Cache Derivatives of carboxylic acid, their pharmaceutically acceptable salts or esters, medicinal agent and pharmaceutical composition based on thereof, their using and methods for treatment and prophylaxis of diseases

Derivatives of carboxylic acid, their pharmaceutically acceptable salts or esters, medicinal agent and pharmaceutical composition based on thereof, their using and methods for treatment and prophylaxis of diseases

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of carboxylic acid represented by the general formula (I): , their pharmaceutically acceptable salts or esters wherein values Y, L, X, T, Z, M, R1, W and are given in the invention claim. Proposed compounds possess insulin-sensitizing effect and they are double agonists with respect to PPARα and γ, and triple agonists with respect to PPARα, β(δ) and γ. Except for, the invention relates to a medicinal agent and pharmaceutical compositions based on the claimed derivatives of carboxylic acid, to methods for prophylaxis or treatment of diseases, and to using derivatives carboxylic acid for preparing a medicinal agent.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

56 cl, 2 tbl, 609 ex

 

The technical field to which the invention relates.

The present invention relates to a new carboxylic acid derivative, useful for the prevention or treatment of hyperglycemia, hyperlipemia and inflammatory diseases, salts thereof or their hydrate and containing drug.

Prior art

Diabetes mellitus refers to persistent hyperglycemic condition characterized by an absolute or relative deficiency of its own insulin (which lowers the level of glucose in the blood hormone produced and secreted islet β-cells of Langerhans in the pancreas), and at the specified disease occur caused by this state of metabolic disorders in the form of various pathological conditions.

Diabetes pre-diabetes can be classified into insulin-dependent diabetes mellitus (IDDM), i.e. diabetes mellitus type 1, treatment absolutely necessary insulin, non-insulin dependent diabetes mellitus (NIDDM), i.e. diabetes mellitus type 2, and another type of diabetes (secondary diabetes mellitus: diabetes is one of the symptoms of other diseases).

In particular, as a result of lifestyle changes rapidly growing number of patients with NIDDM due to overeating and lack of exercise that vyzyvae the social problem. If IDDM occurs mostly in children, NIDDM appears among people of middle and older age, which explains its wide distribution in Japan. It is believed that NIDDM occurs, in addition to hereditary factors, factors, oppressive action of insulin (insulin resistance), such as overeating, lack of exercise, obesity and stress.

Since, as described above, diabetes is associated with excess calorie intake and obesity, which is the result of inadequate physical activity, treatment is based on 3 types of therapeutic activities, namely, diet therapy, exercise therapy and chemotherapy.

However, there are many reasons why it is difficult to diet therapy and stress therapy due to increase in recent years in the number of elderly persons in this age category.

Chemotherapy NIDDM as oral depressant blood glucose was applied based medications sulfonylureas, such as tolbutamide, hlorpropamid and tolazamide, and medicines on the basis of biguanide (BG), such as hydrochloride Metformin and buformin, but pathological condition NIDDM is characterized by a deficiency of insulin and insulin resistance, and we cannot say that medicines on the basis of sulfonylureas, which stimulate the secretion of insuli the and β -cells of the pancreas, are effective therapies for patients with NIDDM who have the potential of insulin secretion is sufficient, but because of insulin resistance in target organs does not provide adequate regulation of glucose levels in the blood, which leads to hyperglycemia. In addition, based medications sulfonylureas can cause molochnokislogo acidosis, which to some extent limits the use of such medicines. And still, these chemicals are often caused severe hypoglycemia as a side effect.

To solve these problems made successful steps in the creation of chemical substances with a new mechanism of action, and already described derivatives of thiazolidine, such as troglitazone, pioglitazone and rosiglitazone, called insulin sensitizers, which has recently attracted attention because they can reduce insulin resistance (or increase the action of insulin and to lower glucose levels in the blood, without activating the secretion of insulin from the pancreas.

Discovered that these chemical substances such as thiazolidine cause differentiation of adipocytes and exert their effects through intracellular receptor PPARγ (activated peroxisome proliferator gamma receptor: a factor of transcripti is, important for the differentiation of adipocytes) (J. Biol. Chem., 270, 12953-12956, 1995). In the differentiation of preadipocytes growing number of immature and small adipocytes with less secretion of TNFα, FFA, and leptin, which leads to attenuation of insulin resistance.

Derivatives of thiazolidine, such as the above troglitazone, pioglitazone and rosiglitazone, also act as agonists of PPARγshowing the effect of attenuation of insulin resistance.

In addition to PPARγfound the PPAR subtypes, such as α, β(δ), etc. any of which regulates the expression of genes involved in lipid metabolism. The homology of each subtype among different species is higher than the homology of these subtypes in the same species, and with regard to the distribution of each subtype in tissues, PPARγ located mainly in adipose tissue, PPARα is mainly in the liver, heart and kidneys, and is therefore considered that each subtype has its own function. In recent years it was found that PPARγ mainly mediates lipid anabolism, promotora the expression of groups of genes for LPL, the acyl-COA-carboxylase, GPDH, etc. with conversion of glucose into lipid storage and lipid, and PPARα mediates lipid catabolism by regulating the expression of groups of genes involved in the implementation process of fatty acids in cells and oxidation them with razlozheny the m lipid.

In addition, in recent years we have conducted extensive research regarding the relationship between specific subtypes of PPAR and various diseases (J. Med. Chem., 2000, 43(4), 527-550; Trends Cardiovasc. Med., 2000, 10, p238-245).

Compounds disclosed, for example, in JP-A 9-48771, known as derivatives of thiazolidine acting as dual PPAR agonistsγ and α.

In addition, some compounds having in its structure a fragment of carboxylic acids (Current Pharmaceutical Design, 2, No.1, p85-102, 1996; Bioorganic & Medicinal Chemistry Letters, 6, No. 17, p2121-2126, 1996; WO200075103; WO9918066; WO9916758), known as insulin sensitizers

However, there are reports that some of the chemicals that act as agonists of PPARγcause liver damage and therefore should be used with caution, so that chemical substance satisfactory from the point of view of therapeutic effects and side effects, such as toxicity, still not received.

In addition, compounds having a carboxyl group instead thiazolidinones groups described in the literature, but not on the market. In addition, there are no reports indicating that such compounds can be used as a dual agonist of PPARγ and αand, of course, unknown to their action as triple agonists of PPARγ, α and β(δ). However, there is also an opinion that unusual toxicity op the sled above agonists of PPARγ gives thiazolidinones fragment and, if it can be found in connection with the above action, with a new structure, instead of the above, it can be expected that such a connection will solve the problem of toxicity and can be very useful.

Traditional chemicals are still unsatisfactory in respect of neutral fat (triglyceride (TG)), which is of great importance when arteriosclerosis.

In addition, it is known that PPARβ(δ) induce the differentiation of adipocytes J. Biol. Chem., 274, No. 31, pp. 21920-21925), and reportedly (WO9904815), as a result of this action decreases the level of cholesterol, so if it can be found in connection with agonistic action on the specified subtype, it can be expected that this combination will exhibit higher activity than conventional sensitizers, insulin, and reduce side effects, such as toxic effects on the liver.

Further, as a receptor PPAR ligand disclosed dianiline acid derivatives in WO 00/64888A and triazine acid derivatives in WO 00/64876A.

From the above it is clear that there is a need to establish an excellent chemical substances.

Description of the invention

To create drugs effective in the prevention or treatment of hyperglycemia, which satisfies the various requirements of the, the creators of the present invention have conducted extensive studies and as a result have found that carboxylic acid derivative having a new structure, has excellent activity against hyperglycemia and against hyperlipemia, which led to the present invention.

Thus, in accordance with the present description of the following embodiments of the invention:

1) carboxylic acid derivative represented by the following formula:

(where R1represents a hydrogen atom, hydroxyl group, halogen, a carboxyl group or a C1-6alkyl group, a C1-6alkoxygroup, C1-6allylthiourea, C1-6hydroxyalkyl group, a C1-6hydroxyalkoxy, C1-6hydroxyalkyloxy, C1-6aminoalkyl group, amino1-6alkoxygroup, aminos1-6allylthiourea, Halogens1-6alkyl group, Halogens1-6alkoxygroup, Halogens1-6allylthiourea,2-12alkoxyalkyl group2-12alkoxyalkyl,2-12alkoxyalkyl,3-7cycloalkyl group3-7cycloalkylation,4-13cycloalkylcarbonyl,3-7cycloalkylation,2-6alkenylphenol group2-6alkenylacyl,2-6altertekhnogrupp,2-6alkinyl the th group, With2-6alkyloxy,2-6alinytjara,6-12aryl group6-12alloctype,6-12killigrew,7-18alcylaryl group7-18alkylammonium,7-18alkylation,7-18aracelio group7-18aralkylated or7-18arkitip, each of which may have one or more substituents; L represents a single bond or C1-6alkylenes group2-6alkenylamine group or2-6alkynylamino group, each of which may have one or more substituents; M represents a single bond or C1-6alkylenes group2-6alkenylamine group or2-6alkynylamino group, each of which may have one or more substituents; T represents a single bond or C1-3alkylenes group2-3alkenylamine group or2-3alkynylamino group, each of which may have one or more substituents; W represents a carboxyl group;

represents a single bond or a double bond; X represents a single bond, an oxygen atom, a group represented by the formula-NRX1CQ1O- (where Q1represents an oxygen atom or a sulfur atom, and RX1represents a hydrogen atom, formyl group is u or C 1-6alkyl group, a C1-6hydroxyalkyl group, a C1-6aminoalkyl group, Halogens1-6alkyl group, a C2-12alkoxyalkyl group3-7cycloalkyl group2-6alkenylphenol group2-6alkylamino group6-C12aryl group7-18alcylaryl group7-18aracelio group, C2-7aliphatic acyl group, or With7-19aromatic acyl group, each of which may have one or more substituents), -OCQ1NRX1- (where Q1and RX1defined above), -CQ1NRX1O- (where Q1and RX1defined above), -ONRX1CQ1- (where Q1and RX1defined above), -Q2SO2- (where Q2represents an oxygen atom or-NRx10- (where Rx10represents a hydrogen atom, formyl group or a C1-6alkyl group, a C1-6hydroxyalkyl group, a C1-6aminoalkyl group, Halogens1-6alkyl group, a C2-12alkoxyalkyl group3-7cycloalkyl group2-6alkenylphenol group2-6alkylamino group6-With12aryl group7-18alcylaryl group7-18aracelio group2-7aliphatic acyl group, or With7-19aromatic acyl group, each of which can have one or the number of substituents), or-SO 2Q2- (where Q2defined above)or a group represented by the formula:

or

(where Q1, Q2and RX1defined above; k is 0-5; m is 1-5; n and p are the same or different from each other and represent each 1-5; RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are the same or different from each other and represent each a hydrogen atom, a hydroxy-group, halogen, -N(RX11RX12- (where RX11and RX12are the same or different from each other and represent each a hydrogen atom, formyl group or a C1-6alkyl group, a C1-6hydroxyalkyl group, a C1-6aminoalkyl group, Halogens1-6alkyl group, a C2-12alkoxyalkyl group3-7cycloalkyl group2-6alkenylphenol group2-6alkylamino group6-With12aryl group7-18alcylaryl group7-18aracelio group, C2-7aliphatic acyl group or a C7-19aromatic Acelino the group, each of which may have one or more substituents), or C1-6alkyl group, a C1-6alkoxygroup, C1-6allylthiourea, C1-6hydroxyalkyl group, a C1-6hydroxyalkoxy, C1-6hydroxyalkyloxy, C1-6aminoalkyl group1-6aminoalkoxide, C1-6aminoalkyl group, Halogens1-6alkyl group, Halogens1-6alkoxygroup, Halogens1-6allylthiourea,2-12alkoxyalkyl group2-12alkoxyalkyl,2-12alkoxyalkyl,3-7cycloalkyl group3-7cycloalkylation,4-13cycloalkylcarbonyl,3-7cycloalkyl group2-6alkenylphenol group2-6alkenylacyl,2-6altertekhnogrupp,2-6alkylamino group2-6alkyloxy,2-6alinytjara,6-12aryl group6-12alloctype,6-12killigrew,7-18alcylaryl group7-18alkylammonium,7-18alkylation,7-18aracelio group7-18aralkylated or7-18arkitip, each of which may have one or more substituents, provided that RX2and RX3and/or RX4and RX5may together form a ring; and Q3and Q4are the same or different from each other and represent each an oxygen atom, (O)S(O) or NRX10(where RX10defined above)); Y represents a 5 to 14-membered aromatic group or3-7alicyclic hydrocarbon group, each of which may have one or more substituents and one or more heteroatoms; and ring Z represents a 5 to 14-membered aromatic group which may have 1-4 substituent and one or more heteroatoms, and in which a portion of the ring can be saturated), its salt, its ester or hydrate;

2) carboxylic acid derivative in accordance with the embodiment 1, its salt, its ester or its hydrate, where in the formula (I), Y represents a 5 to 14-membered aromatic group which may have 1-4 substituent and one or more heteroatoms;

3) carboxylic acid derivative in accordance with embodiment 1 or 2, its salt, its ester or its hydrate, where in the formula (I), X represents a group represented by the formula - NRX1CQ1O- (where Q1and RX1defined above), -OCQ1NRX1- (where Q1and RX1defined above), -CQ1NRX1O- (where Q1and RX1defined above), - ONRX1CQ1- (where Q1and RX1defined above), -Q2SO2- (where Q2defined above) or-SO2Q2- (where Q2defined above)or a group represented by the formula:

or

where Q1, Q2, k, m, n, p, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9defined above;

4) carboxylic acid derivative according to any embodiment 1 to 3, its salt, its ester or its hydrate, where in the formula (I), X represents a group-NRX1CQ1O- (where Q1and RX1defined above) or-OCQ1NRX1- (Q1and RX1defined above);

5) carboxylic acid derivative according to any embodiment 1 to 3, its salt, its ester or its hydrate, where in the formula (I), X represents a group represented by the formula:

where n, Q3, Q4, RX2and RX3defined above;

6) carboxylic acid derivative in accordance with the embodiment 1, its salt, its ester or its hydrate, where in the formula (I), L represents a single bond or C1-6alkylenes group which may have one or more substituents; X represents a single bond or an oxygen atom and T represents C2-6alkynylamino group which may have one or more substituents;

7) derivative of the carboxylic acid in accordance with the embodiment 1, its salt, its ester or its hydrate, where in the formula (I), L represents a C2-6akinyan, which may have one or more substituents; X represents a single bond or an oxygen atom, and T represents a single bond or C1-6alkylenes group which may have one or more substituents;

8) carboxylic acid derivative in accordance with the embodiment 1, its salt, its ester or its hydrate, where in the formula (I), X represents a group represented by the formula:

or

where Q2and RX2defined above;

9) carboxylic acid derivative in accordance with the embodiment 1, its salt, its ester or its hydrate, where in the formula (I), X represents a group represented by the formula:

where n, Q1, Q4, RX1, RX2and RX3defined above;

10) carboxylic acid derivative in accordance with the embodiment 1, its salt, its ester or its hydrate, where in the formula (I), X represents a group represented by the formula:

where Q3and Q4represent an oxygen atom and n, RX2and RX3defined above;

11) carboxylic acid derivative according to embodiment 10, its salt, its ester or its hydrate, where the form is e (I) X denotes the group represented by the formula:

(where Q3and Q4represent an oxygen atom, n is 2-5 and RX2and RX3defined above, provided that one of RX2and RX3must represent a group other than hydrogen atom); L represents a single bond or C1-3alkylenes group which may have one or more substituents, and T represents a single bond or C1-3alkylenes group which may have one or more substituents;

12) carboxylic acid derivative in accordance with embodiment 4, its salt, its ester or its hydrate, where in the formula (I), X represents a group represented by the formula NRX1CQ1O- (where Q1represents an oxygen atom, RX1defined above) or-OCQ1NRX1- (where Q1represents an oxygen atom, RX1defined above), L represents a single bond or C1-3alkylenes group which may have one or more substituents, and T represents a single bond or C1-3alkylenes group which may have one or more substituents;

13) carboxylic acid derivative according to embodiment 8, its salt, its ester or its hydrate, where in the formula (I), X represents a group represented by the formula:

and the and

(where Q2represents an oxygen atom and RX2defined above); L represents a single bond or C1-3alkylenes group which may have one or more substituents, and T represents a single bond or C1-3alkylenes group which may have one or more substituents;

14) carboxylic acid derivative according to embodiment 9, its salt, its ester or its hydrate, where in the formula (I), X represents a group represented by the formula:

(where Q1and Q4represent an oxygen atom, RX1, RX2and RX3defined above, and n is 1-5); L represents a single bond or C1-3alkylenes group which may have one or more substituents, and T represents a single bond or C1-3alkylenes group which may have one or more substituents;

15) carboxylic acid derivative in accordance with embodiment 3, its salt, its ester or its hydrate, where in the formula (I), X represents-Q2SO2- or-SO2Q2- (where Q2represents an oxygen atom); L represents a single bond or C1-3alkylenes group which may have one or more substituents, and T represents a single bond or C1-3alkylenes group, which can and who know one or more substituents;

16) carboxylic acid derivative in accordance with embodiment 3, its salt, its ester or its hydrate, where in the formula (I), X represents-CQ1NRX1O - or-ONRX1CQ1- (where Q1represents an oxygen atom and RX1defined above); L represents a single bond or C1-3alkylenes group which may have one or more substituents, and T represents a single bond or C1-3alkylenes group which may have one or more substituents;

17) carboxylic acid derivative according to embodiment 11, its salt, its ester or its hydrate, where in the formula (I), M represents C1-6alkylenes group, R1represents carboxyl group or a C1-6alkyl group, a C1-6alkoxygroup, C1-6allylthiourea,6-C12alloctype or7-18aralkylated, each of which may have one or more substituents;

18) carboxylic acid derivative according to embodiment 17, its salt, its ester or its hydrate, where in the formula (I), the ring Z is 1,3-fenelonov group which may have 1-4 substituent;

19) carboxylic acid derivative according to embodiment 11 or 18, its salt, its ester or its hydrate, where in the formula (I), X represents a group represented by the formula:

where Q3and Q4represent an oxygen atom; n represents from 3 to 5 and RX2and RX3represent a hydrogen atom, a hydroxyl group or a fluorine atom, provided that one of RX2and RX3must be a group other than a hydrogen atom;

20) carboxylic acid derivative in accordance with embodiment 19, its salt, its ester or its hydrate, where in the formula (I) X is represented by the formula:

21) carboxylic acid derivative in accordance with embodiment 19, its salt, its ester or its hydrate, where in the formula (I) X is represented by the formula:

22) carboxylic acid derivative in accordance with any embodiment of 19 to 21, its salt, its ester or its hydrate, where in the formula (I), M represents a methylene group and R1represents C1-6alkoxygroup, which may have one or more substituents;

23) carboxylic acid derivative according to embodiment 12, its salt, its ester or its hydrate, where in the formula (I), M represents C1-6alkylenes group, and R1represents carboxyl group or a C1-6alkyl group, a C1-6alkoxygroup,1-6allylthiourea,6-C12alloctype or7-18aralkylated, each of which may have one or n is how many deputies;

24) carboxylic acid derivative according to embodiment 23, its salt, its ester or its hydrate, where in the formula (I), L represents a C1-3alkylenes group which may have one or more substituents, and T represents C1-3alkylenes group which may have one or more substituents;

25) carboxylic acid derivative according to embodiment 24, its salt, its ester or its hydrate, where in the formula (I), the ring Z is 1,3-fenelonov group which may have 1-4 substituent;

26) carboxylic acid derivative according to embodiment 25, its salt, its ester or its hydrate, where in the formula (I), M represents a methylene group and R1represents C1-6alkoxygroup, which may have one or more substituents;

27) carboxylic acid derivative according to any of embodiments 6, 7, 13, 14, 15 and 16, its salt, its ester or its hydrate, where in the formula (I), M represents C1-6alkylenes group, R1represents carboxyl group or a C1-6alkyl group, a C1-6alkoxygroup, C1-6allylthiourea,6-C12alloctype or7-18aralkylated, each of which may have one or more substituents;

28) carboxylic acid derivative in accordance with any waples is of from 11 to 27, its salt, its ester or its hydrate, where in the formula (I), Y represents a phenyl group which may have 1 or 2 substituent;

29) carboxylic acid derivative in accordance with the embodiment 1, its salt, its ester or its hydrate, where in the formula (I), the group represented by the formula:

(where each symbol represents a group as defined above), and a group represented by the formula:

(where each symbol represents a group as defined above), connected to each other in the ring Z through 2-8 atoms;

30) carboxylic acid derivative in accordance with the embodiment 1, its salt, its ester or its hydrate, where the compound represented by formula (I)is a compound selected from:

(1) 2-isopropoxy-3-(3-[3-(2,4-dichlorophenyl)-2-PROPYNYL]oxyphenyl)propanoic acid;

(2) 3-(3-[3-(4-triptoreline)-1-hydroxy-1-methyl-2-PROPYNYL]phenyl)-2-isopropoxyphenol acids;

(3) 2-isopropoxy-3-[3-([4-(trifluoromethyl)benzyl]acetanilide)phenyl]propanoic acid;

(4) 2-ethoxy-3-{3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid;

(5) 3-{3-[3-(4-chloro-2-cianfrocca)-2-hydroxypropoxy]phenyl}-2-isopropoxyphenol acids;

(6) 2-isopropoxy-3-(3-{[({[4-cryptomaterial]oxy}carbonyl)amino]methyl}phenyl)propanoic acid is;

(7) 3-{3-[3-(2,4-dichlorophenoxy)-2(S)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acids;

(8) 3-{3-[3-(4-chloro-2-cianfrocca)-2(S)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acids;

(9) 3-(3-{2(S)-hydroxy-3-[3-(1-hydroxy-1-methylethyl)phenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acids;

(10) 3-(3-{2(R)-hydroxy-3-[4-chlorophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acids;

(11) 3-(3-{2(S)-hydroxy-3-[2,4-dimethylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acids;

(12) 3-(3-{2(S)-hydroxy-3-[4-chloro-2-fervency]propoxy}phenyl)-2(S)-isopropoxypropylamine acids;

(13) 3-{3-[3-(2,4-dichlorophenoxy)-2(R)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acids;

(14) 3-{3-[3-(4-chloro-2-cianfrocca)-2(R)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acids;

(15) 3-(3-{2(R)-hydroxy-3-[2,4-dimethylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acids;

(16) 3-{3-[3-(2,4-dichlorophenoxy)-2(R)-forproperty]phenyl}-2(S)-isopropoxypropylamine acids;

(17) 3-{3-[3-(4-chlorophenoxy)-2(S)-forproperty]phenyl}-2(S)-isopropoxypropylamine acids;

(18) 3-{3-[3-(4-chloro-2-cianfrocca)-2(R)-forproperty]phenyl}-2(S)-isopropoxypropylamine acids;

(19) 3-{3-[3-(2,4-dichlorophenoxy)-2(S)-forproperty]phenyl}-2(S)-isopropoxypropylamine acids;

(20) 3-{3-[3-(4-chlorophenoxy)-2(R)-forproperty]phenyl}-2(S)-isopropoxypropylamine acids;

(21) 3-{3-[3-(4-chloro-2-CANopen the XI)-2(S)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid;

(22) 3-{3-[3-(2,4-dimethylphenoxy)-2(S)-forproperty]phenyl}-2(S)-isopropoxypropylamine acids;

(23) 2(S)-isopropoxy-3-{3-[(4-triftoratsetilatsetonom)methyl]phenyl}propanoic acid;

(24) 2(S)-isopropoxy-3-{3-[(3-triftoratsetilatsetonom)methyl]phenyl}propanoic acid;

(25) 2(S)-isopropoxy-3-{3-[(4-triftormetilfullerenov)methyl]phenyl}propanoic acid;

(26) 3-(3-{[4-(1-hydroxy-1-methylethyl)benzyloxycarbonylamino]methyl}phenyl)-2(S)-isopropoxypropylamine acids;

(27) 3-(3-{[2,5-dichlorobenzonitrile]methyl}phenyl)-2(S)-isopropoxypropylamine acids;

(28) 3-(3-{[4-ethoxymethyleneamino]methyl}phenyl)-2(S)-isopropoxypropylamine acids;

(29) 3-(3-{[3-triftormetilfullerenov]methyl}phenyl)-2(S)-isopropoxypropylamine acids;

(30) 3-(3-{[2-(4-chlorophenyl)ethoxycarbonyl]methyl}phenyl)-2(S)-isopropoxypropylamine acids;

(31) 2(S)-isopropoxy-3-{3-[(quinoline-2-ylmethoxycarbonyl)methyl]phenyl}propanoic acid;

(32) 3-{[3-(2,4-dichlorophenyl)carbamoyloxymethyl-4-ethoxy]phenyl}-2-isopropoxyphenol acids;

(33) 3-({4-[5-(benzo[1,3]dioxole)]carbamoyloxymethyl}phenyl)-2-isopropoxyphenol acids;

(34) 3-{3-[3-(2,4-dichlorophenoxy)-1-PROPYNYL]phenyl}-2(S)-isopropoxypropylamine acids;

(35) 3-{3-[3-(2,4-dichlorophenyl)-2-propenyloxy]phenyl}-2(S)-isopropoxypropylamine sour is you;

(36) 3-{3-[3-(4-chlorophenyl)-2-propenyloxy]phenyl}-2(S)-isopropoxypropylamine acids;

(37) 2(5)-3-{[3-(2,4-dichlorophenyl)carbamoyloxymethyl-4-ethoxy]phenyl}-2-isopropoxyphenol acids;

(38) 3-{3-[2-(4-chlorphenoxy)acetylamino]-4-ethoxyphenyl}-2-isopropoxyphenol acids;

(39) 3-{3-[2-(2,4-dichlorophenoxy)acetylamino]-4-ethoxyphenyl}-2-isopropoxyphenol acid and

(40) 3-{4-[3-(4-chloro-2-cianfrocca)-2-hydroxypropoxy]phenyl}-2-isopropoxyphenol acids;

31) the drug-containing carboxylic acid derivative represented by the following formula:

(where R1represents a hydrogen atom, hydroxyl group, halogen, a carboxyl group or a C1-6alkyl group, a C1-6alkoxygroup, C1-6allylthiourea, C1-6hydroxyalkyl group, a C1-6hydroxyalkoxy, C1-6hydroxyalkyloxy, C1-6aminoalkyl group, amino1-6alkoxygroup, aminos1-6allylthiourea, Halogens1-6alkyl group, Halogens1-6alkoxygroup, Halogens1-6allylthiourea,2-12alkoxyalkyl group2-12alkoxyalkyl,2-12alkoxyalkyl,3-7cycloalkyl group3-7cycloalkylation,4-13cycloalkylcarbonyl,3-7cycloalkylation the PU, With2-6alkenylphenol group2-6alkenylacyl,2-6altertekhnogrupp,2-6alkylamino group2-6alkyloxy,2-6alinytjara,6-12aryl group6-12alloctype,6-12killigrew,7-18alcylaryl group7-18alkylammonium,7-18alkylation,7-18aracelio group7-18aralkylated or7-18arkitip, each of which may have one or more substituents; L represents a single bond or C1-6alkylenes group2-6alkenylamine group or2-6alkynylamino group, each of which may have one or more substituents; M represents a single bond or C1-6alkylenes group2-6alkenylamine group or2-6alkynylamino group, each of which may have one or more substituents; T represents a single bond or C1-3alkylenes group2-3alkenylamine group or2-3alkynylamino group, each of which may have one or more substituents; W represents a carboxyl group;

represents a single bond or a double bond; X represents a single bond, an oxygen atom, a group represented by the formula-NRX1CQ1 O- (where Q1represents an oxygen atom or a sulfur atom, and RX1represents a hydrogen atom, formyl group or a C1-6alkyl group, a C1-6hydroxyalkyl group, a C1-6aminoalkyl group, Halogens1-6alkyl group, a C2-12alkoxyalkyl group3-7cycloalkyl group2-6alkenylphenol group2-6alkylamino group6-C12aryl group7-18alcylaryl group7-18aracelio group2-7aliphatic acyl group, or With7-19aromatic acyl group, each of which may have one or more substituents), -OCQ1NRX1- (where Q1and RX1defined above), -CQ1NRX1O- (where Q1and RX1defined above), -ONRX1CQ1- (where Q1and RX1defined above), -Q2SO2- (where Q2represents an oxygen atom or-NRX10- (where RX10represents a hydrogen atom, formyl group or a C1-6alkyl group, a C1-6hydroxyalkyl group, a C1-6aminoalkyl group, Halogens1-6alkyl group, a C2-12alkoxyalkyl group3-7cycloalkyl group2-6alkenylphenol group2-6alkylamino group6-C12aryl group7-18alcylaryl group7-18aracelio gr the PPU, With2-7aliphatic acyl group, or With7-19aromatic acyl group, each of which may have one or more substituents), or-SO2Q2- (where Q2defined above)or a group represented by the formula:

or

(where Q1, Q2and RX1defined above; k is 0-5; m is 1-5; n and p are the same or different from each other and represent each 1-5; RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are the same or different from each other and represent each a hydrogen atom, a hydroxy-group, halogen, -N(RX11RX12- (where RX11and RX12are the same or different from each other and represent each a hydrogen atom, formyl group or a C1-6alkyl group, a C1-6hydroxyalkyl group, a C1-6aminoalkyl group, Halogens1-6alkyl group, a C2-12alkoxyalkyl group3-7cycloalkyl group2-6alkenylphenol group2-6alkylamino group6-C12 aryl group7-18alcylaryl group7-18aracelio group2-7aliphatic acyl group, or With7-19aromatic acyl group, each of which may have one or more substituents) or (C1-6alkyl group, a C1-6alkoxygroup, C1-6allylthiourea, C1-6hydroxyalkyl group, a C1-6hydroxyalkoxy, C1-6hydroxyalkyloxy, C1-6aminoalkyl group, C1-6aminoalkoxide, C1-6aminoalkylation, Halogens1-6alkyl group, Halogens1-6alkoxygroup, Halogens1-6allylthiourea,2-12alkoxyalkyl group2-12alkoxyalkyl,2-12alkoxyalkyl,3-7cycloalkyl group3-7cycloalkylation,4-13cycloalkylcarbonyl,3-7cycloalkylation,2-6alkenylphenol group2-6alkenylacyl,2-6altertekhnogrupp,2-6alkylamino group2-6alkyloxy,2-6alinytjara,6-12aryl group6-12alloctype,6-12killigrew,7-18alcylaryl group7-18alkylammonium,7-18alkylation,7-18aracelio group7-18aralkylated or7-18arkitip, each cat is, which may have one or more substituents, provided that RX2and RX3and/or RX4and RX5may together form a ring; and Q3and Q4are the same or different from each other and represent each an oxygen atom (O)S(O) or NRX10(where RX10defined above)); Y represents a 5 to 14-membered aromatic group or3-7alicyclic hydrocarbon group, each of which may have one or more substituents and one or more heteroatoms; and ring Z represents a 5 to 14-membered aromatic group which may have 1-4 substituent and one or more heteroatoms, and in which a portion of the ring can be saturated), its salt, its ester or hydrate;

32) the medicinal product in accordance with an embodiment of 31, which is based on a double agonize in respect of PPARα and γ;

33) the medicinal product in accordance with an embodiment of 31, which is based on the triple agonism in respect of PPARα, β(δ) and γ;

34) the medicinal product in accordance with any embodiment of 31 to 33, which is an insulin sensitizer;

35) the medicinal product in accordance with any embodiment of 31 to 33, which is an agent for the prophylaxis or treatment of diabetes;

36) the medicinal product in accordance with any embodiment of 31 to 33, which is the tool the La prevention or treatment of syndrome X;

37) the medicinal product in accordance with any embodiment of 31 to 33, which is an agent for the prophylaxis or treatment of diabetic complications;

38) the medicinal product in accordance with any embodiment of 31 to 33, which is an agent for the prevention or treatment of hyperlipemia;

39) the medicinal product in accordance with any embodiment of 31 to 33, which is a means for reducing the level of lipids;

40) the medicinal product in accordance with any embodiment of 31 to 33, which is an agent for the prophylaxis or treatment of obesity;

41) the medicinal product in accordance with any embodiment of 31 to 33, which is an agent for the prevention or treatment of osteoporosis;

42) the medicinal product in accordance with any embodiment of 31 to 33, which is anti-inflammatory;

43) the medicinal product in accordance with any embodiment of 31 to 33, which is an agent for the prevention or treatment of diseases of the digestive organs;

44) the medicinal product in accordance with an embodiment 43, where the disease of the digestive organs is a disease selected from the group consisting of 1) inflammatory diseases of the digestive organs, 2) proliferative diseases of the digestive organs, and 3) ulcerative ill the deposits of the digestive organs;

45) the drug according to embodiment 44, where inflammatory disease of the digestive organs is a disease selected from the group consisting of 1) ulcerative colitis, (2) Crohn's disease, 3) pancreatitis and 4) gastritis;

46) the drug according to embodiment 44, where inflammatory disease of the digestive organs is ulcerative colitis;

47) the agent for the prevention or treatment of diseases against which it is effective insulinsensitizing the action (the agent) contains a compound according to any embodiment 1 to 30 as an active ingredient;

48) the agent for the prevention or treatment of diseases of the digestive organs according to embodiment 44, where the proliferative disease of the digestive organs is a disease selected from the group consisting of 1) benign tumors of the digestive organs, 2) polyps in the digestive organs, 3) the syndrome of hereditary polyposis, 4) colon cancer, 5) cancer of the rectum and 6) cancer of the stomach;

49) the medicinal product in accordance with any embodiment of 31 to 33, with improving energy metabolism effect, which is an agent for the prevention or treatment 1) angina and myocardial infarction and its complications, 2) elderly is dementia or 3) cerebrovascular dementia;

50) the medicinal product in accordance with any embodiment of 31 to 33, which is an immunomodulatory agent;

51) the medicinal product in accordance with any embodiment of 31 to 33, which is an agent for the prophylaxis or treatment of cancer;

52) a method of preventing or treating a disease against which it is effective insulinsensitizing action, which includes the introduction of the patient a pharmaceutically effective amount of carboxylic acid derivative according to any embodiment 1 to 30, its salts, its complex ester or hydrate; and

53) the use of carboxylic acid derivative according to any embodiment 1 to 30, its salts, its complex ester or hydrate for the manufacture of products for the prevention or treatment of diseases against which it is effective insulinsensitizing action.

