-229(400 MHz, DMSO-d6) to 4.41 (DD, J=10,7, 2.8 Hz, 1H), 4,68-of 4.75 (m, 2H), return of 6.58 (d, J=7.9 Hz, 1H), 6,84 (t, J=7.9 Hz, 1H), 7,05 (DD, J=7,9, 1.5 Hz, 1H), 7,26 (DD, J=8.0 a, and 4.5 Hz, 1H), 7,69 (d, J=8.0 Hz, 2H), 7.95 is-8,00 (m, 3H), scored 8.38 (DD, J=4,5, 1.5 Hz, 1H), 10,53 (s, 1H), 13,04 (s, 1H)
2301-230(400 MHz, DMSO-d6) 3,63 (s, 3H), 4,01 (d, J=3,7 Hz, 2H), 5,45 (who, J=3,7 Hz, 1H), 6,50 (DD, J=7,9, and 1.4 Hz, 1H), 6.87 in (t, J=7.9 Hz, 1H), 7.23 percent (DD, J=7,9, and 1.4 Hz, 1H), 7,33 (DD, J=8.0 a, 4,8 Hz, 1H), 7,38 (d, J=8.5 Hz, 2H), 7,88 (d, J=8.5 Hz, 2H), 8,04 (DD, J=7,9, and 1.4 Hz, 1H), 8,44 (DD, J=4,6, and 1.4 Hz, 1H), 10,33 (s, 1H)
2311-231(400 MHz, DMSO-d6) to 3.67 (DD, J=13,0, 7,4 Hz, 1H), 3,74 (t, J=5.5 Hz, 2H), 3,92 (DD, J=13,0, 2.8 Hz, 1H), 4,48-of 4.54 (m, 1H), 5,22 (t, J=5.5 Hz, 1H), 6,56 (DD, J=7,9, 1.5 Hz, 1H), 6,85 (t, J=7.9 Hz, 1H), 7,27 (DD, J=to 7.9, 1.5 Hz, 1H), 7,32 (DD, J=7,9, and 4.5 Hz, 1H), 7,38 (d, J=8,8 Hz, 2H), 7,89 (d, J=8,8 Hz, 2H), with 8.05 (DD, J=7,9, 1.9 Hz, 1H), 8,44 (DD, J=4,5, and 1.4 Hz, 1H), the 10.40 (s, 1H)
2321-232(400 MHz, DMSO-d6) 3,93-4,08 (m, 2H), 5,31 (t, J=4,2 Hz, 1H), 6,53 (DD, J=7,9, and 1.4 Hz, 1H), 6.87 in (t, J=7.9 Hz, 1H), 7,27-7,34 (m, 2H), 7,38 (d, J=8,3 Hz, 2H), 7,88 (d, J=9,3 Hz, 2H), 8,03 (DD, J=8,3, and 1.4 Hz, 1H), 8,44 (DD, J=4,8, 2.0 Hz, 1H), 10,45 (s, 1H), 13,59 (s, 1H)
2331-233(400 MHz, DMSO-d6) 4,27 (DD, J=10,7, 2.5 Hz, 1H), 4,58-4,60 (m, 1H), 4,74 (DD, J=10,7, 2.5 Hz, 1H), return of 6.58 (DD, J=7,9, and 1.4 Hz, 1H), 6,85 (t, J=7.9 Hz, 1H), 7,07 (DD, J=7,4, and 1.4 Hz, 1H), 7,33-7,37 (m, 2H), 7,52 (s, 1H), of 7.70 (d, J=8,8 Hz, 2H), of 7.96 (d, J=8,3 Hz, 2H), of 8.06 (DD, J=7,9, and 1.4 Hz, 1H), 8,42 (DD, J=4,6, and 1.4 Hz, 1H), 10,53 (s, 1H)
2341-234 (400 MHz, DMSO-d6) 2,60 (d, J=4,6 Hz, 3H), 4.26 deaths (d, J=8.5 Hz, 1H), 4,60 (s, 1H), 4,74 (d, J=8.5 Hz, 1H), 6,60 (d, J=7.9 Hz, 1H), 6,86 (t, J=7.9 Hz, 1H), was 7.08 (d, J=6,5 Hz, 1H), 7,33 (kV, J=4,2 Hz, 1H), 7,70 (d, J=8,8 Hz, 2H), 7,95-of 8.06 (m, 4H), 8,42 (DD, J=4,6, and 1.4 Hz, 1H), 10,52 (s, 1H)

[Table 31]
No. approx.Chemical compoundNMR
2351-2 35mm(400 MHz, DMSO-d6) a 3.83 (DD, J=13, and 6.5 Hz, 1H), 4,10 (DD, J=13, 4.0 Hz, 1H), 5,07 (DD, J=6,5, 4.0 Hz, 1H), 6,56 (DD, J=8,0, 1.5 Hz, 1H), 6.89 in (t, J=8.0 Hz, 1H), 7,26 (DD, J=7,7, 1.5 Hz, 1H), 7,31 (DD, J=7,7, 4.0 Hz, 1H), 7,37 (d, J=8,3 Hz, 2H), 7,71 (d, J=6,5 Hz, 2H), of 7.90 (d, J=8,3 Hz, 2H), 8,03 (DD, J=8,0, 1.5 Hz, 1H), 8,44 (DD, J=4,0, 1.5 Hz, 1H), 10,77 (s, 1H)
2361-236(400 MHz, DMSO-d6), and 2.27 (s, 3H), 3,34 (s, 3H), 4,10 (user. s, 4H), 6,78 (t, J=7,0 Hz, 1H), of 6.96 (d, J=6,5 Hz, 1H), 7.18 in-7,29 (m, 6H), 7,79 (d, J=7.9 Hz, 1H), 8,16 (s, 1H)
2372-01(400 MHz, DMSO-d6) of 3.75 (t, J=4.4 Hz, 2H), and 4.40 (t, J=4.4 Hz, 2H), 4,53 (d, J=5.6 Hz, 2H), 5,39 (t, J=5.6 Hz, 1H), 5,97 (2H), 6.42 per (DD, J=8,1, 1,6 Hz, 1H), 6.75 in (DD, J=8,1, 7,6 Hz, 1H), 6,85 (d, J=8,4 Hz, 1H), 7,02 (DD, J=7,6, and 1.6 Hz, 1H), 7,13 (DD, J=8,4, and 2.1 Hz, 1H), 7,42 (d, J=2.1 Hz, 1H), 7,92 (d, J= 2.0 Hz, 1H), 8.34 per (d, J=2.0 Hz, 1H), 10,01 (s, 1H)
2382-02(400 MHz, DMSO-d6) of 3.77 (t, J=4.4 Hz, 2H), 4,21-4,24 (m, 4H), 4,42 (t, J=4.4 Hz, 2H), 4,56 (d, J=5.6 Hz, 2H), 5,43 (t, J=5.6 Hz, 1H), 6,45 (DD, J=8,1, 1,6 Hz, 1H), 6,78 (DD, J=8,1, 7.9 Hz, 1H), 6,80 (d, J=8,8 Hz, 1H),? 7.04 baby mortality (DD, J=7,9, and 1.6 Hz, 1H), 7,15 (DD, J=8,8, 2.6 Hz, 1H), 7,38 (d, J=2.6 Hz, 1H), 7,95 (d, J= 2.1 Hz, 1H), of 8.37 (d, J=2.1 Hz, 1H), 9,96 (s, 1H)
2392-03(400 MHz, DMSO-d6) of 3.78 (t, J=4,2 Hz, 2H), 4,42 (t, J=4.4 Hz, 2H), 4,56 (d, J=4,6 Hz, 2H), 5,44 (t, J=5,1 Hz, 1H), 6,47 (DD, J=8,3, and 1.4 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,4, and 1.4 Hz, 1H), 7,35 (d, J=8,8 Hz, 2H), 7,86 (d, J=8,8 Hz, 2H), 7,95 (d, J=2.3 Hz, 1H), of 8.37 (d, J=1.9 Hz, 1H), 10,35 (s, 1H)
2402-04(400 MHz, DMSO-d6) of 3.78 (t, J=4,2 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4,56 (d, J=5.6 Hz, 2H), 5,44 (t, J=5.6 Hz, 1H), of 6.49 (DD, J=7,9, and 1.4 Hz, 1H), for 6.81 (t, J=7.7 Hz, 1H), 7,05 (DD, J=7,7, 1.2 Hz, 1H), 7,56 (DD, J=9,0, 1.2 Hz, 1H), 7,78 (DD, J=8,8, 2.3 Hz, 1H), 7,95 (d, J=1.9 Hz, 1H), 8,14 (d, J=2.3 Hz, 1H), of 8.37 (d, J=1.4 Hz, 1H), 10,49 (s, 1H)
2412-05 (400 MHz, DMSO-d6) 3,79 (t, J=4.4 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4,56 (d, J=4,2 Hz, 2H), 5,44 (user. s, 1H), of 6.49 (DD, J=7,9, and 1.4 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,05 (DD, J=7,7, and 1.6 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), 7,97 (t, J=4,6 Hz, 3H), of 8.37 (d, J=2.3 Hz, 1H), 10,52 (s, 1H)
2422-06(300 MHz, DMSO-d6) 3,79 (t, J=4,2 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4,56 (d, J=5,1 Hz, 2H), 5,42 (t, J=5.3 Hz, 1H), 6,50 (DD, J=8,1, 1.5 Hz, 1H), PC 6.82 (t, J=7.7 Hz, 1H), 7,05 (DD, J=7,3, 1.5 Hz, 1H), 7,66-7,78 (m, 2H), of 7.96-of 7.97 (m, 2H), of 8.37 (d, J=1.8 Hz, 1H), 10,69 (s, 1H)

[Table 32]
No. approx.Chemical compoundNMR
2432-07(300 MHz, DMSO-d6) 4,08 (t, J=4.4 Hz, 2H), 4,39 (t, J=4,2 Hz, 2H), 4,50 (t, J=13,2 Hz, 2H), 6,98 (t, J=7.9 Hz, 1H), 7,28 (DD, J=7,7, 1.5 Hz, 1H), was 7.36 (d, J=8,8 Hz, 1H), 7,50 (dt, J=8,1, 1.5 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), a 7.85 (DD, J=8,8, 2.2 Hz, 1H), of 7.96 (d, J=8,4 Hz, 2H), of 8.25 (d, J=1.8 Hz, 1H), 10,53 (s, 1H)
2442-08(300 MHz, DMSO-d6) of 0.98 (d, J=6.6 Hz, 6H), 1.91 a-2,08 (m, 1H), and 3.72 (d, J=6,6 Hz, 2H), a 4.03 (t, J=2,9 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), of 4.45 (s, 2H), 6.87 in-to 6.95 (m, 3H), 7.18 in-of 7.23 (m, 2H), 7,44 (DD, J=8,1, 1.5 Hz, 1H), 7,63 (m, 3H), 8,24 (d, J=1.8 Hz, 1H), becomes 9.97 (s, 1H)
2452-09(300 MHz, DMSO-d6) δ: 3,34 (s, 3H), 3,80 (t, J=4,2 Hz, 2H), 4,43 (t, J=4.0 Hz, 2H), 4,48 (s, 2H), 6,50-is 6.54 (m, 1H), for 6.81 (t, J=7.7 Hz, 1H), 7,07 (DD, J=7,5, 1.3 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), of 7.97 (d, J=8,4 Hz, 3H), scored 8.38 (d, J=1.5 Hz, 1H), 10,51 (s, 1H)
2462-10(400 MHz, DMSO-d6) 4,06 (t, J=4.4 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 4,49 (d, J=5,1 Hz, 2H), lower than the 5.37 (t, J=5.6 Hz, 1H), 6,86 (d, J=5,1 Hz, 1H), of 6.96 (t, J=7.9 Hz, 1H), 7,21-of 7.23 (m, 2H), 7,50 (DD, J=8,1, 1,6 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), of 7.96 (d, J=8,8 Hz, 2H), 8,23 (d, J=5,1 Hz, 1H)
2472-11(400 MHz, DMSO-d6) 3,71 (t, J=4.4 Hz, 2H), of 4.44-to 4.46 (m, 2H), 5,33 (t, J=5.3 Hz, 1H), of 6.26 (DD, J=8.0 a, and 1.6 Hz, 1H), 6,74 (t, J=8.0 Hz, 1H), 6,98 (DD, J=8.0 a, and 1.6 Hz, 1H), 7,32 and 7.36 (m, 3H), a 7.85 (d, J=9.0 Hz, 2H), of 8.00 (DD, J=8,0, 2.0 Hz, 1H), scored 8.38 (DD, J=4,8 and 2.2 Hz, 1H), 10,3 (s, 1H)
2482-12(300 MHz, DMSO-d6) δ: 1,40 (d, J=6.6 Hz, 3H), of 3.77-of 3.78 (m, 2H), to 4.41-of 4.44 (m, 2H), 4,82-4,84 (m, 1H), 5,43-5,46 (m, 1H), 6,47 (DD, J=8,1, 1.5 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,05 (the d, J=7,3, 1.5 Hz, 1H), 7,71 (d, J=8,4 Hz, 2H), of 7.96 (t, J=3.1 Hz, 3H), 8,40 (d, J=2.2 Hz, 1H), 10,51 (s, 1H)
2492-13(300 MHz, DMSO-d6) δ: 1,40 (d, J=6.6 Hz, 3H), 3,76-of 3.80 (m, 2H), to 4.41-of 4.44 (m, 2H), 4.80 to 4,84 (m, 1H), 5,43-vs. 5.47 (m, 1H), 6,47 (d, J=8,4 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,05 (t, J=3,9 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), of 7.96 (t, J=2,9 Hz, 4H), 8,40 (d, J=1.8 Hz, 1H), 10,51 (s, 1H)
[Table 33]
No. approx.Chemical compoundNMR
2502-14(400 MHz, DMSO-d6) of 1.39 (d, J=6.5 Hz, 3H), of 3.77 (t, J=4.4 Hz, 2H), to 4.41 (t, J=4.4 Hz, 2H), 4,79-is 4.85 (m, 1H), 5,44 (d, J=4.4 Hz, 1H), 6,46 (DD, J=8.0 a, and 1.4 Hz, 1H), 6,79 (t, J=8.0 Hz, 1H), 7,03 (DD, J=8.0 a, 1,4 Hz, 1H), 7,34 (d, J=8,8 Hz, 2H), a 7.85 (d, J=8,8 Hz, 2H), of 7.96 (d, J=1.9 Hz, 1H), 8,39 (d, J=1.9 Hz, 1H), 10,3 (s, 1H)
2512-15(400 MHz, DMSO-d6) of 1.39 (d, J=6.5 Hz, 3H), of 3.77 (t, J=4.4 Hz, 2H), to 4.41 (t, J=4.4 Hz, 2H), 4,79-a 4.86 (m, 1H), 5,44 (d, J=4.4 Hz, 1H), 6,46 (DD, J=8,0, 1.5 Hz, 1H), 6,79 (t, J=8.0 Hz, 1H), 7,03 (DD, J=8.0 a, 1,5 Hz, 1H), 7,34 (d, J=9.0 Hz, 2H), a 7.85 (d, J=9.0 Hz, 2H), of 7.96 (d, J=1.9 Hz, 1H), 8,39 (d, J=1.9 Hz, 1H), 10,3 (s, 1H)
2522-16(300 MHz, DMSO-d6) δ: of 3.80 (t, J=4.4 Hz, 2H), 4,45 (t, J=4.4 Hz, 2H), 4,57 (d, J=4,8 Hz, 2H), 5,43 (t, J=5.3 Hz, 1H), 6,51 (DD, J=8,1, 1.5 Hz, 1H), 6,83 (t, J=7.9 Hz, 1H), to 7.09 (DD, J=7,3, 1.5 Hz, 1H), 7,93 (DD, J=14,3, 7.2 Hz, 2H), scored 8.38 (d, J=1.8 Hz, 1H), of 8.47 (d, J=8,8 Hz, 1H), 9,04 (d, J=2.2 Hz, 1H), of 10.73 (s, 1H)
2532-17(400 MHz, DMSO-d6) of 3.78 (t, J=4.3 Hz, 2H), 4,43 (t, J=4.3 Hz, 2H), 4,57 (d, J=5,1 Hz, 2H),5,43 (t, J=5,1 Hz, 1H), 6.48 in (DD, J=8,2, 1.5 Hz, 1H), 6,80 (DD, J=8,2, 7,6 Hz, 1H), 7,05 (DD, J=7,6, 1.5 Hz, 1H), 7,63 (DD, to 8.6, 2.4 Hz, 1H), 7,73 (d, J=8.6 Hz, 1H), 7,95 (d, J=2.0 Hz, 1H), 8,14 (d, J=2.4 Hz, 1H), of 8.37 (d, J=2.0 Hz, 1H), 10,43 (s, 1H)
2542-18(300 MHz, DMSO-d6) δ: of 1.37 (s, 6H), was 4.02 (t, J=4,2 Hz, 2H), 4,33 (t, J=4,2 Hz, 2H), 5,07 (s, 1H), 6,93 (t, J=7.9 Hz, 1H), 7,15-7,20 (m, 2H), of 7.48 (DD, J=8,3, 1.7 Hz, 1H), 7,71-7,76 (m, 3H), 7,95 (d, J=8,4 Hz, 2H), 8,40 (d, J=1.8 Hz, 1H), 10,48 (s, 1H)
2552-19(400 MHz, DMSO-d6) δ: 1,27 (d, J=6.0 Hz, 6H), of 3.77 (t, J=3,9 Hz, 2H), 4,42 (t, J=4,2 Hz, 2H), 4,55 (d, J=4,6 Hz, 2H), 4,71-of 4.77 (m, 1H), 5,41-5,44 (m, 1H), 6,46 (DD, J=7,9, and 1.4 Hz, 1H), 6,79 (t, J=7.9 Hz, 1H), 7,05 (DD, J=7,4, and 1.4 Hz, 1H), 7,29 (d, J=9,3 Hz, 1H), 7,89 (d, J=9,3 Hz, 1H), 7,94 (s, 1H), 8,08 (s, 1H), with at 8.36, 1H), 10,22 (s, 1H)
2562-20(400 MHz, DMSO-d6) 3,79 (t, J=4.4 Hz, 2H), of 4.44 (t, J=4.4 Hz, 2H), 4,56 (d, J=5,1 Hz, 2H), 5,44 (t, J=5,1 Hz, 1H), 6,51 (DD, J=7,9, and 1.6 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), to 7.09 (DD, J=7,9, and 1.6 Hz, 1H), 7,95 (d, J=2.3 Hz, 1H), of 8.37 (d, J=1.9 Hz, 1H), 8,54 (d, J=2.3 Hz, 1H), 8,73 (d, J=2.3 Hz, 1H), 10,65 (s, 1H)

[Table 34]
No. approx.Chemical compoundNMR
2572-21(400 MHz, DMSO-d6) 3,79 (t, J=4,2 Hz, 2H), of 4.44 (t, J=4,2 Hz, 2H), 4,56 (d, J=5,1 Hz, 2H), 5,43 (t, J=5,1 Hz, 1H), 6,50 (DD, J=7,9, and 1.4 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), 7,06 (DD, J=7,9, and 1.4 Hz, 1H), 7,95 (d, J=1.9 Hz, 1H), 8,07 (s, 2H), of 8.37 (d, J=1.9 Hz, 1H), 10,53 (s, 1H)
2582-22(400 MHz, DMSO-d6) 3,81 (t, J=3,7 Hz, 2H), 4,49 (t, J=3,7 Hz, 2H), 4,57 (d, J=5.6 Hz, 2H), 5,44 (t, J=5.6 Hz, 1H), 6,56 (d, J=7.9 Hz, 1H), 6,85 (t, J=7.9 Hz, 1H), 7,19 (d, J=7.9 Hz, 1H), 7,31 (t, J=9,3 Hz, 1H), to 7.77-7,79 (m, 1H), 7,93-of 7.96 (m, 2H), scored 8.38 (s, 1H), 12,18 (s, 1H)
2592-23 (400 MHz, DMSO-d6) 3,79 (t, J=3,9 Hz, 2H), 4,43 (t, J=3,9 Hz, 2H), 4,57 (d, J=5.6 Hz, 2H), 5,44 (t, J=5.6 Hz, 1H), of 6.49 (DD, J=7,9, and 1.4 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,06 (DD, J=7,4, and 1.4 Hz, 1H), a 7.85 (d, J=8,3 Hz, 1H), 7,95 (d, J=7,4 Hz, 2H), at 8.36 (d, J=7.9 Hz, 2H), 10,57 (s, 1H)
2602-24(400 MHz, DMSO-d6) of 3.80 (t, J=4,2 Hz, 2H), 4,46 (t, J=4,2 Hz, 2H), 4,58 (s, 2H), 5,45 (user. s, 1H), of 6.49 (DD, J=7,9, and 1.4 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), 7,10 (DD, J=7,4, and 1.4 Hz, 1H), to 7.59 (user. s, 1H), 7,71 (d, J=8,3 Hz, 1H), of 7.96 (d, J=1.9 Hz, 1H), scored 8.38 (d, J=1.9 Hz, 1H), 8,40 (user. s, 1H), 10,35 (s, 1H), 13,82 (user. s, 1H)
2612-25(400 MHz, DMSO-d6) of 3.78 (t, J=4.4 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 4,56 (s, 2H), 5,43 (s, 1H), of 6.49 (DD, J=8,1, 1,6 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,9, and 1.4 Hz, 1H), 7,69 (DD, J=10,7, 6.5 Hz, 2H), of 7.95 (d, J=1.4 Hz, 1H), of 8.37 (d, J=1.4 Hz, 1H), 10,49 (s, 1H)
2622-26(400 MHz, DMSO-d6) 3,79 (t, J=4,2 Hz, 2H), of 4.44 (t, J=4,2 Hz, 2H), 4,57 (d, J=4,2 Hz, 2H), 5,44 (t, J=4.9 Hz, 1H), 6,50 (DD, J=8,1, 1.2 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), 7,07 (d, J=6,5 Hz, 1H), to 7.59 (DD, J=11,1, 9,3 Hz, 1H), of 7.96 (d, J=1.9 Hz, 1H), 8,05-of 8.06 (m, 1H), of 8.37 (d, J=1.9 Hz, 1H), 8,70-8,71 (m, 1H), 10,61 (s, 1H)
2632-27 (400 MHz, DMSO-d6) of 3.78 (t, J=4.4 Hz, 2H), 4,42 (t, J=4.4 Hz, 2H), 4,56 (d, J=5.6 Hz, 2H), 5,14 (s, 2H), 5,43 (t, J=5.8 Hz, 1H), 6,45 (DD, J=7,9, and 1.4 Hz, 1H), 6,76-PC 6.82 (m, 2H), 6.87 in-6,94 (m, 1H), 7,03 (DD, J=to 7.4 and 1.4 Hz, 1H), 7,31 (DD, J=8,3, 2.8 Hz, 1H), 7,95 (d, J=1.9 Hz, 1H), at 8.36 (d, J=1.9 Hz, 1H), to 9.91 (s, 1H)
2642-28(300 MHz, DMSO-d6) of 1.28 (s, 9H), Android 4.04 (t, J=4.4 Hz, 2H), 4,33 (t, J=4.4 Hz, 2H), 4,45 (d, J=5.5 Hz, 2H), 5,16 (t, J=5.7 Hz, 1H), 6,93 (t, J=7.9 Hz, 1H), 7.18 in-7,22 (m, 2H), 7,34 (d, J=8,4 Hz, 2H), 7,45 (DD, J=8,1, 1.5 Hz, 1H), to 7.64 (t, J=4.4 Hz, 3H), 8,24 (d, J=1.8 Hz, 1H), of 10.05 (s, 1H)