In accordance with the present invention it is also proposed pharmaceutical composition comprising a carboxylic acid derivative represented by the formula (I), its salt, its ester or its hydrate and a pharmaceutically acceptable carrier.

In accordance with this invention features a method of preventing or treating a disease against which an effective double agonism in respect of PPARα and γ or triple ganism in respect of PPARα that β(δ) and γ, which includes the introduction of the patient pharmaceutically effective amount of carboxylic acid derivative according to any embodiment 1 to 30, its salts, its complex ester or hydrate.

And in accordance with the present invention features the use of carboxylic acid derivative according to any embodiment 1 to 30, its salts, its complex ester or hydrate for the manufacture of products for the prevention or treatment of a disease against which an effective double agonism in respect of PPARα and γ or triple agonism in respect of PPARα, β(δ) and γ.

In the present invention the disease against which an effective double agonism in respect of PPARα and γ or triple agonism in respect of PPARα, β(δ) and γ", includes diabetes mellitus, syndrome X, diabetic complications, hyperlipemia, a disease against which effectively received lipid-reducing action, obesity, osteoporosis, a disease against which an effective anti-inflammatory action, diseases of the digestive organs including 1) inflammatory diseases of the digestive organs including ulcerative colitis, disease Crown, pancreatitis and gastritis, 2) proliferative diseases of the digestive organs including benign tumor of the digestive is lanov, the polyp in the digestive organs, the syndrome of hereditary polyposis, colon cancer, colorectal cancer and stomach cancer, and 3) ulcerative diseases of the digestive organs, 1) angina and myocardial infarction and its complications, 2) senile dementia or 3) cerebrovascular dementia on the basis of improving energy metabolism actions, respectively, the disease effectively immunomodulatory effects, and neoplastic disease.

In this specification, the structural formula of the compounds may for convenience to mean a specific isomer, but the present invention covers every possible isomer, which may be in the structures of the compounds of the present invention, such as geometric isomers, optical isomers based on asymmetric carbon atoms, a stereoisomer and tautomer, and mixtures of these isomers, and therefore, the compounds of the present invention is not limited to the formulas shown for convenience.

The following is a detailed description of the terms used in this description.

When each of R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10represents C1-6alkyl group which may have one or more substituents, the alkyl group means C1-6unbranched is whether branched alkyl group, specific examples of which include methyl group, ethyl group, n-sawn group, isopropyl group, n-boutelou group, isobutylene group, sec-boutelou group, tert-boutelou group, n-pentelow group, isopentyl group, sec-pentelow group, tert-pentelow group, neopentyl group, 1-methylbutyl group, 2-methylbutyl group, 1,1-dimethylpropyl group, 1,2-dimethylpropyl group, n-hexoloy group, isohexyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 2,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 3,3-dimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group, 1,1,2-trimethylpropyl group, 1,2,2-trimethylpropyl group, 1-ethyl-1-methylpropyl group and 1-ethyl-2-methylpropyloxy group, preferably methyl group, ethyl group, n-sawn group, isopropyl group, n-boutelou group, isobutylene group, sec-boutelou group, tert-boutelou group n-pentelow group, isopentyl group, sec-pentelow group, tert-pentelow group, neopentyl group, 1-methylbutyl group, 2-methylbutyl group, 1,1-dimethylpropyl group, 1,2-dimethylpropyl group, n-hexoloy the group and of hexoloy group, more preferably methyl group, ethyl group, n-sawn group, isopropyl group, n-boutelou group, isobutylene group, sec-boutelou group, tert-boutelou group, n-pentelow group, isopentyl group, sec-pentelow group, tert-pentelow group, neopentyl group, 1-methylbutyl group, 2-methylbutyl group, 1,1-dimethylpropylene group and 1,2-dimethylpropylene group, more preferably methyl group, ethyl group, n-sawn group, isopropyl group, n-boutelou group, isobutylene group, second-boutelou group and tert-boutelou group, and most preferably methyl group, ethyl group, n-through the group, and isopropyl group.

In this description, the expression "which may have a Deputy" means that the group may be substituted by the Deputy, such as a hydroxyl group; Tolna group; a nitro-group; morpholinopropan; thiomorpholine; halogen atom such as fluorine atom, chlorine atom, bromine atom and iodine atom; a nitrile group; azide group; formyl group; an alkyl group such as methyl group, ethyl group, through the group, isopropyl group and bucilina group; Alchemilla group such as vinyl group, allyl group and protanilla group; Alchemilla group, such as ethynylene the group, Butyrina group and propargyl group; alkoxygroup, such as a methoxy group, ethoxypropan, propoxylate and butoxypropan; halogenation group, such as permetrina group, deformational group, triptorelin group and florachilena group; a hydroxyalkyl group such as hydroxymethylene group, hydroxyethylene group and hydroxiproline group; guanidinium; formimidoyl group; acetimidoyl group; carnemolla group; thiocarbamoyl group; carbamylcholine group, such as carbamoylmethyl group and carbamoylethyl group; alkylcarboxylic group, such as methylcarbamoyl group and dimethylcarbamoyl group; a urea group; alcoolica group such as acetyl group; amino group; alkylamino, such as methylaminopropyl, atramentaria and isopropylamino; dialkylamines, such as dimethylaminopropyl, methylethylamine and diethylaminopropyl; aminoalkyl group such as aminomethyl group, aminoaniline group and aminopropylene group; carboxyl group; alkoxycarbonyl group, such as methoxycarbonyl group, ethoxycarbonyl group and propoxycarbonyl group; alkoxycarbonyl group, such as methoxycarbonylmethyl group, ethoxycarbonylmethyl the group, propoxycarbonyl group, methoxycarbonylethyl group, ethoxycarbonylethyl group and propoxycarbonyl group; alkyloxyalkyl group, such as methoxymethyl group, methylacetylene group, ethoxymethylene group and ethoxyethylene group; allylthiourea group, such as methylthiomethyl group, methylthioethyl group, ethylthiomethyl group and ethylthioethyl group; aminoalkylsilyl group, such as aminoethylaminomethyl group and aminoethylaminomethyl group; alkylcarboxylic, such as methylcarbonate, ethylcarboxylate and isopropylcarbonate; allakariallak group, such as benzyloxyaniline, benzyloxyaniline group; hydroxyethoxyethyl group, such as hydroxyethoxymethyl group and hydroxyethoxyethyl group; allakariallak group, such as benzoyloxymethyl group, benzyloxyethyl group and benzyloxypropionic group; Quaternary AMERIGROUP, such as trimethylammonium, methylethylenediamine and triethylammonium; cycloalkyl group, such as cyclopropyl group, cyclobutyl group, cyclopentenone group and tsiklogeksilnogo group; cycloalkenyl group, such as cyclopropene the other group, cyclobutenyl group, cyclopentenyl group and cyclohexenyl group; aryl group such as phenyl group, peridiniella group, thienyl group, furilla group and pyrrolidine group; allylthiourea, such as methylthiourea, ethylthiourea, PropertyGroup and butylthiourea; aristocrata, such as phenylthiourea, pyridinethione, tailtip, forestiera and pyrrolidine; aryl(lower)alkyl group such as benzyl group, triticina group and dimethoxytrityl group; substituted sulfonylurea group, such as sulfonylurea group, mesyl group, a p-toluensulfonyl group; Ariola group, such as benzoline group; halogenoalkane group such as Fortunella group and bratinella group; and oxoalkoxide, such as methylendioxy.

The expression "which may have one or more substituents" means that the group may have one or more of these groups in an arbitrary combination and includes, for example, alkyl group, alkenylphenol group, alkylamino group and alkoxygroup, substituted hydroxyl group, Tilney group, a nitrogroup, morpholinopropan, thiomorpholine, halogen atom, nitrile group, an azide group, formyl group, amino group, alkylamino, dialkylamino what agropol, carbamoyl group and sulfonyloxy group.

Further, the expression "which may have a Deputy and which may have one or more substituents" in the present invention has such meanings as defined above.

When R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are1-6alkoxygroup, which may have one or more substituents, alkoxygroup represents a C1-6unbranched or branched alkoxygroup and refers to a group having an oxygen atom attached to the end of the alkyl groups. Its specific examples include a methoxy group, ethoxypropan, n-propoxylate, isopropoxy, n-butoxypropyl, isobutoxy, sec-butoxypropyl, tert-butoxypropyl, n-pentyloxy, isopentylamine, sec-pentyloxy, tert-pentyloxy, neopentylglycol, 1-methylbutoxy, 2-methylbutoxy, 1,1-DIMETHYLPROPANE, 1,2-DIMETHYLPROPANE, n-hexyloxy, isohexadecane, 1-methylpentylamino, 2-methylpentylamino, 3-methylpentylamino, 1,1-Dimethylbutane, 1,2-Dimethylbutane, 2,2-Dimethylbutane, 1,3-Dimethylbutane, 2,3-Dimethylbutane, 3,3-Dimethylbutane, 1-ethylbutane, 2-ethylbutane, 1,1,2-trimethyl is oxygraph, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropoxy and 1-ethyl-2-methylpropoxy; preferably a methoxy group, ethoxypropan, n-propoxylate, isopropoxy, n-butoxypropyl, isobutoxy, sec-butoxypropyl, tert-butoxypropyl, n-pentyloxy, isopentylamine, sec-pentyloxy, tert-pentyloxy, neopentylglycol, 1-methylbutoxy, 2-methylbutoxy, 1,1-DIMETHYLPROPANE, 1,2-DIMETHYLPROPANE, n-hexyloxy and isohexadecane; more preferably a methoxy group, ethoxypropan, n-propoxylate, isopropoxy, n-butoxypropyl, isobutoxy, sec-butoxypropyl, tert-butoxypropyl, n-pentyloxy, isopentylamine, sec-pentyloxy, tert-pentyloxy, neopentylglycol, 1-methylbutoxy, 2-methylbutoxy, 1,1-DIMETHYLPROPANE, 1,2-dimethylpropanoyl; even more preferably a methoxy group, ethoxypropan, n-propoxylate, isopropoxy, n-butoxypropyl, isobutoxy, sec-butoxypropyl and tert-butoxypropan and most preferably a methoxy group, ethoxypropan, n-propoxylate and isopropoxy.

When R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are1-6allylthiourea, which may have one or n is how many deputies, allylthiourea represents a C1-6unbranched or branched allylthiourea and refers to a group having a sulfur atom attached to the end of the alkyl groups. Its specific examples include metalcorp, ethylthiourea, n-PropertyGroup, isopropylthio, n-butylthiourea, isobutylthiazole, sec-butylthiourea, tert-butylthiourea, n-intelligroup, isopentype, sec-intelligroup, tert-intelligroup, pointertype, 1-methylbutyrate, 2-methylbutyrate, 1,1-dimethylpropylene, 1,2-dimethylpropylene, n-vexillographer, isohexanoate, 1-methylpentylamino, 2-methylpentylamino, 3-methylpentylamino, 1,1-dimethylbutylamino, 1,2-dimethylbutylamino, 2,2-dimethylbutylamino, 1,3-dimethylbutylamino, 2,3-dimethylbutylamino, 3,3-dimethylbutylamino, 1-ethylbutyrate, 2-ethylbutyrate, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyloxy and 1-ethyl-2-methylpropionate; preferably metalcorp, ethylthiourea, n-PropertyGroup, isopropylthio, n-butylthiourea, isobutylthiazole, sec-butylthiourea, tert-butylthiourea, n-intelligroup, isopentype, sec-intelligroup, tert-intelligroup, pointertype, 1-methylbutyrate, 2-methylbutyl is Gruppo, 1,1-dimethylpropylene, 1,2-dimethylpropylene, n-vexillographer and isohexanoate; more preferably metalcorp, ethylthiourea, n-PropertyGroup, isopropylthio, n-butylthiourea, isobutylthiazole, sec-butylthiourea, tert-butylthiourea, n-intelligroup, isopentype, sec-intelligroup, tert-intelligroup, pointertype, 1-methylbutyrate, 2-methylbutyrate, 1,1-dimethylpropyleneurea and 1,2-dimethylpropyleneurea; even more preferably metalcorp, ethylthiourea, n-PropertyGroup, isopropylthio, n-butylthiourea, isobutylthiazole, sec-butylthiourea and tert-butylthiourea and most preferably metalcorp, ethylthiourea, n-PropertyGroup and isopropylthio.

When R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10are1-6hydroxyalkyl group which may have one or more substituents, hydroxyalkyl group is a group having From1-6unbranched or branched alkyl group substituted at substitutable position by a hydroxy-group. Its specific examples include hydroxymethylene group, 2-hydroxyethyloxy group and 1-hydroxyethylene group.

Similarly, when R1 , RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are1-6hydroxyalkoxy, which may have one or more substituents, hydroxyalkoxy represents a group having a1-6unbranched or branched alkoxygroup, substituted at substitutable position by a hydroxy-group. Its specific examples include hydroxyethoxy, 2-hydroxyethoxy and 1-hydroxyethoxy.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are1-6hydroxyalkyloxy, which may have one or more substituents, hydroxyalkyloxy represents a group having a1-6unbranched or branched allylthiourea, substituted at substitutable position by a hydroxy-group. Its specific examples include hydroxymethylation, 2-hydroxyethylthio and 1-hydroxyethylthio.

When R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10are1-6aminoalkyl group which may have one or more substituents, aminoalkyl group is a group having From1-6unbranched or branched alkyl which the Rupp, substituted at substitutable position of the amino group. Its specific examples include an aminomethyl group, 2-aminoethyl group and 1-aminoethyl group.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are1-6aminoalkoxide, which may have one or more substituents, aminoalkoxide represents a group having a1-6unbranched or branched alkoxygroup, substituted at substitutable position of the amino group. Its specific examples include aminoethoxy, 2-aminoethoxy and 1-aminoethoxy.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are1-6aminoalkylation, which may have one or more substituents, aminoalkylation represents a group having a1-6unbranched or branched allylthiourea, substituted at substitutable position of the amino group. Its specific examples include aminomethylation, 2-aminoethylamino and 1-aminoacylation.

When R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10are Halogens1-6alkyl group that can in order to have one or more substituents, halogenation group is a group having From1-6unbranched or branched alkyl group substituted at substitutable positions with one or more halogen atoms. In this case, the halogen atoms are fluorine atom, chlorine atom, bromine atom and iodine atom. Specific examples of such groups include pharmacylow group, triptorelin group, 2-foretelling group and 1-foretelling group.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are1-6the halogenated alkoxygroup, which may have one or more substituents, a halogenated alkoxygroup represents a group having a1-6unbranched or branched alkoxygroup, substituted at substitutable positions with one or more halogen atoms. Its specific examples include formatexpr, cryptometer, 2-floridacheap and 1-floridacheap.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are1-6the halogenated allylthiourea, which may have one or more substituents, a halogenated allylthiourea represents a group having a1-6nerasvetlena is or branched allylthiourea, substituted at substitutable positions with one or more halogen atoms. Its specific examples include formattertype, triptoreline, 2-foretelltarotve and 1-foretelltarotve.

When R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10are2-12alkoxyalkyl group which may have one or more substituents, alkoxyalkyl group is a group having From1-6unbranched or branched alkyl group substituted at substitutable position With1-6unbranched or branched alkoxygroup. Its specific examples include methoxymethyl group, ethoxymethyl group, 1-methoxyamino group, 2-methoxyaniline group, 1-ethoxyethylene group and 2-ethoxyethylene group.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are2-12alkoxyalkyl, which may have one or more substituents, alkoxyalkyl represents a group having a1-6unbranched or branched alkoxygroup, substituted at substitutable position With1-6unbranched or branched alkoxygroup. Its specific examples include ketoxime is xygraph, ethoxyethoxy, 1-methoxyethoxy, 2-methoxyethoxy, 1-ethoxyethoxy and 2-ethoxyethoxy.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are2-12alkoxylation, which may have one or more substituents, alkoxyalkyl represents a group having a1-6unbranched or branched allylthiourea, substituted at substitutable position With1-6unbranched or branched alkoxygroup. Its specific examples include methoxymethylethoxy, ethoxymethylene, 1-methoxyaniline, 2-methoxyaniline, 1-amoxicillinum and 2-amoxicillinum.

When R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10are3-7cycloalkyl group which may have one or more substituents, cycloalkyl group represents a3-7cyclic alkyl group, and specific examples include cyclopropyl group, cyclobutyl group, cyclopentyl group, tsiklogeksilnogo group and cycloheptyl group.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and R are3-7cycloalkylation, which may have one or more substituents, cycloalkylation represents a group having an oxygen atom attached to an end With3-7cyclic alkyl group, and specific examples include cyclopropylamino, cyclobutylamine, cyclopentylamine, cyclohexyloxy and cycloheptylamine.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are3-7cycloalkylation, which may have one or more substituents, cycloalkylation represents a group having a sulfur atom attached to an end With3-7cyclic alkyl group, and specific examples include cyclopropylamino, cyclobutylamine, cyclopentylamine, cyclohexylprop and cycloheptylamine.

When R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10are2-6alkenylphenol group which may have one or more substituents, Alchemilla group represents a2-6unbranched or branched alkenylphenol group and refers to the residue of the compound having a double bond in the alkyl group containing 2 and the or more carbon atoms. Its specific examples include atenolol group, 1-propene-1-ilen group, 2-propene-1-ilen group, 3-propene-1-ilen group, 1-butene-1-ilen group, 1-butene-2-ilen group, 1-butene-3-ilen group, 1-butene-4-ilen group, 2-butene-1-ilen group, 2-butene-2-ilen group, 1-methyl-1-propen-1-ilen group, 2-methyl-1-propen-1-ilen group, 1-methyl-2-propen-1-ilen group, 2-methyl-2-propen-1-ilen group, 1-methyl-1-butene-1-ilen group, 2-methyl-1-butene-1-ilen group, 3-methyl-1-butene-1-ilen group, 1-methyl-2-butene-1-ilen group, 2-methyl-2-butene-1-ilen group, 3-methyl-2-butene-1-ilen group, 1-methyl-3-butene-1-ilen group, 2-methyl-3-butene-1-ilen group, 3-methyl-3-butene-1-ilen group, 1-ethyl-1-butene-1-ilen group, 2-ethyl-1-butene-1-ilen group, 3-ethyl-1-butene-1-ilen group, 1-ethyl-2-butene-1-ilen group, 2-ethyl-2-butene-1-ilen group, 3-ethyl-2-butene-1-ilen group, 1-ethyl-3-butene-1-ilen group, 2-ethyl-3-butene-1-ilen group, 3-ethyl-3-butene-1-ilen group, 1,2-dimethyl-1-butene-1-ilen group, 1,3-dimethyl-1-butene-1-ilen group, 3,3-dimethyl-1-butene-1-ilen group, 1,1-dimethyl-2-butene-1-ilen group, 1,2-dimethyl-2-butene-1-ilen group, 1,3-dimethyl-2-butene-1-ilen group, 2,2-dimethyl-2-butene-1-ilen group, 3,3-dimethyl-2-butene-1-ilen group, 1,1-dimethyl-3-butene-1-ilen group, 1,2-dimethyl-3-butene-1-strong group, 1,3-dimethyl-3-butene-1-ilen group, 1-penten-1-ilen group, 2-pins is EN-1-ilen group, 3-penten-1-ilen group, 4-penten-1-ilen group, 1-penten-2-ilen group, 2-penten-2-ilen group, 3-penten-2-ilen group, 4-penten-2-ilen group, 1-penten-3-ilen group, 2-penten-3-ilen group, 1-methyl-1-penten-1-ilen group, 2-methyl-1-penten-1-ilen group, 3-methyl-1-penten-1-ilen group, 4-methyl-1-penten-1-ilen group, 1-methyl-2-penten-1-ilen group, 2-methyl-2-penten-1-ilen group, 3-methyl-2-penten-1-ilen group, 4-methyl-2-penten-1-ilen group, 1-methyl-3-penten-1-ilen group, 2-methyl-3-penten-1-ilen group, 3-methyl-3-penten-1-ilen group, 4-methyl-3-penten-1-ilen group, 1-methyl-4-penten-1-ilen group, 2-methyl-4-penten-1-ilen group, 3-methyl-4-penten-1-ilen group, 4-methyl-4-penten-1-ilen group, 1-methyl-1-penten-2-ilen group, 2-methyl-1-penten-2-ilen group, 3-methyl-1-penten-2-ilen group, 4-methyl-1-penten-2-ilen group, 1-methyl-2-penten-2-ilen group, 3-methyl-2-penten-2-ilen group, 4-methyl-2-penten-2-ilen group, 1-methyl-3-penten-2-ilen group, 2-methyl-3-penten-2-ilen group, 3-methyl-3-penten-2-ilen group, 4-methyl-3-penten-2-ilen group, 1-methyl-4-penten-2-ilen group, 2-methyl-4-penten-2-ilen group, 3-methyl-4-penten-2-ilen group, 4-methyl-4-penten-2-ilen group, 1-methyl-1-penten-3-ilen group, 2-methyl-1-penten-3-ilen group, 3-methyl-1-penten-3-ilen group, 4-methyl-1-penten-3-ilen group, 1-methyl-2-penten-3-ilen groups who, 2-methyl-2-penten-3-ilen group, 4-methyl-2-penten-3-ilen group, 1-HEXEN-1-ilen group, 1-HEXEN-2-ilen group, 1-HEXEN-3-ilen group, 1-HEXEN-4-ilen group, 1-HEXEN-5-ilen group, 1-HEXEN-6-ilen group, 2-HEXEN-1-ilen group, 2-hexene-2-ilen group, 2-HEXEN-3-ilen group, 2-hexene-4-ilen group, 2-hexene-5-ilen group, 2-hexene-6-ilen group, 3-HEXEN-1-ilen group, 3-HEXEN-2-ilen group and 3-HEXEN-3-ilen group; preferably atenolol group, 1-propene-1-ilen group, 2-propene-1-ilen group, 3-propene-1-ilen group, 1-butene-1-ilen group, 1-butene-2-ilen group, 1-butene-3-ilen group, 1-butene-4-ilen group, 2-butene-1-ilen group, 2-butene-2-ilen group, 1-methyl-1-propen-1-ilen group, 2-methyl-1-propen-1-ilen group, 1-methyl-2-propen-1-ilen group, 2-methyl-2-propen-1-ilen group, 1-methyl-1-butene-1-ilen group, 2-methyl-1-butene-1-ilen group, 3-methyl-1-butene-1-ilen group, 1-methyl-2-butene-1-ilen group, 2-methyl-2-butene-1-ilen group, 3-methyl-2-butene-1-ilen group, 1-methyl-3-butene-1-ilen group, 2-methyl-3-butene-1-ilen group, 3-methyl-3-butene-1-ilen group, 1-ethyl-1-butene-1-ilen group, 2-ethyl-1-butene-1-ilen group, 3-ethyl-1-butene-1-ilen group, 1-ethyl-2-butene-1-ilen group, 2-ethyl-2-butene-1-ilen group, 3-ethyl-2-butene-1-ilen group, 1-ethyl-3-butene-1-ilen group, 2-ethyl-3-butene-1-ilen group, 3-ethyl-3-butene-1-the function group, 1,2-dimethyl-1-butene-1-ilen group, 1,3-dimethyl-1-butene-1-ilen group, 3,3-dimethyl-1-butene-1-ilen group, 1,1-dimethyl-2-butene-1-ilen group, 1,2-dimethyl-2-butene-1-ilen group, 1,3-dimethyl-2-butene-1-ilen group, 1,1-dimethyl-3-butene-1-ilen group, 1,2-dimethyl-3-butene-1-strong group, 1,3-dimethyl-3-butene-1-ilen group, 2,2-dimethyl-3-butene-1-ilen group, and more preferably atenolol group, 1-propene-1-ilen group, 2-propene-1-ilen group, 3-propene-1-ilen group, 1-butene-1-ilen group, 1-butene-2-ilen group, 1-butene-3-ilen group, 1-butene-4-ilen group, 2-butene-1-ilen group, 2-butene-2-ilen group, 1-methyl-1-propen-1-ilen group, 2-methyl-1-propen-1-ilen group, 1-methyl-2-propen-1-ilen group, 2-methyl-2-propen-1-ilen group, 1-methyl-1-butene-1-ilen group, 2-methyl-1-butene-1-ilen group, 3-methyl-1-butene-1-ilen group, 1-methyl-2-butene-1-ilen group, 2-methyl-2-butene-1-ilen group, 3-methyl-2-butene-1-ilen group, 1-methyl-3-butene-1-ilen group, 2-methyl-3-butene-1-ilen group and 3-methyl-3-butene-1-ilen group, and most preferably atenolol group, 1-propene-1-ilen group 2-propen-1-ilen group, 3-propene-1-ilen group, 1-butene-1-ilen group, 1-butene-2-ilen group, 1-butene-3-ilen group, 1-butene-4-ilen group, 2-butene-1-ilen group and 2-butene-2-ilen group.

Similarly, when R1, RX2, RX3, RX4, R X5, RX6, RX7, RX8and RX9submit C2-6alkenylacyl, which may have one or more substituents, alkenylacyl represents a group having an oxygen atom attached to an end With2-6unbranched or branched alkenylphenol group. Its specific examples include atenololviagrawp, 1-propen-1-lexigraphy, 2-propen-1-lexigraphy, 3-propene-1-lexigraphy, 1-butene-1-lexigraphy, 1-butene-2-lexigraphy, 1-butene-3-lexigraphy, 1-butene-4-lexigraphy, 2-butene-1-lexigraphy, 2-butene-2-lexigraphy, 1-methyl-1-propen-1-lexigraphy, 2-methyl-1-propen-1-lexigraphy, 1-methyl-2-propen-1-lexigraphy, 2-methyl-2-propen-1-lexigraphy, 1-methyl-1-butene-1-lexigraphy, 2-methyl-1-butene-1-lexigraphy, 3-methyl-1-butene-1-lexigraphy, 1-methyl-2-butene-1-lexigraphy, 2-methyl-2-butene-1-lexigraphy, 3-methyl-2-butene-1-lexigraphy, 1-methyl-3-butene-1-lexigraphy, 2-methyl-3-butene-1-lexigraphy, 3-methyl-3-butene-1-lexigraphy, 1-ethyl-1-butene-1-lexigraphy, 2-ethyl-1-butene-1-lexigraphy, 3-ethyl-1-butene-1-lexigraphy, 1-ethyl-2-butene-1-lexigraphy, 2-ethyl-2-butene-1-lexigraphy, 3-ethyl-2-butene-1-lexigraphy, 1-ethyl-3-butene-1-lexigraphy, 2-ethyl-3-butene-1-lexigraphy, 3-ethyl-3-butene-1-lexigraphy, 1,2-dimethyl-1-butene-1-lexigraphy, 1,3-dimethyl-1-butene-1-lexigraphy, 3,3-dimethyl-1-butene-1-lexigraphy, 1,1-dimethyl-2-b the ten-1-lexigraphy, 1,2-dimethyl-2-butene-1-lexigraphy, 1,3-dimethyl-2-butene-1-lexigraphy, 1,1-dimethyl-3-butene-1-lexigraphy, 1,2-dimethyl-3-butene-1-lexigraphy, 1,3-dimethyl-3-butene-1-lexigraphy, 2,2-dimethyl-3-butene-1-lexigraphy, 1-penten-1-lexigraphy, 2-penten-1-lexigraphy, 3-penten-1-lexigraphy, 4-penten-1-lexigraphy, 1-penten-2-lexigraphy, 2-penten-2-lexigraphy, 3-penten-2-lexigraphy, 4-penten-2-lexigraphy, 1-penten-3-lexigraphy, 2-penten-3-lexigraphy, 1-methyl-1-penten-1-lexigraphy, 2-methyl-1-penten-1-lexigraphy, 3-methyl-1-penten-1-lexigraphy, 4-methyl-1-penten-1-lexigraphy, 1-methyl-2-penten-1-lexigraphy, 2-methyl-2-penten-1-lexigraphy, 3-methyl-2-penten-1-lexigraphy, 4-methyl-2-penten-1-lexigraphy, 1-methyl-3-penten-1-lexigraphy, 2-methyl-3-penten-1-lexigraphy, 3-methyl-3-penten-1-lexigraphy, 4-methyl-3-penten-1-lexigraphy, 1-methyl-4-penten-1-lexigraphy, 2-methyl-4-penten-1-lexigraphy, 3-methyl-4-penten-1-lexigraphy, 4-methyl-4-penten-1-lexigraphy, 1-methyl-1-penten-2-lexigraphy, 2-methyl-1-penten-2-lexigraphy, 3-methyl-1-penten-2-lexigraphy, 4-methyl-1-penten-2-lexigraphy, 1-methyl-2-penten-2-lexigraphy, 3-methyl-2-penten-2-lexigraphy, 4-methyl-2-penten-2-lexigraphy, 1-methyl-3-penten-2-lexigraphy, 2-methyl-3-penten-2-lexigraphy, 3-methyl-3-penten-2-lexigraphy, 4-methyl-3-penten-2-lexigraphy, 1-methyl-4-penten-2-lexigraphy, 2-methyl-4-penten-2-yloxy the Rupp, 3-methyl-4-penten-2-lexigraphy, 4-methyl-4-penten-2-lexigraphy, 1-methyl-1-penten-3-lexigraphy, 2-methyl-1-penten-3-lexigraphy, 3-methyl-1-penten-3-lexigraphy, 4-methyl-1-penten-3-lexigraphy, 1-methyl-2-penten-3-lexigraphy, 2-methyl-2-penten-3-lexigraphy, 4-methyl-2-penten-3-lexigraphy, 1-HEXEN-1-lexigraphy, 1-HEXEN-2-lexigraphy, 1-HEXEN-3-lexigraphy, 1-HEXEN-4-lexigraphy, 1-HEXEN-5-lexigraphy, 1-HEXEN-6-lexigraphy, 2-HEXEN-1-lexigraphy, 2-hexene-2-lexigraphy, 2-HEXEN-3-lexigraphy, 2-HEXEN-4-lexigraphy, 2-HEXEN-5-lexigraphy, 2-hexene-6-lexigraphy, 3-HEXEN-1-lexigraphy, 3-HEXEN-2-lexigraphy and 3-HEXEN-3-lexigraphy; preferably atenololviagrawp, 1-propen-1-lexigraphy, 2-propen-1-lexigraphy, 3-propene-1-lexigraphy, 1-butene-1-lexigraphy, 1-butene-2-lexigraphy, 1-butene-3-lexigraphy, 1-butene-4-lexigraphy, 2-butene-1-lexigraphy, 2-butene-2-lexigraphy, 1-methyl-1-propen-1-lexigraphy, 2-methyl-1-propen-1-lexigraphy, 1-methyl-2-propen-1-lexigraphy, 2-methyl-2-propen-1-lexigraphy, 1-methyl-1-butene-1-lexigraphy, 2-methyl-1-butene-1-lexigraphy, 3-methyl-1-butene-1-lexigraphy, 1-methyl-2-butene-1-lexigraphy, 2-methyl-2-butene-1-lexigraphy, 3-methyl-2-butene-1-lexigraphy, 1-methyl-3-butene-1-lexigraphy, 2-methyl-3-butene-1-lexigraphy, 3-methyl-3-butene-1-lexigraphy, 1-ethyl-1-butene-1-lexigraphy, 2-ethyl-1-butene-1-lexigram is, 3-ethyl-1-butene-1-lexigraphy, 1-ethyl-2-butene-1-lexigraphy, 2-ethyl-2-butene-1-lexigraphy, 3-ethyl-2-butene-1-lexigraphy, 1-ethyl-3-butene-1-lexigraphy, 2-ethyl-3-butene-1-lexigraphy, 3-ethyl-3-butene-1-lexigraphy, 1,1-dimethyl-1-butene-1-lexigraphy, 1,2-dimethyl-1-butene-1-lexigraphy, 1,3-dimethyl-1-butene-1-lexigraphy, 3,3-dimethyl-1-butene-1-lexigraphy, 1,1-dimethyl-2-butene-1-lexigraphy, 1,2-dimethyl-2-butene-1-lexigraphy, 1,3-dimethyl-2-butene-1-lexigraphy, 1,1-dimethyl-3-butene-1-lexigraphy, 1,2-dimethyl-3-butene-1-lexigraphy, 1,3-dimethyl-3-butene-1-lexigraphy, 2,2-dimethyl-3-butene-1-lexigraphy; more preferably atenololviagrawp, 1-propen-1-lexigraphy, 2-propen-1-lexigraphy, 3-propene-1-lexigraphy, 1-butene-1-lexigraphy, 1-butene-2-lexigraphy, 1-butene-3-lexigraphy, 1-butene-4-lexigraphy, 2-butene-1-lexigraphy, 2-butene-2-lexigraphy, 1-methyl-1-propene-1-lexigraphy, 2-methyl-1-propen-1-lexigraphy, 1-methyl-2-propen-1-lexigraphy, 2-methyl-2-propen-1-lexigraphy, 1-methyl-1-butene-1-lexigraphy, 2-methyl-1-butene-1-lexigraphy, 3-methyl-1-butene-1-lexigraphy, 1-methyl-2-butene-1-lexigraphy, 2-methyl-2-butene-1-lexigraphy, 3-methyl-2-butene-1-lexigraphy, 1-methyl-3-butene-1-lexigraphy, 2-methyl-3-butene-1-lexigraphy and 3-methyl-3-butene-1-lexigraphy; even more preferably atenololviagrawp, 1-propen-1-lexigraphy, 2-propen-1-lexigraphy, 3-propene-1-lexigraphy, buten-1-lexigraphy, 1-butene-2-lexigraphy, 1-butene-3-lexigraphy, 1-butene-4-lexigraphy, 2-butene-1-lexigraphy and 2-butene-2-lexigraphy and most preferably atenololviagrawp, 1-propen-1-lexigraphy, 2-propen-1-lexigraphy and 3-propene-1-lexigraphy.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are2-6altertekhnogrupp, which may have one or more substituents, alchemistjoshua represents a group having a sulfur atom attached to an end With2-6unbranched or branched alkenylphenol group, and its specific examples include attentiongrabber, 1-propen-1-itigroup, 2-propen-1-itigroup, 3-propene-1-itigroup, 1-butene-1-itigroup, 1-butene-2-itigroup, 1-butene-3-itigroup, 1-butene-4-itigroup, 2-butene-1-itigroup, 2-butene-2-itigroup, 1-methyl-1-propen-1-itigroup, 2-methyl-1-propen-1-itigroup, 1-methyl-2-propen-1-itigroup, 2-methyl-2-propen-1-itigroup, 1-methyl-1-butene-1-itigroup, 2-methyl-1-butene-1-itigroup, 3-methyl-1-butene-1-itigroup, 1-methyl-2-butene-1-itigroup, 2-methyl-2-butene-1-itigroup, 3-methyl-2-butene-1-itigroup, 1-methyl-3-butene-1-itigroup, 2-methyl-3-butene-1-itigroup, 3-methyl-3-butene-1-itigroup, 1-ethyl-1-butene-1-itigroup, 2-ethyl-1-butene-1-itigroup, 3-ethyl-1-butene-1-itigroup, 1-ethyl-2-bout the n-1-itigroup, 2-ethyl-2-butene-1-itigroup, 3-ethyl-2-butene-1-itigroup, 1-ethyl-3-butene-1-itigroup, 2-ethyl-3-butene-1-itigroup, 3-ethyl-3-butene-1-itigroup, 1,2-dimethyl-1-butene-1-itigroup, 1,3-dimethyl-1-butene-1-itigroup, 2,2-dimethyl-1-butene-1-itigroup, 3,3-dimethyl-1-butene-1-itigroup, 1,2-dimethyl-2-butene-1-itigroup, 1,3-dimethyl-2-butene-1-itigroup, 1,1-dimethyl-3-butene-1-itigroup, 1,2-dimethyl-3-butene-1-itigroup, 1,3-dimethyl-3-butene-1-itigroup, 2,2-dimethyl-3-butene-1-itigroup, 1-penten-1-itigroup, 2-penten-1-itigroup, 3-penten-1-itigroup, 4-penten-1-itigroup, 1-penten-2-itigroup, 2-penten-2-itigroup, 3-penten-2-itigroup, 4-penten-2-itigroup, 1-penten-3-itigroup, 2-penten-3-itigroup, 1-methyl-1-penten-1-itigroup, 2-methyl-1-penten-1-itigroup, 3-methyl-1-penten-1-itigroup, 4-methyl-1-penten-1-itigroup, 1-methyl-2-penten-1-itigroup, 2-methyl-2-penten-1-itigroup, 3-methyl-2-penten-1-itigroup, 4-methyl-2-penten-1-itigroup, 1-methyl-3-penten-1-itigroup, 2-methyl-3-penten-1-itigroup, 3-methyl-3-penten-1-itigroup, 4-methyl-3-penten-1-itigroup, 1-methyl-4-penten-1-itigroup, 2-methyl-4-penten-1-itigroup, 3-methyl-4-penten-1-itigroup, 4-methyl-4-penten-1-itigroup, 1-methyl-1-penten-2-itigroup, 2-methyl-1-penten-2-itigroup, 3-methyl-1-penten-2-itigroup, 4-methyl-1-penten-2-itigroup, 1-methyl-2-penten-2-itigroup, 3-methyl-2-Penta is-2-itigroup, 4-methyl-2-penten-2-itigroup, 1-methyl-3-penten-2-itigroup, 2-methyl-3-penten-2-itigroup, 3-methyl-3-penten-2-itigroup, 4-methyl-3-penten-2-itigroup, 1-methyl-4-penten-2-itigroup, 2-methyl-4-penten-2-itigroup, 3-methyl-4-penten-2-itigroup, 4-methyl-4-penten-2-itigroup, 1-methyl-1-penten-3-itigroup, 2-methyl-1-penten-3-itigroup, 3-methyl-1-penten-3-itigroup, 4-methyl-1-penten-3-itigroup, 1-methyl-2-penten-3-itigroup, 2-methyl-2-penten-3-itigroup, 4-methyl-2-penten-3-itigroup, 1-HEXEN-1-itigroup, 1-HEXEN-2-itigroup, 1-HEXEN-3-itigroup, 1-HEXEN-4-itigroup, 1-HEXEN-5-itigroup, 1-HEXEN-6-itigroup, 2-HEXEN-1-itigroup, 2-hexene-2-itigroup, 2-HEXEN-3-itigroup, 2-HEXEN-4-itigroup, 2-HEXEN-5-itigroup, 2-hexene-6-itigroup, 3-HEXEN-1-itigroup, 3-hexene-2-itigroup and 3-HEXEN-3-itigroup; preferably attentiongrabber, 1-propen-1-itigroup, 2-propen-1-itigroup, 3-propene-1-itigroup, 1-butene-1-itigroup, 1-butene-2-itigroup, 1-butene-3-itigroup, 1-butene-4-itigroup, 2-butene-1-itigroup, 2-butene-2-itigroup, 1-methyl-1-propen-1-itigroup, 2-methyl-1-propen-1-itigroup, 1-methyl-2-propen-1-itigroup, 2-methyl-2-propen-1-itigroup, 1-methyl-1-butene-1-itigroup, 2-methyl-1-butene-1-itigroup, 3-methyl-1-butene-1-itigroup, 1-methyl-2-butene-1-itigroup, 2-methyl-2-butene-1-itigroup, 3-methyl-2 the bout is-1-itigroup, 1-methyl-3-butene-1-itigroup, 2-methyl-3-butene-1-itigroup, 3-methyl-3-butene-1-itigroup, 1-ethyl-1-butene-1-itigroup, 2-ethyl-1-butene-1-itigroup, 3-ethyl-1-butene-1-itigroup, 1-ethyl-2-butene-1-itigroup, 2-ethyl-2-butene-1-itigroup, 3-ethyl-2-butene-1-itigroup, 1-ethyl-3-butene-1-itigroup, 2-ethyl-3-butene-1-itigroup, 3-ethyl-3-butene-1-itigroup, 1,2-dimethyl-1-butene-1-itigroup, 1,3-dimethyl-1-butene-1-itigroup, 3,3-dimethyl-1-butene-1-itigroup, 1,1-dimethyl-2-butene-1-itigroup, 1,2-dimethyl-2-butene-1-itigroup, 1,3-dimethyl-2-butene-1-itigroup, 1,1-dimethyl-3-butene-1-itigroup, 1,2-dimethyl-3-butene-1-itigroup, 1,3-dimethyl-3-butene-1-itigroup, 2,2-dimethyl-3-butene-1-itigroup, more preferably attentiongrabber, 1-propen-1-itigroup, 2-propen-1-itigroup, 3-propene-1-itigroup, 1-butene-1-itigroup, 1-butene-2-itigroup, 1-butene-3-itigroup, 1-butene-4-itigroup, 2-butene-1-itigroup, 2-butene-2-itigroup, 1-methyl-1-propen-1-itigroup, 2-methyl-1-propen-1-itigroup, 1-methyl-2-propen-1-itigroup, 2-methyl-2-propen-1-itigroup, 1-methyl-1-butene-1-itigroup, 2-methyl-1-butene-1-itigroup, 3-methyl-1-butene-1-itigroup, 1-methyl-2-butene-1-itigroup, 2-methyl-2-butene-1-itigroup, 3-methyl-2-butene-1-itigroup, 1-methyl-3-butene-1-itigroup, 2-methyl-3-butene-1-itigroup and 3-methyl-3-butene-1-itigroup; even more preferably attentiongrabber, 1-propene-itigroup, 2-propen-1-itigroup, 3-propene-1-itigroup, 1-butene-1-itigroup, 1-butene-2-itigroup, 1-butene-3-itigroup, 1-butene-4-itigroup, 2-butene-1-itigroup and 2-butene-2-itigroup and most preferably attentiongrabber, 1-propen-1-itigroup, 2-propen-1-itigroup and 3-propene-1-itigroup.

When R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10are2-6alkylamino group which may have one or more substituents, Alchemilla group represents a2-6unbranched or branched alkylamino group and refers to the residue of the compound having a triple bond in the alkyl group containing 2 or more carbon atoms. Its specific examples include etinilnoy group, 1-propyne-1-ilen group, 2-propyne-1-ilen group, 3-propyne-1-ilen group, 1-butyn-1-ilen group, 1-buten-2-ilen group, 1-butyn-3-ilen group, 1-butyn-4-ilen group, 2-butyn-1-ilen group, 1-methyl-2-propyne-1-ilen group, 3-methyl-1-butyn-1-ilen group, 1-methyl-2-buten-1-ilen group, 2-methyl-2-buten-1-ilen group, 3-methyl-2-buten-1-ilen group, 1-methyl-3-buten-1-ilen group, 2-methyl-3-buten-1-ilen group, 1-ethyl-2-butyn-1-ilen group, 1-ethyl-3-butyn-1-ilen group, 2-ethyl-3-buten-1-ilen group, 3,3-dimethyl-1-butyn-1-ilen group, 1,1-dimethyl-2-Buti is-1-ilen group, 1,1-dimethyl-3-butyn-1-ilen group, 1,2-dimethyl-3-butyn-1-ilen group, 1,3-dimethyl-3-butyn-1-ilen group, 2,2-dimethyl-3-butyn-1-ilen group, 1-pentyn-1-ilen group, 2-pentyn-1-ilen group, 3-pentyn-1-ilen group, 4-pentyn-1-ilen group, 3-pentyn-2-ilen group, 4-pentyn-2-ilen group, 1-pentyn-3-ilen group, 3-methyl-1-pentyn-1-ilen group, 4-methyl-1-pentyn-1-ilen group, 1-methyl-2-penten-1-ilen group, 4-methyl-2-penten-1-ilen group, 1-methyl-3-penten-1-ilen group, 2-methyl-3-penten-1-ilen group, 3-methyl-3-penten-1-ilen group, 4-methyl-3-penten-1-ilen group, 1-methyl-4-penten-1-ilen group, 2-methyl-4-penten-1-ilen group, 3-methyl-4-penten-1-ilen group; preferably etinilnoy group, 1-propyne-1-ilen group, 2-propyne-1-ilen group, 3-propyne-1-ilen group, 1-butyn-1-ilen group, 1-butyn-2-ilen group, 1-butyn-3-ilen group, 1-butyn-4-ilen group, 2-butyn-1-ilen group, 1-methyl-2-propyne-1-ilen group, 3-methyl-1-butyn-1-ilen group, 1-methyl-2-buten-1-ilen group, 1-ethyl-2-butyn-1-ilen group, 1-ethyl-3-butyn-1-ilen group 2-ethyl-3-butyn-1-ilen group, 3,3-dimethyl-1-butyn-1-ilen group, 1,1-dimethyl-2-butyn-1-ilen group, 1,1-dimethyl-3-butyn-1-ilen group, 1,2-dimethyl-3-butyn-1-ilen group, 2,2-dimethyl-3-butyn-1-ilen group; more preferably etinilnoy group, 1-propyne-1-ilen group, 2-propyne-1-ilen group, 3-propyne-1-the function group, 1-buten-1-ilen group, 1-buten-2-ilen group, 1-butyn-3-ilen group, 1-butyn-4-ilen group, 2-butyn-1-ilen group, 1-methyl-2-propyne-1-ilen group, 3-methyl-1-butyn-1-ilen group, 1-methyl-2-buten-1-ilen group, 1-methyl-3-buten-1-ilen group, 2-methyl-3-buten-1-ilen group; even more preferably etinilnoy group, 1-propyne-1-ilen group, 2-propyne-1-ilen group, 3-propyne-1-ilen group, 1-butyn-1-ilen group, 1-buten-2-ilen group, 1-butyn-3-ilen group, 1-butyn-4-ilen group, 2-butyn-1-ilen group, and most preferably etinilnoy group, 1-propyne-1-ilen group, 2-propyne-1-ilen group and 3-propyne-1-ilen group.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are2-6alkenylacyl, which may have one or more substituents, alkyloxy represents a group having an oxygen atom attached to the end of C2-6unbranched or branched alkenylphenol group, and its specific examples include atenololviagrawp, 1-propyne-1-lexigraphy, 2-propyne-1-lexigraphy, 3-propyne-1-lexigraphy, 1-butyn-1-lexigraphy, 1-buten-2-lexigraphy, 1-butyn-3-lexigraphy, 1-butyn-4-lexigraphy, 2-butyn-1-lexigraphy, 1-methyl-2-propyne-1-lexigraphy, 3-methyl-1-butyn-1-lexigraphy, 1-methyl-2-buten-1-yloxy is the SCP, 1-methyl-3-buten-1-lexigraphy, 2-methyl-3-buten-1-lexigraphy, 1-ethyl-2-butyn-1-lexigraphy, 1-ethyl-3-butyn-1-lexigraphy, 2-ethyl-3-butyn-1-lexigraphy, 3,3-dimethyl-1-butyn-1-lexigraphy, 1,1-dimethyl-2-butyn-1-lexigraphy, 1,1-dimethyl-3-butyn-1-lexigraphy, 1,2-dimethyl-3-buten-1-lexigraphy, 1,3-dimethyl-3-butyn-1-lexigraphy, 2,2-dimethyl-3-butyn-1-lexigraphy, 1-penten-1-lexigraphy, 2-pentyn-1-lexigraphy, 3-pentyn-1-lexigraphy, 4-pentyn-1-lexigraphy, 3-penten-2-lexigraphy, 4-penten-2-lexigraphy, 1-penten-3-lexigraphy, 3-methyl-1-pentyn-1-lexigraphy, 4-methyl-1-pentyn-1-lexigraphy, 1-methyl-2-penten-1-lexigraphy, 4-methyl-2-penten-1-lexigraphy, 1-methyl-3-penten-1-lexigraphy, 2-methyl-3-penten-1-lexigraphy, 3-methyl-3-penten-1-lexigraphy, 4-methyl-3-penten-1-lexigraphy, 1-methyl-4-penten-1-lexigraphy, 2-methyl-4-penten-1-lexigraphy, 3-methyl-4-penten-1-lexigraphy; preferably atenololviagrawp, 1-propyne-1-lexigraphy, 2-propyne-1-lexigraphy, 3-propyne-1-lexigraphy, 1-butyn-1-lexigraphy, 1-buten-2-lexigraphy, 1-butyn-3-lexigraphy, 1-butyn-4-lexigraphy, 2-butyn-1-lexigraphy, 1-methyl-2-propyne-1-lexigraphy, 3-methyl-1-butyn-1-lexigraphy, 1-methyl-2-buten-1-lexigraphy, 1-methyl-3-buten-1-lexigraphy, 2-methyl-3-buten-1-lexigraphy, 1-ethyl-2-butyn-1-lexigraphy, 1-ethyl-3-butyn-1-lexigraphy, 2-ethyl-3-butyn-1-lexigraphy, 3,3-dimethyl-1-butyn--lexigraphy, 1,1-dimethyl-2-butyn-1-lexigraphy, 1,1-dimethyl-3-butyn-1-lexigraphy, 1,2-dimethyl-3-butyn-1-lexigraphy, 2,2-dimethyl-3-butyn-1-lexigraphy; more preferably atenololviagrawp, 1-propyne-1-lexigraphy, 2-propyne-1-lexigraphy, 3-propyne-1-lexigraphy, 1-butyn-1-lexigraphy, 1-buten-2-lexigraphy, 1-butyn-3-lexigraphy, 1-butyn-4-lexigraphy, 2-butyn-1-lexigraphy, 1-methyl-2-propyne-1-lexigraphy, 3-methyl-1-butyn-1-lexigraphy, 1-methyl-2-buten-1-lexigraphy, 1-methyl-3-buten-1-lexigraphy, 2-methyl-3-buten-1-lexigraphy; even more preferably atenololviagrawp, 1-propyne-1-lexigraphy, 2-propyne-1-lexigraphy, 3-propyne-1-lexigraphy, 1-butyn-1-lexigraphy, 1-buten-2-lexigraphy, 1-butyn-3-lexigraphy, 1-butyn-4-lexigraphy, 2-butyn-1-lexigraphy and most preferably atenololviagrawp, 1-propyne-1-lexigraphy, 2-propyne-1-lexigraphy and 3-propyne-1-lexigraphy.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are2-6alinytjara, which may have one or more substituents, alinytjara represents a group having a sulfur atom attached to the end of C2-6unbranched or branched alkenylphenol group, and its specific examples include tinytip, 1-propyne-1-itigroup, 2-propyne-1-itigroup 3-propyne-1-itigroup, 1-buten-1-itigroup, 1-buten-2-itigroup, 1-butyn-3-itigroup, 1-butyn-4-itigroup, 2-butyn-1-itigroup, 1-methyl-2-propyne-1-itigroup, 3-methyl-1-butyn-1-itigroup, 1-methyl-2-buten-1-itigroup, 1-methyl-3-buten-1-itigroup, 2-methyl-3-buten-1-itigroup, 1-ethyl-2-butyn-1-itigroup, 1-ethyl-3-butyn-1-itigroup, 2-ethyl-3-butyn-1-itigroup, 3,3-dimethyl-1-butyn-1-itigroup, 1,1-dimethyl-2-butyn-1-itigroup, 1,1-dimethyl-3-butyn-1-itigroup, 1,2-dimethyl-3-butyn-1-itigroup, 1,3-dimethyl-3-butyn-1-itigroup, 2,2-dimethyl-3-buten-1-itigroup, 1-penten-1-itigroup, 2-pentyn-1-itigroup, 3-pentyn-1-itigroup, 4-pentyn-1-itigroup, 3-penten-2-itigroup, 4-penten-2-itigroup, 1-penten-3-itigroup, 3-methyl-1-pentyn-1-itigroup, 4-methyl-1-pentyn-1-itigroup, 1-methyl-2-penten-1-itigroup, 4-methyl-2-penten-1-itigroup, 1-methyl-3-penten-1-itigroup, 2-methyl-3-penten-1-itigroup, 3-methyl-3-penten-1-itigroup, 4-methyl-3-penten-1-itigroup, 1-methyl-4-penten-1-itigroup, 2-methyl-4-penten-1-itigroup, 3-methyl-4-penten-1-itigroup; preferably tinytip, 1-propyne-1-itigroup, 2-propyne-1-itigroup, 3-propyne-1-itigroup, 1-butyn-1-itigroup, 1-buten-2-itigroup, 1-butyn-3-itigroup, 1-butyn-4-itigroup, 2-butyn-1-itigroup, 1-methyl-2-propyne-1-itigroup, 3-methyl-1-butyn-1-itigroup, 1-methyl-2-buten-1-itigroup, 1-methyl-3-butyn-itigroup, 2-methyl-3-buten-1-itigroup, 1-ethyl-2-butyn-1-itigroup, 1-ethyl-3-butyn-1-itigroup, 2-ethyl-3-butyn-1-itigroup, 3,3-dimethyl-1-butyn-1-itigroup, 1,1-dimethyl-2-butyn-1-itigroup, 1,2-dimethyl-2-butyn-1-itigroup, 1,3-dimethyl-2-butyn-1-itigroup, 2,2-dimethyl-2-buten-1-itigroup, 3,3-dimethyl-2-butyn-1-itigroup, 1,1-dimethyl-3-butyn-1-itigroup, 1,2-dimethyl-3-butyn-1-itigroup and 3,3-dimethyl-3-butyn-1-itigroup; more preferably tinytip, 1-propyne-1-itigroup, 2-propyne-1-itigroup, 3-propyne-1-itigroup, 1-butyn-1-itigroup, 1-buten-2-itigroup, 1-butyn-3-itigroup, 1-butyn-4-itigroup, 2-butyn-1-itigroup, 1-methyl-2-propyne-1-itigroup, 3-methyl-1-butyn-1-itigroup, 1-methyl-2-buten-1-itigroup, 1-methyl-3-buten-1-itigroup and 3-methyl-3-buten-1-itigroup; even more preferably tinytip, 1-propyne-1-itigroup, 2-propyne-1-itigroup, 3-propyne-1-itigroup, 1-butyn-1-itigroup, 1-buten-2-itigroup, 1-butyn-3-itigroup, 1-butyn-4-itigroup, and most preferably tinytip, 1-propyne-1-itigroup, 2-propyne-1-itigroup and 3-propyne-1-itigroup.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are2-6alinytjara, which may have one or more substituents, alinytjara made the focus of a group, having the sulfur atom attached to an end With2-6unbranched or branched alkenylphenol group, and its specific examples include tinytip, 1-propyne-1-itigroup, 2-propyne-1-itigroup, 3-propyne-1-itigroup, 1-butyn-1-itigroup, 1-buten-2-itigroup, 1-butyn-3-itigroup, 1-butyn-4-itigroup, 2-butyn-1-itigroup, 2-Butin-2-itigroup, 1-methyl-1-propyne-1-itigroup, 2-methyl-1-propyne-1-itigroup, 1-methyl-2-propyne-1-itigroup, 2-methyl-2-propyne-1-itigroup, 1-methyl-1-butyn-1-itigroup, 2-methyl-1-butyn-1-itigroup, 3-methyl-1-butyn-1-itigroup, 1-methyl-2-buten-1-itigroup, 2-methyl-2-buten-1-itigroup, 3-methyl-2-buten-1-itigroup, 1-methyl-3-buten-1-itigroup, 2-methyl-3-buten-1-itigroup, 3-methyl-3-buten-1-itigroup, 1-ethyl-1-butyn-1-itigroup, 2-ethyl-1-butyn-1-itigroup, 3-ethyl-1-butyn-1-itigroup, 1-ethyl-2-butyn-1-itigroup, 2-ethyl-2-butyn-1-itigroup 3-ethyl-2-butyn-1-itigroup, 1-ethyl-3-butyn-1-itigroup, 2-ethyl-3-butyn-1-itigroup, 3-ethyl-3-butyn-1-itigroup, 1,1-dimethyl-1-butyn-1-itigroup, 1,2-dimethyl-1-butyn-1-itigroup, 1,3-dimethyl-1-butyn-1-itigroup, 2,2-dimethyl-1-butyn-1-itigroup, 3,3-dimethyl-1-butyn-1-itigroup, 1,1-dimethyl-2-butyn-1-itigroup, 1,2-dimethyl-2-butyn-1-itigroup, 1,3-dimethyl-2-butyn-1-itigroup, 2,2-dimethyl-2-butyn-1-itigroup, 3,3-dimethyl-2-butyn-1-itigroup, 1,1-dimethyl-3-butyn-1-yl is igroup, 1,2-dimethyl-3-butyn-1-itigroup, 1,3-dimethyl-3-butyn-1-itigroup, 2,2-dimethyl-3-butyn-1-itigroup, 3,3-dimethyl-3-butyn-1-itigroup, 1-penten-1-itigroup, 2-pentyn-1-itigroup, 3-pentyn-1-itigroup, 4-pentyn-1-itigroup, 1-pentyn-2-itigroup, 2-penten-2-itigroup, 3-penten-2-itigroup, 4-penten-2-itigroup, 1-penten-3-itigroup, 2-pentyn-3-itigroup, 1-methyl-1-pentyn-1-itigroup, 2-methyl-1-pentyn-1-itigroup, 3-methyl-1-pentyn-1-itigroup, 4-methyl-1-pentyn-1-itigroup, 1-methyl-2-penten-1-itigroup, 2-methyl-2-penten-1-itigroup, 3-methyl-2-penten-1-itigroup, 4-methyl-2-penten-1-itigroup, 1-methyl-3-penten-1-itigroup, 2-methyl-3-penten-1-itigroup, 3-methyl-3-penten-1-itigroup, 4-methyl-3-penten-1-itigroup, 1-methyl-4-penten-1-itigroup, 2-methyl-4-penten-1-itigroup, 3-methyl-4-penten-1-itigroup, 4-methyl-4-penten-1-itigroup, 1-methyl-1-pentyn-2-itigroup, 2-methyl-1-pentyn-2-itigroup, 3-methyl-1-pentyn-2-itigroup, 4-methyl-1-pentyn-2-itigroup, 1-methyl-2-penten-2-itigroup, 2-methyl-2-penten-2-itigroup, 3-methyl-2-penten-2-itigroup, 4-methyl-2-penten-2-itigroup, 1-methyl-3-penten-2-itigroup, 2-methyl-3-penten-2-itigroup, 3-methyl-3-penten-2-itigroup, 4-methyl-3-penten-2-itigroup, 1-methyl-4-penten-2-itigroup, 2-methyl-4-penten-2-itigroup, 3-methyl-4-penten-2-itigroup, 4-methyl-4-penten-2-itigroup, 1-methyl-1-pentyn-3-is stogroup, 2-methyl-1-pentyn-3-itigroup, 3-methyl-1-pentyn-3-itigroup, 4-methyl-1-pentyn-3-itigroup, 1-methyl-2-penten-3-itigroup, 2-methyl-2-penten-3-itigroup, 3-methyl-2-penten-3-itigroup, 4-methyl-2-penten-3-itigroup, 1-hexyne-1-itigroup, 1-hexyne-2-itigroup, 1-hexyne-3-itigroup, 1-hexyne-4-itigroup, 1-hexyne-5-itigroup, 1-hexyne-6-itigroup, 2-hexyne-1-itigroup, 2-hexyne-2-itigroup, 2-hexyne-3-itigroup, 2-hexyne-4-itigroup, 2-hexyne-5-itigroup, 2-hexyne-6-itigroup, 3-hexyne-1-itigroup, 3-hexyne-2-itigroup and 3-hexyne-3-itigroup; preferably tinytip, 1-propyne-1-itigroup, 2-propyne-1-itigroup, 3-propyne-1-itigroup, 1-butyn-1-itigroup, 1-buten-2-itigroup, 1-butyn-3-itigroup, 1-butyn-4-itigroup, 2-butyn-1-itigroup, 2-Butin-2-itigroup, 1-methyl-1-propyne-1-itigroup, 2-methyl-1-propyne-1-itigroup, 1-methyl-2-propyne-1-itigroup, 2-methyl-2-propyne-1-itigroup, 1-methyl-1-butyn-1-itigroup, 2-methyl-1-butyn-1-itigroup, 3-methyl-1-butyn-1-itigroup, 1-methyl-2-buten-1-itigroup, 2-methyl-2-buten-1-itigroup, 3-methyl-2-buten-1-itigroup, 1-methyl-3-buten-1-itigroup, 2-methyl-3-buten-1-itigroup, 3-methyl-3-buten-1-itigroup, 1-ethyl-1-butyn-1-itigroup, 2-ethyl-1-butyn-1-itigroup, 3-ethyl-1-butyn-1-itigroup, 1-ethyl-2-butyn-1-itigroup, 2-ethyl-2-butyn-1-itigroup, 3-ethyl-2-buten-1-itigroup, etyl-3-buten-1-itigroup, 2-ethyl-3-butyn-1-itigroup, 3-ethyl-3-butyn-1-itigroup, 1,1-dimethyl-1-butyn-1-itigroup, 1,2-dimethyl-1-butyn-1-itigroup, 1,3-dimethyl-1-butyn-1-itigroup, 2,2-dimethyl-1-butyn-1-itigroup, 3,3-dimethyl-1-butyn-1-itigroup, 1,1-dimethyl-2-butyn-1-itigroup, 1,2-dimethyl-2-buten-1-itigroup, 1,3-dimethyl-2-butyn-1-itigroup, 2,2-dimethyl-2-butyn-1-itigroup, 3,3-dimethyl-2-butyn-1-itigroup, 1,1-dimethyl-3-butyn-1-itigroup, 1,2-dimethyl-3-butyn-1-itigroup, 1,3-dimethyl-3-butyn-1-itigroup, 2,2-dimethyl-3-butyn-1-itigroup and 3,3-dimethyl-3-butyn-1-itigroup; more preferably tinytip, 1-propyne-1-itigroup, 2-propyne-1-itigroup, 3-propyne-1-itigroup, 1-butyn-1-itigroup, 1-buten-2-itigroup, 1-butyn-3-itigroup, 1-butyn-4-itigroup, 2-butyn-1-itigroup, 2-Butin-2-itigroup, 1-methyl-1-propyne-1-itigroup, 2-methyl-1-propyne-1-itigroup, 1-methyl-2-propyne-1-itigroup, 2-methyl-2-propyne-1-itigroup, 1-methyl-1-butyn-1-itigroup, 2-methyl-1-butyn-1-itigroup, 3-methyl-1-butyn-1-itigroup, 1-methyl-2-buten-1-itigroup, 2-methyl-2-buten-1-itigroup, 3-methyl-2-buten-1-itigroup, 1-methyl-3-buten-1-itigroup, 2-methyl-3-buten-1-itigroup and 3-methyl-3-buten-1-itigroup; even more preferably tinytip, 1-propyne-1-itigroup, 2-propyne-1-itigroup, 3-propyne-1-itigroup, 1-butyn-1-itigroup, 1-buten-2-itigroup, 1-butyn-3-altior the PPU, 1-butyn-4-itigroup, 2-butyn-1-itigroup and 2-Butin-2-itigroup and most preferably tinytip, 1-propyne-1-itigroup, 2-propyne-1-itigroup and 3-propyne-1-itigroup.