[Table 35]
No. approx.Chemical compoundNMR
2652-29(400 MHz, DMSO-d6) of 3.78 (t, J=4.4 Hz, 2H), of 4.44 (t, J=4.4 Hz, 2H), 4,56 (d, J=5.6 Hz, 2H), 5,43 (t, J=5.6 Hz, 1H), 6,50 (DD, J=8,2, and 1.4 Hz, 1H), PC 6.82 (DD, J=8,2, 7,6 Hz, 1H), to 7.09 (DD, J=7,6, and 1.4 Hz, 1H), 7,79 (s, 1H), 7,95 (d, J=2.1 Hz, 1H), of 8.37 (d, J=2.1 Hz, 1H), 8,46 (s, 2H), 10,78 (s, 1H)
2662-30 (400 MHz, DMSO-d6) of 3.75 (t, J=4.6 Hz, 2H), and 4.40 (t, J=4.6 Hz, 2H), 4,53 (d, J=5,1 Hz, 2H), 4,80 (kV, J=8,8 Hz, 2H), of 5.40 (t, J=5,1 Hz, 1H), 6,44 (DD, J=8,1, 1.4 Hz, 1H), 6,76 (DD, J=8,1, 7.7 Hz, 1H), 7,03 (DD, J=7,7, and 1.4 Hz, 1H), 7,25 (d, J=9.0 Hz, 1H), 7,63 (DD, J=9,0, 2.6 Hz, 1H), to $ 7.91-7,94 (m, 2H), 8.34 per (d, J=2.1 Hz, 1H), 10,19 (s, 1H)
2672-31(400 MHz, CHLOROFORM-d) 3,93 (t, J=4.4 Hz, 2H), 4,80 (kV, J=8,8 Hz, 2H), to 4.62 (t, J=4.4 Hz, 2H), and 4.75 (s, 2H), 6,65 (DD, J=8,1, 1,6 Hz, 1H), 6.89 in (DD, J=8,1, 7.9 Hz, 1H), of 6.96 (d, J=8,8 Hz, 2H), to 7.64 (d, J=8,8 Hz, 2H), 7,80 (DD, J=7,9, and 1.6 Hz, 1H), a 7.85 (d, J=1.9 Hz, 1H), 9,34 (d, J=1.9 Hz, 1H), 9,59 (s, 1H)
2682-32(400 MHz, DMSO-d6) of 3.75 (t, J=4.4 Hz, 2H), 4,39 (t, J=4.4 Hz, 2H), to 4.52 (d, J=4,6 Hz, 2H), of 5.40 (t, J=4.6 Hz, 1H), 6,45 (DD, J=8,1, 1.7 Hz, 1H), 6,77 (DD, J=8,1, 7.7 Hz, 1H), 7,01 (DD, J=7,7, 1.7 Hz, 1H), 7,66 (d, J=8.5 Hz, 1H), 7,88 (d, J=8.5 Hz, 2H), 7,92 (d, J=2.1 Hz, 1H), 8.34 per (d, J=2.1 Hz, 1H), 10,45 (s, 1H)
2692-33(300 MHz, DMSO-d6) δ: of 0.85 (s, 9H), 0,99-1,08 (m, 1H), 1,19-of 1.36 (m, 1H), 1,75-of 1.78 (m, 2H), 1.93 and-of 1.97 (m, 2H), 3,60-3,68 (m, 1H), to 3.73 of 3.75 (m, 2H), and 4.40 (t, J=4.4 Hz, 2H), 4,55 (d, J=5.5 Hz, 2H), 5,41 (t, J=5.7 Hz, 1H), 6,40 (DD, J=8,1, 1.5 Hz, 1H), 6.73 x (t, J=7.7 Hz, 1H), was 7.08 (DD, J=7,7, 1.5 Hz, 1H), 7,88 (d, J=8,1 Hz, 1H), 7,92 (d, J=1.5 Hz, 1H), 8.34 per (d, J=1.5 Hz, 1H)
270 2-34(300 MHz, DMSO-d6) δ: 1,27 (d, J=5,9 Hz, 6H), of 3.78 (t, J=4,2 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4,50-of 4.57 (m, 3H), 5,43 (t, J=5.7 Hz, 1H), 6,46 (DD, J=8,1, 1.5 Hz, 1H), 6,62-6,87 (m, 1H),? 7.04 baby mortality (DD, J=7,5, 1.3 Hz, 1H), 7,14 (t, J=9,2 Hz, 1H), 7,41 (d, J=9.5 Hz, 1H), 7,73 (DD, J=13,6, 2.2 Hz, 1H), 7,95 (d, J=1.8 Hz, 1H), of 8.37 (d, J=1.8 Hz, 1H), 10,16 (s, 1H)
2712-35(300 MHz, DMSO-d6) δ: 1,53-of 1.64 (m, 6H), of 2.92 (t, J=5.1 Hz, 4H), of 3.78 (t, J=4,2 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 4,56 (d, J=5,9 Hz, 2H), 5,42 (t, J=5.7 Hz, 1H), 6,46 (DD, J=8,1, 1.5 Hz, 1H), 6,79 (t, J=7,9 Hz, 1H), 6,99? 7.04 baby mortality (m, 2H), 7,40 (DD, J=8,6, 1.7 Hz, 1H), 7,65 (DD, J=14,9, 2.4 Hz, 1H), 7,95 (d, J=1.8 Hz, 1H), at 8.36 (d, J=1.8 Hz, 1H), 10,12 (s, 1H)

[Table 36]
No. approx.Chemical compoundNMR
2722-36(300 MHz, DMSO-d6) of 1.28 (s, 9H), of 3.78 (t, J=4.4 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 4,56 (d, J=5,1 Hz, 2H), 5,42 (t, J=5.7 Hz, 1H), 6,46 (DD, J=8,1, 1.5 Hz, 1H), 6,79 (t, J=7.9 Hz, 1H), 7,06 (DD, J=7,7, 1.5 Hz, 1H), 7,35 (d, J=8,8 Hz, 2H), 7,65 (d, J=8,4 Hz, 2H), 7,95 (d, J=1.8 Hz, 1H), of 8.37 (d, J=1.8 Hz, 1H), of 10.05 (s, 1H)
273 2-37(400 MHz, DMSO-d6) 3,79 (t, J=4,2 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4,56 (d, J=5.6 Hz, 2H), 5,43 (t, J=5.6 Hz, 1H), 6.48 in (DD, J=7,9, and 1.4 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,05 (DD, J=7,9, and 1.4 Hz, 1H), to 7.64 (d, J=8,8 Hz, 2H), 7,87 (d, J=8,8 Hz, 2H), 7,95 (d, J=1.9 Hz, 1H), of 8.37 (d, J=1.9 Hz, 1H), to 8.62 (s, 1H), 10,37 (s, 1H)
2742-38(400 MHz, DMSO-d6) of 3.78 (t, J=4.4 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 4,56 (d, J=5.6 Hz, 2H), 5,44 (t, J=5.6 Hz, 1H), 6.48 in (DD, J=7,9, and 1.4 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,05 (DD, J=7,9, and 1.4 Hz, 1H), 7,46 (d, J=8,8 Hz, 1H), to 7.61 (DD, J=8,8, 2.3 Hz, 1H), 7.95 is-of 7.96 (m, 2H), of 8.37 (d, J=1.9 Hz, 1H), 10,47 (s, 1H)
2752-39(400 MHz, DMSO-d6) of 0.98 (d, J=7,0 Hz, 6H), 1,97-2,04 (m, 1H), and 3.72 (d, J=6,5 Hz, 2H), 3,78 (t, J=4.4 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 4,56 (s, 2H), 6,45 (DD, J=8,1, 1,6 Hz, 1H), 6,78 (t, J=7.9 Hz, 1H), 6.90 to (d, J=9,3 Hz, 2H), 7,06 (DD, J=7,7, and 1.6 Hz, 1H), to 7.64 (d, J=8,8 Hz, 2H), 7,95 (d, J=2.3 Hz, 1H), of 8.37 (d, J=1.9 Hz, 1H), 9,99 (s, 1H)
2762-40(400 MHz, DMSO-d6) of 3.78 (t, J=4,2 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4,56 (d, J=5,1 Hz, 2H), 5,43 (t, J=5.8 Hz, 1H), 6.48 in (DD, J=7,9, and 1.4 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,05 (DD, J=7,4, and 1.4 Hz, 1H), 7,60 (d, J=8,8 Hz, 1H), of 7.70 (DD, J=9,0, 2.6 Hz, 1H), 7,95 (d, J=1.9 Hz, 1H), 8,14 (d, J=2.3 Hz, 1H), of 8.37(d, J=1.9 Hz, 1H), 10,43 (s, 1H)
2772-41(400 MHz, DMSO-d6) of 3.78 (t, J=4,2 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 4,56 (d, J=5,1 Hz, 2H), 5,43 (t, J=5.8 Hz, 1H), 6.48 in (DD, J=7,9, and 1.4 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,7, and 1.6 Hz, 1H), 7,49 (DD, J=8,8, 1.9 Hz, 1H), 7,66 (t, J=8,3 Hz, 1H), of 7.90 (DD, J=11,6, 2.3 Hz, 1H), 7,95 (d, J=1.9 Hz, 1H), of 8.37 (d, J=1.9 Hz, 1H), 10,47 (s, 1H)
2782-42(400 MHz, DMSO-d6) of 3.78 (t, J=4.4 Hz, 2H), 4,42 (t, J=4,2 Hz, 2H), 4,56 (s, 2H), 5,42 (s, 1H), 6,47 (DD, J=8,3, and 1.4 Hz, 1H), 6,79 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,7, and 1.6 Hz, 1H), 7,52 (DD, J=7,0, 1.9 Hz, 2H), 7,73 (d, J=8,8 Hz, 2H), 7,95 (d, J=1.9 Hz, 1H), of 8.37 (d, J=1.9 Hz, 1H), 10,28 (s, 1H)
2792-43(400 MHz, DMSO-d6) of 3.78 (t, J=4.4 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4,56 (d, J=5.6 Hz, 2H), 5,43 (t, J=5.8 Hz, 1H), of 6.49 (DD, J=8,3, and 1.4 Hz, 1H), for 6.81 (t, J=7.7 Hz, 1H), 7,05 (DD, J=7,9, and 1.4 Hz, 1H), 7,31 (m, J=1.9 Hz, 1H), 7,86 (d, J=1.4 Hz, 2H), 7,97 (t, J=5.8 Hz, 1H), of 8.37 (d, J=1.9 Hz, 1H), 10,47 (s, 1H)

[Table 37]
No. approx.Chemical compoundNMR
2802-44(400 MHz, DMSO-d6) of 3.78 (t, J=4.4 Hz, 2H), 4,43 (t, J=4.4 Hz, 2H), 4,56 (d, J=5.6 Hz, 2H), 5,43 (t, J=5.6 Hz, 1H), 6,47 (DD, J=8,1, 1,6 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,05 (DD, J=7,9, and 1.4 Hz, 1H), 7,16 (t, J=74,4 Hz, 1H), 7,17 (d, J=8,8 Hz, 2H), 7,79 (d, J=8,8 Hz, 2H), 7,95 (d, J=1.9 Hz, 1H), of 8.37 (d, J=2.3 Hz, 1H), 10,22 (s, 1H)
2812-45(300 MHz, DMSO-d6) of 3.78 (t, J=4,2 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4,56 (d, J=5,1 Hz, 2H), 5,42 (t, J=5.7 Hz, 1H), 6,47 (DD, J=8,1, 1.5 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,05 (DD, J=7,7, 1.5 Hz, 1H), 7,39 (dt, J=a 9.5, 2.6 Hz, 2H), 7,79 (d, J=9,2 Hz, 2H), 7,95 (d, J=2.2 Hz, 1H), of 8.37 (d, J=1.8 Hz, 1H), 10,28 (s, 1H)
2822-46(300 MHz, DMSO-d6) of 1.20 (d, J=7,0 Hz, 6H), 2,82-only 2.91 (m, 1H), 3,78 (t, J=4,2 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4,56 (d, J=5,1 Hz, 2H), 5,42 (t, J=5.5 Hz, 1H), 6,46 (d, J=8,1 Hz, 1H), 6,79 (t, J=7.9 Hz, 1H), 7,06 (d, J=7.7 Hz, 1H), 7,20 (d, J=8,4 Hz, 2H), 7,65 (d, J=8,4 Hz, 2H), 7,95 (d, J=1.5 Hz, 1H), of 8.37 (d, J=1.1 Hz, 1H), 10,04 (s, 1H)
2832-47(300 MHz, DMSO-d6) of 3.78 (t, J=4.0 Hz, 2H), 4,43 (t, J=4,2 Hz, 2H), 4,56 (d, J=5,1 Hz, 2H), 5,42 (t, J=5.5 Hz, 1H), 6.48 in (DD, J=8,1, 1.5 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,05-7,06 (m, 2H), 7,47 (t, J=8,3 Hz, 1H), to 7.67 (d, J=7,3 Hz, 1H), 7,95 (who, J=1.8 Hz, 2H), of 8.37 (d, J=1.8 Hz, 1H), 10,42 (s, 1H)
2842-48(300 MHz, DMSO-d6) δ: 1,39 (d, J=7.9 Hz, 3H), of 3.78 (s, 2H), to 4.41 was 4.42 (m, 2H), 4,82-4,84 (m, 1H), 6,46 (DD, J=8,1, 1.5 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H),? 7.04 baby mortality-7,05 (m, 1H), 7,35 (d, J=8,8 Hz, 2H), 7,86 (d, J=9,2 Hz, 2H), of 7.97 (d, J=1.5 Hz, 1H), 8,40 (d, J=1.8 Hz, 1H), 10,33 (s, 1H)
2853(400 MHz, DMSO-d6) δ: 5,04 (2H, s), 6,40-6.42 per (1H, m),? 7.04 baby mortality (1H, DD, J=7,9, 3,9 Hz), 7,32 (1H, DD, J=7,9, and 1.4 Hz), 7,38 (2H, d, J=8,3 Hz), 7,71 (1H, q, J=4, 2 Hz), 7,86 (2H, DD, J=12,3, 3.0 Hz), 8,32 (1H, DD, J=of 7.9 and 1.4 Hz), 8,69 (1H, DD, J=4,6, and 1.4 Hz), 10,51 (1H, s)
2864-01(400 MHz, DMSO-d6) 3,50-3,55 (m, 1H), 3,69-of 3.77 (m, 1H), 3.96 points-of 4.00 (m, 1H), 4,17-4,19 (m, 1H), 4,60-of 4.67 (m, 1H), 5,08 (t, J=5.3 Hz, 1H), gold 6.43 (DD, J=8,9, and 1.4 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,03 (DD, J=7,9, 1,4 Hz, 1H), 7,33-7,40 (m, 3H), 7,88 (d, J=8,8 Hz, 2H), 8,07 (DD, J=7,9, 1.9 Hz, 1H), of 8.47 (DD, J=4,6, and 1.4 Hz, 1H), accounted for 10.39 (s, 1H)
2874-02(400 MHz, DMSO-d6) 3,50-3,55 (m, 1H), 3,70-of 3.77 (m, 1H), 3.95 to 4,01 (m, 1H), 4,18-4,20 (m, 1H), 4,60-of 4.66 (m, 1H), 5,08 (t, J=5.3 Hz, 1H), 6,44 (DD, J=7,9, and 1.6 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,9, 1,6 Hz, 1H), 7,37 (DD, J=7,9, 4.6 Hz, 1H), 772 (d, J=8,8 Hz, 2H), 7,98 (d, J=8,8 Hz, 2H), 8,08 (DD, J=7,9, and 1.4 Hz, 1H), of 8.47 (DD, J=4,6, and 1.4 Hz, 1H), 10,56 (s, 1H)

[Table 38]
No. approx.Chemical compoundNMR
2884-03(400 MHz, DMSO-d6) 3,47 of 3.56 (m, 1H), 3,69 of 3.75 (m, 1H), 3.95 to as 4.02 (m, 1H), 4,16-4,19 (m, 1H), br4.61 with 4.64 (m, 1H), 5,07 (t, J=5.5 Hz, 1H), 6.42 per (DD, J=8,1, 1.5 Hz, 1H), for 6.81 (t, J=7.7 Hz, 1H), 7,03 (DD, J=7,3, 1,5 Hz, 1H), 7,34-7,38 (m, 3H), 7,87 (d, J=9,2 Hz, 2H), 8,07 (DD, J=7,9, 1.7 Hz, 1H), 8,46 (DD, J=4,6, 1.0 Hz, 1H), 10,37 (s, 1H)
2894-04(300 MHz, DMSO-d6) 3,49-of 3.54 (m, 1H), 3,71 of 3.75 (m, 1H), 3.95 to 4.00 points (m, 1H), 4,17-4,20 (m, 1H), 4,60 with 4.64 (m, 1H), 5,07 (t, J=5.3 Hz, 1H), gold 6.43 (DD, J=8,1, 1.5 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,5, 1,7 Hz, 1H), was 7.36 (DD, J=8,1, 4.8 Hz, 1H), 7,72 (d, J=8,8 Hz, 2H), of 7.97 (d, J=8.1 Hz, 2H), 8,07 (DD, J=7,9, 1.7 Hz, 1H), 8,46 (DD, J=4,6, 1.7 Hz, 1H), 10,54 (s, 1H)
2904-05(400 MHz, DMSO-d6) of 3.43-3.49 points (m, 1H), 3,59-to 3.64 (m, 1H), 4,11 (DD, J=11,1, 2.3 Hz, 1H), 4,48 (t, J=7,0 Hz, 1H), 4,58 (d, J=10,2 Hz, 1H), 5,14 (t, J=5.6 Hz, 1H), 6,93 (t, J=7.9 Hz, 1H), 717 (DD, J=7,4, and 1.4 Hz, 1H), 7,31 (d, J=8,8 Hz, 1H), was 7.36 (d, J=8,3 Hz, 2H), 7,44 (DD, J=8,3, and 1.4 Hz, 1H), 7,79 (DD, J=9,0, 2.6 Hz, 1H), a 7.85 (d, J=9,3 Hz, 2H), 8,32 (d, J=2,8 Hz, 1H), 10,38 (s, 1H)
2914-06(400 MHz, DMSO-d6) 3,42-to 3.50 (m, 1H), 3,59-the 3.65 (m, 1H), 4,12 (DD, J=10,9, and 2.6 Hz, 1H), 4,48 (t, J=7,0 Hz, 1H), 4,58 (d, J=10,7 Hz, 1H), 5,15 (t, J=5.6 Hz, 1H), 6,93 (t, J=7.9 Hz, 1H), 7,18 (DD, J=7,7, and 1.6 Hz, 1H), 7,31 (d, J=9,3 Hz, 1H), 7,45 (DD, J=8,1, 1,6 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), 7,79 (DD, J=8,8, 2.8 Hz, 1H), 7,95 (d, J=8,3 Hz, 2H), with 8.33 (d, J=2,8 Hz, 1H), 10,54 (s, 1H)
2924-07(400 MHz, DMSO-d6) 3,42-to 3.49 (m, 1H), 3,62-to 3.67 (m, 1H), 4,08 (DD, J=11,1, 2.3 Hz, 1H), and 4.40 (t, J=7.2 Hz, 1H), 4,59 (d, J=10,2 Hz, 1H), 5,14 (t, J=5.6 Hz, 1H), 6.89 in (t, J=7.9 Hz, 1H), 7,10 (DD, J=7,9, and 1.4 Hz, 1H), 7,21 (d, J=8,3 Hz, 1H), 7,32-7,37 (m, 3H), 7,55 (DD, J=8,8, 2.3 Hz, 1H), 7,86 (d, J=9,3 Hz, 2H), 8,16 (d, J=2.3 Hz, 1H), 10,37 (s, 1H)
2934-08(400 MHz, DMSO-d6) 3,42-to 3.49 (m, 1H), 3,62-to 3.67 (m, 1H), 4.09 to (DD, J=10,7, 2.3 Hz, 1H), and 4.40 (t, J=7.2 Hz, 1H), 4,58 (d, J=10,7 Hz, 1H), 5,15 (t, J=5.6 Hz, 1H), 6.90 to (t, J=7.9 Hz, 1H), 7,11 (DD, J=7,4, and 1.4 Hz, 1H), 7,21 (d, J=8,3 Hz, 1H), 7,35 (DD, J=8,3, and 1.4 Hz, 1H), 7,56 (DD, J=8,6, and 2.6 Hz, 1H), 7,71 (d, J=8,3 Hz, 2H), of 7.96 (d, J=8,3 Hz, 2H), 8,16 (d, J=2.3 Hz, 1H), 10,54 (s, 1H)
2944-09 (400 MHz, DMSO-d6) of 1.27 (d, J=6.0 Hz, 6H), 3,48-3,55 (m, 1H), 3,70 of 3.75 (m, 1H), 3.96 points-to 3.99 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), 4,50-4,59 (m, 1H), 4,63 (DD, J=11,1, 1.9 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), 6,41 (DD, J=8,1, 1,6 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,02 (DD, J=7,7, and 1.6 Hz, 1H), 7,15 (t, J=9,3 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,41-7,44 (m, 1H), 7,74 (DD, J=13,7, 2.6 Hz, 1H), 8,07 (DD, J=8,1, 1,6 Hz, 1H), 8,46 (DD, J=4,6, and 1.4 Hz, 1H), of 10.21 (s, 1H)