When R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10are6-12aryl group which may have one or more substituents, aryl group represents an aromatic cyclic group, and its specific examples include phenyl group, 1-naftalina group, 2-naftalina group, as-industrynow group, s-industrynow group and acenaphthylene group; preferably a phenyl group, 1-naftalina group and 2-naftalina group; more preferably a phenyl group.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are6-12alloctype, which may have one or more substituents, alloctype represents a group having an oxygen atom attached to an end With6-12aryl group, and specific examples include fenoxaprop, 1-naphthyloxy, 2-naphthyloxy, as indatadialogruta, s-indatadialogruta and acenaphthylene; preferably fenoxaprop, 1-naphthyloxy and 2 in which tyloxapol; more preferably fenoxaprop.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are6-12killigrew, which may have one or more substituents, aristocrata represents a group having a sulfur atom attached to an end With6-12aryl group, and specific examples include phenylthiourea, 1-naphthylthiourea, 2-naphthylthiourea, as indzenieru, s-indzenieru and acenaphthylene; preferably phenylthiourea, 1-naphthylthiourea and 2-naphthylthiourea; more preferably phenylthiourea.

When R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10are7-18alcylaryl group which may have one or more substituents, alcylaryl group is a group having From6-12aryl group, substituted at substitutable position With1-6alkyl group. Its specific examples include taillow group, kalilou group, colaninno group, mesitylene group, ciminillo group and stielow group; preferably taillow group, kalilou group, colaninno group, mesitylene group, ciminillo group and stielow group; more prepact the positive taillow group, kalilou group, colaninno group and mesitylene group, and even more preferably taillow group, kalilou group and colaninno group.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are7-18alkylammonium, which may have one or more substituents, alkylammonium represents a group having an oxygen atom attached to an end With7-18alcylaryl group. Its specific examples include on-tolyloxy, m-tolyloxy, p-tolyloxy, 2,3-xylyl-1-oxygraph, 2,4-xylyl-1-oxygraph, 2,5-xylyl-1-oxygraph, comunicasimplu, m-comunicasimplu, p-comunicasimplu, mesityloxide, 2,3-ciminal-1-oxygraph, 2,4-ciminal-1-oxygraph 2,5-ciminal-1-oxygraph, stereochrome, m-stereochrome and p-stereochrome; preferably about-tolyloxy, m-tolyloxy, p-tolyloxy, 2,3-xylyl-1-oxygraph, 2,4-xylyl-1-oxygraph, 2,5-xylyl-1-oxygraph, comunicasimplu, m-comunicasimplu, p-comunicasimplu, mesityloxide, 2,3-ciminal-1-oxygraph, 2,4-ciminal-1-oxygraph 2,5-ciminal-1-oxygraph, stereochrome, m-stereochrome and p-stereochrome; more preferably about-tolyloxy, m-tolyloxy, p-tolyloxy, 2,3-what silyl-1-oxygraph, 2,4-xylyl-1-oxygraph, 2,5-xylyl-1-oxygraph, comunicasimplu, m-comunicasimplu, p-comunicasimplu, mesityloxide, stereochrome, m-stereochrome and p-stereochrome; even more preferably about-tolyloxy, m-tolyloxy, p-tolyloxy, 2,3-xylyl-1-oxygraph, 2,4-xylyl-1-oxygraph, 2,5-xylyl-1-oxygraph and mesityloxide and most preferably about-tolyloxy, m-tolyloxy and p-tolyloxy.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are7-18alkylation, which may have one or more substituents, alkylallminum represents a group having a sulfur atom attached to an end With7-18alcylaryl group. Its specific examples include on-tolylthiourea, m-tolylthiourea, p-tolylthiourea, 2,3-xylyl-1-togroup, 2,4-xylyl-1-togroup, 2,5-xylyl-1-togroup, kaministiqua, m-kaministiqua, p-kaministiqua, methicilline, 2,3-ciminal-1-togroup, 2,4-ciminal-1-togroup 2,5-ciminal-1-togroup, sterillium, m-sterillium and p-sterillium; preferably about-tolylthiourea, m-tolylthiourea, p-tolylthiourea, 2,3-xylyl-1-togroup, 2,4-xylyl-1-togroup, 2,5-xylyl-1-togroup, kaministiqua, m-cumene is tigroup, p-kaministiqua, methicilline, 2,3-ciminal-1-togroup, 2,4-ciminal-1-togroup 2,5-ciminal-1-togroup, sterillium, m-sterillium and p-stijlgroep; more preferably about-tolylthiourea, m-tolylthiourea, p-tolylthiourea, 2,3-xylyl-1-togroup, 2,4-xylyl-1-togroup, 2,5-xylyl-1-togroup, kaministiqua, m-kaministiqua, p-kaministiqua, methicilline, sterillium, m-sterillium and p-sterillium; even more preferably about-tolylthiourea, m-tolylthiourea, p-tolylthiourea, 2,3-xylyl-1-togroup, 2,4-xylyl-1-togroup, 2,5-xylyl-1-togroup and methicilline and most preferably about-tolylthiourea, m-tolylthiourea and p-tolylthiourea.

When R1, RX1, RX2, RX3, RX4, RX5, RX6, RX7, RX8, RX9and RX10are7-18aracelio group which may have one or more substituents, kalkilya group is a group having From1-6alkyl group, substituted at substitutable position With6-12aryl group. Its specific examples include a benzyl group, fenetylline group, 3-phenylpropyl group, 4-phenylbutyl group, 5-phenylmethylene group, 6-phenylhexanoic group, 1-naphthylmethyl group, 2-naphthylmethyl group, 1-naphthylethylene group, 2-naphthyl is tilen group, 1-afterripening group and 2-afterripening group; preferably benzyl group, fenetylline group, 3-phenylpropyl group, 4-phenylbutyl group, 5-phenylmethylene group, 6-phenylhexanoic group, 1-naphthylmethyl group, 2-naphthylmethyl group, 1-naphthylethylene group, 2-naphthylethylene group, 1-afterripening group and 2-afterripening group; more preferably a benzyl group, fenetylline group, 3-phenylpropyl group, 4-phenylbutyl group, 5-phenylmethylene group, 6-phenylhexanoic group, 1-naphthylmethyl group and 2-naphthylmethyl group; more preferably a benzyl group, fenetylline group, 3-phenylpropyl group and 4-phenylbutyl group and most preferably a benzyl group and fenetylline group.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are7-18aralkylated, which may have one or more substituents, arancelaria represents a group having an oxygen atom attached to an end With7-18aranceles group. Its specific examples include benzyloxy, penetrometry, 3-phenylpropoxy, 4-phenylbutyraldehyde, 5-finalinternship, 6-vanillacracker, 1-naphthalenyloxy, 2-is affiliateshop, 1-naphthylisocyanate, 2-naphthylisocyanate, 1-afterpropertiesset and 2-afterpropertiesset; preferably benzyloxy, penetrometry, 3-phenylpropoxy, 4-phenylbutyraldehyde, 5-finalinternship, 6-vanillacracker, 1-naphthalenyloxy, 2-naphthalenyloxy, 1-naphthylisocyanate, 2-naphthylisocyanate, 1-afterpropertiesset and 2-afterpropertiesset; more preferably benzyloxy, penetrometry, 3-phenylpropoxy, 4-phenylbutyraldehyde, 5-finalinternship, 6-vanillacracker, 1-naphthalenyloxy and 2-naphthalenyloxy; even more preferably benzyloxy, penetrometry, 3-phenylpropylamine and 4-phenylbutyraldehyde and most preferably benzyloxy and penetrometry.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are7-18arkitip, which may have one or more substituents, kalkiliya represents a group having a sulfur atom attached to an end With7-18aranceles group. Its specific examples include menzilcioglu, penitentiary, 3-phenylpropionate, 4-phenylbutyrate, 5-phenylperhydro, 6-familycentered, 1-naphthyl is milligramme, 2-naphthylethylene, 1-naphthylacetyl, 2-naphthylacetyl, 1-afterpropertiesset and 2-afterpropertiesset; preferably menzilcioglu, penitentiary, 3-phenylpropionate, 4-phenylbutyrate, 5-phenylperhydro, 6-familycentered, 1-naphthylethylene, 2-naphthylethylene, 1-naphthylacetyl, 2-naphthylacetyl, 1-afterpropertiesset and 2-afterpropertiesset; more preferably menzilcioglu, penitentiary, 3-phenylpropionate, 4-phenylbutyrate, 5-phenylperhydro, 6-familycentered, 1-naphthylethylene and 2-naphthylethylene; even more preferably menzilcioglu, penitentiary, 3-phenylpropionate and 4-phenylbutyrate and most preferably menzilcioglu and penitentiary.

Similarly, when R1, RX2, RX3, RX4, RX5, RX6, RX7, RX8and RX9are4-13cycloalkylcarbonyl, which may have one or more substituents, cycloalkylcarbonyl represents a group having an unbranched or branched C1-6alkoxygroup, in which the substituted position substituted With a3-7cyclic alkyl group, and specific examples include cyclopropylmethoxy, cyclobutylmethyl is the SCP, cyclopentyloxy, cyclohexylmethoxy, cycloheptylmethyl, 1-cyclopropylmethoxy, 2-cyclopropylethyl, 1-cyclopropyl-n-propoxylate, 2-cyclopropyl-n-propoxylate, 3-cyclopropyl-n-propoxylate, cyclopropanecarboxylate, cyclopropyl-n-butoxypropyl, cyclopropylmethoxy, cyclopropyl-Deut-butoxypropyl, cyclopropyl-tert-butoxypropyl, cyclopropyl-n-pentyloxy, cyclopropylmethoxy, cyclopropyl-Deut-pentyloxy, cyclopropyl-tert-pentyloxy and cyclopropylmethoxy; more preferably cyclopropylmethoxy, cyclopropylmethoxy, cyclopropyl-n-propoxylate, cyclopropanecarboxylate, cyclopropyl-n-butoxypropyl, cyclopropylmethoxy, cyclopropyl-Deut-butoxypropyl, cyclopropyl-tert-butoxypropyl, cyclopropyl-n-pentyloxy, cyclopropylmethoxy, cyclopropyl-Deut-pentyloxy, cyclopropyl-tert-pentyloxy, cyclopropanemethylamine and most preferably cyclopropylmethoxy, cyclopropylmethoxy, cyclopropyl-n-propoxylate, cyclopropanecarboxylate and the like.

In this description and the specific examples of "heteroatom" includes oxygen atom, sulfur atom, nitrogen atom, phosphorus, arsenic, antimony, silicon, germanium, tin, is vines, boron, mercury and the like, of which preferred are oxygen atom, sulfur atom, nitrogen atom and phosphorus, and more preferred is an oxygen atom, a sulfur atom and a nitrogen atom.

Further, when use of the expression "which may have heteroatom" refers to such heteroatom as defined above.

In the expression Y and the ring Z represent a 5 to 14-membered aromatic group which may have one or more heteroatoms" aromatic group means With6-12aryl group or6-12aryl group in which a substitutable position is substituted With1-6aliphatic hydrocarbon group, and specific examples of which include phenyl group, o-taillow group, m-trillou group, p-taillow group, 2,3-kalilou group, 2,4-kalilou group, 2,5-kalilou group, mesitylene group, ciminillo group, colaninno group, m-colaninno group, p-colaninno group, benzyl group, fenetylline group α-methylbenzyl group, benzhydryl group, trityloxy group, benzylidene group, stielow group, cinnamyl group, cannabilizing group, 3-phenylpropyl group 4-phenylbutyl group, 5-phenylmethylene group, 6-phenylhexanoic group, 1-naftalina group, 2-naftalina group, 1-naphthylmethyl group, 2-naphthylmethyl group, 1-naphthas is lateline group, 2-naphthylethylene group, as-industrynow group, s-industrynow group, acenaphthylene group and the like. Preferred are a phenyl group, o-tolila group, m-tolila group, p-tolila group, 2,3-xylella group, 2,4-xylella group, 2,5-xylella group, mesitylene group, ciminella group, cominella group, m-cominella group, p-cominella group, benzyl group, penicilina group α-methylbenzyl group, benzydamine group, triticina group, benzylidene group, sterelny group, cinnamonny group, cinnamonea group, 3-phenylpropionate group, 4-phenylbutyrate group, 5-phenylmethylene group, 6-phenylhexane group, 1-naftalina group, 2-naftalina group, 1-naphthylmethyl group, 2-naphthylmethyl group, 1-naphthylethylene group, 2-naphthylethylene group, as-Indianola group, s-Indianola group and acenaphthylene group; more preferred are a phenyl group, o-tolila group, m-tolila group, p-tolila group, 2,3-xylella group, 2,4-xylella group, 2,5-xylella group, mesitylene group, ciminella group, cominella group, m-cominella group, p-cominella group, benzyl group, penicilina group α-methylbenzyl group, benzydamine group, triticina group, benzile enova group, stiralnaya group, cinnamonny group, cinnamonea group, 3-phenylpropionate group, 4-phenylbutyrate group, 5-phenylmethylene group, 6-phenylhexane group, 1-naftalina group, 2-naftalina group, 1-naphthylmethyl group and 2-naphthylmethyl group; even more preferred are a phenyl group, o-tolila group, m-tolila group, p-tolila group, 2,3-xylella group, 2,4-xylella group, 2,5-xylella group, mesitylene group, ciminella group, cominella group, m-cominella group, p-cominella group, benzyl group, penicilina group α-methylbenzyl group, benzydamine group, triticina group, benzylidene group, sterelny group, cinnamonny group and cinnamomea group; and more preferred are a phenyl group, o-tolila group, m-tolila group, p-tolila group, 2,3-xylella group, 2,4-xylella group, 2,5-xylella group, mesitylene group, ciminella group, cominella group, m-cominella group, p-cominella group, benzyl group and penicilina group, and most preferred are a phenyl group, o-tolila group, m-tolila group, p-tolila group, 2,3-xylella group, 2,4-xylella group, 2,5-xylella group and benzyl group. Thus, specific examples and omatically group, having a heteroatom include follow group, thienyl group, pyrrolidino group, pyridyloxy group, pinolillo group, izohinolinove group, cinnoline group, chinadaily group, khinoksalinona group, indolenine group, indazolinone group, oxazolidinyl group, isoxazolyl group, thiazolidine group, isothiazolinone group, imidazolidinyl group, pyrazolidine group, foratenolol group, pyridazinyl group, pyramidalnou group, perilou group and the like.

In the expression "the ring Z represents a 5 to 14-membered aromatic group, a ring which may be partially saturated", the aromatic group means 9-14-membered aromatic group, which is condensed with two or three rings, with 1 or 2 of them are non-aromatic, and specific examples of which include dihydrobenzofuranyl group, falanruw group, romanello group, chromadorina group, isopropanolol group, tetrahydronaphthyl group, dihydrobenzofuranyl group, indolinyl group, satinelle group, indenolol group, indianonline group, tetralinyl group, coumarinyl group, naphthenoyloxy group and Astrakhanenergo group; preferably dihydrobenzofuranyl group, falanruw group, romanello group, chromadorina GRU is PU, tetrahydronaphthalene group and indenolol group, and more preferably dihydrobenzofuranyl group and romanello group.

The expression "Y represents C3-7alicyclic hydrocarbon" refers to an alicyclic hydrocarbon group, which is a3-7the cyclic aliphatic hydrocarbon group, and specific examples of which include cyclopropyl group, cyclobutyl group, cyclopentyl group, tsiklogeksilnogo group, cycloheptyl group, cyclopropyl group, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group, cycloheptenyl group and the like. Preferred are cyclopropyl group, cyclobutyl group, cyclopentenone group, tsiklogeksilnogo group, cycloheptyl group, cyclopropylamino group, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group and cycloheptenyl group; more preferred are cyclopropyl group, cyclobutyl group, cyclopentenone group, tsiklogeksilnogo group and cycloheptyl group; even more preferred are cyclopropyl group, cyclobutyl group, cyclopentenone group and tsiklogeksilnogo group, and most preferred are cyclopropyl group, cyclobutyl the group and cyclopentenone group. Thus, specific examples of the alicyclic hydrocarbon having a heteroatom include pyrrolidino group, pyrrolidinyl group, imidazolidinyl group, imidazolidinyl group, pyrazolidine group, pyrazolidine group, piperidinyl group, piperazinilnom group, morpholinyl group, dihydropyrazolo group and tetrahydrofuranyl group, of which preferred are dihydropyridine group and tetrahydrofuranyl group.

When L represents a single bond, the compounds of the present invention are, for example, derivatives of carboxylic acids having a group X is attached via a single bond to the group of Y, represented by the following formula:

(wherein each symbol has the same meaning as defined above), and their salts, ester or hydrate.

When M represents a single bond, the compounds of the present invention are, for example, derivatives of carboxylic acids, represented by the following formula:

(wherein each symbol has the same meaning as defined above), and their salt, ester or hydrate.

When T represents a single bond, the compounds of the present invention are, for example, derivatives ka is oil acids, represented by the following formula:

(wherein each symbol has the same meaning as defined above), and their salt, ester or hydrate.

When X represents a single bond, the compounds of the present invention are, for example, derivatives of carboxylic acids, represented by the following formula:

(wherein each symbol has the same meaning as defined above), and their salt, ester or hydrate.

When L, T and M are1-6alkylenes group which may have one or more substituents, Allenova group means a divalent group derived by removal of one hydrogen atom from C1-6alkyl group, and specific examples include a methylene group, ethylene group, melatoninbuy group, propylene group, ethylethylene group, 1,1-dimethylethylene group, 1,2-dimethylethylene group, trimethylene group, 1-methyltrienolone group, 1-ethyltrimethylammonium group, 2-methyltrienolone group, 1,1-dimethyltrimethylene group, tetramethylene group, pentamethylene group, hexamethylene group and the like. Preferred are methylene group, ethylene group, metilidinovy group, propylene group, ethylethylene group,1,1-dimethylethylene group, 1,2-dimethylethylene group, trimethylene group, 1-methyltrienolone group, 1-ethyldimethylamine group, 2-methyltrienolone group, 1,1-dimethyltrimethylene group, tetramethylene group, pentamethylene group and hexamethylene group; more preferred are a methylene group, ethylene group, metilidinovy group, propylene group, ethylethylene group, 1,1-dimethylethylene group, 1,2-dimethylethylene group, trimethylene group, 1-methyltrienolone group, 1-ethyldimethylamine group, 2-methyltrienolone group and 1,1-dimethyltrimethylene group; even more preferred are methylene group, ethylene group, metilidinovy group, propylene group, ethylethylene group, 1,1-dimethylethylene group, 1,2-dimethylethylene group and trimethylene group, and most preferred are a methylene group, ethylene group, metilidinovy group and propylene group.

Similarly, when T represents C1-3alkylenes group which may have one or more substituents, Allenova group means a divalent group derived by removal of one hydrogen atom from C1-3alkyl group, and specific examples include1-3alkylenes group, such as those listed above. Pre is respectful are a methylene group, ethylene group and propylene group, more preferred are a methylene group and ethylene group, and most preferred is methylene group.

When L, T and M are2-6alkenylamine group which may have one or more substituents, alkenylamine group means a divalent group derived by removal of one hydrogen atom from alkenylphenol group with 2-6 carbon atoms, and specific examples include vanilinovoi group, propenylidene group, butenylamine group, pentesilea group, hexadecanoyl group and the like. Preferred are venelinova group, propylea group, battilana group and Penthesilea group; more preferred are venelinova group, propylea group and battilana group; even more preferred are venelinova group and propylea group, and most preferred is venelinova group.

When L and T are2-6alkynylamino group which may have one or more substituents, akinlana group means a divalent group derived by removal of one hydrogen atom from C2-6alkenylphenol group, and specific examples include ethynylene group, propylene group, butilyenov group of pins is onlinebuy group, hexylamino group and the like. Preferred are atenolola group, Propylaea group, budininova group and pentesilea group; more preferred are atenolola group, Propylaea group and budininova group; even more preferred are budininova group and Propylaea group, and most preferred is Propylaea group.

Similarly, when M represents C2-6alkynylamino group which may have one or more substituents, akinlana group means a divalent group derived by removal of one hydrogen atom from C2-6alkenylphenol group, and specific examples include2-6alkynylamino group, such as those listed above. Preferred are atenolola group and Propylaea group, and more preferred is atenolola group.

When RX1, RX10, RX11and RX12are2-7aliphatic acyl group which may have one or more substituents, aliphatic acyl group represents a C1-6alkyl group, a C2-6alkenylphenol group or2-6alkylamino group, one end of which is attached a carbonyl group, and specific examples include acetyl group, PR is pinelog group, butyryloxy group, isobutyryloxy group, valerino group, isovaleryl group, pivaloyl group, hexanoyl group, octanoyl group, acryloyloxy group, methacryloyloxy group, crotonoyl group and the like. Preferred are an acetyl group, propylaniline group, Butyrina group, isobutylene group, valerina group, isovaleryl group, pivellina group, hexanoyl group, octonaria group, calolina group, methacryloyl group and crotonylene group; more preferred are an acetyl group, propylaniline group, Butyrina group, isobutylene group, valerina group, isovaleryl group, pivellina group, hexanoyl group and octonaria group; even more preferred are an acetyl group, propylaniline group, Butyrina group and isobutylene group, and most preferred are acetyl group and propylaniline group.

When RX1, RX10, RX11and RX12are7-19aromatic acyl group which may have one or more substituents, With5-12aromatic acyl group represents a C5-12aryl group, one end of which is attached a carbonyl group or a group obtained by removal of one at the mA of hydrogen from C 2-7aliphatic acyl group, and specific examples include benzoyloxy group, toluylene group, m-toluylene group, p-toluylene group, cinnamoyl group, 1-naftolin group, 2-naftolin group and the like. Preferred are benzoline group, toluylene group, m-toluylene group, p-toluylene group, cinnamonny group, 1-napolina group and 2-napolina group; more preferred are benzoline group, toluylene group, m-toluylene group, p-toluylene group and cinnamonny group; even more preferred are benzoline group and cinnamonny group, and most preferred is benzoline group.

- - -represents a single bond or a double bond. Therefore, the compounds of the present invention, represented by the following formula (I):

(where each symbol represents a group as defined above)include carboxylic acid derivative represented by the following formula:

(where the symbols described above), its salt, its ester or its hydrates.

The group represented by the formula:

(where each symbol represents a group as defined above), and a group represented by the formula:

(where each symbol represents a group as defined above), connected to each other in the ring Z through 2-8 atoms. The expression "related to each other in the ring Z through 2-8 atoms" represents the following cases.

For example, when ring Z is a benzene and in the specified binding participate 2 of the atom, the formula has the following form:

where each symbol represents a group as defined above.

When ring Z is the anthracene and the specified binding to participate in the t 8 atoms, the formula is as follows:

where each symbol represents a group as defined above.

Thus, the group ring Z, the group represented by the formula:

(where each symbol represents a group as defined above), and a group represented by the formula:

(where each symbol represents a group as defined above)can be connected in any positions. Preferred compounds represented by the formula:

(where each symbol represents a group as defined above, and the aromatic group may optionally have 1-4 substituent), and more preferred is represented by the formula:

or

(where each symbol represents a group as defined above, and the aromatic group may optionally have 1-4 Deputy).

"Salt"used in the present invention are not particularly limited in terms of their type, and their specific examples include additive salts of inorganic acids, such as hydroptere, hydrochloride, sulfate, nitrate, perchlorate, phosphate, carbonate, is carbonat, the hydrobromide or hydroiodide; additive salts of organic carboxylic acids, such as acetate, maleate, fumarate, oxalate, lactate, tartrate or triptorelin; additive salts of organic sulfonic acids, such as methanesulfonate, triftorbyenzola, aconsultant, hydroxyethanesulfonic, hydroxyethanesulfonic, bansilalpet, toluensulfonate or salt of taurine, and the like; additive salts of amine, such as salt, trimethylamine salt of triethylamine, salt, pyridine salt of procaine, picoline salt, salt dicyclohexylamine, salt N,N'-dibenzylideneacetone, salt, N-methylglucamine, diethanolamine salt, triethanolamine salt, salt of Tris(hydroxymethylamino)methane or salt penicillamine; additive salts of alkaline metal such as sodium salt or potassium salt; additive salts of alkaline-earth metal such as magnesium salt or calcium salt, and an additive salts of amino acids such as arginine salt, lysine salt, serine salt, salt of glycine, aspartate or glutamate, and the like. Preferred are pharmaceutically acceptable salts.

Pharmaceutically acceptable salts are not particularly limited in terms of their type and their specific examples include additive salts of inorganic acids such as hydrochloride, sulfate, carbonate, bicarbonate, hydrogen bromide or hydroiodide; additive salts of organic is coy carboxylic acid, such as acetate, maleate, lactate, tartrate or triptorelin; additive salts of organic sulfonic acids, such as methanesulfonate, hydroxyethanesulfonic, hydroxyethanesulfonic, bansilalpet, toluensulfonate or salt of taurine; additive salts of amine, such as salt, trimethylamine salt of triethylamine, salt, pyridine salt of procaine, picoline salt, salt dicyclohexylamine, salt N,N'-dibenzylideneacetone, salt, N-methylglucamine, diethanolamine salt, triethanolamine salt, salt of Tris(hydroxymethylamino)methane or salt penicillamine; additive salts of alkaline metal such as sodium salt or potassium salt; additive salts of amino acids such as arginine salt, lysine salt, serine salt, salt of glycine, aspartate or glutamate.

"Ester", as used in the present invention, refers to esters at the carboxyl group W in the General formula (I). They are not particularly limited, if only they were commonly used in organic synthesis, and cover a physiologically acceptable ester groups that are hydrolyzed under physiological conditions. Specific examples include1-6alkyl group, a C6-12aryl group7-20kalkilya groups such as benzyl group, With7-20heteroallyl group, 4-methoxybenzyloxy group, alkanoyloxy group, t is the cue as acetoxymethyl group, propionylthiocholine group or pivaloyloxymethyl group, alkoxycarbonylmethyl groups, such as methoxycarbonylmethyl group, ethoxycarbonylmethyl group or 2-methoxycarbonylmethylene group, (5-methyl-2-oxo-1,3-dioxo-4-yl)methyl group and the like.

It should be noted that if the carboxylic acid derivative having the General formula (I), its pharmacologically acceptable salt or a pharmacologically acceptable ester form a solvate, all such solvate included in the scope of the present invention.

Salts, hydrates or esters of the compounds of the present invention are preferably pharmaceutically acceptable.

The compound of the present invention, represented by formula (I):

(where each symbol represents a group as defined above)can be synthesized by conventional method or may be synthesized, for example, as described below.

A common example And receive

where each symbol represents a group as defined above, and Hal represents halogen.

The compound represented by formula (3A), is obtained by treating compound represented by the formula (2A), the compound represented by formula (1A).

Reaction conditions are not particularly limiting the Ute and for example, the reaction is carried out in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, in the presence of a base such as lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydride, sodium hydride or potassium hydride, at a temperature of from 0°to 150°C.

The compound represented by the formula (4A)can be obtained by halogenoalkanes compounds represented by formula (3A).

Reaction conditions are not particularly limited, and for example, the connection can be obtained using phosphorus oxychloride, thionyl chloride, trichloride phosphorus or tribromide phosphorus in a solvent such as dioxane, tetrahydrofuran or dimethoxyethane. The reaction temperature is in the range from 0°to 150°C. Can also be used conditions with a combination of triphenylphosphine, carbon tetrachloride, tetrabromide carbon, N-bromosuccinimide and the like.

The compound represented by formula (7a)can be obtained by treating compound represented by the formula (6A), the compound represented by formula (5A).

Reaction conditions are not particularly limited, and the reaction can be carried out in a solvent such as methanol, ethanol, propanol, dimetilan XID, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, in the presence of from 0.0001 to 0.5 molar equivalent of the halide of copper, from 0.0001 to 0.5 molar equivalent of a palladium catalyst such as tetrakis(triphenylphosphine)palladium or dichlorobis(triphenylphosphine)palladium, and organic bases such as triethylamine, N,N-diisopropylethylamine, butylamine or tributylamine, at a temperature of from 0°to 150°C.

The compound represented by the formula (8A)can be obtained by halogenoalkanes compounds represented by formula (7a).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (4A) in the sample As received.

The compound represented by the formula (10A), is obtained by reaction of aldol condensation of the compound represented by the formula (9a), and aliphatic esters, ethers alkoxyalkyl acid (these alkyl groups or alkoxygroup correspond to R1in the formula, and ester groups correspond to W in the formula) and the like, or the reaction of the Wittig-Horner-Emmons using esters alkylphosphonic acids, esters alkoxyacetic acids (these alkyl groups or alkoxygroup correspond to R1in the formula, and ester groups correspond to W in the formula) and the like, with subsequent restoration with the IRTA or double bonds.

Conditions of aldol condensation and reaction of the Wittig-Horner-Emmons not particularly limited, and the reaction can be conducted, for example, in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, in the presence of a base such as lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydride, sodium hydride, potassium hydride, utility, motility, bestremembered lithium, bestremembered sodium or bestremembered potassium and so like, at temperatures from 0°to 150°C.

As for the reaction conditions of the recovery and the like, the reaction can be carried out in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, in the presence of a metal catalyst such as palladium carbon, platinum oxide or Raney Nickel, in an atmosphere of hydrogen at a temperature of from 0°to 150°C. Recovery may not necessarily be performed after the acylation or sulfonylurea alcohol group in andolina the adduct.

The compound represented by the formula (11a)can be obtained by hydrolysis of ester in the molecule after alkilirovanie the connection, represented by the formula (10A), a compound represented by the formula (4A), or a compound represented by the formula (8A).

Conditions for alkylation conditions appropriate to obtain the compounds of formula (4A) in the sample As received.

Reaction conditions of the hydrolysis is not particularly limited, and the reaction can be carried out by treatment with an aqueous solution of lithium hydroxide, sodium hydroxide, potassium hydroxide and the like, for example, in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane or tetrahydrofuran, at temperatures from 0°to 150°C.

The compound represented by the formula (13A)can be obtained by hydrolysis of ester in the molecule after alkylation of the compounds represented by the formula (10A), a compound represented by the formula (8A), or by hydrolysis of ester in the molecule after the reaction between the compound represented by the formula (10A), and propylbromide, followed by conducting the reaction in combination with a palladium catalyst.

Reaction conditions for the alkylation and hydrolysis conditions appropriate to obtain the compounds of formula (11a) in the sample As received.

Reaction conditions combinations correspond to the conditions for obtaining the compounds of formula (7a) in the sample As received.

The connection represented by the shape of the Oh (15A), can be obtained by treating compound represented by the formula (1A), after alkylation of the compounds represented by the formula (10A), a compound represented by the formula (14a).

Conditions for the alkylation of compounds of formula (14a) comply with the conditions for obtaining compounds of formula (3A) in the sample As received.

The processing conditions, the compounds of formula (1A) is not particularly limited, and it can be conducted in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane or tetrahydrofuran, in the presence of from 0.0001 to 1.0 molar equivalent of a catalyst, such as potassium carbonate, triethylamine or cesium fluoride, at a temperature of from 0°to 150°C.

The compound represented by the formula (16A)can be obtained by hydrolysis of ester in the molecule after fluorination of the compound represented by the formula (15A).

The fluorination conditions are not particularly limited, and it can be done, for example, by treatment with a reagent such as TRIFLUORIDE (diethylamino)sulfur in a solvent such as dichloromethane or chloroform, at temperatures between 0°to 150°C.

The hydrolysis conditions correspond to the conditions for obtaining the compounds of formula (11a) in the sample As received.

The compound represented by the formula (17A)can be obtained by hydrolysis of ester in front of the ferry after alkylation of the compounds represented by the formula (15A), alkylhalogenide.

The reaction conditions correspond to the conditions for obtaining the compounds of formula (3A) in the sample As received.

The compound represented by formula (19a)can be obtained by hydrolysis of ester in the molecule after modifying compounds represented by the formula (10A), sulfonates using sulphonylchloride.