[Table 39]
No. approx.Chemical compoundNMR
2954-10(400 MHz, DMSO-d6) 1,52 by 1.68 (m, 6H), of 2.92 (t, J=5.1 Hz, 4H), 3,51 (TD, J=10,3, 6.2 Hz, 1H), 3,70 of 3.75 (m, 1H), 3.95 to 3,99 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), to 4.62 (DD, J=10,7, 1.9 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), 6,41 (DD, J=7,9, and 1.4 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,01 (dt, J=11,3, 3.1 Hz, 2H), was 7.36 (kV, J=4,2 Hz, 1H), 7,41 (DD, J=8,6, and 1.6 Hz, 1H), 7,66 (DD, J=14,8, 2.8 Hz, 1H), 8,07 (DD, J=8,1, 1,6 Hz, 1H), 8,45-of 8.47 (m, 1H), 10,18 (s, 1H)
2964-11(400 MHz, DMSO-d6) 3,47-3,55 (m, 1H), 3,70 is 3.76 (m, 1H), 3.96 points-of 4.00 (m, 1H), 4,15-4,20 (m, 1H), 4,63 (DD, J=10,9, and 1.6 Hz, 1H), 5,09 (t, J=5.3 Hz, 1H), 6,44 (DD, J=8,1, 1,6 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), 7,03 (DD, J=7,4, and 1.4 Hz, 1H), was 7.36 (kV =4,2 Hz, 1H), 7,58 (DD, J=9,0, 1.2 Hz, 1H), 7,79 (DD, J=8,8, 2.3 Hz, 1H), 8,08 (DD, J=7,9, 1.9 Hz, 1H), 8,16 (d, J=2,8 Hz, 1H), 8,46 (kV, J=2.2 Hz, 1H), 10,54 (s, 1H)
2974-12(400 MHz, DMSO-d6) to 2.74 (s, 6H), 3,47-3,55 (m, 1H), 3,70 of 3.75 (m, 1H), 3.96 points-to 3.99 (m, 1H), 4,17 (DD, J=10,9, and 2.1 Hz, 1H), 4,63 (DD, J=11,1, 1.9 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), 6,41 (DD, J=8,1, 1,6 Hz, 1H), 6,80 (t, J=7.7 Hz, 1H), of 6.96 (DD, J=10,0, 9.0 Hz, 1H), 7,02 (DD, J=7,4, and 1.4 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,40 (DD, J=8,8, 1.9 Hz, 1H), 7,66 (DD, J=15,5, and 2.6 Hz, 1H), 8,07 (DD, J=8,1, 1,6 Hz, 1H), 8,46 (DD, J=4,9, 1,6 Hz, 1H), 10,15 (s, 1H)
2984-13(400 MHz, DMSO-d6) of 2.20 (s, 3H), 3,48-of 3.54 (m, 1H), 3,70-3,74 (m, 1H), 3.95 to 3,99 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), to 4.62 (DD, J=11,1, 1.9 Hz, 1H), 5,09 (t, J=5.3 Hz, 1H), 6.42 per (DD, J=8,1, 1,6 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,02 (DD, J=7,7, and 1.6 Hz, 1H), 7,24 (t, J=8,8 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 2H), 7,40 (DD, J=8,1, 2,1 Hz, 2H), of 7.70 (DD, J=12,3, 2.1 Hz, 1H), 8,07 (DD, J=7,9, 1.9 Hz, 1H), 8,46 (kV, J=2.2 Hz, 1H), 10,29 (s, 1H)
2994-14(400 MHz, DMSO-d6) of 0.85 (s, 9H), 0.95 to-1,12 (m, 3H), 1.26 in (kV, J=12,2 Hz, 2H), 1.77 in (d, J=10,7 Hz, 2H), 1,96 (DD, J=12,8, 3.0 Hz, 2H), 3,41-to 3.49 (m, 1H), 3,61-and 3.72 (m, 2H), 3.95 to 3,99 (m, 1H), 4,12 (DD, J=10,9, and 2.6 Hz, 1H), br4.61 (DD, J=10,9, and 1.6 Hz, 1H), 5,09 (DD, J=6,0, 5,1 Hz, 1H), 6,34 (DD, J=8,1, 1,6 Hz, 1H), 6,74 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,7, and 1.6 Hz, 1H), 7,34 (to whom, J=4,2 Hz, 1H), to 7.93 (d, J=7.9 Hz, 1H), with 8.05 (DD, J=7,9, 1.9 Hz, 1H), 8,44 (DD, J=4,6, and 1.4 Hz, 1H)
3004-15(400 MHz, DMSO-d6) of 0.87 (s, 8H), 1,23-of 1.40 (m, 4H), 1,89 of 1.99 (m, 4H), is 3.08 (s, 2H), 3,16-is 3.21 (m, 1H), 3.43 points-to 3.49 (m, 1H), 3,66-of 3.77 (m, 2H), 3.95 to 3,99 (m, 1H), 4,12 (DD, J=11,1, 2.3 Hz, 1H), br4.61 (DD, J=11,1, 1,9 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), 6.35mm (DD, J=8,1, 1,6 Hz, 1H), 6,74 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,7, and 1.6 Hz, 1H), 7,34 (TD, J=5,1, 2.6 Hz, 1H), of 7.97 (d, J=7.9 Hz, 1H), with 8.05 (DD, J=8,1, 1,6 Hz, 1H), 8,44 (DD, J=4,6, and 1.4 Hz, 1H)
3014-16(400 MHz, DMSO-d6) 3,48-3,55 (m, 1H), 3,70 of 3.75 (m, 1H), 3.96 points-to 3.99 (m, 1H), 4,17 (DD, J=10,9, and 2.1 Hz, 1H), to 4.62 (DD, J=10,9, and 1.6 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), 6.42 per (DD, J=8,3, and 1.4 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,02 (DD, J=7,4, and 1.4 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,41 (dt, J=a 9.6, 2.6 Hz, 2H), 7,80 (DD, J=7,0, 1.9 Hz, 2H), 8,07 (DD, J=7,9, 1.9 Hz, 1H), 8,46 (kV, J=2.2 Hz, 1H), 10,33 (s, 1H)
[Table 40]
No. approx.Chemical compoundNMR
3024-17(400 MHz, DMSO-d6) of 1.20 (d, J=7,0 Hz, 6H), 2,83-2,90 (m, 1H), 3,48-3,55 (m, 1H), 3,70 of 3.75 (m, 1H), 3.95 to 4.00 points (m, 1H), 4,18 (DD, J=10,7, 2.3 Hz, 1H), 463 (DD, J=10,7, 1.9 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), 6,41 (DD, J=8,1, 1,6 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,03 (DD, J=7,7, and 1.6 Hz, 1H), 7,21 (d, J=8,8 Hz, 2H), was 7.36 (kV, J=4,2 Hz, 1H), 7,66 (d, J=8,8 Hz, 2H), 8,07 (DD, J=7,9, and 1.4 Hz, 1H), 8,46 (DD, J=4,6, and 1.4 Hz, 1H), 10,10 (s, 1H)
3034-18(400 MHz, DMSO-d6) 3,48-of 3.54 (m, 1H), 3,70 is 3.76 (m, 1H), 3.96 points-of 4.00 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), 4,63 (DD, J=10,9, and 1.6 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), 6,44 (DD, J=8,1, 1,6 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,4, and 1.4 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,53 (t, J=9.7 Hz, 1H), 8,01-with 8.05 (m, 1H), 8,07 (DD, J=8,1, 1,6 Hz, 1H), 8,28 (DD, J=6,5, and 2.3 Hz, 1H), 8,46 (DD, J=4,6, and 1.4 Hz, 1H), 10,54 (s, 1H)
3044-19(400 MHz, DMSO-d6) 3,47-of 3.54 (m, 1H), 3,70 of 3.75 (m, 1H), 3.96 points-to 3.99 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), 4,63 (DD, J=10,9, and 1.6 Hz, 1H), 5,09 (DD, J=6,0, 5,1 Hz, 1H), gold 6.43 (DD, J=8,1, 1,6 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), 7,03 (DD, J=7,7, and 1.6 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), to 7.64 (DD, J=8,8, 2.3 Hz, 1H), 7,74 (d, J=8,8 Hz, 1H), 8,07 (DD, J=7,9, and 1.4 Hz, 1H), 8,14 (d, J=2.3 Hz, 1H), 8,46 (DD, J=4,6, and 1.4 Hz, 1H), 10,47 (s, 1H)
3054-20(400 MHz, DMSO-d6) 2,63 (s, 6H), 3,48-of 3.54 (m, 1H), 3,70 of 3.75 (m, 1H), 3.95 to 4.00 points (m, 1H), 4,17 (DD, J=10,9, and 2.1 Hz, 1H), to 4.62 (DD, J=10,7, 1.9 Hz, 1H), 5,08 (t, J=5.6 Hz, 1H), 6.42 per (DD, J=7,9, and 1.4 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,03 (DD, J=7,7, and 1.6 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), EUR 7.57 (d, J=8,8 is C, 1H), 7,95 (DD, J=8,8, 2.3 Hz, 1H), 8,07 (DD, J=7,9, and 1.4 Hz, 1H), 8,14 (d, J=2.3 Hz, 1H), 8,46 (kV, J=2.2 Hz, 1H), 10,38 (s, 1H)
3064-21(400 MHz, DMSO-d6) of 1.28 (d, J=6.0 Hz, 6H), 3,48-3,55 (m, 1H), 3,70 of 3.75 (m, 1H), 3.96 points-of 4.00 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), 4,63 (DD, J=11,1, 1.9 Hz, 1H), 4.72 in-4,78 (m, 1H), 5,09 (t, J=5.6 Hz, 1H), 6.42 per (DD, J=7,9, and 1.4 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,03 (DD, J=7,7, and 1.6 Hz, 1H), 7,31 (d, J=8,8 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), of 7.90 (DD, J=9,0, 2.6 Hz, 1H), 8,07 (DD, J=7,9, 1.9 Hz, 1H), 8,10 (d, J=2.3 Hz, 1H), 8,46 (kV, J=2.2 Hz, 1H), 10,28 (s, 1H)
3074-22(400 MHz, DMSO-d6) 1,50-1,55 (m, 2H), 1,59-of 1.66 (m, 4H), and 2.79 (t, J=5.1 Hz, 4H), 3,48-3,55 (m, 1H), 3,70 of 3.75 (m, 1H), 3.95 to 4.00 points (m, 1H), 4,17 (DD, J=10,9, and 2.1 Hz, 1H), to 4.62 (DD, J=10,9, and 1.6 Hz, 1H), 5,08 (t, J=5,3 Hz, 1H), 6.42 per (DD, J=8,1, 1,6 Hz, 1H), for 6.81 (t, J=7.7 Hz, 1H), 7,02 (DD, J=7,9, and 1.4 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,52 (d, J=8,8 Hz, 1H), 7,95 (DD, J=8,8, 2.3 Hz, 1H), 8,07 (DD, J=7,9, and 1.4 Hz, 1H), 8,14 (d, J=2.3 Hz, 1H), 8,46 (DD, J=4,6, and 1.4 Hz, 1H), 10,38 (s, 1H)
3084-23(400 MHz, DMSO-d6) of 1.34 (t, J=7.0 Hz, 3H), 3,48-of 3.54 (m, 1H), 3,70 of 3.75 (m, 1H), 3.96 points-to 3.99 (m, 1H), 4,08 (kV, J=7,0 Hz, 2H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), 4,63 (DD, J=10,7, 1.9 Hz, 1H), 5,09 (t, J=5.8 Hz, 1H), 6,41 (DD, J=8,1, 1,6 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,02 (DD, J=7,4, and 1.4 Hz, 1H), 7,14 (t, J=9.5 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,42-745 (m, 1H), 7,74 (DD, J=13,7, 2.6 Hz, 1H), 8,07 (DD, J=7,9, and 1.4 Hz, 1H), 8,46 (kV, J=2.2 Hz, 1H), and 10.20 (s, 1H)

[Table 41]
No. approx.Chemical compoundNMR
3094-24(400 MHz, DMSO-d6) 3,48-3,55 (m, 1H), 3,70 of 3.75 (m, 1H), 3,88 (s, 3H), 3.96 points-of 4.00 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), 4,63 (DD, J=10,9, and 1.6 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), 6.42 per (DD, J=8,1, 1,6 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,4, and 1.4 Hz, 1H), 7,28 (d, J=9,3 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,95 (DD, J=9,0, 2.6 Hz, 1H), 8,07 (DD, J=7,9, and 1.4 Hz, 1H), 8,12 (d, J=2,8 Hz, 1H), 8,46 (DD, J=4,9, and 1.6 Hz, 1H), 10,29 (s, 1H)
3104-25(400 MHz, DMSO-D6) δ: 3,49-to 3.52 (m, 1H), 3,57-3,59 (m, 1H), 3,80-of 3.85 (m, 1H), with 3.89 (s, 3H), 4,17 (d, J=9,3 Hz, 1H), 4,56 (d, J=8,8 Hz, 1H), to 4.98 (t, J=5.6 Hz, 1H), 6,24 (DD, J=8,1, 1,6 Hz, 1H), 6,77 (t, J=7.9 Hz, 1H), 6,93 (DD, J=7,9, and 1.4 Hz, 1H), of 7.70 (d, J=8,8 Hz, 2H), 7,79 (d, J=2,8 Hz, 1H), of 7.96 (d, J=8,3 Hz, 2H), 8,24 (d, J=2,8 Hz, 1H), 10,53 (s, 1H)
3114-26(400 MHz, DMSO-D6) δ: 3,48-to 3.50 (m, 1H), 3,56-3,59 (m, 1H), 3,78-3,81 (m, 1H), with 3.89 (s, 3H), 4,16 (d, J=8,8gts, 1H), 4,56 (d, J=8,3 Hz, 1H), equal to 4.97 (t, J=5.6 Hz, 1H), 6,23 (DD, J=8,1, 1,6 Hz, 1H), 6,76 (t, J=7.9 Hz, 1H), 6,91 (DD, J=7,7, and 1.6 Hz, 1H), 7,34 (d, J=8,8 Hz, 2H), 7,79 (d, J=2,8 Hz, 1H), a 7.85 (d, J=9,3 Hz, 2H), 8,24 (d, J=2,8 Hz, 1H), 10,36 (s, 1H)
3124-27(400 MHz, DMSO-d6) δ: 2,24 (s, 3H), 3.43-3.45 points (m, 1H), 3,57-of 3.78 (m, 1H), 4,08 (DD, J=10,9, and 2.6 Hz, 1H), to 4.38 (t, J=7,4 Hz, 1H), 4,58 (d, J=10,2 Hz, 1H), 5,14 (t, J=5.6 Hz, 1H), 6.90 to (t, J=7.9 Hz, 1H), 7,13 (DD, J=7,7, and 1.6 Hz, 1H), 7,21 (d, J=8,3 Hz, 1H), was 7.36 (DD, J=8,1, 1,6 Hz, 1H), 7,55 (DD, J=8,3, 1.9 Hz, 1H), to $ 7.91 (d, J=8,8 Hz, 1H), 8,15 (t, J=1.2 Hz, 1H), 8,45 (d, J=6,5 Hz, 1H), 9,02 (d, J=2.3 Hz, 1H), 10,77 (s, 1H)
3134-28(400 MHz, DMSO-d6) δ: of 2.23 (s, 3H), 3,42 is-3.45 (m, 1H), 3,61-to 3.67 (m, 1H), a 3.87 (s, 3H), 4,06 (DD, J=10,9, and 2.6 Hz, 1H), 4,39 (t, J=7,4 Hz, 1H), 4,58 (d, J=9.7 Hz, 1H), 5,14 (s, 1H), to 6.88 (t, J=7.9 Hz, 1H), 7,10 (DD, J=7,7, and 1.6 Hz, 1H), 7,20 (d, J=8,3 Hz, 1H), 7,26 (d, J=9,3 Hz, 1H), 7,32 (DD, J=8,3, and 1.4 Hz, 1H), 7,54 (DD, J=9,0, 2.6 Hz, 1H), 7,92 (DD, J=9,3, 2.3 Hz, 1H), 8,12 (DD, J=21,6, and 2.6 Hz, 2H), 10,29 (s, 1H)
3144-29(400 MHz, DMSO-d6) δ: of 2.23 (s, 3H), 2,82 (t, J=4.4 Hz, 4H), 3,41 is-3.45 (m, 1H), 3,59-the 3.65 (m, 1H), 3,69 (t, J=4.4 Hz, 4H), 3,99-4,07 (m, 1H), to 4.38 (t, J=7,4 Hz, 1H), 4,56 (d, J=10,2 Hz, 1H), 5,13 (t, J=5.3 Hz, 1H), to 6.88 (t, J=7.9 Hz, 1H), was 7.08 (DD, J=7,7, and 1.6 Hz, 1H), 7,20 (d, J=8,3 Hz, 1H), 7,32 (DD, J=8,1, 1,6 Hz, 1H), 7,55-7,58 (m, 2H), 7,94 (DD, J=8,6, and 2.6 Hz, 1H), 8,15 (d, J=2.3 Hz, 2H), the 10.40 (s, 1H)
3154-30(300 MHz, DMSO-d6) δ: 2,24 (s, 3H), 3,42-3,47 (m, 1H), 3,60-to 3.67 (m, 1H), 3,99-4,10 (m, 1H), 4,36-to 4.38 (m, 1H), 4,58 (d, J=9.9 Hz, 1H), 5,13 (t, J=5.5 Hz, 1H), 6.90 to (t, J=7.9 Hz, 1H), 7,10 (DD, J=7,7, 1.5 Hz, 1H), 7,21 (d, J=8,4 Hz, 1H), was 7.36 (DD, J=8,3, 1.7 Hz, 1H), 7,56 (DD, J=8,6, and 2.4 Hz, 1H), 7,66 (d, J=9.5 Hz, 1H), 7,76 (t, J=8,4 Hz, 1H), of 7.96 (d, J=a 13.9 Hz, 1H), 8,16 (d, J=2.2 Hz, 1H), of 10.73 (s, 1H)