Conditions sulfonylamine not particularly limited, and the reaction can be carried out in a solvent such as pyridine, dichloromethane or chloroform, in the presence of organic bases such as triethylamine, N,N-diisopropylethylamine or tributylamine, at a temperature of from 0°to 150°C.

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (11a) in the sample As received.

The compound represented by the formula (20A)can be obtained by hydrolysis of compounds represented by the formula (15A).

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (11a) in the sample As received.

A common example In receipt

where each symbol represents a group as defined above, and Tf represents trifloromethyl group.

The compound represented by formula (2b), can be obtained by triftormetilfullerenov compounds represented by formula (1b).

Reaction conditions are not particularly limited, and the compound can be synthesized by treatment of N,N-bestattorney.com, triftormetilfullerenov anhydride, triftormetilfullerenov and the like in a solvent such as pyridine, dichloromethane or chloroform, in the presence of organic bases such as triethylamine, N,N-diisopropylethylamine or tributylamine, at a temperature of from 0°to 150°C.

The compound represented by formula (3b)can be obtained by palladium combination of compounds represented by formula (2b).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (7a) in the sample As received.

The compound represented by formula (4b)can be obtained by halogenoalkanes compounds represented by formula (3b).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (4A) in the sample As received.

The compound represented by formula (5b)can be obtained by alkylation of compounds represented by formula (4b).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (3A) in the sample As received.

The compound represented by the formula (6b), can be obtained by palladium combination of connections, the notion is of formula (2b).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (7a) in the sample As received.

The compound represented by formula (7b), can be obtained by hydrolysis of ester in the molecule after palladium combination of compounds represented by the formula (6b).

The reaction conditions for palladium combination and hydrolysis conditions appropriate to obtain the compounds of formula (7a) in the sample And obtain and conditions for obtaining compounds of formula (11a) in the sample And receiving, respectively.

The compound represented by the formula (8b)can be obtained by treating a carbonyl compound such as a ketone or aldehyde, a compound represented by the formula (6b).

Reaction conditions are not particularly limited, and the reaction can be carried out, for example, in a solvent such as dioxane, tetrahydrofuran or dimethoxyethane, in the presence of a base, such as bestremembered lithium, bestremembered sodium or bestremembered potassium, at a temperature of from 0°C to room temperature.

The compound represented by the formula (9b), can be obtained by palladium combination of compounds represented by formula (2b).

Reaction conditions are not particularly limited, and the compound can be synthesized, for example, in a solvent such as dioxane, tetrahydrofuran, dimethoxyethane or Tolu is l, by reacting 1,1-ethoxybenzothiazole, simple butylvinyl ether and the like in the presence of from 0.0001 to 0.5 molar equivalent of a palladium catalyst such as tetrakis(triphenylphosphine)palladium or dichlorobis(triphenylphosphine)palladium, and lithium chloride at a temperature of from 0°to 150°C.

The compound represented by formula (10b)can be obtained by the addition of acetylene to the compound represented by the formula (9b).

Reaction conditions are not particularly limited, and the reaction can be carried out, for example, in a solvent such as dioxane, tetrahydrofuran or dimethoxyethane, in the presence of a base, such as utility, motility, edelmandigital, bestremembered lithium, bestremembered sodium or bestremembered potassium, and a Lewis acid such as a complex of boron TRIFLUORIDE-simple ether, at a temperature of from 0°C to room temperature.

The compound represented by the formula (11b), can be obtained by hydrolysis after palladium combination with the compound represented by formula (10b).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (7b) in the example in the receipt.

A common example of obtaining

where each symbol represents a group as defined above, and Boc represents tert-butoxycarbonyl the th group, and Hal represents halogen.

The compound represented by the formula (2C)can be obtained by formirovanie compounds represented by formula (1C), with the subsequent implementation of aldol condensation or reaction of the Wittig-Horner-Emmons, restore, and remove the protection.

Reaction conditions of formirovaniya not particularly limited, and it is possible to carry out the action of utility in a solvent such as dioxane, tetrahydrofuran or dimethoxyethane, followed by N,N-dimethylformamide and the like at temperatures from -78°0°C.

Conditions aldol condensation or reaction of the Wittig-Horner-Emmons meet the conditions for obtaining compounds of formula (10A) in the sample As received.

Reaction conditions recovery comply with the conditions for obtaining compounds of formula (10A) in the sample As received.

Reaction conditions unprotect not particularly limited, and can be carried out by the action of acid, such as hydrochloric or triperoxonane acid, in an organic solvent, such as dichloromethane, chloroform, tetrahydrofuran or dioxane, at temperatures between 0°to 150°C.

The compound represented by formula (3C)can be obtained by the action of carbon dioxide and Y-L-Hal to the compound represented by the formula (2C), with formation of carbamate, and hydrolysis of ester in the molecule.

The synthesis conditions CT is Amata match, but not particularly limited to, the conditions described in the document (J. Org. Chem. 2000, 66, 1035).

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (11a) in the sample As received.

A common example D get

where each symbol represents a group as defined above, Hal represents halogen, PhtNOH is N-hydroxyphthalimide and-NCO represents the isocyanate group.

The compound represented by formula (2d), can be obtained by halogenoalkanes compounds represented by formula (1d).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (4A) in the sample As received.

The compound represented by the formula (3d), can be obtained by the action of N-hydroxyphthalimide on the compound represented by formula (2d).

Reaction conditions are not particularly limited, and it can be done, for example, in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, in the presence of a base, such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydride, sodium hydride, potassium hydride, triethyl is min, N,N-diisopropylethylamine or tributylamine, at a temperature of from 0°to 150°C.

The compound represented by the formula (4d), can be obtained by removing protection phthalimide group of compounds represented by formula (3d).

Reaction conditions are not particularly limited, and hydrazine, N-methylhydrazine and the like, for example, you can enter into the reaction in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, at a temperature of from 0°to 150°C.

The compound represented by the formula (5d), can be obtained by amidation of the compound represented by the formula (4d), and hydrolysis of ester in the molecule.

Conditions the amidation reaction are not particularly limited, and it can be done by introducing in the reaction of the corresponding carboxylic acid in a solvent such as N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran, toluene, dichloromethane or chloroform, in the presence of a condensing agent such as diphenylphosphonate, diethylacrylamide or dicyclohexylcarbodiimide, and bases, such as triethylamine, N,N-diisopropylethylamine, tributylamine, sodium bicarbonate or potassium bicarbonate, at a temperature of from 0°to 150°C.

Reaction conditions of the hydrolysis conditions appropriate to obtain the connection fo the formula (11a) in the sample As received.

The compound represented by the formula (6d)can be obtained by minireunion compounds represented by the formula (4d), followed by hydrolysis of ester in the molecule.

Reaction conditions of aminirovaniya not particularly limited, and it can be done, for example, by introducing into the reaction of the corresponding carbonyl compound such as a ketone or aldehyde in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, at a temperature of from 0°to 150°C. May contain an acid, such as acetic acid, triperoxonane acid or hydrochloric acid.

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (11a) in the sample As received.

The compound represented by the formula (7d)can be obtained by treating the Y-NCO compound represented by formula (1d), with formation of carbamate and hydrolysis of ester in the molecule.

The conditions of synthesis of the carbamate is not particularly limited, and it can be done by entering into the reaction, an organic base such as pyridine or triethylamine, in a solvent such as tetrahydrofuran, toluene, ether or dioxane, at temperatures between 0°to 150°C.

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (11a) in the ore As received.

The compound represented by formula (8d)can be obtained by the action of the Y-NCO on the compound represented by formula (1d), with formation of carbamate, followed by alkylation using Rx1-Hal and hydrolysis of ester in the molecule.

Conditions for the synthesis of carbamate meet the conditions for obtaining compounds of formula (7d) example D receipt.

Reaction conditions for the alkylation conditions appropriate to obtain the compounds of formula (4A) in the sample As received.

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (11a) in the sample As received.

The compound represented by the formula (10d)can be obtained by treating N-hydroxyphthalimide compounds represented by formula (9d), with the subsequent removal of the protection phthalimide group.

Hydroxypyrimidinone can be carried out in accordance with the document (Org. Lett. 2001, 3, 139).

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (4d) in the example D is received.

The compound represented by the formula (11d), can be obtained by amidation of the compound represented by the formula (10d), with subsequent hydrolysis of ester in the molecule.

The reaction conditions correspond to the conditions for obtaining the compounds of formula (5d) in the example D is received.

The compound represented by formula (12d), can be obtained by minireunion connection represented by the formula (10d), with subsequent hydrolysis of ester in the molecule.

The reaction conditions correspond to the conditions for obtaining the compounds of formula (6d) in the example D is received.

The compound represented by formula (14d)can be obtained by minireunion compounds represented by formula (13d).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (6d) in the example D is received.

The compound represented by formula (15d)can be obtained by alkylation of compounds represented by formula (14d), using Y-L-Hal.

The reaction conditions correspond to the conditions for obtaining the compounds of formula (3A) in the sample As received.

The compound represented by formula (16d)can be obtained by minireunion compounds represented by formula (13d), using Y-Q2-NH2and subsequent hydrolysis of ester in the molecule.

The reaction conditions correspond to the conditions for obtaining the compounds of formula (6d) in the example D is received.

A common example E receive

where each symbol represents a group as defined above, and Hal represents halogen.

The compound represented by formula (2E), can be obtained by sulfonamideubul, acting Y-L-SO2-Hal on the compound represented by the formula (1E), and hydrolysis of ester in the forefront of the Le.

The synthesis conditions sulfonamida not particularly limited, and it can be done, for example, by introducing into the reaction, an organic base such as pyridine or triethylamine, in an organic solvent such as dichloromethane or chloroform, at temperatures between 0°to 150°C.

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (11a) in the sample As received.

A common example F receive

where each symbol represents a group as defined above, and Oh* is aldorino asymmetric auxiliary group Evans (chiral oxazolidinone), Le represents a leaving group such as halogen or sulfonate, and the symbol * represents an asymmetric carbon atom.

The compound represented by formula (3f), can be obtained by treating compound represented by the formula (2f), a compound represented by the formula (1f), in conditions of asymmetric aldol condensation by Evans.

Reaction conditions are not particularly limited, and it can be done, for example, in a solvent such as dichloromethane, chloroform, dioxane, tetrahydrofuran or toluene, in the presence of a base such as triethylamine or diisopropylethylamine, at a temperature of from 0°to 150°C.

The connection represented by Faure who Ulai (4f), can be obtained by sulfonylamine compounds represented by formula (3f), with the subsequent recovery of sulfate groups.

Reaction conditions of sulfonylamine not particularly limited, and it can be done, for example, by treatment with methanesulfonamido, mozillateam, 4-nitrobenzenesulfonamide and the like in a solvent such as dichloromethane, chloroform, dioxane, tetrahydrofuran, toluene or pyridine, in the presence of a base, such as triethylamine, diisopropylethylamine, pyridine or N,N-dimethylaminopyridine, at a temperature of from 0°to 150°C.

The recovery is carried out in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, in the presence of a metal catalyst such as palladium carbon, platinum oxide or Raney Nickel, in an atmosphere of hydrogen, at a temperature of from 0°to 150°C. if necessary, there may be a base, such as sodium acetate, potassium acetate or pyridine.

The compound represented by formula (5f)can be obtained by hydrolysis of compounds represented by formula (4f), followed by esterification of the carboxyl group.

The conditions of hydrolysis is not particularly limited, and it can be done by introducing into the reaction aqueous solution of hydroxide lit the I, sodium hydroxide, potassium hydroxide and the like in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane or tetrahydrofuran, in the presence of hydrogen peroxide solution at a temperature of from 0°to 150°C.

Conditions of esterification is not particularly limited, and it can be done, for example, by treatment with alkylhalogenide, such as logmean, Iodate, improper or benzylbromide, in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, in the presence of a base such as lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydride, sodium hydride, potassium hydride, utility, motility, bestremembered lithium, sodium bestremembered or bestremembered potassium, at a temperature of from 0°to 150°C.

The compound represented by formula (9f)can be obtained by treating compound represented by the formula (5f), the alkylation agent containing epoxide represented by the formula (6f) or formula (7f), or the like, and disclosure of epoxypropyl phenol represented by the formula (8f), and the like.

The conditions of the alkylation reaction of the epoxide of formula (6f), formula (7f) and the and the like, not particularly limited, and it can be done, for example, by conducting the reaction in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, in the presence of a base such as lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, lithium hydride, sodium hydride, potassium hydride, utility, motility, bestremembered lithium, bestremembered sodium, bestremembered potassium or cesium fluoride, at a temperature of from 0°to 150°C.

The processing conditions, the compounds of formula (8f) is not particularly limited, and it can be done, for example, by conducting the reaction in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane or tetrahydrofuran, in the presence of from 0.0001 to 1.0 molar equivalent of a catalyst, such as potassium carbonate, triethylamine or cesium fluoride, at a temperature of from 0°to 150°C.

The compound represented by formula (10f)can be obtained by fluorination of the compound represented by formula (9f), followed by hydrolysis of ester in the molecule.

Conditions for the fluorination reaction is not particularly restricted, and it can be done, for example, by treatment with a reagent such as TRIFLUORIDE IER is aluminosilicate, in a solvent such as dichloromethane or chloroform, at temperatures between 0°to 150°C.

Reaction conditions of the hydrolysis is not particularly limited, and it can be done, for example, by treatment with an aqueous solution of lithium hydroxide, sodium hydroxide, potassium hydroxide and the like, in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane or tetrahydrofuran, in the presence of hydrogen peroxide solution at a temperature of from 0°to 150°C.

The compound represented by formula (11f), can be obtained by hydrolysis of ester compounds represented by the formula (9f).

The conditions of hydrolysis is not particularly limited, and it can be done, for example, by treatment with an aqueous solution of lithium hydroxide, sodium hydroxide, potassium hydroxide and the like, in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane or tetrahydrofuran, in the presence of hydrogen peroxide solution at a temperature of from 0°to 150°C.

A common example of G receive

where each symbol represents a group as defined above, Oh* is aldorino asymmetric auxiliary group Evans (chiral oxazolidinone), Le Ave is dstanley leaving group, such as halogen or sulfonate, and the symbol * represents an asymmetric carbon atom.

The compound represented by the formula (2g), can be obtained by formirovanie compounds represented by formula (1g).

Reaction conditions of formirovaniya not particularly limited, and it can be done, for example, by treatment with butyllithium in a solvent such as dioxane, tetrahydrofuran or dimethoxyethane, followed by interaction with N,N-dimethylformamide, N-formylmorpholine and the like at temperatures from -78°0°C.

The compound represented by formula (4g)can be obtained by introducing in the reaction of the compound represented by formula (3g), and compounds represented by the formula (2g), under conditions of asymmetric aldol condensation by Evans.

Conditions of asymmetric aldol condensation by Evans comply with the conditions for obtaining compounds represented by formula (3f), in the General example F receipt.

The compound represented by formula (5g), can be obtained by sulfonylamine compounds represented by formula (4g), with subsequent restoration sulphonate group.

Reaction conditions of sulfonylurea meet the conditions for obtaining compounds of formula (4f) in the General example F receipt.

Reaction conditions recovery meet the conditions for soedineniya (4f) in the General example F receipt.

The compound represented by formula (6g), can be obtained by hydrolysis of compounds represented by formula (5g), and esterification of the carboxyl group with a subsequent removal of the protection of the amino group.

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (5f) in the General example F receipt.

The conditions of the esterification reaction conditions appropriate to obtain the compounds of formula (5f) in the General example F receipt.

As for removing the protection of the amino group, the methods for its implementation is different depending on the protective group, for example, the removal of the tert-BUTYLCARBAMATE group can be carried out using a solution of anhydrous hydrochloric acid in methanol, a solution of anhydrous hydrochloric acid in ethanol, a solution of anhydrous hydrochloric acid in dioxane, triperoxonane acid, formic acid, and the like.

The compound represented by formula (7g)can be obtained by processing carbon dioxide and Y-L-Hal compounds represented by formula (6g), or by treatment with phosgene, diphosgene, triphosgene and similar compounds represented by formula (6g), to obtain the corresponding isocyanate by the action of benzyl alcohol, such as Y-L-OH, with the formation of carbamate and hydrolysis of ester in the molecule.

Conditions the Intesa carbamate not particularly limited, and it can be implemented in accordance with the document (J. Org. Chem. 2000, 66, 1035) or by entering in the reaction of the phosgene, diphosgene, triphosgene and the like in a solvent such as dichloromethane, chloroform, dioxane, tetrahydrofuran or toluene, in the presence of a base, such as triethylamine, diisopropylethylamine, pyridine or N,N-dimethylaminopyridine, at a temperature of from 0°to 150°and then introducing into the reaction of benzyl alcohol, such as Y-L-OH, at a temperature of from 0°to 150°C. Alternatively, it is possible to perform processing carbonyldiimidazole alcohol Y-L-OH in a solvent such as dichloromethane, chloroform, tetrahydrofuran, toluene or acetonitrile, at temperatures from 0°C to 50°and then introducing into the reaction of the compound represented by formula (6g), at a temperature of from 0°C to 50°C.

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (10f) in the General example F receipt.

Total sample N get

The compound represented by formula (2h), can be obtained by the reaction of the Wittig-Horner-Emmons using compounds represented by formula (1h), and recovering the obtained compound. Reaction conditions of the Wittig-Horner-Emmons meet the conditions for obtaining compounds of formula (10A) in the sample As received.

Reaction conditions at which the service match the conditions for obtaining the compounds of formula (10A) in the sample As received.

The compound represented by the formula (3h), can be obtained by treating compounds of formula (2h) with phosgene, diphosgene, triphosgene, di-tert-BUTYLCARBAMATE and the like in a solvent such as dichloromethane, tetrahydrofuran or acetonitrile, in the presence of a base, such as pyridine, triethylamine or 4-dimethylaminopyridine, to obtain the isocyanate and isocyanate, using Y-T-OH, obtaining carbamate, followed by alkaline hydrolysis of the carbamate. The reaction temperature at the time of formation of the isocyanate is from 0°C to 50°C.

A common example I get

The compound represented by formula (3i)can be obtained by the interaction of the compounds represented by the formula (1i), and compounds represented by the formula (2i). Reaction conditions are not particularly limited, and it can be done, for example, by treatment with a base such as potassium carbonate or sodium hydride, compounds represented by the formula (1i), in a solvent such as tetrahydrofuran, N,N-dimethylformamide or dioxane and the like, and then by treatment with a compound represented by the formula (2i). The reaction temperature is in the range from 0°to 100°C.

The compound represented by formula (4i), may be is obtained by the interaction of the compounds represented by formula (3i), and compounds represented by the formula (2h), with subsequent hydrolysis. Reaction conditions are not particularly limited, and the condensation reaction can be carried out by treating compound represented by the formula (3i), a compound represented by the formula (2h), in a solvent such as tetrahydrofuran or N,N-dimethylformamide, in the presence of a base such as triethylamine or pyridine and in the presence of a condensing agent such as 1,1-carbonyldiimidazole, diethylthiophosphate or carbodiimide. The reaction temperature is in the range from 0°to 100°C. the reaction Conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (11a) in the sample As received.

A common example J receive

where each symbol represents a group as defined above, Oh* is aldorino asymmetric auxiliary group Evans (chiral oxazolidinone), Tf is trifloromethyl group, Hal represents a leaving group such as halogen or sulfonate, and the symbol * represents an asymmetric carbon atom.

The compound represented by formula (3j), can be obtained by treating compound represented by the formula (2j), the compound represented by the formula (1j).

Conditions re the work is not particularly limited, the reaction can be carried out, for example, in a solvent such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, in the presence of from 0.0001 to 0.5 molar equivalent of the halide of copper, from 0.0001 to 0.5 molar equivalent of a palladium catalyst such as tetrakis(triphenylphosphine)palladium or dichlorobis(triphenylphosphine)palladium, in the presence of organic bases such as triethylamine, N,N-diisopropylethylamine, butylamine or tributylamine, at a temperature of from 0°to 150°C.

The compound represented by formula (4j), can be obtained by halogenoalkanes compounds represented by formula (3j).

The compound represented by formula (6j), can be obtained by the action of the compounds represented by formula (5j), the compound represented by formula (4j), followed by hydrolysis.

Reaction conditions for the alkylation conditions appropriate to obtain the compounds of formula (4A) in the sample As received.

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (5f) in example F of receipt.

The compound represented by the formula (8)can be obtained by triftormetilfullerenov compounds represented by formula (7j).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (2b) ol the least of receipt.

The compound represented by formula (9j), can be obtained by palladium combination of compounds represented by formula (8).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (7a) in the sample As received.

The compound represented by formula (10j), can be obtained by halogenoalkanes compounds represented by formula (9j).

The reaction conditions correspond to the conditions for obtaining the compounds of formula (4A) in the sample As received.

The compound represented by formula (11j), can be obtained by alkylation of compounds represented by formula (10j), compound Y-QH, followed by hydrolysis.

Reaction conditions for the alkylation conditions appropriate to obtain the compounds of formula (4A) in the sample As received.

Reaction conditions of the hydrolysis conditions appropriate to obtain the compounds of formula (5f) in example F of receipt.

A common example To retrieve

where each symbol represents a group as defined above.

The compound represented by formula (2k)can be obtained by treating compound represented by the formula (1k), Jodorowsky agent.

Reaction conditions are not particularly limited, and it can be done, for example, by treatment with iodine or Jodorowsky agent such as N-jodatime, in rest retele, such as methanol, ethanol, propanol, dimethylsulfoxide, N,N-dimethylformamide, N-organic, dioxane, tetrahydrofuran or toluene, or a mixture of these solvents, in the presence of silver salts such as silver sulfate, at a temperature of from 0°to 100°C.

The compound represented by formula (3k), can be obtained by the interaction of the compounds represented by formula (2k), with an organic compound of zinc in the presence of palladium catalyst.

Reaction conditions are not particularly limited, and it can be done, for example, by the action of organic zinc reagent, such as dialkoxyphosphinothiolic, in the ether solvent such as tetrahydrofuran, in the presence of a palladium catalyst such as palladium acetate or dichloromonofluoromethane, at a temperature of from 0°to 100°C.

The compound represented by formula (4k), can be obtained by oxidation of compounds represented by formula (3k).

Reaction conditions are not particularly limited, and it can be done, for example, by the action of hydrogen peroxide in a mixed solvent consisting of an alcohol solvent such as methanol, ethanol or propanol, and the ether solvent such as tetrahydrofuran, or in a solvent such as N,N-dimethylformamide, at a temperature of from 0°C to 80°C.

Compounds according to the present invention can be synthesized by the methods described above but they can also synthesize commonly used General methods of organic synthesis. As for the protective group for hydroxyl group, which can be used in the present invention, the hydroxyl group can be used without any limitations, if only they were protected groups, usually known as a protective group for hydroxyl group in organic synthesis, and specific examples of protective groups for the hydroxyl group include lower alkylsilane groups, such as trimethylsilyl group or tert-butyldimethylsilyl group; lower alkoxymethyl groups, such as methoxymethyl group or 2-methoxyethoxymethyl group; tetrahydropyranyl group; kalkilya groups such as benzyl group, p-methoxybenzyl group, 2,4-dimethoxybenzidine group, nitroaniline, p-nitroaniline group or triticina group; acyl groups such as formyl group or acetyl group; a lower alkoxycarbonyl group, such as tert-butoxycarbonyl group, 2-iodoxybenzene group or 2,2,2-trichlorocarbanilide group; altneratively groups such as 2-propanecarboxylate group, 2-chloro-2-propanecarboxylate group, 3-methoxycarbonyl-2-propanecarboxylate group, 2-methyl-2-propenyl starmanila group, 2-butyloxycarbonyl group or cinnamoylcocaine group; aracelikarsaalyna groups, such as benzyloxycarbonyl group, p-methoxybenzenesulfonyl group, nitrobenzisoxazole group or p-nitrobenzisoxazole group and the like.

These protective groups can be removed by conventional methods, such as hydrolysis and recovery, depending on the form used protective group.

Although the compounds of the present invention can be synthesized by the methods described above but can also synthesize commonly used General methods of organic synthesis. Specific examples of protective groups for amino groups which can be used in the present invention include, but are not limited to, any group that is usually known as a protective group for the amino group in organic synthesis. For example, you can name a substituted or unsubstituted lower alcoholnye groups such as formyl group, acetyl group, chlorocichla group, dichloroacetylene group, propylaniline group, phenylacetylene group, phenoxyacetyl group or trilaterally group; substituted or unsubstituted lower alkoxycarbonyl groups, such as benzyloxycarbonyl group, tert-butoxycarbonyl group or p-n is Transilvania group; substituted lower alkyl groups such as methyl group, tert-bucilina group, 2,2,2-trichlorethylene group, triticina group, p-methoxybenzyl group, p-nitrobenzyl group, diphenylmethylene group or pivaloyloxymethyl group; substituted silyl groups such as trimethylsilyl group or tert-butyldimethylsilyl group; substituted similartextile groups, such as trimethylsilylamodimethicone group, trimethylsilylamodimethicone group, tert-butyldimethylsilyloxy group or tert-butyldimethylsilyloxy group; substituted or unsubstituted benzylidene groups, such as benzylidene group, salicylidene group, p-nitrobenzylidene group, m-chlorobenzylidene group, 3,5 di(tert-butyl)-4-hydroxybenzylidene group or 3,5-di(tert-butyl)benzylidene group.

These protective groups can be removed by conventional methods, such as hydrolysis and recovery, depending on the form used protective group.

Compounds of the present invention can be synthesized by the methods described above but can also synthesize commonly used General methods of organic synthesis. As for the protective group for the carboxyl group, which can be used in this invention is about any carboxyl group can be used without any restrictions, if only they were protected groups, usually known as a protective group for carboxyl groups in organic synthesis, and specific examples of protective groups for the carboxyl group include linear or branched lower alkyl group with 1-4 carbon atoms, such as methyl group, ethyl group, isopropyl group or tert-bucilina group; halogen-substituted lower alkyl groups such as 2-Jogaila group or 2,2,2-trichlorethylene group; lower alkoxymethyl groups, such as methoxymethyl group, ethoxymethylene group or isobutoxyethene group; lower aliphatic acyloxymethyl groups, such as butylacetyl group or group pivaloyloxymethyl; 1 being the lowest alkoxycarbonylmethyl groups such as 1-methoxycarbonylmethylene group or 1-ethoxycarbonylmethylene group; kalkilya groups such as benzyl group, p-methoxybenzyl group, nitrobenzyl group or p-nitrobenzyl group; benzhydryl group; phthalidyl group, etc.

The removal of these protective groups can be carried out by conventional methods, such as hydrolysis, recovery, etc. depending on the type used protective group.

Compounds of the present invention can be synthesized by the above-described SP the ways, but they can also synthesize commonly used General methods of organic synthesis. Specific examples of solvents that can be used in the present invention include, but are not limited to, any solvents which do not inhibit the reaction and are usually used in organic synthesis, for example lower alcohols such as methanol, ethanol, propanol or butanol; polyhydric alcohols such as ethylene glycol or glycerin; ketones such as acetone, methyl ethyl ketone, diethylketone or cyclohexanone; ethers such as diethyl ether, isopropyl ether, tetrahydrofuran, dioxane, 2-methoxyethanol or 1,2-dimethoxyethane; NITRILES, such as acetonitrile or propionitrile; complex esters such as methyl acetate, ethyl acetate, isopropylacetate, butyl acetate or diethylphthalate; hydrocarbon halides such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, trichloroethylene or tetrachloroethylene; aromatic compounds such as benzene, toluene, xylene, monochlorobenzene, nitrobenzene, inden, pyridine, quinoline, kallidin or phenol; hydrocarbons, such as pentane, cyclohexane, hexane, heptane, octane, isooctane, petroleum, gasoline, or petroleum ether; amines, such as ethanolamine, diethylamine, triethylamine, pyrrolidine, piperidine, piperazine, morpholine, aniline, dimethylaniline, benzylamine and the and toluidine; amides, such as formamide, N-organic, N,N-dimethylimidazole, N,N-dimethylacetamide or N,N-dimethylformamide; phosphatidy, such as hexamethylphosphorotriamide or hexamethylphosphorotriamide; water and mixed solvents of one or several types of commonly used solvents. Mixing ratio is not particularly limited.

Compounds of the present invention can be synthesized by the methods described above but can also synthesize commonly used General methods of organic synthesis. Specific examples of bases which can be used in the present invention include, but are not limited to, any cause that does not inhibit the reaction and are usually used in organic synthesis, for example sodium carbonate, sodium bicarbonate, potassium carbonate, sodium hydride, potassium hydride, tert-piperonyl potassium, pyridine, dimethylaminopyridine, trimethylamine, triethylamine, N,N-diisopropylethylamine, N-methylmorpholine, N-methylpyrrolidine, N-methylpiperidine, N,N-dimethylaniline, 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU), 4-dimethylaminopyridine, picoline, lutidine, quinoline, isoquinoline, sodium hydroxide, potassium hydroxide, lithium hydroxide, utility, a sodium alcoholate or potassium, such as sodium methylate, potassium methylate or sodium ethylate, and the like.

Compounds of the present invention can be the ü synthesized by the methods described above but they can also synthesize commonly used General methods of organic synthesis. Specific examples of reducing agents that can be used in the present invention include, but are not limited to, any reducing agent that does not inhibit the reaction and are usually used in organic synthesis, such as NaBH4, LiBH4, Zn(BH4)2, Me4NBH(OAc)3, NaBH3CN, Selected (Selectride), Superseded (Super Hydride) (LiBHEt3), LiAlH4, DIBAL, LiAlH(t-BuO)3Red-al (Red-al), BINAP, as well as catalysts, such as platinum, palladium, rhodium, ruthenium, Nickel and the like.

Upon completion of the reaction product can be purified by conventional methods such as column chromatography on silica gel or an adsorption resin, or recrystallization from a suitable solvent.

The drug of the present invention, as described above, improves insulin resistance by agonism in relation to PPAR, and the present invention can be applied not only in the form of insulinsensitizing, but in the form of various medicines based on agonize against PPAR (α, β, γ) (based on, for example, double agonism in respect of PPAR α and γ or triple agonism in respect of PPAR α, β and γ).

For example, the well-known relationship PPAR is e only with insulin resistance, but with diseases associated with lipid levels in the blood, or inflammatory diseases (Current Opinion in Lipidol. 10:245-257, 1999; Jiang, C., et al., PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines, Nature 391:82-86 (1998); Jackson, S.M., et al., Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction., Arterioscler. Thromb. Vasc. Biol. 19:2094-2104 (1999); Su, C.G., et al., A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response., J Clin Invest 1999 Aug; 104(4):383-9; Ricote, M., et al., The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation., Nature 1998 Jan 1; 391(6662):79-82), and the drug of the present invention can be applied to diseases against which, as reported in these materials, it is effective.

The dose of the pharmaceutical preparation of the present invention, although varies depending on the severity of the symptom, age, sex, body weight, route of administration and type of disease, but is usually from 100 μg to 10 g/day for adult patients, the recommended dose is administered one or divided doses.

Route of administration of the medicinal product according to the present invention is not particularly limited, and the drug can be administered orally or parenterally commonly used method.

For the manufacture of medicines, you can use commonly used fillers, binders, lubricants, dyes, corrigentov and the EU is required, stabilizers, emulsifying agents, promoters suction, surfactants, etc. and ingredients commonly used as raw materials for medicines, mix in the usual way.

These ingredients include, for example, animal and vegetable oils (such as soybean oil, animal fat and synthetic glycerides, hydrocarbons such as liquid paraffin, squalane and solid paraffin), ester oils (such as octyldodecanol and isopropylmyristate), higher alcohols (such as cetosteatil alcohol and beganovic alcohol), silicone resin, silicone oil, surfactants (polyoxyethylene ether fatty series, arbitarily ether fatty series, glycerin ester of fatty series, polyoxyethylenesorbitan ether fatty series, polyoxyethylenated castor oil and a block copolymer of polyoxyethylene and polyoxypropylene)water-soluble polymers (such as hydrocellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinylpyrrolidone and methylcellulose), alcohols (such as ethanol and isopropanol), polyhydric alcohols (such as glycerin, propylene glycol, dipropyleneglycol and sorbitol), sugars (such as glucose and sucrose, inorganic powder such as silicic anhydride, aluminum silicate of magnesium and alumosilicate) and distilled water. For regulating the pH it is possible to use inorganic acids (such as hydrochloric acid and phosphoric acid), salt of an inorganic acid and an alkali metal (such as sodium phosphate), inorganic bases (such as sodium hydroxide), organic acids (such as lower fatty acids, citric acid and lactic acid), salts of organic acids and alkali metal (such as sodium citrate and sodium lactate) and organic bases (such as arginine and ethanolamine). If necessary, may be added as preservatives, antioxidants, etc.