[Table 42]
No. approx.Chemical compoundNMR
3164-31(300 MHz, DMSO-d6) δ: of 2.25 (s, 3H), 3,44 (t, J=9.9 Hz, 1H), 3,62-the 3.65 (m, 1H), 4,07-4.09 to (m, 1H), 4,39-to 4.41 (m, 1H), 4,58 (d, J=9.9 Hz, 1H), 6.90 to (t, J=7.9 Hz, 1H), 7,10 (DD, J=7,3, 1.5 Hz, 1H), 7,21 (d, J=and 8.4 Hz, 1H), 7,35 (DD, J=8,1, 1.5 Hz, 1H), 7,56 (DD, J=9,0, 1.3 Hz, 2H), to 7.77 (DD, J=9,0, 2.4 Hz, 1H), 8,15 (DD, J=8,3, 2.4 Hz, 2H), 10,51 (s, 1H)
3174-32(300 MHz, DMSO-d6) δ: 2,24 (s, 3H), 3,44 (t, J=9.9 Hz, 1H), 3,61-the 3.65 (m, 1H), 4,07 (d, J=5.3 Hz, 1H), 4,39 (t, J=6,8 Hz, 1H), 4,59 (d, J=9.9 Hz, 1H), 6.89 in (t, J=7.9 Hz, 1H), 7,0 (DD, J=7,7, 1.5 Hz, 1H), 7,21 (d, J=8,4 Hz, 1H), 7,34 (DD, J=8,1, 1.5 Hz, 1H), 7,54-7,71 (m, 3H), 8,14 (DD, J=10,3, 2,2 Hz, 2H), 10,45 (s, 1H)
3184-33(400 MHz, DMSO-d6) of 1.00 (d, J=6.5 Hz, 6H), 2,00-2,09 (m, 1H), 3,48-3,55 (m, 1H), 3,70 of 3.75 (m, 1H), a 3.87 (d, J=6.0 Hz, 2H), 3.96 points-of 4.00 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), 4,63 (DD, J=11,1, 1.9 Hz, 1H), 5,09 (t, J=5.3 Hz, 1H), 6.42 per (DD, J=8,1, 1,6 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H),? 7.04 baby mortality (DD, J=7,7, and 1.6 Hz, 1H), 7,24 (d, J=8,8 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,92 (DD, J=8,8, 2.3 Hz, 1H), 8,07 (DD, J=8,1, 1,6 Hz, 1H), to 8.12 (d, J=2,8 Hz, 1H), 8,46 (DD, J=4,9, and 1.6 Hz, 1H), 10,28 (s, 1H)
3194-34(400 MHz, DMSO-d6) 3,48-of 3.54 (m, 1H), 3,70 of 3.75 (m, 1H), 3.95 to 4.00 points (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), 4,63 (DD, J=10,9, and 1.6 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), gold 6.43 (DD, J=7,9, and 1.4 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), 7,03 (DD, J=7,7, and 1.6 Hz, 1H), was 7.36 (kV, J=4.3 Hz, 1H), to 7.61 (d, J=8,8 Hz, 1H), 7,71 (DD, J=8,8, 2.3 Hz, 1H), 8,07 (DD, J=7,9, and 1.4 Hz, 1H), 8,15 (d, J=2.3 Hz, 1H), 8,46 (kV, J=2.2 Hz, 1H), 10,48 (s, 1H)
3204-35(400 MHz, DMSO-d6) 3,47-3,55 (m, 1H), 3,70 is 3.76 (m, 1H), 3.96 points-of 4.00 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), to 4.62 (DD, J=11,1, 1.9 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), 6,44 (DD, J=7,9, and 1.4 Hz, 1H), PC 6.82 (t, J=7.7 Hz, 1H), 7,03 (DD, J=7,4, and 1.4 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,71 (d, J=8,8 Hz, 1H), 8,03 (DD, J=8,8, 2.3 Hz, 1H), 8,08 (DD, J=7,9, 1.9 Hz, 1H), of 8.37 (d, J=2.3 Hz, 1H) 8,46 (DD, J=4,6, and 1.4 Hz, 1H), to 10.62 (s, 1H)
3214-36(400 MHz, DMSO-d6) 3,47-3,55 (m, 1H), 3,70 of 3.75 (m, 1H), 3.96 points-to 3.99 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), to 4.62 (DD, J=10,9, and 1.6 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), gold 6.43 (DD, J=8,1, 1,6 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), 7,02 (DD, J=7,4, and 1.4 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,50 (DD, J=8,8, 1.9 Hz, 1H), to 7.67 (t, J=8,3 Hz, 1H), 7,92 (DD, J=11,6, 2.3 Hz, 1H), 8,07 (DD, J=8,1, 1,6 Hz, 1H), 8,46 (DD, J=4,6, and 1.4 Hz, 1H), 10,52 (s, 1H)
3224-37(300 MHz, DMSO-d6) δ: 2,24 (s, 3H), 3,40-to 3.49 (m, 1H), 3,60-to 3.67 (m, 1H), of 4.05-4.09 to (m, 1H), 4,39 (t, J=7.2 Hz, 1H), 4,58 (d, J=10.3 Hz, 1H), 5,13 (t, J=5.5 Hz, 1H), 6.90 to (t, J=7.9 Hz, 1H), 7,11 (DD, J=7,7, 1.5 Hz, 1H), 7,21 (d, J=8,4 Hz, 1H), 7,35 (DD, J=8,1, 1.5 Hz, 1H), 7,56 (DD, J=8,4, 2.2 Hz, 1H), 7,71 (d, J=8,8 Hz, 1H), 8,00 (DD, J=8,6, and 2.4 Hz, 1H), 8,16 (d, J=2.2 Hz, 1H), 8,35 (d, J=2.6 Hz, 1H), or 10.60 (s, 1H)

[Table 43]
No. approx.Chemical compoundNMR
3234-38(300 MHz, DMSO-d6) δ: 1,28 (d, J=3.1 Hz, 6H), 2,24 (s, 3H), of 3.45 (t, J=10.3 Hz, 1H), 3,62-the 3.65 (m, 1H), 4,07 (d, J=10.3 G is, 1H), to 4.38-to 4.41 (m, 1H), 4,59 (d, J=a 10.6 Hz, 1H), 4,74 was 4.76 (m, 1H), to 6.88 (t, J=7,3 Hz, 1H), 7,11 (d, J=7.7 Hz, 1H), 7,21 (d, J=8,1 Hz, 1H), 7,31 (t, J=8,4 Hz, 2H), 7,55 (d, J=8,4 Hz, 1H), 7,88 (d, J=9,2 Hz, 1H), 8,12 (d, J=22.7 Hz, 2H), of 10.25 (s, 1H)
3244-39(400 MHz, DMSO-d6) 2,84 (t, J=4.4 Hz, 4H), 3,48-of 3.54 (m, 1H), 3,68 of 3.75 (m, 5H), 3.95 to 4.00 points (m, 1H), 4,17 (DD, J=10,9, and 2.1 Hz, 1H), to 4.62 (DD, J=10,7, 1.9 Hz, 1H), 5,08 (t, J=5.3 Hz, 1H), gold 6.43 (DD, J=8,1, 1,6 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,02 (DD, J=7,4, and 1.4 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,60 (d, J=8,8 Hz, 1H), 7,98 (DD, J=8,8, 2.3 Hz, 1H), 8,07 (DD, J=7,9, and 1.4 Hz, 1H), 8,18 (d, J=2,8 Hz, 1H), 8,46 (DD, J=4,6, 1,4 Hz, 1H), 10,42 (s, 1H)
3254-40(300 MHz, DMSO-d6) δ: of 2.25 (s, 3H), 3,44-to 3.49 (m, 1H), 3,65-to 3.67 (m, 1H), 4,29-or 4.31 (m, 1H), 4,45-4,48 (m, 1H), 4,82 (d, J=10.3 Hz, 1H), 5,19 (t, J=5.3 Hz, 1H), 6,99 (t, J=7.9 Hz, 1H), 7,22 (d, J=8,4 Hz, 1H), 7,44 (DD, J=8,1, 1.5 Hz, 1H), 7,55 to 7.62 (m, 2H), 7,80 (d, J=8,8 Hz, 1H), 8,01 (d, J=1.8 Hz, 1H), 8,17 (d, J=2.2 Hz, 1H), 8,72 (d, J=8,8 Hz, 1H), 10,77 (s, 1H)
3264-41(300 MHz, DMSO-d6) of 2.16 (s, 3H), 3,37 (user. s, 1H), 3,50 (t, J=9.7 Hz, 1H), 3,65 (user. s, 1H), 3.96 points (d, J=2,9 Hz, 1H), 4,24 (DD, J=10,6, 2.2 Hz, 1H), 4,60 (DD, J=11,0, 2.2 Hz, 1H), 6,18 (DD, J=8,1, 1.5 Hz, 1H), 6,78 (t, J=7.9 Hz, 1H), 6,95 (DD, J=7,7, 1.5 Hz, 1H), 7,29 (DD, J=7,7, 4.8 Hz, 1H), of 7.36 (d, J=8,4 Hz, 2H), 7,79 (DD, J=7,7, 1.1 Hz, 1H), 7,87 (who, J=8,8 Hz, 2H), scored 8.38 (DD, J=4,6, 1.7 Hz, 1H), 10,35 (s, 1H)
3274-42(300 MHz, DMSO-d6) of 2.16 (s, 3H), 3,50 (t, J=9.7 Hz, 1H), 3,65 (s, 1H), 3.96 points (d, J=2,9 Hz, 1H), 4,24 (DD, J=10,6, 2.2 Hz, 1H), 4,60 (DD, J=11,0, 2.2 Hz, 1H), 6,18 (DD, J=8,1, 1.5 Hz, 1H), 6,78 (t, J=7.9 Hz, 1H), to 6.95 (DD, J=7,7, 1.5 Hz, 1H), 7,29 (DD, J=7,7, 4.8 Hz, 1H), was 7.36 (d, J=8,4 Hz, 2H), 7,79 (DD, J=7,7, 1.1 Hz, 1H), 7,87 (d, J=8,8 Hz, 2H), scored 8.38 (DD, J=4,6, 1.7 Hz, 1H), 10,35 (s, 1H)
3284-43(400 MHz, DMSO-d6) of 1.30 (s, 9H), 3,47-3,55 (m, 1H), 3,69 of 3.75 (m, 1H), 3.95 to 4.00 points (m, 1H), 4,16 (DD, J=10,7, 2.3 Hz, 1H), to 4.62 (DD, J=10,7, 1.9 Hz, 1H), 5,08 (t, J=5.3 Hz, 1H), 6.42 per (DD, J=8,3, and 1.4 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,01 (DD, J=7,7, and 1.6 Hz, 1H), 7,12 (t, J=9.0 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,41 (dt, J=8,8, 1.2 Hz, 1H), to 7.77 (DD, J=13,0, 2.8 Hz, 1H), 8,07 (DD, J=7,9, 1.9 Hz, 1H), 8,46 (DD, J=4,6, and 1.4 Hz, 1H), 10,30 (s, 1H)
3294-44(400 MHz, DMSO-d6) 0,99 (d, J=6.5 Hz, 6H), 1,98-of 2.08 (m, 1H), 3,47-3,55 (m, 1H), 3,70 of 3.75 (m, 1H), 3,80 (d, J=6,5 Hz, 2H), 3.96 points-to 3.99 (m, 1H), 4,17 (DD, J=10,7, 2.3 Hz, 1H), 4,63 (DD, J=10,7, 1.9 Hz, 1H), 5,09 (t, J=5.6 Hz, 1H), 6,41 (DD, J=7,9, and 1.4 Hz, 1H), 6,80 (t, J=7.9 Hz, 1H), 7,02 (DD, J=7,7, and 1.6 Hz, 1H), 7,14 (t, J=9,3 Hz, 1H), was 7.36 (kV, J=4,2 Hz, 1H), 7,44 (DD, J=8,8, and 1.4 Hz, 1H), 7,74 (DD, J=13,7, 2.6 Hz, 1H), 8,07 (DD, J=7,9, and 1.4 Hz, 1H), 8,46 (DD, J=4,6, and 1.4 Hz, 1H), and 10.20 (s, 1H)

[Table 44]No. approx.Chemical compoundNMR3304-45(300 MHz, DMSO-d6) δ: 1.00 m (d, J=7,0 Hz, 6H), 2,00-2,09 (m, 1H), 2,24 (s, 3H), of 3.45 (t, J=9.9 Hz, 1H), 3,61-the 3.65 (m, 1H), a 3.87 (d, J=6.2 Hz, 2H), 4,07 (DD, J=11,0, 2.2 Hz, 1H), and 4.40 (t, J=7.2 Hz, 1H), 4,59 (d, J=a 10.6 Hz, 1H), to 6.88 (t, J=7.9 Hz, 1H), 7,12 (DD, J=7,3, 1.5 Hz, 1H), 7,22 (t, J=8,1 Hz, 2H), 7,33 (DD, J=8,4, 1.5 Hz, 1H), 7,56 (DD, J=8,4, 2.2 Hz, 1H), 7,89 (DD, J=9,0, 2.4 Hz, 1H), 8,13 (DD, J=19,4, 2.2 Hz, 2H), of 10.25 (s, 1H)3314-46(300 MHz, DMSO-d6) δ: 1,27 (d, J=5,9 Hz, 6H), 2,24 (s, 3H), 3,42-of 3.46 (m, 1H), 3,60-to 3.64 (m, 1H), 4,06 (d, J=8,4 Hz, 1H), to 4.38-to 4.41 (m, 1H), 4.53-in-4,58 (m, 2H), 5,11-5,14 (m, 1H), to 6.88 (t, J=7.9 Hz, 1H), 7,12-7,17 (m, 4H), 7,32-7,38 (m, 2H), 7,55 (DD, J=8,4, 2.2 Hz, 1H), 7,72 (DD, J=13,8, 2.4 Hz, 1H), 8,16 (s, 1H), 10,18 (s, 1H)332About 4-47(300 MHz, DMSO-d6) δ: 2,24 (s, 3H), 2,96 (t, J=4.8 Hz, 4H), 3,43-3,47 (m, 1H), 3,63 (s, 1H), 3,74 (t, J=4.6 Hz, 4H), 4,06 (DD, J=10,5, 2.4 Hz, 1H), 4,37-4,39 (m, 1H), 4,58 (d, J=9.9 Hz, 1H), 5,11-of 5.15 (m, 1H), to 6.88 (t, J=7.7 Hz, 1H), 6,99-7,11 (m, 2H), 7,20 (d, J=8,4 Hz, 1H), 7,32 (DD, J=8,1, 1.5 Hz, 1H), 7,41 (DD, J=8,6, 1.7 Hz, 1H), 755 (DD, J=an 8.4 and 2.2 Hz, 1H), 7,68 (DD, J=15,0, and 2.6 Hz, 1H), 8,16 (d, J=2.2 Hz, 1H), 10,18 (s, 1H)3334-48(300 MHz, DMSO-d6) δ: 2,24 (s, 3H), 3,45-3,47 (m, 1H), 3,63-to 3.64 (m, 1H), 4,06 (d, J=8,4 Hz, 1H), 4,37-to 4.41 (m, 1H), 4,58 (d, J=a 10.6 Hz, 1H), 5,13 (t, J=5.5 Hz, 1H), to 6.88 (t, J=7.9 Hz, 1H), to 7.09 (DD, J=7,7, 1.5 Hz, 1H), 7,20 (d, J=8,4 Hz, 1H), 7,34-7,38 (m, 3H), 7,55 (DD, J=9,0, 2.4 Hz, 1H), to 7.77 (d, J=8,8 Hz, 2H), 8,16 (d, J=2.2 Hz, 1H), 10.30 a.m. (s, 1H)3344-49(300 MHz, DMSO-d6) δ: of 2.25 (s, 3H), 2,90-only 2.91 (m, 4H), 3,42-3,51 (m, 1H), 3,67-3,74 (m, 1H), 3,81 (t, J=4.4 Hz, 4H), 4,29 (t, J=5.3 Hz, 1H), 4,50-to 4.52 (m, 1H), 4,87 (d, J=10.3 Hz, 1H), 5,18 (t, J=5,1 Hz, 1H), 6,98 (t, J=8,1 Hz, 1H), 7.23 percent (d, J=8,4 Hz, 1H), 7,41 (DD, J=8,1, 1.5 Hz, 1H), 7,55 to 7.62 (m, 4H), 8,18 (d, J=1.8 Hz, 1H), 8,64 (d, J=8,4 Hz, 1H), 10,57 (s, 1H)3354-50(400 MHz, DMSO-d6) of 1.29 (s, 9H), 2,24 (s, 3H), 3,41-3,47 (m, 1H), 3,60-the 3.65 (m, 1H), 4,06 (DD, J=10,9, and 2.6 Hz, 1H), 4,39 (t, J=7,0 Hz, 1H), 4,58 (DD, J=10,9, 1.2 Hz, 1H), 5,14 (t, J=5.3 Hz, 1H), to 6.88 (t, J=7.9 Hz, 1H), 7,06-7,14 (m, 2H), 7,21 (d, J=8,3 Hz, 1H), 7,32 (DD, J=8,1, 1,6 Hz, 1H), 7,38 (DD, J=8,8, and 1.4 Hz, 1H), 7,55 (DD, J=8,8, 2.3 Hz, 1H), of 7.75 (DD, J=13,2, and 2.6 Hz, 1H), 8,16 (d, J=2.3 Hz, 1H), 10,28 (s, 1H)3364-51 (400 MHz, DMSO-d6) 2,24 (s, 3H), 3,40-3,47 (m, 1H), 3,60-the 3.65 (m, 1H), 4,06 (DD, J=10,9, and 2.6 Hz, 1H), to 4.38 (t, J=7,0 Hz, 1H), 4,58 (DD, J=11,1, 0.9 Hz, 1H), 5,15 (t, J=5.6 Hz, 1H), 6.89 in (t, J=7.9 Hz, 1H), to 7.09 (DD, J=7,4, and 1.4 Hz, 1H), 7,20 (d, J=8,3 Hz, 1H), 7,34 (DD, J=8,1, 1,6 Hz, 1H), 7,47 (DD, J=8,8, 1.9 Hz, 1H), 7,55 (DD, J=8,3, 1.9 Hz, 1H), 7,66 (t, J=8,3 Hz, 1H), of 7.90 (DD, J=11,1, 2.3 Hz, 1H), 8,16 (d, J=2.3 Hz, 1H), 10,50 (s, 1H)[Table 45]No. approx.Chemical compoundNMR3374-52(300 MHz, DMSO-d6) δ: 3,48-to 3.52 (m, 1H), 3,71-to 3.73 (m, 1H), 4,01-a 4.03 (m, 1H), 4,18 (d, J=10.3 Hz, 1H), 4,63 (d, J=a 10.6 Hz, 1H), 6.42 per (DD, J=8,1, 1.5 Hz, 1H), for 6.81 (t, J=7.9 Hz, 1H), 7,03 (d, J=7.7 Hz, 1H), 7,35-7,37 (m, 3H), 7,88 (d, J=9,2 Hz, 2H), 8,07 (DD, J=7,9, 1.7 Hz, 1H), 8,46-of 8.47 (m, 1H), 10,36 (s, 1H)3384-53(300 MHz, DMSO-d6) δ: 3,48-of 3.53 (m, 1H), 3.72 points-3,74 (m, 1H), 3.95 to 3,98 (m, 1H), 4,18 (d, J=9.5 Hz, 1H), to 4.62 (d, J=9.9 Hz, 1H), of 5.05 is 5.07 (m, 1H), 6,44 (d, J=7,0 Hz, 1H), 6,83 (t, J=7.7 Hz, 1H), 7,03 (d, J=7,3 Hz, 1H), was 7.36 (DD, J=7,9, 4.6 Hz, 1H), to 7.67-7,79 (m, 2H), 7,98 (d, J=14,7 Hz, 1H), 8,07 (d, J=6,6 Hz, 1H), 8,46 (d, J=3.3 Hz, 1H), a 10.74 (s, 1H)3394-54 (400 MHz, DMSO-d6) of 0.98 (d, J=7,0 Hz, 6H), 1,97-2,07 (m, 1H), 2,24 (s, 3H), 3,41-3,47 (m, 1H), 3,60-the 3.65 (m, 1H), 3,80 (d, J=6,5 Hz, 2H), 4,06 (DD, J=10,9, and 2.6 Hz, 1H), 4,39 (t, J=7,0 Hz, 1H), 4,59 (d, J=10,2 Hz, 1H), 5,14 (t, J=5.6 Hz, 1H), to 6.88 (t, J=7.7 Hz, 1H), 7,08-7,11 (m, 1H), 7,15 (d, J=9,3 Hz, 1H), 7,20 (d, J=8,3 Hz, 1H), 7,32 (DD, J=8,3, and 1.4 Hz, 1H), 7,41 (DD, J=9,3, and 1.4 Hz, 1H), 7,55 (DD, J=8,8, 2.3 Hz, 1H), 7,72 (DD, J=13,7, 2.6 Hz, 1H), 8,16 (d, J=2.3 Hz, 1H), 10,18 (s, 1H)3404-55(300 MHz, DMSO-d6) of 2.25 (s, 3H), 3.43 points-of 3.46 (m, 1H), 3,60-to 3.67 (m, 1H), 4,07 (DD, J=11,0, 2.6 Hz, 1H), and 4.40 (t, J=7.2 Hz, 1H), 4,59 (d, J=10.3 Hz, 1H), 5,13 (t, J=5.5 Hz, 1H), 6.90 to (t, J=7.9 Hz, 1H), 7,11 (DD, J=to 7.3, 1.5 Hz, 1H), 7,21 (d, J=8,4 Hz, 1H), 7,34 (DD, J=8,1, 1.5 Hz, 1H), 7,51-of 7.55 (m, 2H), 7,97-8,03 (m, 1H), 8,16 (d, J=2.2 Hz, 1H), compared to 8.26 (DD, J=6,6, and 2.6 Hz, 1H), 10,52 (s, 1H)3414-56(300 MHz, DMSO-d6) δ: 1.14 in (d, J=6.2 Hz, 3H), 3,93-of 3.96 (m, 1H), 4,08-4,12 (m, 1H), 4,77 (d, J=9,2 Hz, 1H), 4.95 points (d, J=5.5 Hz, 1H), 6,53 (t, J=3,9 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), 7,05 (d, J=7.7 Hz, 1H), 7,32-7,37 (m, 4H), 7,87 (d, J=9,2 Hz, 3H), of 8.04 (DD, J=7,9, 1.7 Hz, 1H), 8,48-8,48 (m, 1H), 10,33 (s, 1H)3424-57(300 MHz, DMSO-d6) a 3.87 (user. s, 1H), 4,24 is 4.35 (m, 3H), 4,51 (kV, J=5.3 Hz, 1H), 6,36 (d, J=2.2 Hz, 1H), 6,79-6,83 (m, 3H), 7,06 (DD, J=7,7, 4.8 Hz, 1H), 7,33 (d, J=8,8 Hz, 2H), to 7.84 (d, J=9,2 Hz, 2H), 7,92 (DD, J=7,7, 1.1 Hz, 1H), ,13 (DD, J=4,6, 1.3 Hz, 1H), 10,22 (s, 1H)3434-58(300 MHz, DMSO-d6) 3,83-to 3.92 (m, 1H), 4,24 is 4.35 (m, 3H), 4,51 (DD, J=10,8, a 5.4 Hz, 1H), 6,38 (d, J=2.6 Hz, 1H), 6,77-6,86 (m, 3H), 7,06 (DD, J=7,7, 4.8 Hz, 1H), 7,69 (d, J=8,4 Hz, 2H), of 7.90-of 7.96 (m, 3H), 8,13 (DD, J=5.0 and 1.7 Hz, 1H), 10,38 (s, 1H)[Table 46]No. approx.Chemical compoundNMR3444-59(400 MHz, DMSO-d6) a 3.87 (m, 1H), 4.26 deaths and 4.4 (m, 3H), 4,51 (m, 1H), 6,37 (d, J=2.4 Hz, 1H), 6,7-6,86 (m, 3H), 7,06 (m, 1H), 7,33 (d, J=8,4 Hz, 2H), 7,83 (DD, J=6,8, and 1.6 Hz), 7,92 (DD, J=7,2, 1.2 Hz), 8,13 (DD, J=to 4.4, 1.6 Hz, 1H), 10,23 (s, 1H)3455-01(300 MHz, DMSO-d6) δ: 1,25 (s, 9H), 4,06 (t, J=4,2 Hz, 2H), to 4.38 (t, J=4.4 Hz, 2H), of 6.96 (t, J=7.9 Hz, 1H), 7,27 (DD, J=7,7, 1.5 Hz, 1H), 7,35 (d, J=8,8 Hz, 2H), to 7.59-the 7.65 (m, 3H), 8,12 (d, J=2.6 Hz, 1H), 8,30 (DD, J=1,3, 0.7 Hz, 1H), at 8.60 (d, J=1.5 Hz, 1H), 10,06 (s, 1H)3465-02(400 MHz, DMSO-d6) of 1.18 (t, J=7.4 Hz, 3H), 2,54 (kV, J=4 Hz, 2H), 4,22 (t, J=4,2 Hz, 2H), 4,36 (t, J=4.4 Hz, 2H), of 6.96 (t, J=7.9 Hz, 1H), 7,24 (DD, J=7,4, and 1.4 Hz, 1H), 7,39 (t, J=4.4 Hz, 2H), to 7.77 (d, J=8,8 Hz, 2H), 8,04 (DD, J=8,3, and 1.4 Hz, 1H), 8,45 (s, 2H), 10,27 (s, 1H)3475-03(400 MHz, DMSO-d6) of 1.18 (t, J=7.7 Hz, 3H), 1,32 (t, J=7.0 Hz, 3H), 2,54 (kV, J=7.7 Hz, 1H), 4.00 points (kV, J=7,0 Hz, 2H), 4,22 (t, J=4.4 Hz, 2H), 4,37 (t, J=4.4 Hz, 2H), 6.89 in (d, J=8,8 Hz, 2H), 6,95 (t, J=7.9 Hz, 1H), 7,25 (d, J=7,4 Hz, 1H), 7,63 (d, J=8,8 Hz, 2H), 8,01 (d, J=8,3 Hz, 1H), 8,45 (s, 2H), becomes 9.97 (s, 1H)3485-04(400 MHz, DMSO-d6) of 4.12 (d, J=4,6 Hz, 2H), to 4.38 (d, J=4,6 Hz, 2H), 6,95 (DD, J=8,1, 7,6 Hz, 1H), 7,27 (DD, J=7,6, 1.5 Hz, 1H), of 7.48 (DD, J=8,1, 1.5 Hz, 1H), to 7.61 (d, J=9,3 Hz, 1H), to 7.67 (d, J=9,3 Hz, 1H), 7,68 (d, 8,8 Hz, 2H), 7,92 (l, 8,8 Hz, 2H), 10,50 (s, 1H)3495-05(400 MHz, DMSO-d6) of 2.26 (s, 3H), a 4.03 (t, J=4.4 Hz, 2H), 4,37 (t, J=4.4 Hz, 2H), 6,65 (d, J=1.6 Hz, 1H),? 7.04 baby mortality (t, J=8 Hz, 1H), 7,25 (d, J=8 Hz, 1H), 7,26 (d, J=9,2 Hz, 2H), 7,83 (d, J=9,2 Hz, 2H), 8,19 (d, J=8 Hz, 1H), 10,36 (s, 1H)3505-06(300 MHz, DMSO-d6) of 2.33 (s, 3H), 3,40 (t, J=4.4 Hz, 2H), 4,36 (t, J=4.4 Hz, 2H), 6,9-7,1 (m, 2H), 7.23 percent (d, J=1.8 Hz, 1H), 7,34 (d, J=9,2 Hz, 2H), to 7.84 (d, J=2 Hz, 2H), 8,10 (d, J=8 Hz, 1H), 10,34 (s, 1H)3516-01(400 MHz, DMSO-d6) of 2.34 (d, J=1.4 Hz, 3H), 3.46 in-of 3.60 (m, 2H), 4,14 (DD, J=11,1, 2.8 Hz, 1H), 4,35-to 4.41 (m, 1H), 4,56 (d, J=11,1 Hz, 1H), 5,19 (t, J=5.8 Hz, 1H), 7,00 (t, J=7.9 Hz, 1H), 7,07 (d, J=1.4 Hz, 1H), 7,19 (DD, J=7,9, and 1.6 Hz, 1H), was 7.36 (d, J=8,3 Hz, 2H), to 7.84 (d, J=8,3 Hz, 2H), 8,00 (DD, J=7,9, and 1.6 Hz, 1H), accounted for 10.39 (s, 1H)

[Table 47]
No. approx.Chemical compoundNMR
3526-02(400 MHz, DMSO-d6) of 2.34 (d, J=1.4 Hz, 3H), 3,47-of 3.60 (m, 2H), 4,15 (DD, J=11,1, 2.3 Hz, 1H), 4,34 was 4.42 (m, 1H), 4,57 (d, J=11,1 Hz, 1H), 5,20 (t, J=5.8 Hz, 1H), 7,01 (t, J=7.9 Hz, 1H), 7,07 (d, J=1.4 Hz, 1H), then 7.20 (DD, J=7,9, and 1.4 Hz, 1H), 7,72 (d, J=8,3 Hz, 2H), 7,94 (d, J=8,3 Hz, 2H), 8,02 (DD, J=7,9, and 1.4 Hz, 1H), 10,56 (s, 1H)
3536-03(400 MHz, DMSO-d6) of 2.34 (d, J=1.4 Hz, 3H), 3,48-3,59 (m, 2H), 4,16 (DD, J=11,1, 2.3 Hz, 1H), 4,37-4,43 (m, 1H), 4,58 (d, J=11,1 Hz, 1H), 6,51 (user., 2H), 7,01 (t, J=7.9 Hz, 1H), to 7.09 (d, J=1.4 Hz, 1H), 7,21 (DD, J=7,9, and 1.4 Hz, 1H), to 7.61 (d, J=8,8 Hz, 1H), 7,68 (DD, J=8,8, 2.3 Hz, 1H), 8,01 (DD, J=79, the 1.4 Hz, 1H), 8,12 (d, J=2.3 Hz, 1H), 10,51 (s, 1H)
3546-04(400 MHz, DMSO-d6) of 1.27 (d, J=6.0 Hz, 7H), was 2.34 (d, J=1.4 Hz, 3H), 3.46 in-3,59 (m, 2H), 4,13 (DD, J=11,1, 2.3 Hz, 1H), 4,35-to 4.41 (m, 1H), 4,49-4,60 (m, 2H), 5,19 (t, J=5.6 Hz, 1H), 6,99 (t, J=8,1 Hz, 1H), 7,07 (d, J=1.4 Hz, 1H), 7,12-7,20 (m, 2H), was 7.36-7,40 (m, 1H), 7,71 (DD, J=13,7, 2.6 Hz, 1H), to 7.99 (DD, J=8,1, 1.4 Hz, 1H), of 10.21 (s, 1H)
3556-05(400 MHz, DMSO-d6) of 1.29 (s, 9H), was 2.34 (d, J=1.4 Hz, 3H), 3.45 points-of 3.60 (m, 2H), 4,13 (DD, J=11,1, 2.8 Hz, 1H), 4,34-to 4.41 (m, 1H), 4,57 (d, J=11,1 Hz, 1H), 5,19 (t, J=5.8 Hz, 1H), 7,00 (t, J=8,1 Hz, 1H), 7,07 (d, J=1.4 Hz, 1H), 7,11 (t, J=9.0 Hz, 1H), 7,17 (DD, J=8,1, 1,6 Hz, 1H), 7,33-7,39 (m, 1H), 7,73 (DD, J=13,0, 2.3 Hz, 1H), 8,00 (DD, J=8,1, 1,6 Hz, 1H), 10.30 a.m. (s, 1H)
3566-06(400 MHz, DMSO-d6) of 0.98 (d, J=6.5 Hz, 6H), 1,99-2,05 (m, 1H), 2,34 (d, J=1.4 Hz, 3H), 3.46 in-3,59 (m, 2H), 3,80 (d, J=6,5 Hz, 2H), 4,13 (DD, J=11,1, 2.8 Hz, 1H), 4,35-to 4.41 (m, 1H), 4,57 (d, J=11,1 Hz, 1H), 5,20 (t, J=5.6 Hz, 1H), 6,99 (t, J=7.9 Hz, 1H), 7,07 (d, J=1.4 Hz, 1H), 7,13 (t, J=9,3 Hz, 1H), 7,18 (DD, J=7,9, and 1.4 Hz, 1H), 7,37-7,41 (m, 1H), of 7.70 (DD, J=13,7, 2.6 Hz, 1H), to 7.99 (DD, J=8,9, and 1.4 Hz, 1H), 10,19 (s, 1H)
3576-07(400 MG is, DMSO-d6) 2,35 (d, J=0.9 Hz, 3H), 3,49-3,61 (m, 2H), 4,15 (DD, J=11,1, 2.8 Hz, 1H), 4,37 (t, J=5,1 Hz, 1H), 4,58 (DD, J=11,1, 0.9 Hz, 1H), total of 5.21 (t, J=5.8 Hz, 1H), 7,02 (t, J=7.9 Hz, 1H), was 7.08 (d, J=1.4 Hz, 1H), 7,20 (DD, J=7,7, and 1.6 Hz, 1H), 7,46 (DD, J=8,8, 1.9 Hz, 1H), 7,68 (t, J=8,3 Hz, 1H), of 7.90 (DD, J=11,6, 2.3 Hz, 1H), 8,03 (DD, J=8,3, and 1.4 Hz, 1H), 10,53 (s, 1H)
3586-08(400 MHz, DMSO-d6) of 2.34 (d, J=0.9 Hz, 3H), 3.46 in-of 3.60 (m, 2H), 4,14 (DD, J=11,4, and 2.6 Hz, 1H), to 4.38 (t, J=7,0 Hz, 1H), 4,58 (DD, J=11,4, 1.2 Hz, 1H), 5,20 (t, J=5.6 Hz, 1H), 7,01 (t, J=8,1 Hz, 1H), 7,07 (d, J=1,4 Hz, 1H), 7,21 (DD, J=7,4, and 1.4 Hz, 1H), 7,52 (t, J=9.7 Hz, 1H), of 7.96-8,03 (m, 2H), 8,25 (kV, J=3.1 Hz, 1H), 10,55 (s, 1H)
3596-09(400 MHz, DMSO-d6) of 2.33 (d, J=1.4 Hz, 3H), 2,96 (t, J=4.6 Hz, 4H), 3,47-of 3.60 (m, 2H), 3,74 (t, J=4.6 Hz, 4H), 4,13 (DD, J=10,9, and 2.6 Hz, 1H), to 4.38 (t, J=6,7 Hz, 1H), 4,57 (DD, J=11,1, 1.4 Hz, 1H), 5,19 (t, J=5,6 Hz, 1H), 6,97-7,05 (m, 2H), 7,07 (d, J=1.4 Hz, 1H), 7,18 (DD, J=7,7, and 1.6 Hz, 1H), 7,39 (d, J=8,8 Hz, 1H), 7,66 (DD, J=14,8, 2.3 Hz, 1H), to 7.99 (DD, J=8,1, 1,6 Hz, 1H), of 10.21 (s, 1H)
[Table 48]
No. approx.Chemical compoundNMR
3606-10 (400 MHz, DMSO-d6) of 2.34 (d, J=1.4 Hz, 3H), 3,47-of 3.53 (m, 1H), 3,55-of 3.60 (m, 1H), 4,15 (DD, J=11,1, 2.3 Hz, 1H), to 4.38 (t, J=7.2 Hz, 1H), 4,58 (DD, J=11,1, 0.9 Hz, 1H), total of 5.21 (t, J=5.3 Hz, 1H), 7,03 (t, J=7.9 Hz, 1H), was 7.08 (d, J=1.4 Hz, 1H), 7.23 percent (DD, J=7,7, and 1.6 Hz, 1H), 7,92 (d, J=8,8 Hz, 1H), with 8.05 (DD, J=8,3, and 1.4 Hz, 1H), 8,44 (DD, J=8,8, 1.9 Hz, 1H), 9,01 (d, J=2.3 Hz, 1H), 10,80 (s, 1H)
3616-11(300 MHz, DMSO-d6) 2,28 (d, J=1.1 Hz, 3H), 3,51 is 3.57 (m, 2H), 4,16 (DD, J=11,2, 2.4 Hz, 1H), 4,43 (t, J=7.2 Hz, 1H), 4,59 (d, J=10.3 Hz, 1H), 5,17 (t, J=5.7 Hz, 1H), 6,69 (d, J=1.5 Hz, 1H), 7,01 (t, J=8,1 Hz, 1H), 7,15 (DD, J=7,7, 1.5 Hz, 1H), 7,35 (d, J=8,4 Hz, 2H), to 7.84 (d, J=9,2 Hz, 2H), by 8.22 (DD, J=8,3, 1.7 Hz, 1H), 10,36 (s, 1H)
3626-12(300 MHz, DMSO-d6) 2,28 (d, J=1.5 Hz, 3H), 3,51 is 3.57 (m, 2H), 4,17 (DD, J=11,2, 2.4 Hz, 1H), of 4.44 (t, J=7.2 Hz, 1H), 4,59 (d, J=9.9 Hz, 1H), 5,18 (t, J=5.7 Hz, 1H), 6,69 (d, J=1.5 Hz, 1H), 7,02 (t, J=7.9 Hz, 1H), 7,16 (DD, J=7,7, 1.5 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), 7,94 (d, J=8,4 Hz, 2H), 8,23 (DD, J=8,3, 1.7 Hz, 1H), 10,53 (s, 1H)
3636-13(400 MHz, DMSO-d6) of 2.15 (s, 3H), of 2.23 (s, 3H), 3,44-to 3.58 (m, 2H), 4,11 (DD, J=11,1, 2.3 Hz, 1H), 4,37-4,43 (m, 1H), 4,56 (d, J=11,1 Hz, 1H), 5,18 (t, J=5.8 Hz, 1H), 7,00 (t, J=7.9 Hz, 1H), 7,18 (DD, J=7,9, 1,4 Hz, 1H), was 7.36 (d, J=8,3 Hz, 2H), 7,83 (d, J=8,3 Hz, 2H), 7,98 (DD, J=7,9, and 1.4 Hz, 1H), accounted for 10.39 (s, 1H)
3646-14(400 MHz, DMSO-d6) of 2.16 (s, 3H), 2,24 (s, 3H), 3,44-3,59 (m, 2H), 4,12 (DD, J=11,1, 2.3 Hz, 1H), 4,37-4,43 (m, 1H), 4,56 (d, J=11,1 Hz, 1H), 5,19 (t, J=5.8 Hz, 1H), 7,01 (t, J=8,1 Hz, 1H), 7,20 (DD, J=8,1, 1,6 Hz, 1H), 7,71 (d, J=8,8 Hz, 2H), 7,94 (d, J=8,8 Hz, 2H), to 7.99 (DD, J=8,1, 1,6 Hz, 1H), 10,56 (s, 1H)
3656-15(400 MHz, DMSO-d6) 2,60 (d, J=4,2 Hz, 3H), 3,51-to 3.64 (m, 2H), 4,22 (DD, J=11,1, 2.8 Hz, 1H), 4,42 (t, J=7,4 Hz, 1H), 4,56 (d, J=10,2 Hz, 1H), 5,24 (t, J=5.8 Hz, 1H),? 7.04 baby mortality (t, J=7.9 Hz, 1H), 7,24 (DD, J=7,9, 1,4 Hz, 1H), was 7.36 (d, J=8,3 Hz, 2H), 7,83 (d, J=8,8 Hz, 2H), of 7.96 (DD, J=8,3, and 1.4 Hz, 1H), 10,41 (s, 1H)
3666-16(400 MHz, DMSO-d6) 2,60 (d, J=2,8 Hz, 3H), 3,52-to 3.64 (m, 2H), 4,23 (DD, J=11,1, 2.8 Hz, 1H), 4,42 (t, J=7,0 Hz, 1H), 4,56 (d, J=10,2 Hz, 1H), 5,24 (t, J=5.8 Hz, 1H), 7,05 (t, J=7.9 Hz, 1H), 7,25 (DD, J=7,7, 1,6 Hz, 1H), 7,72 (d, J=8,8 Hz, 2H), 7,92-7,98 (m, 3H), of 10.58 (s, 1H)
3676-17(400 MHz, DMSO-d6) 2,11 (s, 3H), 2,17 (s, 3H), is 3.08 (t, J=5.6 Hz, 2H), of 4.05 (t, J=5.6 Hz, 2H), 7.23 percent (t, J=7.9 Hz, 1H), 7,32-7,39 (m, 3H), 7,66 (DD, J=7,9, and 1.4 Hz, 1H), 7,83 (d, J=9,3 Hz, 2H), to 10.62 (s, 1H)

[Table 49]
No. approx.Chemical compoundNMR
3686-18(400 MHz, DMSO-d6) 2,19 (s, 3H), of 2.28 (s, 3H), 2,90-a 3.01 (m, 1H), 3,41-of 3.48 (m, 1H), 3.96 points-4,06 (m, 1H), 4,23-or 4.31 (m, 1H), 7,28 (d, J=7,4 Hz, 1H), 7,39 (d, J=8,8 Hz, 2H), to 7.59 (t, J=7.9 Hz, 1H), 7,84-of 7.90 (m, 3H), 10,81 (s, 1H)
3697-01(400 MHz, CHLOROFORM-d) of 1.33 (s, 9H), of 3.75 (t, J=4,2 Hz, 2H), 3,83 (s, 3H), of 4.54 (t, J=4.4 Hz, 2H), 6,76 (DD, J=8,1, 1.2 Hz, 1H), PC 6.82 (t, J=8,1 Hz, 1H), 6,94 (d, J=8,8 Hz, 2H), 7,17 (d, J=8,8 Hz, 2H), 7,38 (d, J=8,8 Hz, 2H), 7,60 (d, J=8,3 Hz, 2H), to 7.64 (DD, J=8,1, 1,6 Hz, 1H), being 9.61 (s, 1H)
3707-02(400 MHz, CHLOROFORM-d) of 1.03 (d, J=7,0 Hz, 6H), 2.05 is-a 2.12 (m, 1H), of 3.73 (d, J=6.5 Hz, 2H, in), 3.75 (t, J=4.4 Hz, 2H), 3,83 (s, 3H), of 4.54 (t, J=4.4 Hz, 2H), 6,76 (DD, J=7,9, 1.9 Hz, 1H), PC 6.82 (t, J=7.9 Hz, 1H), 6.90 to (d, J=8,8 Hz, 2H), 6,94 (DD, J=7,0, 2,3 Hz, 2H), 7,17 (DD, J=6,5, and 2.3 Hz, 2H), 7,58 (d, J=8,8 Hz, 2H), 7,65 (DD, J=7,7, and 1.6 Hz, 1H), to 9.57 (s, 1H)
3717-03(400 MHz, CHLOROFORM-d) 3,76 (user. the, 2H), of 3.84 (s, 3H), 4,56 (user. s, 2H), for 6.81 (d, J=17.6 Hz, 2H), of 6.96 (user. s, 2H), 7,17 (user. s, 2H), 7,33 (user. s, 2H), 7,65 (user. s, 3H), 9,73 (s, 1H)
3727-04(400 MHz, DMSO-d6) of 3.46-with 3.79 (m, 3H), 4,23 (d, J=10 Hz, 1H), 4,56 (d, J=10 Hz, 1H), 4,96 (s, 1H), 6,10 (d, J=7,0 Hz, 1H), of 6.71-of 6.90 (m, 2H), 7,34-7,71 (m, 6H), 7,86 (d, J=8,8 Hz, 2H), 10,36 (s, 1H)
3737-05(400 MHz, DMSO-d6) of 3.46-with 3.79 (m, 3H), 4,23 (d, J=10 Hz, 1H), 4,56 (d, J=10 Hz, 1H), equal to 4.97 (s, 1H), 6,11 (d, J=7,0 Hz, 1H), 6,74-6,91 (m, 2H), 7,39-7,72 (m, 6H), of 7.96 (d, J=8,3 Hz, 2H), 10,53 (s, 1H)
3747-06(400 MHz, DMSO-d6) 3,45-of 3.80 (m, 3H), 4,23 (userd, J=10 Hz, 1H), 4,56 (userd, J=10 Hz, 1H), equal to 4.97 (s, 1H), 6,12 (d, J=7.9 Hz, 1H), 6,74-of 6.90 (m, 2H), 7,40 for 7.78 (m, 6H), of 7.97 (d, J=13,0 Hz, 1H), of 10.73 (s, 1H)
3757-07(300 MHz, DMSO-d6) of 3.46-of 3.60 (m, 2H), 3,79 (t, J=7,0 Hz, 1H), 4,08 (DD, J=10,8, 2.0 Hz, 1H), 4,49 (d, J=10.3 Hz, 1H), 5,09 (t, J=5.3 Hz, 1H), 6,80-6,91 (m, 2H), 7,01 (DD, J=7,3, 1.5 Hz, 1H), 7,35-7,44 (m, 6H), 7,85 (d, J=8,8 Hz, 2H), 10,33 (s, 1H)

[The table is as 50]
No. approx.Chemical compoundNMR
3767-08(400 MHz, DMSO-d6) 3,45-3,66 (m, 3H), of 3.77 (s, 3H), 4,13 (DD, J=10,9, and 2.1 Hz, 1H), 4,49 (DD, J=10,9, and 2.1 Hz, 1H), equal to 4.97 (t, J=5.3 Hz, 1H), 6,51 (DD, J=8,0, 1.5 Hz, 1H), 6,74 (t, J=8.0 Hz, 1H), 6,86 (DD, J=7,4, 1.5 Hz, 1H), 7,01 (d, J=8,8 Hz, 2H), 7,24 (d, J=8,8 Hz, 2H), 7,35 (d, J=8,8 Hz, 2H), a 7.85 (d, J=8,8 Hz, 2H), 10,33 (s, 1H)
3777-09(400 MHz, DMSO-d6) 3,43-3,66 (m, 3H), of 3.77 (s, 3H), 4,14 (d, J=8,8 Hz, 1H), 4,50 (t, J=5.5 Hz, 1H), to 4.98 (t, J=5.5 Hz, 1H), of 6.52 (DD, J=7,9, and 1.4 Hz, 1H), 6.75 in (t, J=7.9 Hz, 1H), 6.87 in (DD, J=7,9, and 1.4 Hz, 1H), 7,01 (d, J=8,8 Hz, 2H), 7,25 (d, J=8,8 Hz, 2H), 7,71 (d, J=8,3 Hz, 2H), of 7.96 (d, J=8,3 Hz, 2H), 10,50 (s, 1H)
3787-10(300 MHz, DMSO-d6) of 3.46-3,61 (m, 2H), 3,79 (t, J=7,0 Hz, 1H), 4.09 to (d, J=8,8 Hz, 1H), 4,50 (d, J=9.9 Hz, 1H), 5,10 (t, J=5.5 Hz, 1H), 6,82-6,93 (m, 2H), 7,02 (DD, J=7,3, 1.8 Hz, 1H), 7,40 (m, 4H), 7,71 (d, J=8,8 Hz, 2H), of 7.96 (d, J=8,4 Hz, 2H), 10,50 (s, 1H)
3797-11(300 MHz, DMSO-d6) 3,51 of 3.56 (m, 2H) 3,79 (t, J=7.2 Hz, 1H), 4,08 (DD, J=10,8, 2.4 Hz, 1H), 4,50 (d, J=9.9 Hz, 1H), 5,10 (t, J=5.3 Hz, 1H), 6,80-6,91 (m, 2H), 7,01 (DD, J=7,2, 1.7 Hz, 1H), 7,33-7,46 (m, 6H), 7,78 (d, J=8,8 Hz, 2H), 10,28 (s, 1H)

Example test

Below will be described the analysis to assess the inhibiting VR1 compounds having features of the invention. The analysis is intended to evaluate the in vitro inhibition of occurrence of CA2+in cells caused by the proton, one of VR1 agonists.