The following are examples of pharmacological experiments that demonstrate the industrial applicability of the present invention.

Experimental example 1: Measuring a decrease in the levels of glucose, triglycerides and neeterificirovannah fatty acids in the blood (score improve sugar and lipid metabolism in mice)

Chemical substance, suspended in 0.5% methylcellulose was administered orally using a probe mice-male db/db (Nippon Charles River, Yokohama, JP) once a day (0.3 to 30 mg/kg·day). Before treatment and after 4 and 9 days of treatment took blood from the tail vein after the mice were subjected to starvation for 1 hour, respectively. 10 day oral glucophagebuy test, in which mice were subjected to gologan the Yu during the night from the previous day and the next morning the mice were given glucose 2 g/kg Measured levels of glucose, triglycerides (TG, TG) and neeterificirovannah fatty acids (NEFA) in plasma using commercial kits, namely Glucose C-II Test Wako (Wako Pure Chemical Industries, Ltd., Tokyo), Deteminer L TG II (Kyowa Medex, Tokyo) and NEFA C-Test Wako (Wako Pure Chemical Industries, Ltd., Tokyo), respectively.

Specific values lower blood glucose, reduce triglycerides in the blood and reduce neeterificirovannah fatty acids in the blood by 9 days after the injection are shown in table 1.

Table 1

In vivo test in mice db/db on day 9 after injection
Dose mg/kgBlood sugarTriglycerides in the bloodBlood free
Ave. 100665,179,360,7
Ave. 142650,475,572,5
Ave. 123670,081,839,5
Ave. 330356,380,335,4
Ave. 345357,281,440,0
Ave. 292317,959,718,4
Ave. 354345,8 61,8to 58.1
Ave. 339337,736,847,5

Compounds of the present invention showed excellent reduction of glucose in the blood, reduction of triglycerides in the blood and decrease in the content neeterificirovannah fatty acids in the blood.

Experimental example 2: Dimension reduction of triglycerides in the blood and lower cholesterol in the blood (score improvement of lipid metabolism in dogs)

Chemical substance, suspended in 0.5% methylcellulose was administered orally by means of the probe of the male short-legged hound (Nosan Corporation, Yokohama) once a day. The dose of the drug was increased every week. Took the blood from the veins of the front paw before drug administration and at each increasing dose measured the levels of triglycerides and cholesterol in non-HDL and HDL fractions by ultracentrifugation. On the day of blood collection, the animal was subjected to starvation and took blood. Compounds of the present invention showed excellent reduction of triglycerides and cholesterol in the blood.

Experimental example 3: Measurement of transcriptional activity

Designed expression vector chimeras GAL4-PPAR LBD (LBD:ligand-binding domain) by ligating amino acid regions of PPAR person 167-468 (PPARα ), 138-440 (NUC-1) and 174-475 (PPARγ) amino acid region of the yeast GAL4 1-147 transcription factor. As gene reporter used PLAP (placental alkaline phosphatase), which is ligated for TK promoter containing DNA-binding element 5-a copy of GAL4 to construct the vector. As the host cells used CV-1 (ATCC CCL-70). That is, the cells CV-1 distributed with density 5×105cells per 35-mm plate and cultured in 10% FCS/DMEM for 24 hours and, using reagent FuGENE 6 transfection, the cells at the same time transfectional expression vector GAL4-PPAR LBD and expression vector GAL4 DBD-TK-PLAP. 24 hours after the specified transfection cells were again distributed in 96-well plate with a density of 1×104cells/well, and then cultured for 24 hours. After 24 hours the medium was replaced with DMEM containing 10% FCS, which was previously treated at 65°for inactivation of native alkaline phosphatase, was added a test compound with an arbitrary concentration. Transcriptional activity was determined through the PLAP activity, secreted within 24 hours after adding the connection with the calculation of the EU50. The PLAP activity was determined after adding 50 μl of buffer for analysis, and 50 μl chemoluminescence substrate 10 μl of culture supernatant and incubation CME and at room temperature for 1 hour. In this way it was possible to determine the values of the transcriptional activity of PPARα, PPARβ and PPARγ. The values of the transcriptional activity of PPARα, PPARβ and PPARγ shown in table 2.

Table 2

Transcriptional activity of the EU50(nm)
PPARαPPARβPPARγ
Ave. 1000,0081,2490,008
Ave. 1420,6041,5440,001
Ave. 1230,0270,9540,115
Ave. 3300,064China 0,6860,024
Ave. 3450,119>300,031
Ave. 2920,062at 1.5210,114
Ave. 3540,0201,7420,038
Ave. 3390,1171,2900,053

Compounds of the present invention showed excellent transcriptional activity.

As described above, the compounds of the present invention have an excellent ability to reduce the levels of glucose and lipids in the blood and are useful as PR is tudiabetes funds funds against hyperlipemia and insulinsensitizing.

Experimental example 4: Anti-inflammatory effect

In female mice of ICR (10 mice/group, Charles River Japan, Yokohama) in the experiment caused colitis, giving them 4% dextran-sodium in drinking water for 5 days. After 8 days, the mice were divided into groups from "0" (normal) to "4" (severe) according to the difference of the signs of diarrhea, bloody stool and weight loss, as described by Cooper HS et al. (Laboratory Invest (69), pp. 238-249, 1993), and the average value was used as an index of disease activity" for colitis. Each test compound suspended in 0.5% solution of methylcellulose and using the probe was administered to mice orally once a day from the initiation of the development of colitis. Compounds of the present invention showed high anti-inflammatory effect.

Examples

The present invention is illustrated hereinafter more definitely and more specifically by the following examples, which should not be considered as limiting the present invention.

Example 1

3-(3-(2-Hydroxy-3-[4-(trifluoromethyl)phenoxy]propoxy)phenyl)-2-isopropoxypropylamine acid

An example of obtaining 1A)

Ethyl 3-(3-hydroxyphenyl)-2-isopropoxyphenol

9.5 g of Ethyl 2-isopropoxyaniline was dissolved in 200 ml of tertrahydrofuran ring ang is drida and the mixture was cooled to -78° C in nitrogen atmosphere. After addition of 6.5 ml of bis(trimethylsilyl)amide lithium (1M solution in tetrahydrofuran) was added under a layer of liquid 15 g of 3-benzyloxybenzaldehyde in tetrahydrofuran (50 ml). The temperature of the solution was raised to room temperature and the mixture was stirred for 3 hours. The reaction solution was treated with saturated aqueous ammonium chloride and was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent. The residue was purified by chromatography on a column of silica gel, to deliver 10.8 g of ethyl 3-[3-(benzyloxy)phenyl]-3-hydroxy-2-isopropoxypropylamine in the form of a mixture of Erythro and threo in the fraction of hexane-ethyl acetate (3:1). The obtained product was dissolved in 50 ml of pyridine was added 3.5 ml of methanesulfonanilide while cooling with ice. After stirring over night at room temperature the reaction mixture was diluted with ethyl acetate and washed with 1 N. hydrochloric acid. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove solvent, receiving of 13.7 g of ethyl 3-[3-(benzyloxy)phenyl]-2-isopropoxy-3-[(methylsulphonyl)oxy]propanoate. The obtained product was dissolved in 450 ml of ethanol, was added to 3.9 g of 10% palladium on coal and the mixture was stirred over night at room temperature in a hydrogen atmosphere. The reaction mixture was filtered the via Celite and the filtrate was concentrated to obtain 7.5 g specified in the connection header.

1H-NMR (CDCl3) δ: 0,98 (d, J=6.4 Hz, 3H), of 1.16 (d, J=6.4 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), 2,89 (DD, J=8,8, of 14.0 Hz, 1H), 2,97 (DD, J=4,8, to 13.6 Hz, 1H), 3,52 (Sept, J=6.0 Hz, 1H) 4,05 (DD, J=4,8, 8,8 Hz, 1H), 4,12-4,19 (m, 2H), 5,01 (width, 1H), 6,09-6,72 (m, 1H), for 6.81-6,83 (m, 1H), 6.75 in (t, J=1.6 Hz, 1H), 7,15 (t, J=7,6 Hz, 1H)

An example of obtaining 1b)

Ethyl 2-isopropoxy-3-[3-(2-oxiranylmethyl)phenyl]propanoate

519 mg of Ethyl 3-(3-hydroxyphenyl)-2-isopropoxypropylamine was dissolved in 7 ml of N,N-dimethylformamide was added sequentially 250 mg of epichlorohydrin and 400 mg of potassium carbonate and the mixture was stirred over night at 50°C. the Reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent. Then the residue was purified by chromatography on a column of silica gel with getting 465 mg specified in the connection header in the fraction of hexane-ethyl acetate (5:1).

1H-NMR (CDCl3) δas 0.96 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.4 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), of 2.75 (DD, J=2,8, 4.8 Hz, 1H), 2,87-of 2.93 (m, 2H), 2,96 (DD, J=8,8, to 13.6 Hz, 1H), 3,34 (dt, J=2,8, 9.6 Hz, 1H), 3,50 (Sept, J=6,0 Hz, 1H), 3,94 (DDD, J=2.0 a, 5,6, 11.2 Hz, 1H), Android 4.04 (DD, J=4,8, 8,8 Hz, 1H), 4,15-4,22 (m, 2H), 6,78 (d, J=8.0 Hz, 1H), PC 6.82 (s, 1H), 6,86 (d, J=7,6 Hz, 1H), 7,19 (t, J=8.0 Hz, 1H)

Example 1C)

3-(3-(2-Hydroxy-3-[4-(trifluoromethyl)phenoxy]propoxy)phenyl)-2-isopropoxypropylamine acid

41 mg Util-isopropoxy-3-[3-(2-oxiranylmethyl)phenyl]propanoate was dissolved in 2 ml of ethanol, added 22 mg of 4-hydroxybenzonitrile and two drops of triethylamine and the mixture was stirred over night at 80°C. the Reaction solution is evaporated and the residue was purified by chromatography on a column of silica gel to obtain 6 mg of ethyl 3-(3-(2-hydroxy-3-[4-(trifluoromethyl)phenoxy]propoxy)phenyl)-2-isopropoxypropylamine in the fraction of hexane-ethyl acetate (4:1). The obtained product was dissolved in 0.4 ml of ethanol was added 0.1 ml of 5 n sodium hydroxide, after which the mixture was stirred over night at room temperature. The reaction solution was acidified using 1 N. hydrochloric acid and was extracted with ethyl acetate. The residue was purified by high-performance liquid chromatography with reversed phase, receiving 3,15 mg specified in the connection header.

MSm/e(ESI) 443 (MN+)

Example 2

3-(3-(3-[4-(tert-Butyl)phenoxy]-2-hydroxypropoxy)phenyl)-2-isopropoxypropylamine acid

Using 4-tert-butylphenol, specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 431 (MN+)

Example 3

3-(3-(3-[4-(Phenyl)phenoxy]-2-hydroxypropoxy)phenyl)-2-isopropoxypropylamine acid

Using 4-hydroxybiphenyl specified in the title compound was obtained according to a similar method as described is ANO in example 1 (C).

MS m/e (ESI) 451 (MN+).

Example 4

3-(3-(3-[4-(2,4-Dichlorophenoxy)]-2-hydroxypropoxy)phenyl)-2-isopropoxypropylamine acid

Using 2,4-dichlorophenyl specified in the title compound was obtained by a similar procedure as described in example 1 (C).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.0 Hz, 3H), of 1.17 (d, J=6.0 Hz, 3H), of 2.93 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, of 14.0 Hz, 1H), 3,55 (Sept, J=6.0 Hz, 1H), 4,14 (DD, J=4,0, 8.0 Hz, 1H), 4,16-to 4.23 (m, 4H), 4,42 (Sept, J=6,4 Hz, 1H), 6,82-6,85 (m, 2H), 6.87 in (d, J=7,6 Hz, 1H), make 6.90 (d, J=8,8 Hz, 1H), 7,19 (DD, J=2,8, 8,8 Hz, 1H), 7,22 (DD, J=7,6, 8,8 Hz, 1H), 7,37 (d, J=2,8 Hz, 1H)

MS m/e (ESI) 443 (MN+)

Example 5

3-(3-(3-[4-(4-Bromo-2-pertenece)]-2-hydroxypropoxy)phenyl)-2-isopropoxypropylamine acid

Using 4-bromo-2-terfenol specified in the title compound was obtained by a similar procedure as described in example 1 (C).

MS m/e (ESI) 471 (MN+)

Example 6

3-(3-(3-[4-(4-Cianfrocca)]-2-hydroxypropoxy)phenyl)-2-isopropoxypropylamine acid

Using 4-hydroxybenzonitrile specified in the title compound was obtained by a similar procedure as described in example 1 (C).

MS m/e (ESI) 400 (MN+)

Example 7

3-(3-[3-(4-Cyano-3-pertenece)-2-hydroxypropoxy]phenyl)-2-isopropoxypropylamine acid

Use the UYa 2-fluoro-4-hydroxybenzonitrile, specified in the title compound was obtained by a similar procedure as described in example 1 (C).

MS m/e (ESI) 418 (MN+)

Example 8

3-(3-[3-(4-Cyano-2-methoxyphenoxy)-2-hydroxypropoxy]phenyl)-2-isopropoxypropylamine acid

Using 3-methoxy-4-hydroxybenzonitrile specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 430 (MN+)

Example 9

3-(3-[3-(3-Cianfrocca)-2-hydroxypropoxy]phenyl)-2-isopropoxypropylamine acid

Using 3-hydroxybenzonitrile specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 400 (MN+)

Example 10

3-(3-[3-(4-Acetaminophenol)-2-hydroxypropoxy]phenyl)-2-isopropoxypropylamine acid

Using 4-acetamidophenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 432 (MN+)

Example 11

3-(3-[3-(3-Acetaminophenol)-2-hydroxypropoxy]phenyl)-2-isopropoxypropylamine acid

Using 3-acetamidophenol specified in the title compound was obtained by a similar procedure as described in example 1C).

<> MSm/e(ESI) 432 (MN+)

Example 12

3-(3-[3-(3-tert-Butoxycarbonylamino)-2-hydroxypropoxy]phenyl)-2-isopropoxypropylamine acid

Using 3-tert-butoxycarbonylamino specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 490 (MN+)

Example 13

3-(3-(2-Hydroxy-3-[(2-oxo-1,2,3,4-tetrahydro-5-chinoline)oxy]propoxy)phenyl)-2-isopropoxypropylamine acid

Using 5-hydroxy-1,2,3,4-tetrahydro-2-chinoline specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 444 (MN+)

Example 14

3-(3-(2-Hydroxy-3-[4-(tetrahydro-1H-1-pyrrolidinone)phenoxy]propoxy)phenyl)-2-isopropoxypropylamine acid

Using (4-hydroxyphenyl)(tetrahydro-1H-1-pyrrolyl)methanon specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 472 (MN+)

Example 15

3-(3-(2-Hydroxy-3-[4-(1-hydroxy-1-methyl-2-oxopropyl)phenoxy]propoxy)phenyl)-2-isopropoxypropylamine acid

Using 3-hydroxy-3-(4-hydroxyphenyl)-2-butanone, specified in the header connect the tion was obtained by the same methodology, as described in example 1C).

MSm/e(ESI) 461 (MN+)

Example 16

3-(3-(3-[(7-Cyano-1-naphthyl)oxy]-2-hydroxypropoxy)phenyl)-2-isopropoxypropylamine acid

Using 8-hydroxy-2-naphthonitrile specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 450 (MN+)

Example 17

3-(3-[2-Hydroxy-3-(1,2,3,4-tetrahydro-8-hyalinelike)propoxy]phenyl)-2-isopropoxypropylamine acid

Using 1,2,3,4-tetrahydro-8-hinolinol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 430 (MN+)

Example 18

3-(3-[2-Hydroxy-3-(2-bromo-3-pyridyloxy)propoxy]phenyl)-2-isopropoxypropylamine acid

Using 2-bromo-3-pyridinol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 454 (MN+)

Example 19

3-(3-[2-Hydroxy-3-(5-methyl-8-hyalinelike)propoxy]phenyl)-2-isopropoxypropylamine acid

Using 5-methyl-8-hinolinol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 440 (MN+)

Por what measures 20

3-(3-(2-Hydroxy-3-[4-(methylsulfanyl)phenoxy]propoxy)phenyl)-2-isopropoxypropylamine acid

Using 4-methylthiophenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 421 (MN+)

Example 21

3-(3-(2-Hydroxy-3-[4-(methylsulphonyl)phenoxy]propoxy)phenyl)-2-isopropoxypropylamine acid

3-(3-(2-Hydroxy-3-[4-(methylsulfanyl)phenoxy]propoxy)phenyl)-2-isopropoxyphenol acid was dissolved in 2 ml of methanol and 0.5 ml of water was added 100 mg oxone. After stirring at room temperature for 2 hours, the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer is evaporated and the residue was purified by high-performance liquid chromatography with reversed phase, getting to 1.86 mg specified in the connection header.

MSm/e(ESI) 453 (MN+)

Example 22

3-[3-(2-Hydroxy-3-[5-(trifluoromethyl)-2-pyridyl]oxopropoxy)phenyl]-2-isopropoxypropylamine acid

Using 2-hydroxy-5-triptorelin specified in the title compound was obtained by a similar procedure as described in example 1C).

1H-NMR (CDCl3) δ: of 1.05 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 2.93 (DD, J=7,6, of 14.0 Hz, 1H), 3,11 (DD, J=3,6, 4,4 Hz, 1H), of 3.56 (Sept, J=6.0 Hz, 1H), 4,11 (d, J=5.6 Hz, 2H), 4,14 (DD, J=4,0, 8.0 Hz, 1H), 4,36-4,43 (m, 1H), 4,57(DD, J=6,0, to 12.8 Hz, 1H), gold 6.43 (DD, J=4.0 a, and 11.6 Hz, 1H), 6,80-6,83 (m, 2H), 6,86 (d, J=7,6 Hz, 1H), 6,91 (d, J=8,4 Hz, 1H), 7,19-7,26 (m, 1H), 7,82 (DD, J=2,8, 8,8 Hz, 1H), 8,42 (s, 1H)

MSm/e(ESI) 444 (MH+)

Example 23

3-[3-(2-Hydroxy-3-[5-chloro-2-pyridyl]oxopropoxy)phenyl]-2-isopropoxypropylamine acid

Using 2-hydroxy-5-chloropyridin specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 410 (MN+)

Example 24

3-(3-[2-Hydroxy-3-(2-hinomisaki)propoxy]phenyl)-2-isopropoxypropylamine acid

Using 2-hydroxyquinolin specified in the title compound was obtained by a similar procedure as described in example 1C).

1H-NMR (CDCl3) δ: of 1.03, 1.04 million (each d, J=6.0 Hz and 6.4 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 2.91 in (DD, J=8,0, to 13.6 Hz, 1H), 3,12 (DD, J=4,0, of 14.0 Hz, 1H), 3,53 (Sept, J=6,4 Hz, 1H), 4.09 to of 4.12 (m, 2H), 4,14 (DD, J=4.0 a, and 8.4 Hz, 1H), 4,37-of 4.44 (m, 1H), 4, 72 (DD, J=5,6, 12.0 Hz, 1H), 4,78 (DDD, J=1,2, 3,2, to 12.8 Hz, 2H), 6,83-6,87 (m, 3H), 6,98-7,01 (m, 1H), 7,22 (DD, J=7,2, an 8.4 Hz, 1H), 7,42 (DDD, J=1,2, 6,8, 8.0 Hz, 1H), 7,65 (dt, J=1,6, and 8.4 Hz, 1H), of 7.75 (d, J=6,8 Hz, 1H), 7,82 (d, J=8,4 Hz, 1H), of 8.06 (d, J=8,8 Hz, 1H)

MSm/e(ESI) 426 (MH+)

Example 25

3-(3-[3-(2-Bromo-4-cianfrocca)-2-hydroxypropoxy]phenyl)-2-isopropoxypropylamine acid

Using 3-bromo-4-hydroxybenzonitrile specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 478 (MN+)

Example 26

3-(3-(3-[(2,4-Dichlorophenyl)sulfinil]-2-hydroxypropoxy)phenyl)-2-isopropoxypropylamine acid

Example 27

3-(3-(3-[(2,4-Dichlorophenyl)sulfonyl]-2-hydroxypropoxy)phenyl)-2-isopropoxypropylamine acid

15 mg of 2,4-Dichlorotoluene and 10 mg of ethyl 2-isopropoxy-3-[3-(2-oxiranylmethyl)phenyl]propanoate was dissolved in 0.4 ml of ethanol was added 2 drops of triethylamine, after which the mixture was stirred at 80°With during the night. The reaction solution is evaporated to obtain ethyl 3-(3-(2-hydroxy-3-[2,4-dichlorophenoxy]propoxy)phenyl)-2-isopropoxypropylamine. The obtained product was dissolved in 2 ml of methanol and 0.5 ml of water was added 100 mg oxone and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was concentrated and the residue was treated with 0.4 ml of ethanol and 0.1 ml of 5 n sodium hydroxide solution, after which the mixture was stirred over night at room temperature. The reaction solution was acidified using 1 N. hydrochloric acid and then was extracted with ethyl acetate. The residue was purified is isoeffective liquid chromatography with reversed phase with the receipt of 5.81 mg specified in the title compound (example 26) (MS m/e(ESI) 475 (MN+)) and 3,44 mg specified in the connection header (example 27).

1H-NMR (CDCl3) δ: 1,04 (d, J=6.0 Hz, 3H), of 1.17 (d, J=6.0 Hz, 3H), of 2.92 (DD, J=8,0, 14.4 Hz, 1H), 3,09 (DD, J=4,0, to 13.6 Hz, 1H), of 3.56 (Sept, J=6.0 Hz, 1H), of 3.73 (DD, J=8,0, of 14.8 Hz, 1H), 3,79 (DD, J=3.2, and 14.4 Hz, 1H), 3,97-of 4.05 (m, 2H), 4,13 (DD, J=4,0, 7,6 Hz, 1H), to 4.52 (dt, J=2,8, 8.0 Hz, 4H), 6.73 x (d, J=6,8 Hz, 1H), 6,74 (s, 1H), 6,86 (d, J=6,8 Hz, 1H), 7,19 (DD, J=7,6, 8,8 Hz, 1H), 7,46 (DDD, J=0,8, 2,0, an 8.4 Hz, 1H), EUR 7.57 (d, J=2.0 Hz, 1H), 8,07 (d, J=8,8 Hz, 1H)

MSm/e(ESI) 491 (MH+)

Example 28

3-(3-(3-[4-tert-Butylphenoxy]-2-forproperty)phenyl)-2-isopropoxypropylamine acid

Using 4-tert-butylphenol, was in the process as described in example 1C), with 32 mg of ethyl 3-(3-(2-hydroxy-3-[4-tert-butylphenoxy]propoxy)phenyl)-2-isopropoxypropylamine. Dissolve 16 mg of the obtained compound in 1 ml of dichloromethane was added 10 mg of DAST. After stirring over night at room temperature the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer is evaporated to obtain ethyl 3-(3-(3-[4-tert-butylphenoxy]-2-forproperty)phenyl)-2-isopropoxypropylamine. The obtained product was dissolved in 0.4 ml of ethanol was added 0.1 ml of 5 n sodium hydroxide solution, after which the mixture was stirred over night at room temperature. The reaction solution was acidified using 1 N. hydrochloric acid and then extra Aravali with ethyl acetate. The residue was purified by high-performance liquid chromatography with reversed phase with obtaining 2,22 mg specified in the connection header.

MS m/e (ESI) 433 (MN+)

Example 29

3-(3-(3-[4-Phenyleneoxy]-2-forproperty)phenyl)-2-isopropoxypropylamine acid

Using 4-hydroxybiphenyl specified in the title compound was obtained by a similar procedure as described in example 28.

MS m/e (ESI) 453 (MN+)

Example 30

3-(3-(3-[4-(2,4-Dichlorophenoxy)]-2-forproperty)phenyl)-2-isopropoxypropylamine acid

Using 2,4-dichlorphenol specified in the title compound was obtained by a similar procedure as described in example 28.

1H-NMR (CDCl3) δ: 1,03, of 1.03 (each d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 2.93 (DD, J=8,0, to 13.6 Hz, 1H), 3,12 (DD, J=4,0, of 14.0 Hz, 1H), 3,55, 3,55 (every Sept, J=6.0 Hz, 1H), 4,11-4,16 (m, 1H), 4,29-to 4.41 (m, 4H), 5,18 (Sept, J=4,8 and 46.8 Hz, 1H), for 6.81-6,85 (m, 2H), 6,98 (d, J=7,6 Hz, 1H), 6,91 (d, J=9,2 Hz, 1H), 7,20 (DD, J=2,4, 8,8 Hz, 1H), 7.23 percent (DD, J=7,6, and 9.2 Hz, 1H), 7,38 (d, J=2.4 Hz, 1H)

MS m/e (ESI) 445 (MH+)

Example 31

3-(3-(3-[4-(4-Bromo-2-pertenece)]-2-forproperty)phenyl)-2-isopropoxypropylamine acid

Using 4-bromo-2-terfenol specified in the title compound was obtained by a similar procedure as described in example 28.

MS m/e (ESI) 473 (MN+)

Example 32

3(3-(3-[4-(2,4-Dichlorophenyl)phenoxy]-2-methoxypropane)phenyl)-2-isopropoxypropylamine acid

Dissolve 15 mg of ethyl 3-(3-(3-[4-(2,4-dichlorophenyl)phenoxy]-2-hydroxypropoxy)phenyl)-2-isopropoxypropylamine in 0.4 ml of tetrahydrofuran, was added 0.1 ml of methyliodide and 10 mg of sodium hydride and the mixture was stirred over night at room temperature. To the reaction solution was added ethanol and 0.1 ml of 5 n sodium hydroxide solution, and the mixture was continued to stir at room temperature for 3 hours, then it was neutralized 1 N. hydrochloric acid and was extracted with ethyl acetate. The organic layer is evaporated and the residue was purified by high-performance liquid chromatography with reversed phase with obtaining 4,32 mg specified in the connection header.

1H-NMR (CDCl3) δ: 1,02 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 2.91 in (DD, J=7,6, to 12.8 Hz, 1H), 3,11 (DD, J=3.2, and to 13.6 Hz, 1H), 3,53 (Sept, J=3,2, and 6.6 Hz, 1H), 3,61 (s, 3H), 3,99 (DD, J=4,8, 10,0 Hz, 1H), 4.09 to 4.26 deaths (m, 5H), 6,80-6,85 (m, 2H), 6,85 (d, J=8.0 Hz, 1H), 6.89 in (d, J=8,8 Hz, 1H), 7,18 (DD, J=2,4, 8,8 Hz, 1H), 7,21 (DD, J=7,2, and 9.2 Hz, 1H), was 7.36 (d, J=2.4 Hz, 1H)

MSm/e(ESI) 457 (MH+)

Example 33

3-(3-[2-(2,4-Dichlorphenoxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Example of getting 33a)

2-(2,4-Dichlorophenoxy)-1-ethanol

To a solution of 15.0 g of 2,4-dichlorophenoxyacetic acid in tetrahydrofuran (300 ml) was added dropwise to 96 ml of 1.0m solution balancerationality sets the/tetrahydrofuran under ice cooling for 1.5 hours. The reaction solution was stirred at room temperature for 22 hours. Then the reaction solution was concentrated and the residue was diluted with saturated aqueous ammonium chloride and ethyl acetate. The organic layer was washed saturated aqueous ammonium chloride, saturated aqueous sodium bicarbonate (2 times) and saturated aqueous ammonium chloride, then dried over anhydrous sodium sulfate and concentrated to obtain 14 g specified in the title compounds as colorless oils.

1H-NMR (CDCl3) δ: of 2.21 (d, J=6,4 Hz, 1H), 3,99 (dt, J=4,4, 6.4 Hz, 2H), 4,12 (t, J=4.4 Hz, 2H), 6.87 in (d, J=8,8 Hz, 1H), 7,20 (DD, J=2,4, 8,8 Hz, 1H), 7,37 (d, J=2.4 Hz, 1H)

Example of getting 33b)

1-(2-Bromoethoxy)-2,4-dichlorobenzene

To a solution of 10.0 g of 2-(2,4-dichlorophenoxy)-1-ethanol in 1,2-dimethoxyethane (200 ml) was added dropwise a solution of 14 g of tribromide phosphorus in 1,2-dimethoxyethane (20 ml) under cooling with ice. The reaction solution was stirred at room temperature for 20 hours. Then the reaction solution was concentrated and the residue was diluted with water and ethyl acetate. The organic layer was added saturated aqueous sodium hydrogen carbonate solution and the resulting emulsion was filtered through Celite. The filtrate was diluted with diethyl ether and saturated aqueous chloride is ammonia. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by chromatography on a column of silica gel with getting 6,15 g specified in the title compounds as a pale yellow oil.

1H-NMR (CDCl3) δ: to 3.67 (t, J=6.4 Hz, 2H), 4,32 (t, J=6.4 Hz, 2H), 6.87 in (d, J=8,8 Hz, 1H), 7,19 (DD, J=2,6, 8,8 Hz, 1H), 7,39 (d, J=2.6 Hz, 1H)

Example 33C)

3-(3-[2-(2,4-Dichlorphenoxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

140 mg of 1-(2-Bromoethoxy)-2,4-dichlorobenzene, 100 mg of ethyl 3-(3-hydroxyphenyl)-2-isopropoxypropylamine and 110 mg of potassium carbonate was dissolved in N,N-dimethylformamide and the mixture was stirred over night at 60°C. the Reaction solution was diluted with saturated aqueous ammonium chloride and ethyl acetate. The organic layer was washed saturated aqueous ammonium chloride, saturated aqueous sodium bicarbonate (2 times) and saturated aqueous ammonium chloride, dried over anhydrous sodium sulfate and concentrated. The residue was dissolved in 4 ml of methanol was added 1 ml of 5 n sodium hydroxide solution and the mixture was stirred at room temperature for 2 hours. The reaction mixture was neutralized 1 N. hydrochloric acid and was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated. The remainder of the PTS is attended by chromatography on a column of silica gel with receipt of 83.6 mg specified in the connection header in the fraction of hexane-ethyl acetate (4:1 → 1:2).

1H-NMR (CDCl3) δ: 1,02 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 2.93 (DD, J=8,2, to 13.8 Hz, 1H), 3,12 (DD, J=3,8, to 13.8 Hz, 1H), 3,55 (Sept, J=6.0 Hz, 1H), 4,14 (DD, J=3,8, 8,2 Hz, 1H), 4,33-to 4.38 (m, 4H), for 6.81-6.89 in (m, 3H), to 6.95 (d, J=8,8 Hz, 1H), 7.18 in-7,25 (m, 2H), 7,37 (d, J=2,8 Hz, 1H)

MSm/e(ESI) 435 (MNa+)

Example 34

3-(3-[2-(4-Triptoreline)ethoxy]phenyl)-2-isopropoxypropylamine acid

Example of getting 34a)

1-(2-Bromoethoxy)-4-cryptomaterial

A suspension of 5.0 g of 4-hydroxybenzonitrile, of 17.4 g of 1,2-dibromethane and 2.6 g of potassium carbonate in acetone (100 ml) was boiled under reflux for 3 days. The reaction solution was diluted with water and ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated solution of ammonium chloride (2 times), dried over anhydrous sodium sulfate and concentrated. The residue was purified by chromatography on a column of silica gel to obtain 1.78 g specified in the title compounds as colorless oils.

1H-NMR (CDCl3) δ: 3,66 (t, J=6.4 Hz, 2H), 4,34 (t, J=6.4 Hz, 2H), 6,98 (d, J=8,4 Hz, 2H), 7,56 (d, J=8,4 Hz, 1H)

Example 34b)

3-(3-[2-(4-Triptoreline)ethoxy]phenyl)-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-cryptomaterial specified in the title compound was obtained by the anal is similar to the method as described in example 33C).