The test example 1: inhibition of the occurrence of CA2+in cells

Glioma rats (6BU1), stably expressing VR1 man, suspended in 20 mm MES buffer (pH 6.8, containing 20 mm 2-morpholinepropanesulfonic (hereinafter referred to as MES), 115 mm NaCl, 5 mm KCl, 1 mm MgCl2and 14 mm D-glucose) to obtain the density of cells 1×106cells/ml of suspension was added to the solution of a fluorescent dye, Fura 2-AM (Dojindo Has, Cat. No. 343-05401), to obtain a concentration of 5 μm. Next was added Pluronic F-127 (Wako Pure Chemical Industries, Ltd., Cat. No. P6866) to get its content of 0.1%. Then the suspension was incubated at 37°C for 30 min the Cells were collected and washed three times with 20 mm MES buffer. Cells are again suspended to obtain the density of cells 5×105cells/ml 500 ál. Portion 500 μl of the suspension were taken cuvette (MC MEDICAL, INC., Cat. No. SSR3121), to the suspension was added 10 μl of 20 mm MES buffer containing 250 mm CaCl2to enable the CA2+in cells. In fact sesame was added 5 μl of a solution of the test compounds (in the range of 100 μm - 10 nm in DMSO) to ensure that its final concentration in the range of 1 μm - 0.1 nm. In the alternative case 5 μl of DMSO was added as a control to ensure a final concentration of 1% DMSO. The suspension was installed in intracellular ionomer (CAF-110; JASCO) after 10 min after these additions. Cells stimulated protons by adding 60 μl of 20 mm MES buffer at pH of 1.1 to suspension to determine its pH at 5.5. The activity of the test compounds was determined as the difference between the minimum fluorescence intensity before stimulation with agonist and its maximum after stimulation. The value of the IC50received from the percentage inhibition of the test compound compared with the control. The results are shown in the following tables 51-56.

In the tables, the symbol “++” means the value of the IC50less than 100 nm, and the symbol ”+” means the value of the IC50100 nm - 1000 nm, inclusive.

[Table 51]

[Table 52]

[Table 53]

[Table 54]

[Table 55]

[Table 56]

INDUSTRIAL APPLICABILITY

Condensed benzamide derivative of the present invention effectively inhibits aktivnosti subtype 1 receptor vanilloid (VR1), and, therefore, it is an effective drug treatment and/or prophylaxis of diseases such as pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic pain, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ischemic symptom, nerve damage, neurogenic skin damage, inflammatory disease, pruritus, allergic rhinitis, apoplexy, the irritable bowel syndrome, asthma, chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer and inflammatory bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and urinary incontinence.

1. Condensed benzamide derivative represented by the following General formula [1]or its pharmaceutically acceptable salt:

where Z is a
(1)-O-,
(2)-NR5-(where R5represents a C1-6-alkyl group is,
(3)-S - or
(4)-SO-
l is 0 or 1;
m is 0 or 1;
R1represents a
(1) a hydrogen atom, or
(2) C1-6-alkyl group which may be substituted by 1-5 substituents selected from the following group:
group a:
(a) a halogen atom,
(b) a hydroxyl group,
(c) C1-6-alkoxygroup,
(d) a carboxyl group,
(e) C1-6-alkoxycarbonyl group,
(f)-CONR6R7(where R6and R7are the same or different and each represents a hydrogen atom, C1-6-alkyl group or acyl group, the above alkyl group may be substituted by a hydroxyl group or alloctype),
(g)-NR6R7(where R6and R7have the values listed above)
(h)-NR6COR7(where R6and R7have the values listed above)
R2represents a
(1) a hydrogen atom,
(2) a hydroxyl group,
(3) C1-6-alkyl group,
(4) a carboxyl group,
(5) C1-6-alkoxycarbonyl group or
(6) -CONR10R11(where R10and R11are the same or different and each represents a hydrogen atom or C1-6-alkyl group);
or R2together with R1forms =O;
R3represents a
(1) a hydrogen atom, or
(2) C1-6-alkyl group;
R4represents a
(1) a hydrogen atom, or
(2) a halogen atom,
V represents the FDS is th
(1) a direct link or
(2)-(CR21R22)n- (where R21and R22are the same or different and each represents a hydrogen atom or C1-6-alkyl group and n is 1 or 2);
ring P1 and P2 are the same or different and each represents a
(1) aromatic or saturated carbocyclic group containing 6 carbon atoms which may be substituted by 1-5 substituents selected from the following group C, or
(2) 5-10-membered saturated or unsaturated heterocyclic group containing 1-3 heteroatoms selected from N, O and S, which may be substituted by 1-5 substituents selected from the following groups:
group:
(a) a halogen atom,
(b) a hydroxyl group,
(c) C1-6-alkoxygroup, which may be substituted by 1-5 substituents selected from group a,
(e) C1-6-alkyl group which may be substituted by 1-5 substituents selected from group a,
(f) -CONR23R24(where R23and R24are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group a),
(g) -NR123R124(where R123and R124are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 deputies who, selected from group a),
(h) -NR223COR224(where R223and R224are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group a),
(j)-SR26(where R26represents a C1-6-alkyl group),
(o) -COR27(where R27represents a C1-6-alkyl group, C1-6-alkoxygroup, cycloalkyl group, aracelio group, urlcategory, cycloalkylcarbonyl or hydroxyl group),
(q) a saturated 5-6-membered heterocyclic group containing 1-2 heteroatoms selected from N, O, which may be substituted by 1-5 substituents selected from (a)-(C), (e)-(h), (j), (o) group,
(r) -O-R28(where R28represents an acyl group, tsiklogeksilnogo group which may be substituted by 1-5 substituents selected from (a)-(o) group, or a heterocyclic group which may be substituted by 1-5 substituents selected from (a)-(C), (e)-(h)), pyridinyl group which may be substituted by 1-5 substituents selected from (a)-(C), (e)-(h), (j), (o) group,
(s) -O-(CR121R122)n-R128(where R121, R122the same or different
and each represents a hydrogen atom, n=1, and R128represents phenyl, cyclohexyl, or pyridinyl group which may be substituted by 1-5 substituents, selected from (a)-(C), (e)-(h), (j), (o)),
(t) the nitro-group and
(u) cyano.

2. Condensed benzamide derivative or its pharmaceutically acceptable salt according to claim 1, where the ring R1 represents an unsaturated 5-membered or 6-membered heterocyclic ring containing 1-4 heteroatoms selected from a nitrogen atom, oxygen atom and sulfur atom, or a phenyl group (where the aforementioned heterocyclic ring may be substituted by halogen atom, hydroxyl group, C1-6-alkyl group which may be substituted by 1-5 substituents selected from group a, and C1-6-alkoxygroup, which may be substituted by 1-5 substituents selected from group a).

3. Condensed benzamide derivative or its pharmaceutically acceptable salt according to claim 2, where the ring R1 represents an unsaturated 5-membered or 6-membered heterocyclic ring containing at least 1 to 3 nitrogen atom, or a phenyl group (where the aforementioned heterocyclic ring may be substituted by C1-6-alkyl group which may be substituted by a hydroxyl group or C1-6-alkoxygroup, a halogen atom, a hydroxyl group, and Cl-6-alkoxygroup, which may be substituted by 1-5 substituents selected from group a).

4. Condensed benzamide derivative or its pharmaceutically acceptable salt according to claim 3 in which the ring P1 performance is possessing a heterocyclic group, selected from peredelnoj group, personalni group and thiazolidine group, or phenyl group (where these heterocyclic groups can be substituted by C1-6-alkyl group which may be substituted by a hydroxyl group, a halogen atom, a hydroxyl group and C1-6-alkoxygroup, which may be substituted by 1-5 substituents selected from group a).

5. Condensed benzamide derivative or its pharmaceutically acceptable salt according to claim 1, where the ring R2 is a carbocyclic group which may be substituted by the Deputy, selected from
the halogen atom,
hydroxyl group,
C1-6-alkoxygroup (where specified alkoxygroup may be substituted by a halogen atom, -CONR622R624(where R623and R624are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group a), C3-8-cycloalkyl group, C1-6-alkoxygroup, a carboxyl group or C1-6-alkoxycarbonyl group),
C1-6-alkyl group (where this alkyl group may be substituted by a halogen atom, a hydroxyl group or C1-6-alkoxygroup),
-NR123R124(where R123and R124have the values listed above)
-NR223COR224(where R223and R224have the values listed you the e),
-COR27(where R27represents a C1-6-alkyl group, C1-6-alkoxygroup, cycloalkyl group, aracelio group, urlcategory, cycloalkylcarbonyl or hydroxyl group),
-CONR23R24(where R23and R24have the values specified above), the heterocyclic group in the form of a saturated or unsaturated group-Deputy, which has 1-3 nitrogen atom as heteroatoms (where specified heterocyclic group may be substituted by a group-Deputy, selected from hydroxyl group,
-CONR723R724(where R723and R724are the same or different and each represents a hydrogen atom or C1-6-alkyl group which may be substituted by 1-5 substituents selected from group a), C1-6-alkoxygroup, carboxyl group, C1-6-alkyl group which may be substituted by C1-6-alkoxygroup, C1-6-alkoxycarbonyl group and alloctype),
-O-R28(where R28represents an acyl group, a carbocyclic group which may be substituted by 1-5 substituents selected from (a)-(i) group, or a heterocyclic group which may be substituted by 1-5 substituents selected from (a)-(i) group (C),
-O(CR121R122)n-R128(where R121and R122are the same or different and each represents the Oh hydrogen atom or C1-6-alkyl group, n is 1 or 2 and R128represents an acyl group, a carbocyclic group which may be substituted by 1-5 substituents selected from (a)-(i) group, or a heterocyclic group which may be substituted by 1-5 substituents selected from (a)to(l)),
nitro and
ceanography, or
heterocyclic group which may be substituted by the Deputy, as described for carbocyclic group (where specified heterocyclic group means a saturated or unsaturated 5-membered or 6-membered heterocyclic ring which has 1 to 4 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, or a condensed ring of these heterocyclic rings or a condensed heterocyclic group specified heterocyclic ring and the carbocyclic ring selected from benzene, cyclopentane and cyclohexane).

6. Condensed benzamide derivative or its pharmaceutically acceptable salt according to claim 5, where the ring P2 as carbocyclic group according to claim 5 represents a phenyl group or tsiklogeksilnogo group, or a ring P2 as the heterocyclic group is thiazolino group, pyridyloxy group, piperidino group, piperidino, pinolillo group, benzo[1,3]dictograph, 2,3-dihydrobenzo[1,4]dictograph or 1,2,3,4-tetrahydroquinolin the second group.

7. Condensed benzamide derivative according to claim 1, chosen from:
1) N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
2) 8-(4-tert-butylphenyl)carbarnoyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid,
3) N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
4) N-(4-tert-butylphenyl)-1-(3-chloropyridin-2-yl)-4-methyl-1,2,3,4-tetrahydroquinoxalin-5-carboxamide,
5) N-(4-tert-butylphenyl)-9-(3-chloropyridin-2-yl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide,
6) N-(4-chlorophenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
7) 4-(3-chloropyridin-2-yl)-N-(4-isopropoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
8) N-(1-tert-butylpiperazine-4-yl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
9) 4-(3-chloropyridin-2-yl)-N-(4-were)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
10) 4-(3-chloropyridin-2-yl)-N-(TRANS-4-methylcyclohexyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
11) 4-(3-chloropyridin-2-yl)-N-(4-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
12) N-benzyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
13) N-(4-chlorophenyl)methyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
14) N-(4-tert-butylphenyl)methyl-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]on casin-8-carboxamide,
15) 4-(3-chloropyridin-2-yl)-N-(4-triptoreline)methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
16) N-(4-tert-butylphenyl)-4-(pyridin-2-yl)-3,4-dihydro-2H-[1,4]oxazin-8-carboxamide,
17) N-(4-tert-butylphenyl)-4-(3-triptorelin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
18) N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-2,2-dimethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
19) N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)-2-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
20) N-(4-tert-butylphenyl)-6-chloro-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
21) 4-(3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
22) 4-(3-chloropyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
23) 4-(3-chloropyridin-2-yl)-N-(4-methoxyphenyl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
24) N-(TRANS-4-tert-butylcyclohexyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
25) 4-(3-chloropyridin-2-yl)-N-(4-chloro-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
26) 4-(3-chloropyridin-2-yl)-N-(4-forfinal)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
27) 4-(3-chloropyridin-2-yl)-N-(3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
28) 4-(3-chloropyridin-2-yl)-N-(4-cryptomaterial-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
29) 4-(3-chloropyridin the-2-yl)-N-(5-triptorelin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
30) 4-(3-chloropyridin-2-yl)-N-(2-triptorelin-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
31) 4-(3-chloropyridin-2-yl)-N-(4-isopropylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
32) 4-(3-chloropyridin-2-yl)-N-(quinoline-7-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
33) 4-(3-chloropyridin-2-yl)-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
34) 4-(3-chloropyridin-2-yl)-N-(4-ethoxycarbonylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
35) 4-[4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carbonyl]aminobenzoic acid,
36) N-(4-carbamoylmethyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
37) 4-(3-chloropyridin-2-yl)-N-(4-methylcarbamoylmethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
38) 4-(3-chloropyridin-2-yl)-N-(4-dimethylcarbamoyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
39) N-(4-acetylphenyl)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
40) 4-(3-chloropyridin-2-yl)-N-[4-(1-hydroxy-1-methyl)ethylphenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
41) 4-(3-chloropyridin-2-yl)-N-[4-(1-hydroxy-1-methyl)propylphenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
42) 4-(3-chloropyridin-2-yl)-N-(1-isobutylpyrazine-4-yl)phenyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
43) N-(TRANS-4-tert-butoxyethoxy)-4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxaze the-8-carboxamide,
44) 4-(3-chloropyridin-2-yl)-N-(3-isopropoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
45) 4-(3-chloropyridin-2-yl)-N-(3-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
46) N-(4-tert-butylphenyl)-4-(pyridin-4-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
47) N-(4-tert-butylphenyl)-4-(3-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
48) 4-(3-chloropyridin-2-yl)-N-(4-piperidinophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
49) 4-(3-chloropyridin-2-yl)-N-(4-dimethylaminophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
50) 4-(3-chloropyridin-2-yl)-N-(4-morpholinyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
51) 4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-isopropoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
52) 4-(3-chloropyridin-2-yl)-N-(2-fluoro-4-isopropoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
53) 4-(3-chloropyridin-2-yl)-N-(4-fluoro-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
54) 4-(3-chloropyridin-2-yl)-N-(4-dimethylamino-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
55) 4-(3-chloropyridin-2-yl)-N-(4-isopropoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
56) 4-(3-chloropyridin-2-yl)-N-(4-methoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
57) 4-(3-chloropyridin-2-yl)-N-(4-isobutoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxaze the-8-carboxamide,
58) N-(4-tert-butylphenyl)-4-(4-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
59) N-(4-tert-butylphenyl)-4-(6-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
60) N-(4-tert-butylphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
61) N-(4-tert-butylphenyl)-4-(pyridin-3-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
62) N-(4-cyanophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
63) N-(3-amino-4-chlorophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
64) N-(3-acetamido-4-chlorophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
65) N-[4-(4-carbamoylbiphenyl-1-yl)-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
66) N-[3-fluoro-4-(4-methylcarbamoylmethyl-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
67) N-[4-(4-dimethylcarbamoyl-1-yl)-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
68) N-[4-(4-ethoxypyridine-1-yl)-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
69) N-[3-fluoro-4-(4-isopropoxypyridine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
70) N-[3-fluoro-4-(3-methoxypiperidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
71) N-[3-fluoro-4-(4-methoxymethyl is peridin-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
72) N-[3-fluoro-4-(3-ethoxypyrrolidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
73) N-(4-isobutoxy-3-ethoxycarbonylphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
74) 2-isobutoxy-{[4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carbonyl]amino}benzoic acid,
75) N-(3-carbarnoyl-4-isobutylphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin - 8-carboxamide,
76) N-(4-isobutoxy-3-methylcarbamoylmethyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
77) N-(3-dimethylcarbamoyl-4-isobutylphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
78) N-(4-acetylphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
79) N-[4-(1-hydroxy-1-methyl)ethylphenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
80) N-(3-acetyl-4-chlorophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
81) N-[4-chloro-3-(1-hydroxy-1-methyl)ethylphenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
82) N-[4-(1-methoxy-1-methyl)ethylphenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
83) N-(3-chloro-4-methoxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
84) 4-(5-methylpyridin-2-yl)-N-(4-propoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8 carbox the Ministry of foreign Affairs,
85) N-(3-fluoro-4-propoxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
86) N-(4-ethoxy-3-forfinal)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
87) N-(3-ethoxy-4-were)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
88) N-(3-carbamoylmethyl-4-were)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
89) N-(3-methoxyethoxy-4-were)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
90) N-[3-fluoro-4-(2-methoxypiperidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
91) N-(4-chlorophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
92) N-(3-fluoro-4-were)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
93) N-(2-chloropyridin-5-yl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
94) 4-(3-chloropyridin-2-yl)-N-(4-ethoxyphenyl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
95) 4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-piperidinophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
96) 4-(3-chloropyridin-2-yl)-N-(TRANS-4-Toxicological)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
97) 4-(3-chloropyridin-2-yl)-N-(TRANS-4-isopropylcyclohexane)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
98) 4-(3-chloropyridin-2-yl)-N-(TRANS-4-cyclopentylacetyl)-3,4-dihydr what-2H-benzo[1,4]oxazin-8-carboxamide,
99) 4-(3-chloropyridin-2-yl)-N-(TRANS-4-cyclohexyloxycarbonyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
100) 4-(3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
101) 4-(3-chloropyridin-2-yl)-N-[3-fluoro-4-(4-methoxypiperidine-1-yl)phenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
102) 4-(3-chloropyridin-2-yl)-N-[4-(4-ethoxypyridine-1-yl)-3-forfinal]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
103) 4-(3-chloropyridin-2-yl)-N-[3-fluoro-4-(4-isopropoxypyridine-1-yl)phenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
104) 4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
105) N-(TRANS-4-Toxicological)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
106) N-(TRANS-4-isopropoxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
107) N-(TRANS-4-cyclohexylmethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
108) N-(TRANS-4-aminocyclohexane)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
109) N-(1,4-dioxaspiro[4,5]DECA-8-yl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
110) 4-(5-methylpyridin-2-yl)-N-(4-oxocyclohexyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
111) 4-(5-methylpyridin-2-yl)-N-(CIS-4-morpholinoethoxy)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carb is xamiga,
112) N-(TRANS-4-dimethylaminoethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
113) N-(TRANS-4-diethylaminoethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
114) 4-(5-methylpyridin-2-yl)-N-[CIS-4-(pyrrolidin-1-yl)cyclohexyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
115) 4-(5-methylpyridin-2-yl)-N-[TRANS-4-(pyrrolidin-1-yl)cyclohexyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
116) 4-(5-methylpyridin-2-yl)-N-(4-piperidinyloxy)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
117) 4-(5-methylpyridin-2-yl)-N-(CIS-4-morpholinoethoxy)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
118) N-(TRANS-4-acetamidophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
119) N-(TRANS-4-cyclohexylmethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
120) 4-(5-chloropyridin-2-yl)-N-(4-ethoxyphenyl)-3,4-dihydro-2H-benzo [1,4] oxazin-8-carboxamide,
121) N-(4-chlorophenyl)-4-(5-chloropyridin-2-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
122) 4-(5-chloropyridin-2-yl)-N-[3-fluoro-4-(4-methoxypiperidine-1-yl)phenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
123) 4-(5-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
124) 4-(5-methylpyridin-2-yl)-N-(2-phenylethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
125) N-[2-(4-chlorophenyl)ethyl]-4-(5-methyl is iridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
126) N-[2-(3-chlorophenyl)ethyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
127) N-[2-(2-chlorophenyl)ethyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
128) 6-[8-(4-triptoreline)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,
129) 4-[3-chloro-5-(1-hydroxy-1-methyl)ethylpyridine-2-yl]-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
130) 4-[3-chloro-5-(1-hydroxyethyl)pyridin-2-yl]-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
131) 5-chloro-6-[8-(3-fluoro-4-triptoreline)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,
132) N-(4-tert-butylphenyl)-4-(5-methoxycarbonylmethyl-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
133) 6-[8-(4-tert-butylphenyl)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,
134) 5-chloro-6-[8-(4-triptoreline)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,
135) 5-chloro-6-[8-(4-tert-butylphenyl)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,
136) 4-(5-acetyl-3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
137) N-(4-tert-butylphenyl)-4-(5-methylcarbamoylmethyl-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
138) N-(4-tert-butylphenyl)-4-(5-carbamoylation-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
139) N-(4-tert-butylphenyl)-4-(5-diethylaminophenyl the Jn-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
140) N-(4-tert-butylphenyl)-4-(5-nitropyridine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
141) 4-(5-aminopyridine-2-yl)-N-(4-tert-butylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
142) 4-(5-acetamidophenyl-2-yl)-N-(4-tert-butylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
143) 4-(5-methoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
144) 4-(5-ethoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
145) 4-(3-chloro-5-methoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
146) 4-(5-hydroxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
147) 4-(5-methoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
148) N-(4-tert-butylphenyl)-4-(4-chloropyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
149) 4-(5-herperidin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
150) 4-(3,5-differencein-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
151) N-(4-tert-butylphenyl)-4-(3-methoxypyridine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
152) N-(4-tert-butylpiperazine-1-yl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
153) 4-[5-(2-hydroxyethoxy)pyridine-2-yl]-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]ox the zine-8-carboxamide,
154) 4-[3-chloro-5-(2-hydroxyethyl)pyridine-2-yl]-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
155) 4-(5-methylpyridin-2-yl)-N-(4-neopentecostal)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
156) N-(3-fluoro-4-piperidinophenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
157) N-(3-fluoro-4-morpholinomethyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
158) N-(3,4-differenl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
159) N-(3-fluoro-4-methoxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
160) N-(4-ethoxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
161) N-[4-(2-oxopiperidin-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
162) 4-(5-methylpyridin-2-yl)-N-(1-methyl-1,2,3,4-tetrahydroquinolin-7-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
163) N-(4-dimethylamino-3-forfinal)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
164) N-{3-fluoro-4-[N-(2-methoxyethyl)isopropylamino]phenyl}-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
165) N-{4-[N-(2-acetoxyethyl)isopropylamino]-3-forfinal}-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
166) N-{3-fluoro-4-[N-(2-hydroxyethyl)isopropylamino]phenyl}-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-CT is oksamida,
167) N-[4-(4-ethoxycarbonylpyrimidine-1-yl)-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
168) 1-(4-{[4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carbonyl]amino}phenyl)piperidine-4-carboxylic acid,
169) N-[3-fluoro-4-(4-methoxypiperidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
170) N-[4-(4-acetoxypiperidine-1-yl)-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
171) N-[3-fluoro-4-(4-hydroxypiperidine-1-yl)phenyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
172) N-(3-methoxy-4-were)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
173) N-[3-(2-hydroxyethoxy)-4-were]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
174) N-[4-(1-tert-butoxycarbonylamino-4-yl)oxy-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
175) N-[4-(piperidine-4-yl)oxy-3-forfinal]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
176) N-(TRANS-4-ethoxycarbonylmethylene)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
177) (TRANS-4-{[4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carbonyl]amino}cyclohexyloxy)acetic acid,
178) N-(TRANS-4-carbamoylmethyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]OK ain-8-carboxamide,
179) N-(TRANS-4-methylcarbamoylmethyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
180) N-(TRANS-4-dimethylcyclohexyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
181) N-[TRANS-4-(2-hydroxyethoxy)cyclohexyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
182) N-(TRANS-4-methoxymethylethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
183) N-(TRANS-4-isopropoxyphenoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
184) N-(CIS-4-methoxymethylethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
185) N-(CIS-4-isopropoxyphenoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
186) N-(TRANS-4-tert-butoxyethoxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
187) N-(TRANS-4-isobutyryloxy)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
188) N-(4,4-dimethylcyclohexyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
189) N-[TRANS-4-(3-methylbutoxy)cyclohexyl]-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
190) N-(TRANS-4-benzyloxyphenyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
191) N-(TRANS-4-from propylcyclohexyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
192) N-(TRANS-4-propylcyclohexyl)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
193) N-(TRANS-4-neopentylglycol)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
194) N-(4-tert-butylphenyl)-4-(5-methoxypyridine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
195) 5-chloro-6-[8-(3-chloro-4-trifloromethyl)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,
196) 5-chloro-6-[8-(4-trifloromethyl)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,
197) 4-(5-methylaminomethyl-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
198) 4-(5-ethoxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
199) 4-(3-chloro-5-methoxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
200) 4-[5-(2-hydroxyethoxy)pyridine-2-yl]-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
201) 4-(5-hydroxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
202) 4-(5-methoxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
203) 4-(3-cyano-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
204) 4-(3-carbamoylation-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
205) 4-(3-m is talkability-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
206) 4-(3-dimethylcarbamoyl-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
207) 4-(3-benzyloxycarbonylamino-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
208) 2-[8-(4-trifloromethyl)carbarnoyl-2,3-dihydrobenzo[1,4]oxazin-4-yl]nicotinic acid,
209) 4-(3-benzyloxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
210) 4-(3-hydroxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
211) 4-[3-(2-hydroxyethoxy)pyridine-2-yl]-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
212) {2-[8-(4-triftormetilfullerenov)-2,3-dihydrobenzo[1,4]oxazin-4-yl]pyridine-3-yl}exucuse acid,
213) 4-(3-carbamoyloximes-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
214) 4-(3-methylcarbamoylmethyl-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
215) 4-(3-dimethylcarbamodithioato-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
216) 4-[3-(pyridin-2-yl)methoxypyridine-2-yl]-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
217) 4-[3-(pyridin-3-yl)methoxypyridine-2-yl]-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
218) 4-(5-cyano-2-yl)-N-(4-trif ormeloxifene)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
219) 4-(5-acetamidomethyl-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
220) 4-(3-chloro-5-methoxypyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
221) 4-[5-(N-methylacetamide)methylpyridin-2-yl]-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
222) 4-(5-aminomethylpyridine-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
223) 4-(5-dimethylaminomethylene-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
224) 4-(3-chloropyridin-2-yl)-2-methylcarbamoyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
225) 4-(6-hydroxymethyluracil-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
226) 4-(3-chloropyridin-2-yl)-2-dimethylcarbamoyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
227) 4-(5-carbarnoyl-3-chloropyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
228) (S)-3-atsetamidometil-4-(3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
229) (R)-4-(3-chloropyridin-2-yl)-8-(4-cryptomaterial)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxylic acid,
230) 4-(3-chloropyridin-2-yl)-2-methoxycarbonyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
231) 4-(3-chlore the one-2-yl)-2-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
232) 4-(3-chloropyridin-2-yl)-8-(4-triftormetilfullerenov)-3,4-dihydro-2H-benzo[1,4]oxazin-2-carboxylic acid,
233) (S)-3-carbarnoyl-4-(3-chloropyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
234) (S)-4-(3-chloropyridin-2-yl)-3-methylcarbamoyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
235) 2-carbarnoyl-4-(3-chloropyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
236) R-(4-chlorophenyl)-N-methyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
237) R-(benzo[1,3]dioxol-5-yl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
238) N-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
239) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
240) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3-chloro-4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
241) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
242) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3-fluoro-4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
243) 4-(5-hydroxymethyluracil-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
244) 4-(5-hydroxy shall ethylpyridine-2-yl)-N-(4-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
245) 4-(3-chloro-5-methoxypyridine-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
246) 4-(4-hydroxymethylpropane-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
247) 4-(3-hydroxymethylpropane-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
248) (+)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
249) (-)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
250) (+)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
251) (-)-4-{3-chloro-5-(1-hydroxyethyl)pyridin-2-yl}-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
252) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(2-triptorelin-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
253) N-(4-bromo-3-chlorophenyl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
254) 4-[5-(1-hydroxy-1-methyl)ethylpyridine-2-yl]-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
255) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-isopropoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
256) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(2,3-dichloropyridine-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
257) 4(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3,4,5-trichlorophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
258) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(6-fermentation-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
259) N-(4-bromo-3-triptoreline)-N-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
260) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(2-triftoratsetata-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
261) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3,4,5-tryptophanyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
262) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-fluoro-3-nitrophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
263) N-(3-amino-4-forfinal)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
264) N-(tert-butylphenyl)-4-(5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
265) N-(3,5-bistrifluormethylbenzene)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
266) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-[(2,2,2-triptoreline)phenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
267) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-[3-chloro-(2,2,2-triptoreline)phenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
268) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-triftormetilfosfinov)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
269) N-(TRANS-4-tert-butylcyclohexyl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxa is in-8-carboxamide,
270) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3-fluoro-4-isopropoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
271) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3-fluoro-4-piperidinophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
272) N-(4-tert-butylphenyl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
273) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-[4-(1-hydroxy-2,2,2-Cryptor-1-trifluoromethyl)ethylphenyl]-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
274) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(2,2,3,3-titrator-2,3-dihydrobenzo[1,4]dioxin-6-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
275) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-isobutylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin - 8-carboxamide,
276) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(2,3-dichlorophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
277) N-(4-bromo-3-forfinal)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
278) N-(4-bromophenyl)-4-(3-chloro-5-hydroxymethyluracil-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
279) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3,5-dichlorophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
280) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-deformational)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
281) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-chlorophenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carbox the amide,
282) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(4-isopropylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
283) 4-(3-chloro-5-hydroxymethyluracil-2-yl)-N-(3-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
284) 4-[3-chloro-5-(1-hydroxyethyl)pyridin-2-yl]-N-(3-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
285) 4-(3-chloropyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-3-oxo-2H-benzo[1,4]oxazin-8-carboxamide,
286) (R)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
287) (R)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
288) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
289) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
290) (S)-4-(5-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
291) (S)-4-(5-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
292) (S)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
293) (S)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide
294) (S)-4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-isopropoxyphenyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
295) (S)-4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-trifloromethyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
296) (S)-4-(3-chloropyridin-2-yl)-N-(3-chloro-4-piperidinophenyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
297) (S)-4-(3-chloropyridin-2-yl)-N-(4-dimethylamino-3-forfinal)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
298) (S)-4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-were)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
299) (S)-N-(TRANS-4-tert-butylcyclohexyl)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
300) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(TRANS-4-neopentylglycol)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
301) (S)-N-(4-chlorophenyl)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
302) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-isopropylphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
303) (S)-4-(3-chloropyridin-2-yl)-N-(4-fluoro-3-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
304) (S)-N-(4-bromo-3-chlorophenyl)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
305) (S)-4-(3-chloropyridin-2-yl)-N-(4-dimethylamino-3-triptoreline)-3-Ki is roximity-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
306) (S)-4-(3-chloropyridin-2-yl)-N-(4-isopropoxy-3-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
307) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-piperidino-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
308) (S)-4-(3-chloropyridin-2-yl)-N-(4-ethoxy-3-forfinal)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
309) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-methoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
310) (S)-4-(3-chloro-5-methoxypyridine-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
311) (S)-4-(3-chloro-5-methoxypyridine-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
312) (S)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-N-(2-triptorelin-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
313) (S)-3-hydroxymethyl-N-(4-methoxy-3-triptoreline)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
314) (S)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-N-(4-piperidino-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
315) (S)-N-(3-fluoro-4-triptoreline)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
316) (S)-N-(3-chloro-4-trifloromethyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
317) (S)-R-(3,4-dichlorophenyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
318) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-isobutoxy-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
319) (S)-4-(3-chloropyridin-2-yl)-N-(3,4-dichlorophenyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
320) (S)-4-(3-chloropyridin-2-yl)-N-(4-chloro-3-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
321) (S)-N-(4-bromo-3-forfinal)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
322) (S)-N-(4-chloro-3-triptoreline)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
323) (S)-3-hydroxymethyl-N-(4-isopropoxy-3-triptoreline)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
324) (S)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-morpholino-3-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
325) (S)-N-(2-chloro-4-triptoreline)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
326) (S)-3-hydroxymethyl-4-(3-methylpyridin-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
327) (S)-3-hydroxymethyl-4-(3-methylpyridin-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
328) (S)-N-(4-tert-butoxy-3-forfinal)-4-(3-chloropyridin-2-yl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
329) (S)-4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-isobutoxy enyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
330) (S)-3-hydroxymethyl-N-(4-isobutoxy-3-triptoreline)-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
331) (S)-N-(3-fluoro-4-isopropoxyphenyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
332) (S)-N-(3-fluoro-4-morpholinomethyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
333) (S)-N-(4-chlorophenyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
334) (S)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-N-(2-morpholino-4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
335) (S)-N-(4-tert-butoxy-3-forfinal)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
336) (S)-N-(4-bromo-3-forfinal)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
337) 4-(3-chloropyridin-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
338) (S)-4-(3-chloropyridin-2-yl)-N-(3-fluoro-4-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
339) (S)-N-(3-fluoro-4-isobutylphenyl)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
340) (S)-N-(4-fluoro-3-triptoreline)-3-hydroxymethyl-4-(5-methylpyridin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
341) 4-(3-chloropyridin-2-yl)-3-(1-hydroxyethyl)-N-(4-trif ormeloxifene)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
342) (R)-9-(3-chloropyridin-2-yl)-7-hydroxy-(4-trifloromethyl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide,
343) (R)-9-(3-chloropyridin-2-yl)-7-hydroxy-(4-triptoreline)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide,
344) (S)-9-(3-chloropyridin-2-yl)-7-hydroxy-(4-trifloromethyl)-6,7,8,9-tetrahydro-5-oxa-9-athensallowed-4-carboxamide,
345) N-(4-tert-butylphenyl)-4-(pyrazin-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
346) N-(4-chlorophenyl)-4-(5-ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
347) N-(4-ethoxyphenyl)-4-(5-ethylpyrimidine-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
348) 4-(6-chloropyridin-3-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
349) 4-(4-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
350) 4-(5-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
351) (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
352) (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
353) (S)-N-(3,4-dichlorophenyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
354) (S)-N-(3-fluoro-4-isopropoxyphenyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxaz the n-8-carboxamide,
355) (S)-R-(3-fluoro-4-tert-butoxyphenyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
356) (S)-N-(3-fluoro-4-isobutylphenyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
357) (S)-N-(4-bromo-3-forfinal)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
358) (S)-R-(4-fluoro-3-triptoreline)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
359) (S)-N-(3-fluoro-4-morpholinomethyl)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
360) (S)-3-hydroxymethyl-4-(5-methylthiazole-2-yl)-N-(2-triptorelin-5-yl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
361) (S)-3-hydroxymethyl-4-(5-methoxazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
362) (S)-3-hydroxymethyl-4-(5-methoxazole-2-yl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
363) (S)-4-(4,5-dimethylthiazol-2-yl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
364) (S)-4-(4,5-dimethylthiazol-2-yl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
365) (S)-3-hydroxymethyl-4-(5-methyl[1,3,4]thiadiazole-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
366) (S)-3-hydroxymethyl-4-(5-methyl[1,3,4]thiadiazole-2-yl)-N-(4-tripto who were)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
367) 4-(4,5-dimethylthiazol-2-yl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]thiazin-8-carboxamide,
368) 4-(4,5-dimethylthiazol-2-yl)-N-(4-trifloromethyl)-1-oxo-3,4-dihydrobenzo[1,4]thiazin-8-carboxamide,
369) N-(4-tert-butylphenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo [1,4]oxazin-8-carboxamide,
370) N-(4-isobutylphenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
371) N-(4-chlorophenyl)-4-(4-methoxyphenyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
372) (S)-4-(2-chlorophenyl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
373) (S)-4-(2-chlorophenyl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
374) (S)-4-(2-chlorophenyl)-N-(3-fluoro-4-triptoreline)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
375) (S)-4-(4-chlorophenyl)-3-hydroxymethyl-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
376) (S)-3-hydroxymethyl-4-(4-methoxyphenyl)-N-(4-trifloromethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
377) (S)-3-hydroxymethyl-4-(4-methoxyphenyl)-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide,
378) (S)-4-(4-chlorophenyl)-3-hydroxymethyl-N-(4-triptoreline)-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide and
379) (S)-4-(4-chlorophenyl)-N-(4-chlorophenyl)-3-hydroxymethyl-3,4-dihydro-2H-benzo[1,4]oxazin-8-carboxamide or a pharmaceutical is viable salt.

8. Pharmaceutical composition having inhibitory activity against subtype 1 receptor vanilloid, including condensed benzamide derivative or its pharmaceutically acceptable salt according to any one of claims 1 to 7 and a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8, used for disease selected from pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ischemic symptom, nerve injury, neurogenic skin damage, inflammatory disease, pruritus, allergic rhinitis, apoplexy, irritable bowel syndrome, asthma, chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer and inflammatory bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and urinary incontinence the eyes.

10. The pharmaceutical composition according to claim 9, where the disease is pain selected from acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy or neurodegenerative diseases.

11. The compound according to claims 1 to 7 as an inhibitor of the activity of subtype 1 receptor vanilloid (VR1).

12. The method of treatment and/or prophylaxis of a disease mediated by the activity of subtype 1 receptor vanilloid selected from pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ischemic symptom, nerve injury, neurogenic skin damage, inflammatory-related disease is evania, pruritus, allergic rhinitis, apoplexy, irritable bowel syndrome, asthma, chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer and inflammatory bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and urinary incontinence, characterized in that it includes the introduction of a pharmacologically effective amount of the condensed benzamide derivative or its pharmaceutically acceptable salt according to any one of claims 1 to 7.

13. The method according to item 12, where the disease is pain selected from acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy or neurodegenerative diseases.

14. The method according to item 12, where the disease is postoperative neuralgia, characterized in that the compound according to claims 1-7 is administered after surgical operation selected from the excision of the scar, curing nerve freeze is m, excision of peripheral nerve excision of the dorsal roots of the spinal cord, sympathectomy, and the destruction of the input zone of the dorsal roots of the spinal cord, cordotomy and excision of the frontal lobe (brain).

15. Commercial package comprising the pharmaceutical composition according to any one of p-10 and related to this pharmaceutical compositions written instructions indicating that the composition can be applied or should be applied for the treatment and/or prevention of a disease selected from pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ischemic symptom, nerve injury, neurogenic skin damage, inflammatory disease, pruritus, allergic rhinitis, apoplexy, irritable bowel syndrome, asthma, chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer and inflammatory what about bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and urinary incontinence.

16. The use of condensed benzamide derivative or its pharmaceutically acceptable salt according to any one of claims 1 to 7 to obtain the pharmaceutical composition of claim 8 for the treatment and/or prevention of a disease selected from pain, acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy, neurodegenerative disease, cerebral apoplexy, ischemic symptom, nerve injury, neurogenic damage to the skin, inflammatory disease, pruritus, allergic rhinitis, apoplexy, irritable bowel syndrome, asthma, chronic obstructive pulmonary disease, dermatitis, inflammation of the mucous membrane, stomach ulcer and duodenal ulcer and inflammatory bowel disease, hypersensitivity of the bladder and overactive bladder type frequent urination and naderian the urine.

17. The application of article 16, where the disease is pain selected from acute pain, chronic pain, neuropathic pain, pain in rheumatoid arthritis, neuralgia, neuropathy, hyperalgesia, migraine, joint pain, acute herpetic neuralgia, post herpetic neuralgia, chronic herpetic neuralgia, postoperative pain, cancer pain, inflammatory pain, interstitial cystitis, posttraumatic neuralgia, diabetic neuropathy or neurodegenerative disease.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I , where R1 is selected from a group comprising hydrogen, lower alkyl, cycloalkyl or lower cycloalkylalkyl, where the cycloalkyl ring can be substituted with lower alkoxyalkyl, lower alkoxyalkyl, and tetrahydropyranyl and lower heterocyclylalkyl, where the heterocyclic ring is oxetanyl or tetrahydropyranyl, which can be substituted with a halogen; R2 is selected from a group comprising hydrogen, lower alkyl, cycloalkyl or lower cycloalkylalkyl, where the cycloalkyl ring can be substituted with lower alkoxyalkyl, lower alkoxyalkyl, and tetrahydropyranyl or lower heterocyclylalkyl, where the heterocyclic ring is oxetanyl or tetrahydropyranyl which can be substituted with a halogen; or R1 and R2 together with the nitrogen atom to which they are bonded form a 4-, 5- or 6-member saturated or partially unsaturated heterocyclic ring which optionally contains the same heteroatom selected from oxygen or sulphur, where the said saturated or partially heterocyclic ring is unsubstituted or substituted with one or two groups independently selected from a group consisting of lower alkyl, halogen, halogenalkyl, cyano group, hydroxy group, lower hydroxyalkyl, lower alkoxy group, oxo group; A is selected from , and , where m equals 0 or 1; R3 is a lower alkyl; n equals 0; R4 is a lower alkyl; p equals 1; q equals 0, 1 or 2; R5 is hydrogen; and their pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition based on formula I compounds.

EFFECT: new quinoline derivatives are obtained, which have antagonistic effect on histamine 3 receptors (H3 receptors).