MSm/e(ESI) 435 (MNa+)

Example 35

3-(3-[2-(4-Cyclohexylmethoxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Example of getting 35A)

1-[2-(Benzyloxy)ethoxy]-4-cyclohexylphenol

A suspension of 2.5 g of 4-cyclohexylphenol, 3.0 g benzyl 2-bromatologia ether and 2.4 g of potassium carbonate in N,N-dimethylformamide (50 ml) was stirred at 60°C for 23 hours. The reaction solution was diluted with water and ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium carbonate and a saturated solution of ammonium chloride (2 times), dried over anhydrous sodium sulfate and concentrated. The residue was purified by chromatography on a column of silica gel with receipt of 3.9 g specified in the title compounds as colorless oils.

1H-NMR (CDCl3) δ: 1,20-of 1.44 (m, 5H), 1,70-1,90 (m, 5H), 2,39-2,48 (m, 1H), 3,82 (t, J=4,8 Hz, 2H), 4,13 (t, J=4,8 Hz, 2H), 4,63 (s, 2H), 6,83-to 6.88 (m, 2H), 7,09-7,14 (m, 2H), 7,26-7,38 (m, 5H)

Example of getting 35b)

1-(2-Hydroxyethoxy)-4-cyclohexylphenol

3.2 g of 1-[2-(Benzyloxy)ethoxy]-4-cyclohexylbenzene was dissolved in 100 ml of ethanol, was added 300 mg of 20% palladium hydroxide and the mixture was stirred at room temperature in a hydrogen atmosphere for 25 hours. The catalyst was filtered and washed atilas what tatom. The filtrate is evaporated and the residue was subjected to azeotropic distillation with toluene (2 times) with the receipt of 2.34 g specified in the title compound as a colourless solid.

1H-NMR (CDCl3) δ: 1,17-of 1.44 (m, 5H), 1,70-1,90 (m, 5H), 2.40 a-2,50 (m, 1H), 3,62 (t, J=6.4 Hz, 2H), 4,27 (t, J=6.4 Hz, 2H), PC 6.82-6.87 in (m, 2H), 7,11-to 7.15 (m, 2H)

Example of getting 35C)

1-(2-Bromoethoxy)-4-cyclohexylphenol

Connection example of getting 35C) was synthesized by a similar procedure as described in example obtaining 33b).

1H-NMR (CDCl3) δ: 1,17-of 1.44 (m, 5H), 1,70-1,90 (m, 5H), 2.40 a-2,50 (m, 1H), 3,62 (t, J=6.4 Hz, 2H), 4,27 (t, J=6.4 Hz, 2H), PC 6.82-6.87 in (m, 2H), 7,11-to 7.15 (m, 2H)

Example 35d)

3-(3-[2-(4-Cyclohexylmethoxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-cyclohexylphenol specified in the title compound was obtained by a similar procedure as described in example 33C).

1H-NMR (CDCl3) δ: 1,02 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), 1,19-of 1.45 (m, 5H), 1,70-1,90 (m, 5H), 2,41-of 2.50 (m, 1H), 2,92 (DD, J=8,4, of 14.0 Hz, 1H), 3,12 (DD, J=4,0, of 14.0 Hz, 1H), 3,54 (Sept, J=6.0 Hz, 1H), 4,13 (DD, J=4,0, an 8.4 Hz, 1H), 4,30 (Sirs, 4H), 6,82-6,91 (m, 4H), 7,11-7,16 (m, 2H), 7,19-7,24 (m, 2H)

MSm/e(ESI) 449 (MNa+)

Example 36

3-(3-[2-(4-Cyclopentyloxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Example of receipt 36A)

1-(2-Bromoethoxy-4-cyclopentylphenol

Using cyclopentylphenol specified in the title compound was obtained by a similar procedure as described in examples obtain 35A), 35b) and (35C).

1H-NMR (CDCl3) δ: 1,48-of 1.84 (m, 6H), 2.00 in of 2.08 (m, 2H), 2,90 are 2.98 (m, 1H), 3,63 (t, J=6.4 Hz, 2H), 4,27 (t, J=6.4 Hz, 2H), 6,83-6,86 (m, 2H), 7,14-to 7.18 (m, 2H)

Example 36b)

3-(3-[2-(4-Cyclopentyloxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-cyclopentylphenol specified in the title compound was obtained by a similar procedure as described in example 33C).

MSm/e(ESI) 435 (MNa+)

Example 37

3-(3-[2-(4-tert-Butylphenoxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Example of getting 37A)

1-(2-Bromoethoxy)-4-tert-butylbenzoyl

Using 4-tert-butylphenol, specified in the title compound was obtained by a similar procedure as described in examples obtain 35A), 35b) and (35C).

1H-NMR (CDCl3) δ: of 1.31 (s, 9H), to 3.64 (t, J=6.4 Hz, 2H), 4,29 (t, J=6.4 Hz, 2H), at 6.84-6.89 in (m, 2H), 7,30-7,34 (m, 2H)

Example 37b)

3-(3-[2-(4-tert-Butylphenoxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-tert-butylbenzoyl specified in the title compound was obtained according to a similar method, the AK described in example 33C).

MSm/e(ESI) 423 (MNa+)

Example 38

3-(3-[2-(4-isopropylphenoxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Example of getting 38A)

1-(2-Bromoethoxy)-4-isopropylbenzene

Using 4-isopropylphenol specified in the title compound was obtained by a similar procedure as described in examples 35A), 35b) and (35C).

1H-NMR (CDCl3) δ: of 1.23 (d, J=6.8 Hz, 6H), 2,87 (Sept, J=6.8 Hz, 1H), 3,63 (t, J=6.4 Hz, 2H), 4,27 (t, J=6.4 Hz, 2H), 6,83-to 6.88 (m, 2H), 7,13-7,17 (m, 2H)

Example 38b)

3-(3-[2-(4-Isopropylphenoxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-isopropylbenzene, specified in the title compound was obtained by a similar procedure as described in example 33C).

MSm/e(ESI) 409 (MNa+)

Example 39

3-(3-[2-(Phenoxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Using 2-(bromoethoxy)benzene, specified in the title compound was obtained by a similar procedure as described in example 33C).

MSm/e(ESI) 367 (MNa+)

Example 40

3-(3-[2-(4-Pertenece)ethoxy]phenyl)-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-torbenson specified in the title compound was obtained by similar method is ke, as described in example 33C).

MSm/e(ESI) 385 (MNa+)

Example 41

3-(3-[2-(4-Benzyloxy)ethoxy]phenyl)-2-isopropoxypropylamine acid

Using 1-[(2-bromoethoxy)methyl]benzene, specified in the title compound was obtained by a similar procedure as described in example 33C).

MSm/e(ESI) 381 (MNa+)

Example 42

2 Isopropoxy-3-[3-(3-phenylpropoxy)phenyl]propanoic acid

Using 3-phenylpropylamine specified in the title compound was obtained by a similar procedure as described in example 33C).

MSm/e(ESI) 365 (MNa+)

Example 43

2 Isopropoxy-3-[3-(3-phenoxypropane)phenyl]propanoic acid

Using 1-(3-bromopropane)benzene, specified in the title compound was obtained by a similar procedure as described in example 33C).

1H-NMR (CDCl3) δ: 1,01 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 2.26 and (Quint, J=6.0 Hz, 2H), 2,90 (DD, J=8,8, to 13.8 Hz, 1H), 3,10 (DD, J=3,6, or 13.8 Hz, 1H), 3,52 (Sept, J=6.0 Hz, 1H), 4,10-4,19 (m, 5H), 6.89 in-of 6.96 (m, 3H), 6,78-6,85 (m, 3H), 7,20 (t, J=8,2 Hz, 1H), 7,25-7,31 (m, 2H)

MS m/e (ESI) 381 (MNa+)

Example 44

3-{3-[3-(2,4-Dichlorphenoxy)propoxy]phenyl}-2-isopropoxypropylamine acid

Using 1-(3-bromopropane)-2,4-dichlorobenzene specified in the header of the group received the same methodology, as described in example 33C).

MS m/e (ESI) 449 (MNa+)

Example 45

3-{3-[3-(4-Acetyl-3-hydroxy-2-propylenoxide)propoxy]phenyl}-2-isopropoxypropylamine acid

Using 1-[4-(3-bromopropane)-2-hydroxy-3-propylphenyl]-1-Etalon specified in the title compound was obtained by a similar procedure as described in example 33 (C).

MS m/e (ESI) 481 (MNa+)

Example 46

3-(3-[2-(2,4-Dichlorphenoxy)ethoxy]phenyl)-2-ethoxypropanol acid

Example of getting 46a)

Ethyl (E,Z)-3-[3-(benzyloxy)phenyl]-2-ethoxy-2-propenoate

3.6 g of Ethyl 2-(diethoxyphosphoryl)-2-ethoxyacetic was dissolved in tetrahydrofuran, was added 520 mg of 60% sodium hydride and the mixture was stirred for 10 minutes. Solution was added 2.5 g of 3-benzyloxybenzaldehyde in 10 ml of N,N-dimethylformamide and the mixture was stirred over night at room temperature. The reaction mixture was diluted with ethyl acetate. The organic layer was added saturated aqueous sodium hydrogen carbonate solution and the resulting emulsion was filtered through Celite. The filtrate was diluted with diethyl ether and saturated aqueous ammonium chloride. The organic layer was dried over anhydrous magnesium sulfate and concentrated to obtain 4.5 g specified in the connection header.

Example of getting 46b)

Ethyl 2-ethoxy-3-(3-hydroxyp the Nile)propanoate

4.5 g of Ethyl (E,Z)-3-[3-(benzyloxy)phenyl]-2-ethoxy-2-propenoate was dissolved in ethyl acetate, the resulting solution was added 450 mg of 10% palladium on coal and the mixture was stirred over night at room temperature in a hydrogen atmosphere. The reaction solution was filtered through Celite and the filtrate evaporated. The residue was purified by chromatography on a column of silica gel to obtain 3.7 g specified in the connection header in the fraction of hexane-ethyl acetate (5:1).

1H-NMR (CDCl3) δ: of 1.16 (t, J=7.2 Hz, 3H), of 1.23 (t, J=7.2 Hz, 3H), 2.95 and are 2.98 (m, 2H), 3,37 (DQC, J=7,2, and 9.2 Hz, 1H), 3,61 (DQC, J=7,2, and 9.2 Hz, 1H), was 4.02 (DD, J=5,6, and 7.6 Hz, 1H), 4,18 (kV, J=7.2 Hz, 2H), 5,14 (s, 1H), 6,69-of 6.73 (m, 1H), 6,74-6,76 (m, 1H), 6,79-PC 6.82 (m, 1H), 7,15 (t, J=8.0 Hz, 1H)

Example C)

3-(3-[2-(2,4-Dichlorphenoxy)ethoxy]phenyl)-2-ethoxypropanol acid

Using 1-(2-bromoethoxy)-2,4-dichlorobenzene and ethyl 2-ethoxy-3-(3-hydroxyphenyl)propanoate specified in the title compound was obtained by a similar procedure as described in example 33C).

MSm/e(ESI) 421 (MNa+)

Example 47

3-(3-[2-(4-Triptoreline)ethoxy]phenyl)-2-ethoxypropanol acid

Using 1-(2-bromoethoxy)-4-cryptomaterial specified in the title compound was obtained by a similar procedure as described in example C).

MSm/e(ESI)421 (MNa +)

Example 48

3-(3-[2-(4-Cyclohexylmethoxy)ethoxy]phenyl)-2-ethoxypropanol acid

Using 1-(2-bromoethoxy)-4-cyclohexylphenol specified in the title compound was obtained by a similar procedure as described in example C).

MSm/e(ESI) 435 (MNa+)

Example 49

3-(3-[2-(4-Cyclopentyloxy)ethoxy]phenyl)-2-ethoxypropanol acid

Using 1-(2-bromoethoxy)-4-cyclopentylphenol specified in the title compound was obtained by a similar procedure as described in example C).

MSm/e(ESI) 421 (MNa+)

Example 50

3-(3-[2-(4-tert-Butylphenoxy)ethoxy]phenyl)-2-ethoxypropanol acid

Using 1-(2-bromoethoxy)-4-tert-butylbenzoyl specified in the title compound was obtained by a similar procedure as described in example C).

MSm/e(ESI) 409 (MNa+)

Example 51

3-(3-[2-(4-Isopropylphenoxy)ethoxy]phenyl)-2-ethoxypropanol acid

Using 1-(2-bromoethoxy)-4-isopropylbenzene, specified in the title compound was obtained by a similar procedure as described in example C).

MSm/e(ESI) 395 (MNa+)

Example 52

3-{3-[2-(2,4-Dichlorphenoxy)ethoxy]-4-methoxyphenyl}-2-isopropoxypropylamine Ki is a lot

Example of getting 52a)

Ethyl 3-(3-hydroxy-4-methoxyphenyl)-2-isopropoxyphenol

Using 3-benzyloxy-4-methoxybenzaldehyde and ethyl 2-(diethoxyphosphoryl)-2-isopropoxyethanol specified in the title compound was obtained by a similar procedure as described in example 46b).

1H-NMR (CDCl3) δ: 0,99 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 1.23 (t, J=7.2 Hz, 3H), 2,85 (DD, J=8,4, of 14.0 Hz, 1H), only 2.91 (DD, J=4,8, of 14.0 Hz, 1H), 3,45-3,55 (m, 1H), a 3.87 (s, 3H), 4,01 (DD, J=4,8, and 8.4 Hz, 1H), 4,14-4,20 (m, 2H), of 5.55 (s, 1H), 6,70-of 6.78 (m, 2H), at 6.84 (d, J=2.0 Hz, 1H)

Example 52b)

3-{3-[2-(2,4-Dichlorphenoxy)ethoxy]-4-methoxyphenyl}-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-2,4-dichlorobenzene and ethyl 3-(3-hydroxy-4-methoxyphenyl)-2-isopropoxyphenol specified in the title compound was obtained by a similar procedure as described in example 33C).

1H-NMR (CDCl3) δ: 1,04 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), 2,89 (DD, J=8,0, of 14.0 Hz, 1H), of 3.07 (DD, J=4,0, of 14.0 Hz, 1H), of 3.56 (Sept, J=6.0 Hz, 1H), 3,84 (s, 3H), 4,13 (DD, J=4,0, 8.0 Hz, 1H), 4,37-of 4.44 (m, 4H), 6,83 (s, 1H), 6,83 (d, J=1.2 Hz, 1H), 6,91 (d, J=1.2 Hz, 1H), 6,98 (d, J=8.6 Hz, 1H), 7,18 (DD, J=2,6, 8.6 Hz, 1H), 7,37 (d, J=2.6 Hz, 1H)

MSm/e(ESI) 465 (MNa+)

Example 53

3-{3-[2-(4-Triptoreline)ethoxy]-4-methoxyphenyl}-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-t is iformative, specified in the title compound was obtained by a similar procedure as described in example 52b).

MSm/e(ESI) 465 (MNa+)

Example 54

3-{3-[2-(4-Cyclohexylmethoxy)ethoxy]-4-methoxyphenyl}-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-cyclohexylphenol specified in the title compound was obtained by a similar procedure as described in example 52b).

MSm/e(ESI) 479 (MNa+)

Example 55

3-{3-[2-(4-Cyclopentyloxy)ethoxy]-4-methoxyphenyl}-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-cyclopentylphenol specified in the title compound was obtained by a similar procedure as described in example 52b).

MSm/e(ESI) 465 (MNa+)

Example 56

3-{3-[2-(4-tert-Butylphenoxy)ethoxy]-4-methoxyphenyl}-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-tert-butylbenzoyl specified in the title compound was obtained by a similar procedure as described in example 52b).

MSm/e(ESI) 453 (MNa+)

Example 57

3-{3-[2-(4-Isopropylphenoxy)ethoxy]-4-methoxyphenyl}-2-isopropoxypropylamine acid

Using 1-(2-bromoethoxy)-4-isopropylbenzene, specified in the title compound was obtained p the same methodology, as described in example 52b).

MSm/e(ESI) 439 (MNa+)

Example 58

3-{3-[2-(2,4-Dichlorphenoxy)ethoxy]phenyl}-2-methylpropanoate acid

Example of getting 58A)

Ethyl 3-(3-hydroxyphenyl)-2-methylpropanoate

Using 3-benzyloxybenzaldehyde and ethyl 2-(diethoxyphosphoryl)-2-methyl acetate, specified in the title compound was obtained according to a similar method as described in the examples get 46a) and (46b).

1H-NMR (CDCl3) δ: 1,15 (d, J=6.8 Hz, 3H), of 1.20 (t, J=7.2 Hz, 3H), 2,62 (DD, J=7,6, 13,2 Hz, 1H), 2,67 was 2.76 (m, 1H), 2,96 (DD, J=7,2, 13,2 Hz, 1H), 4,10 (kV, J=7.2 Hz, 2H), 5,28 (s, 1H), 6,66-6,70 (m, 2H), 6,72 to 6.75 (m, 1H), 7,14 (t, J=6,8 Hz, 1H)

Example 58b)

3-{3-[2-(2,4-Dichlorphenoxy)ethoxy]phenyl}-2-methylpropanoate acid

Using 1-(2-bromoethoxy)-2,4-dichlorobenzene and ethyl 3-(3-hydroxy-4-methoxyphenyl)-2-methylpropanoate specified in the title compound was obtained by a similar procedure as described in example 33C).

MSm/e(ESI) 391 (MNa+)

Example 59

3-{3-[2-(4-Triptoreline)ethoxy]phenyl}-2-methylpropanoate acid

Using 1-(2-bromoethoxy)-4-cryptomaterial specified in the title compound was obtained by a similar procedure as described in example 58b).

1H-NMR (CDCl3) δ: of 1.18 (d, J=6.8 Hz, 3H), of 2.64 (DD, J=8,0, to 13.6 Hz, H), 2,72-of 2.81 (m, 1H), 3,05 (DD, J=6,8, to 13.6 Hz, 1H), 4,30-4,37 (m, 4H), 6,77-6,84 (m, 3H), 6,99? 7.04 baby mortality (m, 2H), 7,19-7,24 (m, 1H), 7,53-7,58 (m, 2H)

MSm/e(ESI) 391 (MNa+)

Example 60

3-{3-[2-(4-Cyclohexylmethoxy)ethoxy]phenyl}-2-methylpropanoate acid

Using 1-(2-bromoethoxy)-4-cyclohexylphenol specified in the title compound was obtained by a similar procedure as described in example 58b).

MSm/e(ESI) 405 (MNa+)

Example 61

3-{3-[2-(4-Cyclopentyloxy)ethoxy]phenyl}-2-methylpropanoate acid

Using 1-(2-bromoethoxy)-4-cyclopentylphenol specified in the title compound was obtained by a similar procedure as described in example 58b).

MSm/e(ESI) 391 (MNa+)

Example 62

3-{3-[2-(4-tert-Butylphenoxy)ethoxy]phenyl}-2-methylpropanoate acid

Using 1-(2-bromoethoxy)-4-tert-butylbenzoyl specified in the title compound was obtained by a similar procedure as described in example 58b).

MSm/e(ESI) 379 (MNa+)

Example 63

3-{3-[2-(4-Isopropylphenoxy)ethoxy]phenyl}-2-methylpropanoate acid

Using 1-(2-bromoethoxy)-4-isopropylbenzene, specified in the title compound was obtained by a similar procedure as described in example 58b).

MSm/e(ESI) 365 (MNa+ )

Example 64

3-{3-[2-(2,4-Dichlorphenoxy)ethoxy]phenyl}-2-ethylpropane acid

Example of getting 64A)

Ethyl 3-(3-hydroxyphenyl)-2-ethylpropane

Using 3-benzyloxybenzaldehyde and ethyl 2-(diethoxyphosphoryl)-2-acetate, is listed in the title compound was obtained according to a similar method as described in the examples get 46a) and (46b).

1H-NMR (CDCl3) δ: to 0.92 (t, J=7.2 Hz, 3H), of 1.16 (t, J=7.2 Hz, 3H), 1,50-1,70 (m, 2H), 2,53-2,60 (m, 1H), 2,70 (DD, J=6,4, to 13.6 Hz, 1H), 2,87 (DD, J=8,6, to 13.6 Hz, 1H), 4,08 (kV, J=7.2 Hz, 2H), 5,26 (s, 1H), 6,64-6,69 (m, 2H), of 6.71-6.75 in (m, 1H), 7,14 (t, J=7.8 Hz, 1H)

Example 64b)

3-{3-[2-(2,4-Dichlorphenoxy)ethoxy]phenyl}-2-ethylpropane acid

Using 1-(2-bromoethoxy)-2,4-dichlorobenzene and ethyl 3-(3-hydroxy-4-methoxyphenyl)-2-ethylpropane specified in the title compound was obtained by a similar procedure as described in example 33C).

MSm/e(ESI) 405 (MNa+)

Example 65

3-{3-[2-(4-Triptoreline)ethoxy]phenyl}-2-ethylpropane acid

Using 1-(2-bromoethoxy)-4-cryptomaterial specified in the title compound was obtained by a similar procedure as described in example 64b).

1H-NMR (CDCl3) δ: of 0.95 (t, J=7.2 Hz, 3H), 1,53-1,72 (m, 2H), 2.57 m-to 2.65 (m, 1H), 2,73 (DD, J=6,8, to 13.6 Hz, 1H), 2,96 (DD, J=8,0, to 13.6 Hz, 1H), 4,29 is 4.36 (who, 4H), 6,77-PC 6.82 (m, 3H), of 6.99-7.03 is (m, 2H), 7.18 in-of 7.23 (m, 1H), 7,53-7,58 (m, 2H)

MSm/e(ESI) 405 (MNa+)

Example 66

3-{3-[2-(4-Cyclohexylmethoxy)ethoxy]phenyl}-2-ethylpropane acid

Using 1-(2-bromoethoxy)-4-cyclohexylphenol specified in the title compound was obtained by a similar procedure as described in example 64b).

MSm/e(ESI) 419 (MNa+)

Example 67

3-{3-[2-(4-Cyclopentyloxy)ethoxy]phenyl}-2-ethylpropane acid

Using 1-(2-bromoethoxy)-4-cyclopentylphenol specified in the title compound was obtained by a similar procedure as described in example 64b).

MSm/e(ESI) 405 (MNa+)

Example 68

3-{3-[2-(4-tert-Butylphenoxy)ethoxy]phenyl}-2-ethylpropane acid

Using 1-(2-bromoethoxy)-4-tert-butylbenzoyl specified in the title compound was obtained by a similar procedure as described in example 64b).

MSm/e(ESI) 393 (MNa+)

Example 69

3-{3-[2-(4-Isopropylphenoxy)ethoxy]phenyl}-2-ethylpropane acid

Using 1-(2-bromoethoxy)-4-isopropylbenzene, specified in the title compound was obtained by a similar procedure as described in example 64b).

MSm/e(ESI) 379 (MNa+)

Example 70

3-(3-[2-(Fenox is)ethoxy]phenyl)-2-ethylpropane acid

Using 1-(2-bromoethoxy)benzene, specified in the title compound was obtained by a similar procedure as described in example 64b).

MSm/e(ESI) 337 (MNa+)

Example 71

3-(3-[2-(4-Pertenece)ethoxy]phenyl)-2-ethylpropane acid

Using 1-(2-bromoethoxy)-4-torbenson specified in the title compound was obtained by a similar procedure as described in example 64b).

MSm/e(ESI) 355 (MNa+)

Example 72

3-(3-[2-(4-Benzyloxy)ethoxy]phenyl)-2-ethylpropane acid

Using 1-[(2-bromoethoxy)methyl]benzene, specified in the title compound was obtained by a similar procedure as described in example 64b).

MSm/e(ESI) 351 (MNa+)

Example 73

2-Ethyl-3-[3-(3-phenylpropoxy)phenyl]propanoic acid

Using 3-phenylpropylamine specified in the title compound was obtained by a similar procedure as described in example 64b).

MSm/e(ESI) 335 (MNa+)

Example 74

2-Ethyl-3-[3-(3-phenoxypropane)phenyl]propanoic acid

Using 1-(3-bromopropane)benzene, specified in the title compound was obtained by a similar procedure as described in example 64b).

MSm/e(ESI) 351 (MNa +)

Example 75

3-{3-[3-(2,4-Dichlorophenoxyacetic)propoxy]phenyl}-2-ethylpropane acid

Using 1-(3-bromopropane)-2,4-dichlorobenzene specified in the title compound was obtained by a similar procedure as described in example 64b).

MS m/e (ESI) 419 (MNa+)

Example 76

3-{3-[3-(4-Acetyl-3-hydroxy-2-propylenoxide)propoxy]phenyl}-2-ethylpropane acid

Using 1-[4-(3-bromopropane)-2-hydroxy-3-propylphenyl]-1-Etalon specified in the title compound was obtained by a similar procedure as described in example 64b).

MS m/e (ESI) 451 (MNa+)

Example 77

2 Isopropoxy-3-(4-methoxy-3-[3-(2-were)-2-PROPYNYL]oxyphenyl)propanoic acid

Example of getting 77A)

Ethyl 2-isopropoxy-3-[3-(2-propenyloxy)-4-methoxyphenyl]propanoate

685 mg of Ethyl 3-(3-hydroxy-4-methoxyphenyl)-2-isopropanolate was dissolved in 10 ml of N,N-dimethylformamide, was added 350 mg of propylbromide and 500 mg of potassium carbonate and the mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with ethyl acetate and washed with water and 1 N. hydrochloric acid. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent to obtain 660 mg of the specified header connection the Oia.

Example 77b)

2 Isopropoxy-3-(4-methoxy-3-[3-(2-were)-2-PROPYNYL]oxyphenyl)propanoic acid

15,5 mg of Ethyl 2-isopropoxy-3-[3-(2-propenyloxy)phenyl]propanoate, 20 mg of 2-iodotoluene, 5 mg of copper iodide, 5 mg of tetrakis(triphenylphosphine)palladium and 50 μl of triethylamine were dissolved in 0.2 ml N,N-dimethylformamide and the mixture was stirred at room temperature for two days under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate and washed with water and 1 N. hydrochloric acid. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent to obtain ethyl 2-isopropoxy-3-(3-[3-(2-were)-2-PROPYNYL]oxyphenyl)propanoate. The obtained product was dissolved in 0.4 ml of ethanol, was added 0.1 ml of 5 n sodium hydroxide solution and the mixture was stirred over night at room temperature. The reaction solution was acidified using 1 N. hydrochloric acid and was extracted with ethyl acetate. The residue was purified by high-performance liquid chromatography with reversed phase with obtaining 1,10 mg specified in the connection header.

MSm/e(ESI) 383 (MN+)

Example 78

2 Isopropoxy-3-(4-methoxy-3-[3-(3-were)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3-totalwar specified in segaloviciene received the same methodology, as described in example 77b).

MSm/e(ESI) 383 (MN+)

Example 79

2 Isopropoxy-3-(4-methoxy-3-[3-(3-were)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3-totalwar specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 383 (MN+)

Example 80

2 Isopropoxy-3-(4-methoxy-3-[3-(4-were)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 4-totalwar specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 383 (MN+)

Example 81

2 Isopropoxy-3-(4-methoxy-3-[3-(4-butylphenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 4-butylidene specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 425 (MN+)

Example 82.

2 Isopropoxy-3-(4-methoxy-3-[3-(3-triptoreline)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3-identitified specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 437 (MN+)

Example 83

2 Isopropoxy-3-(4-methoxy-3-[3-3-methoxyphenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3-methoxybenzoyl specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 399 (MN+)

Example 84

2 Isopropoxy-3-(4-methoxy-3-[3-(4-methoxyphenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 4-methoxybenzoyl specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 399 (MN+)

Example 85

2 Isopropoxy-3-(4-methoxy-3-[3-(3-forfinal)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3-periodental specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 387 (MN+)

Example 86

2 Isopropoxy-3-(4-methoxy-3-[3-(4-forfinal)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 4-periodental specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 387 (MN+)

Example 87

2 Isopropoxy-3-(4-methoxy-3-[3-(4-chlorophenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 4-chlorodibenzo specified in the header of connection produces and on the same methodology, as described in example 77b).

MSm/e(ESI) 403 (MN+)

Example 88

2 Isopropoxy-3-(4-methoxy-3-[3-(3-bromophenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3-bromobenzoyl specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 447 (MN+)

Example 89

2 Isopropoxy-3-(4-methoxy-3-[3-(3,5-bistrifluormethylbenzene)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3,5-bistrifluormethylbenzene specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 505 (MN+)

Example 90

2 Isopropoxy-3-(4-methoxy-3-[3-(2,4-dichlorophenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 2,4-dichlorodibenzo specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 437 (MN+)

Example 91

2 Isopropoxy-3-(4-methoxy-3-[3-(3,4-dichlorophenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3,4-dichlorodibenzo specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 437 (MN+)

Example 92

<> 2 Isopropoxy-3-(4-methoxy-3-[3-(3, 5dimethylphenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3,5-dimethylcarbinol specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 397 (MN+)

Example 93

2 Isopropoxy-3-(4-methoxy-3-[3-(1-naphthyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 1-iodination specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 419 (MN+)

Example 94

2 Isopropoxy-3-(4-methoxy-3-[3-(2-thienyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 2-idioten specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 375 (MN+)

Example 95

2 Isopropoxy-3-(3-[3-(4-were)-2-PROPYNYL]oxyphenyl)propanoic acid

Example of getting 95A)

Ethyl 2-isopropoxy-3-[3-(2-propenyloxy)phenyl]propanoate

Using ethyl 3-(3-hydroxyphenyl)-2-isopropoxyphenol specified in the title compound was obtained by a similar procedure as described in example 77A).

1H-NMR (CDCl3) δas 0.96 (d, J=6.4 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3), 1,25 (t, J=7.2 Hz, 3H), of 2.51 (t, J=2.4 Hz, 1H), 2,92 (DD, J=8,8, of 14.0 Hz, 1H), 2,99 (DD, J=4,8, to 13.6 Hz, 1H), 3,51 (Sept, J=6,4 Hz, 1H), of 4.05 (DD, J=4,4, 8,8 Hz, 1H), 4,14-to 4.23 (m, 2H), and 4.68 (d, J=2.4 Hz, 2H), 6,83-6,86 (m, 1H), 6,88-of 6.90 (m, 1H), 6.90 to (s, 1H), 7,21 (dt, J=0,8, 8.0 Hz, 1H)

Example 95b)

2 Isopropoxy-3-(3-[3-(4-were)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 4-totalwar specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 353 (MN+)

Example 96

2 Isopropoxy-3-(3-[3-(4-chlorophenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 4-sadharana specified in the title compound was obtained by a similar procedure as described in example 77b).

1H-NMR (CDCl3) δ: 0,99 (d, J=6.4 Hz, 3H), of 1.13 (d, J=6.0 Hz, 3H), of 2.93 (DD, J=8,4, of 14.0 Hz, 1H), 3,13 (DD, J=3,6, to 13.6 Hz, 1H), 3,52 (Sept, J=6,4 Hz, 1H), 4,14 (DD, J=3,6, and 8.4 Hz, 1H), 4,89 (s, 2H), 6.87 in-6,93 (m, 3H), 7,22-7,30 (m, 3H), of 7.36 (d, J=8,4 Hz, 2H)

MSm/e(ESI) 373 (MH+)

Example 97

2 Isopropoxy-3-(3-[3-(3-bromophenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3-bromobenzoyl specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 417 (MN+)

Example 98

2 Isopropoxy-3-(3-[3-(3-triptoreline)-2-PROPYNYL]oxyphenyl)p is upanova acid

Using 3-identified specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 407 (MN+)

Example 99

2 Isopropoxy-3-(3-[3-(3,4-dichlorophenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 3,4-dichlorodibenzo specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/e(ESI) 407 (MN+)

Example 100

2 Isopropoxy-3-(3-[3-(2,4-dichlorophenyl)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 2,4-dichlorodibenzo specified in the title compound was obtained by a similar procedure as described in example 77b).