18 cl, 4 tbl, 86 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to benzazepin derivatives of formula (I), where R1 is unsubstituted cyclobutyl, R2 is 3-pyrazinyl, substituted CON(H)(Me) or 2-pyridinyl-M-pyrrolidinyl, where the said pyrrolidinyl group is substituted with a =O group; which is: methylamide 5-(3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy) pyrazine-2-carboxylic acid

or 1-{6-[(3-cyclbutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-2-pyrrolidinone

EFFECT: obtaining compounds which have affinity to histamine H3 receptor and pharmaceutical compositons containing said compounds.

11 cl, 288 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where the carbon atom denoted * is in R- or S-configuration; X is a concentrated bicyclic carbocycle or heterocycle selected from a group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, indazolyl, indolyl, benzooxazolyl, benzothiazolyl, indenyl, indanyl, dihydrobenzocycloheptenyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, quinoxalinyl, 2H-chromenyl, imidazo[1.2-a]pyridinyl, pyrazolo[1.5-a]pyridinyl, and condensed bicyclic carbocycle or condensed bicyclic heterocycle, optionally substituted with substitutes (1 to 4) which are defined below for R14; R1 is H, C1-C6-alkyl, C3-C6-cyclalkyl, C1-C3-alkyl, substituted OR11, -NR9R10 or -CN; R2 is H, C1-C6-alkyl, or gem-dimethyl; R3 is H, -OR11, C1-C6-alkyl or halogen; R4 is H, halogen, -OR11, -CN, C1-C6-alkyl, C1-C6-alkyl, substituted -NR9R10, C3-C6-cycloalkyl, substituted -NR9R10, C(O)R12; or R4 is morpholinyl, piperidinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, isoxazolyl, pyrrolidinyl, piperazinyl, 2-oxo-2H-pyridinyl, [1.2.4]triazolo[4.3-a]pyridinyl, 3-oxo-[1.2.4]triazolo[4.3-a]pyridinyl, quinoxalinyl, which are optionally substituted with substitutes (1 to 4) which are defined below for R14; R5 is H or C1-C6-alkyl; R6 is H, C1-C6-alkyl, or -OR11; R7 is H; R8 is H, -OR9, C1-C6-alkyl, -CN; R9 is H or C1-C4-alkyl; R10 is H or C1-C4-alkyl; or R9 and R10 taken together with the nitrogen atom to which they are bonded form morpholine; R11 is H, C1-C4-alkyl; R12 is C1-C6-alkyl; R14 in each case is independently selected from a substitute selected from a group consisting of halogen, -OR11, -NR11R12, C1-C6-alkyl, which is optionally substituted with 1-3 substitutes, in each case independently selected from a group consisting of C1-C3-alkyl, aryl; or to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, to a method of obtaining formula (I) compounds, as well as to a method of treating disorders.

EFFECT: obtaining new biological active compounds having norepinephrine, dopamine and serotonin reuptake selective inhibitory activity.

90 cl, 162 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) and to their pharmaceutically acceptable salts, optical isomers or their mixture as glucokinase activators. In general formula (I) where R1 is C3-8-cycloalkyl, C3-8-cycloalkenyl, a 6-member heterocyclyl with 1 nitrogen atom, condensed phenyl-C3-8-cycloalkyl, each of which is possibly substituted with one or two substitutes R3, R4, R5 and R6; R2 is C3-8-cycloalkyl, a 5-6-member heterocyclyl with 1-2 heteroatoms selected from N, O, or S, each of which can be substituted with one or two substitutes R30, R31, R32 and R33, and R3, R4, R5, R6, R30, R31, R32 and R33 are independently selected from a group consisting of halogen, hydroxy, oxo, -CF3; or -NR10R12; or C1-6-alkyl, phenyl, C1-6-alkoxy, C1-6-alkyl-C(O)-O-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; or -C(O)-R27, -S(O)2-R27; or two substitutes selected from R3, R4, R5 and R6 or R30, R31, R32 and R33, bonded to the same atom or to neighbouring atoms, together form a -O-(CH2)2-O- radical; R10 and R11 independently represent hydrogen, C1-6-alkyl, -C(O)-C1-6-alkyl, -C(O)-O- C1-6-alkyl, -S(O)2- C1-6-alkyl; R27 is C1-6-alkyl, C1-6-alkoxy, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, phenyl, phenyl-C1-6-alkyl, a 5-6-member heteroaryl with 1-2 heteroatoms selected from N or S, a 6-member heteroaryl-C1-6-alkyl with 1 nitrogen atom, a 6-member heterocyclyl-C1-6-alkyl with 1-2 heteroatoms selected from N or O, R10R11-N- C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; R12 is a halogen, CF3, C1-6-alkoxy, -NR10R11; A is a 5-9-member heteroaryl with 1-3 heteroatoms selected from N, O or S, which is possibly substituted with one or two substitutes independently selected from R7, R8 and R9; R7, R8 and R9 are independently selected from halogen, cyano, -CF3; or C1-6-alkyl, C2-6-alkenyl, C1-6-alkoxy, C1-6-alkylthio, -C(O)-O-C1-6-alkyl, formyl, - C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-O-C(O)-C1-6-alkyl or hydroxy-C1-6-alkyl, each of which is possibly substituted with a substitute independently selected from R16; or phenyl, 5-member heteroaryl-C1-6-alkylthio with 2-4 nitrogen atoms, phenylthio, 5-6-member heteroarylthio with 1-2 nitrogen atoms, each of which is possibly substituted on the aryl or heteroaryl part with one or two substitutes independently selected from R17; or C3-8-cycloalkyl; or a 6-member heterocyclyl with 2 nitrogen atoms, 5-7-member heterocyclyl-C1-6-alkylthio with 1-2 heteroatoms selected from N or O, each of which is possibly substituted with one substitute independently selected from R16; or C1-6-alkyl-NR19R20, -S(O)2-R21 or -S(O)2-NR19R20; or -C(O)NR22R23; R16, R17 and R18 independently represent C1-6-alkyl, carboxy, -C(O)-O-C1-6-alkyl, -NR19R20, -C(O)NR19R20; R19 and R20 independently represent hydrogen, C1-6-alkyl, phenyl, 5-member heteroaryl with 2 heteroatoms selected from N or S, 6-member heterocyclyl with 1 nitrogen atom, -C(O)-O-C1-6-alkyl or -S(O)2-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R24; or R19 and R20 together with a nitrogen atom to which they are bonded form a 5-7-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring possibly contains one additional heteroatom selected from nitrogen, oxygen and sulphur, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R21 is selected from C2-6-alkenyl; or R22 and R23 are independently selected from hydrogen, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-S(O)2-C1-6-alkyl, C3-8-cycloalkyl; or R22 and R23 together with a nitrogen atom to which they are bonded form a 6-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R24 is oxo, C1-6-alkyl, carboxy- C1-6-alkyl, a 6-member heterocyclyl with 1 nitrogen atom, -NH-S(O)2R28 or -S(O)2R28, where each cyclic group is possibly substituted with one substitute independently selected from R29; R28 is C1-6-alkyl, -C1-6-alkyl-C(O)-O- C1-6-alkyl or -N(CH3)2; R29 is C1-6-alkyl.

EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by low glucokinase activity.

21 cl, 1 dwg, 608 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (XXI) where values of R1, Y, Ra and Rb are given in subparagraphs 1 and 2 of the formula of invention, as phosphatidylinositol-3-kinase inhibitors, a pharmaceutical composition based on said compounds and their use.

EFFECT: compounds can be used for treating and preventing diseases mediated by phosphatidylinositol-3-kinase.

5 cl, 5 tbl, 146 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula (I)

Values of radicals R1-R6 are given in the formula of invention. The compounds inhibit protein kinase MEK1/2. Also described is a pharmaceutical composition for administration in diseases mediated by MEK1/2.

EFFECT: compounds are highly efficient.

16 cl, 27 ex

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

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 refers to novel method of obtaining [2S*[R*[R*[R*]]]] and [2R*[S*[S*[S*]]]]-(±)α,α'-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyrane-2-methanol] racemate of the formula (I) (nebivolol) and its pharmaceutically acceptable salts , involving stages indicated in the claim, and to intermediate compounds and methods of obtainment thereof.

EFFECT: improved method.

106 cl, 12 tbl, 20 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I , where R1 is selected from a group comprising hydrogen, lower alkyl, cycloalkyl or lower cycloalkylalkyl, where the cycloalkyl ring can be substituted with lower alkoxyalkyl, lower alkoxyalkyl, and tetrahydropyranyl and lower heterocyclylalkyl, where the heterocyclic ring is oxetanyl or tetrahydropyranyl, which can be substituted with a halogen; R2 is selected from a group comprising hydrogen, lower alkyl, cycloalkyl or lower cycloalkylalkyl, where the cycloalkyl ring can be substituted with lower alkoxyalkyl, lower alkoxyalkyl, and tetrahydropyranyl or lower heterocyclylalkyl, where the heterocyclic ring is oxetanyl or tetrahydropyranyl which can be substituted with a halogen; or R1 and R2 together with the nitrogen atom to which they are bonded form a 4-, 5- or 6-member saturated or partially unsaturated heterocyclic ring which optionally contains the same heteroatom selected from oxygen or sulphur, where the said saturated or partially heterocyclic ring is unsubstituted or substituted with one or two groups independently selected from a group consisting of lower alkyl, halogen, halogenalkyl, cyano group, hydroxy group, lower hydroxyalkyl, lower alkoxy group, oxo group; A is selected from , and , where m equals 0 or 1; R3 is a lower alkyl; n equals 0; R4 is a lower alkyl; p equals 1; q equals 0, 1 or 2; R5 is hydrogen; and their pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition based on formula I compounds.

EFFECT: new quinoline derivatives are obtained, which have antagonistic effect on histamine 3 receptors (H3 receptors).

18 cl, 4 tbl, 86 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new 4-substituted 3-(3-dialkylaminomethyl-indol-1-yl)maleimide derivatives of general formula

and ,

where: X1-X4 denote C; Z denotes H; R1 denotes alkyl, H, -(CH2)3-N-(C2H5)2; R2 and R3 denote alkyl, or together with the nitrogen atom to which they are bonded form a C4-7-monocyclic ring containing 1 or 2 heteroatoms, selected from O and N, possibly substituted with an alkyl; R4 denotes H; Y denotes S, -N-(C2H5); where in formula I compounds R5 and R6 together with the nitrogen atom to which they are bonded form a C9-10 a condensed bicyclic ring containing an N heteroatom, possibly substituted with R, where R denotes -N-(R2)-R3; in formula II compounds R5 denotes phenyl, optionally substituted with OCH3.

EFFECT: obtaining new compounds which can be used as protein kinase inhibiting agents.

2 cl, 6 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to benzazepin derivatives of formula (I), where R1 is unsubstituted cyclobutyl, R2 is 3-pyrazinyl, substituted CON(H)(Me) or 2-pyridinyl-M-pyrrolidinyl, where the said pyrrolidinyl group is substituted with a =O group; which is: methylamide 5-(3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy) pyrazine-2-carboxylic acid

or 1-{6-[(3-cyclbutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-3-pyridinyl}-2-pyrrolidinone

EFFECT: obtaining compounds which have affinity to histamine H3 receptor and pharmaceutical compositons containing said compounds.

11 cl, 288 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where the carbon atom denoted * is in R- or S-configuration; X is a concentrated bicyclic carbocycle or heterocycle selected from a group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, indazolyl, indolyl, benzooxazolyl, benzothiazolyl, indenyl, indanyl, dihydrobenzocycloheptenyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, quinoxalinyl, 2H-chromenyl, imidazo[1.2-a]pyridinyl, pyrazolo[1.5-a]pyridinyl, and condensed bicyclic carbocycle or condensed bicyclic heterocycle, optionally substituted with substitutes (1 to 4) which are defined below for R14; R1 is H, C1-C6-alkyl, C3-C6-cyclalkyl, C1-C3-alkyl, substituted OR11, -NR9R10 or -CN; R2 is H, C1-C6-alkyl, or gem-dimethyl; R3 is H, -OR11, C1-C6-alkyl or halogen; R4 is H, halogen, -OR11, -CN, C1-C6-alkyl, C1-C6-alkyl, substituted -NR9R10, C3-C6-cycloalkyl, substituted -NR9R10, C(O)R12; or R4 is morpholinyl, piperidinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, isoxazolyl, pyrrolidinyl, piperazinyl, 2-oxo-2H-pyridinyl, [1.2.4]triazolo[4.3-a]pyridinyl, 3-oxo-[1.2.4]triazolo[4.3-a]pyridinyl, quinoxalinyl, which are optionally substituted with substitutes (1 to 4) which are defined below for R14; R5 is H or C1-C6-alkyl; R6 is H, C1-C6-alkyl, or -OR11; R7 is H; R8 is H, -OR9, C1-C6-alkyl, -CN; R9 is H or C1-C4-alkyl; R10 is H or C1-C4-alkyl; or R9 and R10 taken together with the nitrogen atom to which they are bonded form morpholine; R11 is H, C1-C4-alkyl; R12 is C1-C6-alkyl; R14 in each case is independently selected from a substitute selected from a group consisting of halogen, -OR11, -NR11R12, C1-C6-alkyl, which is optionally substituted with 1-3 substitutes, in each case independently selected from a group consisting of C1-C3-alkyl, aryl; or to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, to a method of obtaining formula (I) compounds, as well as to a method of treating disorders.

EFFECT: obtaining new biological active compounds having norepinephrine, dopamine and serotonin reuptake selective inhibitory activity.

90 cl, 162 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of structural formula I and their pharmaceutically acceptable salts. In structural formula I , X is oxygen; Y is oxygen; Y1 Y2, R7 and R4 represent H; X1 and X2 are independently selected from a group consisting of hydrogen, an alkyl group containing 1 to 5 carbon atoms, in which one or more hydrogen atoms of the alkyl group can be substituted with a halogen, aryl group containing 6 to 10 carbon atoms or a cycloalkyl group containing 3 to 9 carbon atoms, or a 5-9-member heterocyclic group with 2 heteroatoms selected from N and O, or a cycloalkyl group containing 5 to 9 carbon atoms; values of the rest of the radicals are given in the formula of invention. The invention also pertains to a pharmaceutical composition having properties of selective inhibitors of type IV phosphodiesterase, containing a therapeutically effective amount of the invented compound.

EFFECT: increased effectiveness of the compounds.

6 cl, 23 ex

Chemical method // 2386636

FIELD: chemistry.

SUBSTANCE: present invention relates to a method for synthesis of a compound of formula I , in which X1 is selected from O; and X2 is N; involving successive reaction of a formula II compound with (i) methyl- or optionally substituted aryl-lithium; then (ii) n-butyl-, sec-butyl-, tert-butyl- or n-hexyl-lithium; and then (iii) borate ester. The invention also relates to a method of obtaining formula IV compounds: , which involves combination of [4-(1,3,4-oxadiazol-2-yl)phenyl]boronic acid with a formula III compound, in which P is a nitrogen protecting group, and to a formula IV compound, where P is C1-6alkoxycarbonyl.

EFFECT: design of an efficient method of obtaining the said compound.

9 cl, 9 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to 3,3'-bis-(3,4-dihydro-3-phenyl-2H-1,3-benzoxazin-6-yl)-1(3H)-isobenzofuranone and analogues based on phenolphthalein, formaldehyde and a primary amine of formula 1: , in which R independently represents allyl or phenyl, and to a method of synthesising the said compounds. The invention also pertains to a method of making a refractory cast or layered material based on the said compounds and laminating compositions since through thermal hardening, these compounds form a net which does not catch fire easily and is resistant to high temperatures. The said compounds can be particularly useful in making printed circuit boards.

EFFECT: obtaining fire-resistant compounds.

5 cl, 4 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula Ia: and its pharmaceutically acceptable salt, where: p equals 0 or 1; n assumes values from 1 to 3, q equals 1; R5 is selected from hydrogen, -XNR7R8, pyrimidine-C0-4alkyl, pyridine-C0-4alkyl, phenyl, C3-10cycloalkyl-C0-4alkyl and C3-6heterocycloalkyl-C0-4alkyl, where C3-6heterocycloalkyl is a saturated monocyclic ring system containing the said number of atoms, provided that one or more of the said carbon atoms is substituted with O or NR, where R is hydrogen or C1-4alkyl; R7 and R8 represent C1-4alkyl; R6 denotes hydrogen; or R5 and R6 together with a nitrogen atom to which they are both bonded form morpholine or piperidine; where any piperdine-C0-4alkyl, piperidine-C0-4alkyl or C3-10cycloalkyl-C0-4alkyl of substitute R5 or a combination of radicals R5 and R6 can be optionally substituted with 1-2 radicals which are independently selected from -XNR7R8 and -XOR7, the said phenyl of substitute R5 is substituted with a -XR9 group, the said C3-6heterocycloalkyl-C0-4alkyl of substitute R5 is optionally substituted with a -XOR7 group, where X is a single bond or C1-4alkylene; R7 and R8 are independently selected from hydrogen and C1-4alkyl; R9 is selected from C3-10heterocycloalkyl which is a saturated monocyclic ring system containing the said number of atoms, provided that one or more of the said carbon atoms is substituted with O or NR, where R is as given above; R10 denotes hydrogen; R15 is selected from halogen, C1-6alkyl and C1-6alkoxy; and R16 is selected from halogen, methoxy, nitro, -NR12C(O)R13, -C(O)NR12R12, -NR12R12, -C(O)OR12 and -C(O)NR12R13; each R12 is selected from hydrogen and C1-6alkyl; R13 is selected from phenyl, thienyl, pyrazolyl, pyridinyl or isoxazolyl, where any phenyl, thienyl, pyrazolyl, pyridinyl or isoxazolyl of substitute R13 can be optionally substituted with 1-2 radicals which are independently selected from halogen, C1-6alkyl, halogen-substituted C1-6alkyl, imidazole-C0-4alkyl, C3-10cycloalkyl, C3-10heterocycloalkyl-C0-4alkoxy and C3-10heterocycloalkyl-C0-4alkyl; where the said C3-10heterocycloalkyl-C0-4alkoxy and C3-10heterocycloalkyl-C0-4alkyl each represent a saturated monocyclic ring system containing the said number of atoms, provided that one or more of the said carbon atoms is substituted with O or NR, where R assumes values given above; and the said C3-10heterocycloalkyl-C0-4alkoxy and C3-10heterocycloalkyl-C0-4alkyl can each be optionally substituted with 1 radical independently selected from C1-6alkyl, hydroxyl-substituted C1-6alkyl and NR7R8, where R7 and R8 assume values given above. The invention also relates to pharmaceutical compositions containing the said compounds.

EFFECT: obtaining novel compounds and compositions based on the said compounds which can be used in medicine for treating and preventing diseases or disorders associated with abnormal or uncontrolled kinase activity, particularly diseases or disorders associated with abnormal activity of kinase c-Src, FGFR3, KDR and/or Lck.

12 cl, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a group of novel chemical compounds pharmacologically acceptable salts thereof having formula , where A represents COOH; B represents H; n equals 0; V represents -CH2-, a single bond; W represents a 5-7-member heteroaromatic group with one heteroatom selected from N, O, S which can optionally be substituted with 1-3 substitutes selected from a group of substitutes A, when V represents a -CH2-group, where if V represents a single bond, W represents a bicyclic condensed a ring -member heterocyclic group with one heteroatom selected from O, S, which can optionally be substituted with 1-3 substitutes selected from a group of substitutes A; X represents a 5-7-member heteroaromatic group with one O atom and one or two N atoms, which can optionally be substituted with 1-3 substitutes selected from a group of substitutes A; Y represents C6-C10 aryl which can optionally be substituted with 1-3 substitutes selected from a group of substitutes A, a 5-7-member heteroatomatic group with one S atom which can optionally be substituted with 1-3 substitutes selected from a group of substitutes A; Z represents C1-C8 alkyl, C3-C7 cycloalkyl which can optionally be substituted with 1-5 substitutes selected from a group of substitutes A; C6-C10 aryl which can optionally be substituted with 1-5 substitutes selected from a group of substitutes A; C6-C10 aryloxy which can optionally be substituted with 1-5 substitutes selected from a group of substitutes A, or C1-C12 aralkyl which can optionally be substituted with 1-5 substitutes selected from a group of substitutes A; group of substitutes A represents halogen, C1-C6 alkyl, halogen C1-C6 alkyl, C1-C6 alkoxy.

EFFECT: compounds exhibit inhibitory activity towards HvGR which enables their use to prepare a pharmaceutical composition used in therapy for autoimmune diseases.

33 cl, 6 tbl, 30 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to phenylalanine derivatives and their pharmaceutically acceptable salts. In formula (1) R11 is a hydroxyl group, an alkoxyl group having 1-6 carbon atoms, which can be substituted with a methoxy group, cycloalkoxyl group having 3-6 carbon atoms, or a benzyloxy group; R12 and R13 each independently represents a hydrogen atom, alkyl group having 1-6 carbon atoms, cycloalkyl group having 3-6 carbon atoms, acetyl group or methyloxycarbonyl group, or N(R12)R13 is a 1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group; R14 is a methyl group; R1' is a hydrogen atom, fluorine atom; X1 is -CH(R1a)-, -CH(R1a)CH(R1b)-, -CH(R1a)CH(R1b)CH(R1c)-, -N(R1a)CH(R1b)CH(R1c)-, -OCH(R1a)CH(R1b)-, -OCH(R1a)CH(R1b)CH(R1c)- or 1,3-pyrrolidinylene, where R1a, R1b, each independently represents a hydrogen atom or a methyl group, and R1c is a hydrogen atom; Y11 and Y12 represent any of the combinations (CI, Cl), (CI, Me), (CI, F). Invention also relates to phenylalanine derivatives of formulae (2)-(14), given in the formula of invention.

EFFECT: obtaining a pharmaceutical composition having antagonistic effect on α4-integrin, containing a phenylalanine derivative as an active ingredient, a α4-integrin antagonist and a therapeutic agent.

65 cl, 51 tbl, 244 ex

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