1H-NMR (CDCl3) δ: 0,99 (d, J=6.0 Hz, 3H), 1.14 in (d, J=6.0 Hz, 3H), of 2.92 (DD, J=8,4, of 14.0 Hz, 1H), 3,13 (DD, J=3,6, of 14.0 Hz, 1H), 3,52 (Sept, J=6.0 Hz, 1H), 4,14 (DD, J=3,6, 8.0 Hz, 1H), 4,94 (s, 2H), 6.89 in (d, J=7,6 Hz, 1H), 6,91-to 6.95 (m, 2H), 7,19 (DD, J=2.0 a, and 8.4 Hz, 1H), 7,24 (DD, J=7,2, 8,8 Hz, 1H), 7,39 (d, J=8,4 Hz, 1H), 7,40 (d, J=2.0 Hz, 1H)

MSm/e(ESI) 407 (MH+)

Example 101

2 Isopropoxy-3-(3-[3-(4-triptoreline)-2-PROPYNYL]oxyphenyl)propanoic acid

Using 4-identified specified in the title compound was obtained by a similar procedure as described in example 77b).

MSm/eESI) 407 (MN +)

Example 102

2 Isopropoxy-3-(3-(3-[4-(trifluoromethyl)phenoxy]-1-PROPYNYL)phenyl)propanoic acid

Example of getting 102A)

Ethyl 2-isopropoxy-3-(3-[(trifluoromethyl)sulfonyl]oxyphenyl)propanoic

688 mg of Ethyl 3-(3-hydroxyphenyl)-2-isopropoxypropylamine was dissolved in dichloromethane and was added 600 μl of triethylamine, 15 mg of 4-dimethylaminopyridine and 1,045 g of N,N-bistrifluormethylbenzene. The solution was stirred at room temperature overnight and the solvent evaporated. The residue was purified by chromatography on a column of silica gel with getting 1,132 g specified in the connection header in the fraction of hexane-ethyl acetate (10:1).

Example of getting 102b)

Ethyl 3-[3-(3-hydroxy-1-PROPYNYL)phenyl]-2-isopropoxyphenol

550 mg of Ethyl 2-isopropoxy-3-(3-[(trifluoromethyl)sulfonyl]oxyphenyl)propanoate was dissolved in 5 ml of N,N-dimethylformamide was added 160 mg propargilovyh alcohol, 13 mg of copper iodide, 83 mg of tetrakis(triphenylphosphine)palladium and 1 ml of triethylamine. After stirring at 50°C for 4 hours in nitrogen atmosphere the reaction mixture was diluted with ethyl acetate and washed with water and 1 N. hydrochloric acid. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent. Then OST is OK purified by chromatography on a column of silica gel to obtain 184 mg specified in the connection header in the fraction of hexane-ethyl acetate (4:1 → 2:1).

1H-NMR (CDCl3) δ: of 0.94 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.4 Hz, 3H), 1,24 (t, J=7,6 Hz, 3H), 1,70 (t, J=6.0 Hz, 1H), 2,90 (DD, J=8,8, of 14.0 Hz, 1H), 2,98 (DD, J=4,8, of 14.0 Hz, 1H), 3,49 (Sept, J=6.0 Hz, 1H), was 4.02 (DD, J=to 4.8, and 8.4 Hz, 1H), 4,14-4,22 (m, 2H), 4,50 (d, J=5.6 Hz, 2H), 7,22-7,25 (m, 2H), 7,27-7,34 (m, 2H)

Example obtain 1 0 2)

Ethyl 3-[3-(3-bromo-1-PROPYNYL)phenyl]-2-isopropoxyphenol

184 mg of Ethyl 3-[3-(3-hydroxy-1-PROPYNYL)phenyl]-2-isopropoxypropylamine was dissolved in 4 ml of dimethoxyethane and added 50 μl of tribromide phosphorus. After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate and washed with water and 1 N. hydrochloric acid. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent. Then the residue was purified by chromatography on a column of silica gel to obtain 209 mg specified in the connection header in the fraction of hexane-ethyl acetate (20:1).

1H-NMR (CDCl3) δ: of 0.94 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.4 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), 2,90 (DD, J=8,4, of 14.0 Hz, 1H), 2,98 (DD, J=4,8, to 13.6 Hz, 1H), 3,47 (Sept, J=6.0 Hz, 1H), was 4.02 (DD, J=4,8, 8,8 Hz, 1H), 4, 14-4,22 (m, 2H), 4.16 the (s, 2H), 7.23 percent-of 7.25 (m, 2H), 7,30-7,35 (m, 2H)

Example 102d)

2 Isopropoxy-3-(3-(3-[4-(trifluoromethyl)phenoxy]-1-PROPYNYL)phenyl)propanoic acid

10 mg of Ethyl 3-[3-(3-bromo-1-PROPYNYL)phenyl]-2-isopropoxypropylamine was dissolved in 0, ml N,N-dimethylformamide was added 10 mg of 4-hydroxybenzonitrile and 20 mg of potassium carbonate. After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate and washed with water. After removal of the solvent from the organic layer, the residue was dissolved in 0.4 ml of ethanol, was added 0.1 ml of 5 n sodium hydroxide solution and then the mixture was stirred at room temperature overnight. The reaction solution was acidified using 1 N. hydrochloric acid and was extracted with ethyl acetate. Concentrated solvent and the residue was purified by high-performance liquid chromatography with reversed phase with obtaining 3.55 mg specified in the connection header.

MSm/e(ESI) 395 (MN+)

Example 103

2 Isopropoxy-3-(3-(3-[4-tert-butylphenoxy]-1-PROPYNYL)phenyl)propanoic acid

Using 4-tert-butylphenol, specified in the title compound was obtained by a similar procedure as described in example 102d).

MS m/e (ESI) 395 (MH+)

Example 104

2 Isopropoxy-3-(3-(3-[4-(phenyl)phenoxy]-1-PROPYNYL)phenyl)propanoic acid

Using 4-hydroxybiphenyl specified in the title compound was obtained by a similar procedure as described in example 102d).

MS m/e (ESI) 415 (MN+)

Example 105

2 Isopropoxy-{3-[3-(2,4-dichlorophenoxy)-1-PROPYNYL]phenyl}propanoic acid

Using 2,4-dichlorphenol specified in the title compound was obtained by a similar procedure as described in example 102d).

1H-NMR (CDCl3) δ: 1,00 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.4 Hz, 3H), 2.91 in (DD, J=8,0, to 13.6 Hz, 1H), 3,09 (DD, J=2,8, to 13.6 Hz, 1H), 3,52 (Sept, J=6.0 Hz, 1H), 4,10 (DD, J=3,6, 8.0 Hz, 1H), equal to 4.97 (s, 2H), 7,11 (d, J=8,8 Hz, 1H), 7,22 (DD, J=2,8, 8,8 Hz, 1H), 7.23 percent (t, J=1.2 Hz, 1H), 7,25 (t, J=7,6 Hz, 1H), 7,29-to 7.32 (m, 2H), 7,40 (d, J=2.4 Hz, 1H)

MS m/e (ESI) 407 (MH+)

Example 106

2 Isopropoxy-3-(3-(3-[4-bromo-2-fervency]-1-PROPYNYL)phenyl)propanoic acid

Using 4-bromo-2-terfenol specified in the title compound was obtained by a similar procedure as described in example 102d).

MSm/e(ESI) 435 (MN+)

Example 107

2 Isopropoxy-3-(3-[2-(4-were)-1-ethinyl]phenyl)propanoic acid

Example of getting 107a)

Ethyl 3-[3-(2-(trimethylsilyl)-1-PROPYNYL)phenyl]-2-isopropoxyphenol

932 mg of Ethyl 2-isopropoxy-3-(3-[(trifluoromethyl)sulfonyl]oxyphenyl)propanoate was dissolved in 8 ml of N,N-dimethylformamide was added 480 mg of trimethylsilylacetamide, 40 mg of copper iodide, 280 mg of tetrakis(triphenylphosphine)palladium and 1 ml of triethylamine. After stirring at 50°C for 8 hours in nitrogen atmosphere the reaction mixture was diluted with ethyl acetate and washed with water and 1 N. hydrochloric KIS the Auteuil. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent. Then the residue was purified by chromatography on a column of silica gel with getting 442 mg specified in the connection header in the fraction of hexane-ethyl acetate (30:1).

1H-NMR (CDCl3) δ: 0,24 (s, N), were 0.94 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), 2,89 (DD, J=9,2, of 14.0 Hz, 1H), 2,97 (DD, J=4,8, to 13.6 Hz, 1H), 3,49 (Sept, J=6.0 Hz, 1H), 4,01 (DD, J=6,4, and 12.4 Hz, 1H), 4,14-4,22 (m, 2H), 7,21 (DD, J=1,4, 4.0 Hz, 2H), 7,31-7,35 (m, 1H), 7,37 (s, 1H)

Example of getting 107b)

Ethyl 3-[3-(ethinyl)phenyl]-2-isopropoxyphenol

442 mg of Ethyl 3-[3-(2-(trimethylsilyl)-1-PROPYNYL)phenyl]-2-isopropoxypropylamine was dissolved in 10 ml of tetrahydrofuran was added 0.5 ml of acetic acid and 2 ml of tetrabutylammonium (1M solution in tetrahydrofuran). The solution was stirred at 50°C for 3 hours, the reaction mixture was diluted with ethyl acetate and washed with water and saturated sodium bicarbonate solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent. Then the residue was purified by chromatography on a column of silica gel with getting 233 mg specified in the connection header in the fraction of hexane-ethyl acetate (30:1).

1H-NMR (CDCl3) δ: of 0.94 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), 2.91 in (DD, J=8,8, to 13.6 Hz, 1H), 2,99 (DD, J=4,8, to 13.6 Hz, 1H), 3,05 (s, 1H), 3,50(Sept, J=6,4 Hz, 1H), was 4.02 (DD, J=4,8, 8,8 Hz, 1H), 4,14-4,22 (m, 2H), 7,22-7,26 (m, 2H), 7,35-7,37 (m, 1H), 7,40 (s, 1H)

Example C)

2 Isopropoxy-3-(3-[2-(4-were)-1-ethinyl]phenyl)propanoic acid

10 mg of Ethyl 3-[3-(2-(trimethylsilyl)-1-PROPYNYL)phenyl]-2-isopropoxypropylamine, 20 mg of 4-iodotoluene, 5 mg of copper iodide, 5 mg of tetrakis(triphenylphosphine)palladium and 50 μl of triethylamine were dissolved in 0.2 ml N,N-dimethylformamide and the mixture was stirred at 50°C overnight under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate and washed with water and 1 N. hydrochloric acid. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent to obtain ethyl 2-isopropoxy-3-(3-[2-(4-were)-1-ethinyl]phenyl)propanoate. The obtained product was dissolved in 0.4 ml of ethanol, was added 0.1 ml of 5 n sodium hydroxide solution and the mixture was stirred over night at room temperature. The reaction solution was acidified using 1 N. hydrochloric acid and was extracted with ethyl acetate. The residue was purified by high-performance liquid chromatography with reversed phase with obtaining 1,90 mg specified in the connection header.

MSm/e(ESI) 323 (MN+)

Example 108

2 Isopropoxy-3-(3-[2-(4-chlorophenyl)-1-ethinyl]phenyl)propanoic acid

Using 4-chlorid Sol, received 3,70 mg specified in the title compound by a similar procedure as described in example C).

MSm/e(ESI) 343 (MN+)

Example 109

2 Isopropoxy-3-(3-[2-(3-bromophenyl)-1-ethinyl]phenyl)propanoic acid

Using 3-bromobenzoyl specified in the title compound was obtained by a similar procedure as described in example C).

MSm/e(ESI) 387 (MN+)

Example 110

2 Isopropoxy-3-(3-[2-(3-triptoreline)-1-ethinyl]phenyl)propanoic acid

Using 3-identified specified in the title compound was obtained by a similar procedure as described in example C).

MSm/e(ESI) 377 (MN+)

Example 111

2 Isopropoxy-3-(3-[2-(3,4-dichlorophenyl)-1-ethinyl]phenyl)propanoic acid

Using 3,4-dichlorodibenzo specified in the title compound was obtained by a similar procedure as described in example C).

MSm/e(ESI) 377 (MN+)

Example 112

2 Isopropoxy-3-(3-[2-(2,4-dichlorophenyl)-1-ethinyl]phenyl)propanoic acid

Using 2,4-dichlorodibenzo specified in the title compound was obtained by a similar procedure as described in example C).

MSm/e(ESI) 377 (MN+)

Example 113

3-(3-(2-[4-tert-Butyl-1-hydroxycyclohexyl]-1-ethinyl)phenyl)-2-isopropoxypropylamine acid

Example of getting a)

3-[3-(1-Ethinyl)phenyl]-2-isopropoxypropylamine acid

156 mg of Ethyl 3-[3-(PROPYNYL)phenyl]-2-isopropoxypropylamine was dissolved in 2 ml of ethanol was added 0.5 ml of 5 n sodium hydroxide solution. The mixture was stirred at room temperature for 1 hour, after which the solution was neutralized 1 N. hydrochloric acid and was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent to obtain 138 mg specified in the connection header.

Example 113b)

TRANS-3-(3-(2-[4-tert-Butyl-1-hydroxycyclohexyl]-1-ethinyl)phenyl)-2-isopropoxypropylamine acid

12 mg of 3-[3-(1-Ethinyl)phenyl]-2-isopropoxyphenol acid was dissolved in 1 ml of tetrahydrofuran and added 130 μl of 1M bestremembered lithium and 40 mg of 4-tert-butylcyclohexanone. The solution was stirred at room temperature for 1 hour, neutralized 1 N. hydrochloric acid and was extracted with ethyl acetate. The organic layer was concentrated and the residue was purified by high-performance liquid chromatography with reversed phase with obtaining 4,70 mg specified in the header of the value.

MSm/e(ESI) 409 (MNa+)

Example 114

3-(3-[2-(8-Hydroxy-1,4-dioxaspiro[4,5]Dec-8-yl)-1-ethinyl]phenyl)-2-isopropoxypropylamine acid

Using 1,4-dioxaspiro[4,5]decane-8-he that is listed in the title compound was obtained by a similar procedure as described in example 113b).

MSm/e(ESI) 411 (MNa+)

Example 115

3-(3-(3-Hydroxy-3-[4-(trifluoromethyl)phenyl]-1-butenyl)phenyl)-2-isopropoxypropylamine acid

Using 4-triptoreline specified in the title compound was obtained by a similar procedure as described in example 113b).

MSm/e(ESI) 443 (MNa+)

Example 116

3-(3-[3-(2,4-Dichlorophenyl)-3-hydroxy-1-butenyl]phenyl)-2-isopropoxypropylamine acid

Using 2,4-dichloroacetophenone specified in the title compound was obtained by a similar procedure as described in example 113b).

MSm/e(ESI) 443 (MNa+)

Example 117

3-(3-[3-Biphenyl-3-hydroxy-1-butenyl]phenyl)-2-isopropoxypropylamine acid

Using 4-phenylacetophenone specified in the title compound was obtained by a similar procedure as described in example 113b).

MSm/e(ESI) 451 (MNa+)

Example 118

3-(3-[3-(4-Cyclohexylphenol)-3-hydro is C-1-butenyl]phenyl)-2-isopropoxypropylamine acid

Using 4-cyclohexylacetophenone specified in the title compound was obtained by a similar procedure as described in example 113b).

MSm/e(ESI) 457 (MNa+)

Example 119

3-(3-(3-Hydroxy-3-[4-(trifluoromethyl)phenyl]-1-PROPYNYL)phenyl)-2-isopropoxypropylamine acid

Using 4-triftormetilfosfinov,1,20 mg specified in the title compounds were obtained by a similar procedure as described in example 113b).

MSm/e(ESI) 429 (MNa+)

Example 120

3-(3-(3-Hydroxy-3-[2,4-dichlorophenyl]-1-PROPYNYL)phenyl)-2-isopropoxypropylamine acid

Using 2,4-dichlorobenzaldehyde specified in the title compound was obtained by a similar procedure as described in example 113b).

MSm/e(ESI) 429 (MNa+)

Example 121

3-(3-(3-[4-tert-Butylphenyl]-3-hydroxy-1-PROPYNYL)phenyl)-2-isopropoxypropylamine acid

Using 4-tert-butylbenzaldehyde specified in the title compound was obtained by a similar procedure as described in example 113b).

MSm/e(ESI) 417 (MNa+)

Example 122

3-(3-[3-(4-Chlorophenyl)-1-hydroxy-1-methyl-2-PROPYNYL]phenyl)-2-isopropoxypropylamine acid

Example of getting a)

Ethyl 3-(3-acetylphenyl)-2-isopropoxypropylamine

2,037 g of Ethyl 2-isopropoxy-3-(3-[(trifluoromethyl)sulfonyl]oxyphenyl)propanoate, 2.5 g of ethyl ester [1-(1,1,1-tributylstannyl)vinyl], 500 mg of lithium chloride and 186 mg dichlorobis(triphenylphosphine)palladium were dissolved in 15 ml of dioxane and the mixture was stirred at 90°C overnight under nitrogen atmosphere. The solution was cooled in an ice bath, was added 1 N. hydrochloric acid and was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent. The residue was purified by chromatography on a column of silica gel with getting 1,041 g specified in the connection header in the fraction of hexane-ethyl acetate (6:1).

1H-NMR (CDCl3) δ: of 0.91 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,25 (t, J=7.2 Hz, 3H), at 2.59 (s, 3H), equal to 2.94 (DD, J=8,8, of 14.0 Hz, 1H), is 3.08 (DD, J=4,8, of 14.0 Hz, 1H), 3,50 (Sept, J=6.0 Hz, 1H), of 4.05 (DD, J=4,8, 8,8 Hz, 1H), 4,15-4,22 (m, 2H), 7,38 (t, J=7,6 Hz, 1H), 7,47 (dt, J=1,6 and 7.6 Hz, 1H), 7,82 (dt, J=1,6 and 7.6 Hz, 1H), 7,87 (DD, J=1,2, and 1.6 Hz, 1H)

Example of getting 122b)

Ethyl 3-(3-[1-hydroxy-1-methyl-3-(1,1,1-trimethylsilyl)-2-PROPYNYL]phenyl)-2-isopropoxyphenol

243 mg of Trimethylsilylacetamide was dissolved in 5 ml of tetrahydrofuran and added 1,43 ml utility (1,56M solution in hexane) and 283 μl of the complex of boron TRIFLUORIDE-ether in a nitrogen atmosphere at -78°C, after which the mixture was stirred for 30 minutes. D is balali to the mixture a solution of 345 mg of ethyl 3-(3-acetylphenyl)-2-isopropoxypropylamine in tetrahydrofuran (2 ml) and continued stirring for another 30 minutes. Was added a saturated aqueous solution of ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent. The residue was purified by chromatography on a column of silica gel to obtain 256 mg specified in the connection header in the fraction of hexane-ethyl acetate (6:1).

1H-NMR (CDCl3) δ: of 0.21 (s, 9H), 0,94, of 0.95 (each d, J=6.4 Hz, 3H), 1,15, 1,16 (each d, J=6.0 Hz, 3H), 1,24, 1,25 (each t, J=7.2 Hz, 3H), of 1.74 (s, 3H), 2,35 (s, 1H), 2.93 which was 3.05 (m, 2H), 3,47-of 3.54 (m, 1H), 4,06 (DD, J=4,8, 8,4 Hz, 1H), 4,12-4,19 (m, 2H), 7,18 (d, J=8.0 Hz, 1H), 7,26-7,29 (m, 1H), 7,46-of 7.55 (m, 2H)

Example of getting s)

Ethyl 3-(3-[1-hydroxy-1-methyl-2-PROPYNYL]phenyl)-2-isopropoxyphenol

256 mg of Ethyl 3-(3-[1-hydroxy-1-methyl-3-(1,1,1-trimethylsilyl)-2-PROPYNYL]phenyl)-2-isopropoxypropylamine was dissolved in 4 ml of tetrahydrofuran were added under ice cooling, 0.1 ml of acetic acid and 1 ml of tetrabutylammonium (1M solution in tetrahydrofuran) and the mixture was stirred over night. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate and water. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent. The residue was purified by chromatography on a column of silica gel to obtain 185 mg specified in the connection header in the fraction of g is Xan-ethyl acetate (4:1).

1H-NMR (CDCl3) δ: of 0.94 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,25 (t, J=7.2 Hz, 3H), of 1.78 (s, 3H), 2,43 (s, 1H), 2,67 (s, 1H), 2,98 (DD, J=2.0 a, 8,8 Hz, 1H), 3,03 (DD, J=4,8, to 13.6 Hz, 1H), 3,50 (Sept, J=6.0 Hz, 1H), 4,06 (DDD, J=2,8, 4,8, 8,8 Hz, 1H), 4,14-4,22 (m, 2H), 7,20 (DD, J=1,2, 7,6 Hz, 1H), 7,26 (s, 1H), 7,29 (t, J=7,6 Hz, 1H), 7,51-EUR 7.57 (m, 1H)

Example 122d)

3-(3-[3-(4-Chlorophenyl)-1-hydroxy-1-methyl-2-PROPYNYL]phenyl)-2-isopropoxypropylamine acid

12 mg of Ethyl 3-(3-[1-hydroxy-1-methyl-2-PROPYNYL]phenyl)-2-isopropoxypropylamine, 20 mg of 4-sadharana, 5 mg of copper iodide, 5 mg of tetrakis(triphenylphosphine)palladium and 50 μl of triethylamine were dissolved in 0.2 ml N,N-dimethylformamide and the mixture was stirred at room temperature for 2 days under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate and washed with water and 1 N. hydrochloric acid. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent to obtain ethyl 3-(3-[3-(4-chlorophenyl)-1-hydroxy-1-methyl-2-PROPYNYL]phenyl)-2-isopropoxypropylamine. The obtained product was dissolved in 0.4 ml of ethanol, was added 0.1 ml of 5 n sodium hydroxide solution and the mixture was stirred over night at room temperature. The reaction solution was acidified using 1 N. hydrochloric acid and was extracted with ethyl acetate. The residue was purified by high-performance liquid chromatography with reversed phase with the floor is rising 4,07 mg specified in the connection header.

MSm/e(ESI) 409 (MNa+)

Example 123

3-(3-[3-(4-Triptoreline)-1-hydroxy-1-methyl-2-PROPYNYL]phenyl)-2-isopropoxypropylamine acid

Using 4-identified specified in the title compound was obtained by a similar procedure as described in example 122d).

1H-NMR (CDCl3) δ: of 1.06 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), of 1.87 (s, 3H), and 2.27 (s, 1H), 3,00 (DDD, J=2,4, 8,0, to 13.6 Hz, 1H), 3,17 (DD, J=3,6, of 14.0 Hz, 1H), 3,52-3,59 (m, 1H), 4,14-4,18 (m, 1H), 7,21 (d, J=7,6 Hz, 1H), 7,33 (DD, J=7,6, 8,8 Hz, 1H), EUR 7.57-to 7.61 (m, 6H)

MSm/e(ESI) 443 (MNa+)

Example 124

3-(3-[3-(3-Triptoreline)-1-hydroxy-1-methyl-2-PROPYNYL]phenyl)-2-isopropoxypropylamine acid

Using 3-identified specified in the title compound was obtained by a similar procedure as described in example 122d).

MSm/e(ESI) 443 (MNa+)

Example 125

3-(3-[3-(2,4-Dichlorophenyl)-1-hydroxy-1-methyl-2-PROPYNYL]phenyl)-2-isopropoxypropylamine acid

Using 2,4-dichlorodibenzo specified in the title compound was obtained by a similar procedure as described in example 122d).

MSm/e(ESI) 443 (MNa+)

Example 126

3-(3-[3-(3,4-Dichlorophenyl)-1-hydroxy-1-methyl-2-PROPYNYL]phenyl)-2-isopropoxypropylamine acid

<> Using 3,4-dichlorodibenzo specified in the title compound was obtained by a similar procedure as described in example 122d).

1H-NMR (CDCl3) δ: 1,01, 1,02 (each d, J=6,4 Hz and 6.0 Hz, 3H)and 1.15 (d, J=6.4 Hz, 3H), of 1.85 (s, 3H), 2.05 is (s, 1H), 3,01 (DD, J=8,0, of 14.0 Hz, 1H), 3,18 (DD, J=4,0, 13,2 Hz, 1H), of 3.56 (Sept, J=6.0 Hz, 1H), 4,17 (DD, J=3,6, 7,6 Hz, 1H), 7,21 (d, J=8.0 Hz, 1H), 7,28-7,35 (m, 2H), 7,40 (d, J=8,8 Hz, 1H), 7,54-to 7.59 (m, 3H)

MSm/e(ESI) 443 (MNa+)

Example 127

2 Isopropoxy-3-4-methoxy-3-[([2-(trifluoromethyl)benzyl]oxyimino)methyl]phenyl)propanoic acid

Example of getting a)

[(5-Bromo-2-methoxybenzyl)oxy](tert-butyl)dimethylsilane

14 g of 2-Methoxybenzamido alcohol was dissolved in 200 ml of N,N-dimethylformamide was added 19.5 g of tert-butylcholinesterase and 13.6 g of imidazole. After stirring at room temperature overnight the solution was diluted with ethyl acetate and washed successively 1 N. hydrochloric acid and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. Then the obtained crude product was dissolved in 200 ml of acetonitrile was added 21 g of N-bromosuccinimide while cooling with ice. After stirring at room temperature for 5 hours and the solvent evaporated. The residue was dissolved in ethyl acetate and washed successively the ode and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 26 g specified in the connection header in the fraction of hexane-diethyl ether (2:1).

1H-NMR (CDCl3) δ: of 0.12 (s, 6H), is 0.96 (s, 9H), of 3.80 (s, 3H), 4,70 (s, 2H), of 6.68 (d, J=8,4 Hz, 1H), 7,31 (DD, J=1,6, and 8.4 Hz, 1H), 7,56 (d, J=1.6 Hz, 1H)

Example of getting 127b)

3-({[1-tert-Butyl-1,1-dimethylallyl]oxy}methyl)-4-methoxybenzaldehyde

12 g of [(5-Bromo-2-methoxybenzyl)oxy](tert-butyl)dimethylsilane was dissolved in 150 ml of tetrahydrofuran and the mixture was cooled to -78°C in nitrogen atmosphere. To the mixture was added 28 ml utility (1,52M solution in hexane) and stirred the mixture for 30 minutes, after which was added a solution of 8.3 g of 4-formylmorpholine in 10 ml of tetrahydrofuran. After stirring at -78°C for 1 hour was added to a mixture of 1 N. hydrochloric acid. The mixture was extracted with ethyl acetate and the organic layer was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 5.8 g specified in the connection header in the fraction of hexane-ethyl acetate (5:1).

1H-NMR (CDCl3) δ: of 0.12 (s, 6H), of 0.93 (s, 9H), 3,91 (s, 3H), amounts to 4.76 (s, 2H), 6,94 (d, J=8,4 Hz, 1H), 7,80 (DD, J=1,6, and 8.4 Hz, 1), 8,01 (d, J=1.6 Hz, 1H), 9,90 (s, 1H)

Example of getting 127s)

Ethyl 3-[3-({[1-tert-butyl-1,1-dimethylallyl]oxy}methyl)-4-methoxyphenyl]-2-isopropoxyphenol

Using 3-({[1-tert-butyl-1,1-dimethylallyl]oxy}methyl)-4-methoxybenzaldehyde and diethyl 2-isopropoxyethanol specified in the title compound was obtained as described in examples get 46a) and (46b).

Example of getting 127d)

Ethyl 3-[3-(hydroxymethyl)-4-methoxyphenyl]-2-isopropoxyphenol

3.4 g of Ethyl 3-[3-({[1-tert-butyl-1,1-dimethylallyl]oxy}methyl)-4-methoxyphenyl]-2-isopropoxypropylamine was dissolved in 40 ml of tetrahydrofuran was added 9.4 ml tetrabutylammonium (1M solution in tetrahydrofuran). After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate and the organic layer was washed with water and saturated salt solution and dried over anhydrous magnesium sulfate. After evaporation of the solvent the residue was purified by chromatography on a column of silica gel to obtain 1.5 g specified in the connection header in the fraction of hexane-ethyl acetate (2:1).

1H-NMR (CDCl3) δ: 0,97 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), 2,88 (DD, J=8,4, of 14.0 Hz, 1H), 2,95 (DD, J=5,2, of 14.0 Hz, 1H), 3,50 (Sept, J=6.0 Hz, 1H), 3,85 (s, 3H), of 4.00 (DD, J=5,2, 8,4 Hz, 1H), 4,11-is 4.21 (m, 2H)and 4.65 (d, J=6,4 Hz, 2H), 6,9 (d, J=8,8 Hz, 1H), 7,14-to 7.15 (m, 2H)

Example of getting a)

Ethyl 3-[3-(formyl)-4-methoxyphenyl]-2-isopropoxyphenol

826 mg of Ethyl 3-[3-(hydroxymethyl)-4-methoxyphenyl]-2-isopropoxypropylamine was dissolved in 20 ml of dichloromethane, was added 390 mg of N-oxide N-methylmorpholine, 1.4 g of molecular sieves 4A and 49 mg of tetrapropylammonium and the mixture was stirred at room temperature overnight. The reaction mixture was filtered through Celite, the filtrate was concentrated and the residue was purified by chromatography on a column of silica gel with getting 782 mg specified in the connection header in the fraction of hexane-ethyl acetate (5:1 → 2:1).

1H-NMR (CDCl3) δ: of 0.95 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,25 (t, J=7.2 Hz, 3H), 2.91 in (DD, J=8,8, of 14.0 Hz, 1H), 2,99 (DD, J=4,8, of 14.0 Hz, 1H), 3,51 (Sept, J=6.0 Hz, 1H), 3,91 (s, 3H), was 4.02 (DD, J=a 4.4, and 8.4 Hz, 1H), 4,11-4,20 (m, 2H), 6,92 (DD, J=2,4, and 8.4 Hz, 1H), 7,46 (DD, J=2,4, and 8.4 Hz, 1H), 7,72 (d, J=2.4 Hz, 1H), 10,45 (s, 1H)

Example 127f)

2 Isopropoxy-3-4-methoxy-3-[([2-(trifluoromethyl)benzyl]oxyimino)methyl]phenyl)propanoic acid

138 mg of Ethyl 3-[3-(formyl)-4-methoxyphenyl]-2-isopropoxypropylamine was dissolved in 2 ml ethanol and 0.5 ml of water, was added 40 mg of hydroxylamine hydrochloride and 70 ml of sodium acetate and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was diluted with ethyl acetate and amywali water and 1 N. hydrochloric acid. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent to obtain 178 mg of ethyl 3-[3-(gidroksilaminami)-4-methoxyphenyl]-2-isopropanolate. Dissolve 12 mg of the obtained compound in 0.2 ml of tetrahydrofuran, was added 20 mg of 2-triftormetilfosfinov and 10 mg of sodium hydride and the mixture was stirred at room temperature overnight. To the reaction mixture were added 0.4 ml of ethanol and 0.1 ml of 5 n sodium hydroxide solution and the mixture was stirred at room temperature for 4 hours. Then the reaction mixture was neutralized 1 N. hydrochloric acid, was extracted with ethyl acetate and concentrated the solvent. The residue was purified by high-performance liquid chromatography with reversed phase to obtain 2.1 mg specified in the connection header.

MSm/e(ESI) 440 (MN+)

Example 128

2 Isopropoxy-3-4-methoxy-3-[([3-(trifluoromethyl)benzyl]oxyimino)methyl]phenyl)propanoic acid

Using 3-triftormetilfosfinov specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 440 (MN+)

Example 129

2 Isopropoxy-3-4-methoxy-3-[([4-(trifluoromethyl)benzyl]oxyimino)methyl]phenyl)propanoic acid

Using 4-triftormetilfosfinov specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 440 (MN+)

Example 130

2 Isopropoxy-3-4-methoxy-3-[([4-bromo-2-terbisil]oxyimino)methyl]phenyl)propanoic acid

Using 4-bromo-2-florantyrone specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 468 (MN+)

Example 131

2 Isopropoxy-3-4-methoxy-3-[([2,6-dichlorobenzyl]oxyimino)methyl]phenyl)propanoic acid

Using 2,6-dichlorobenzamide specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 440 (MN+)

Example 132

2 Isopropoxy-3-4-methoxy-3-[([3,4-dichlorobenzyl]oxyimino)methyl]phenyl)propanoic acid

Using 3,4-dichlorobenzamide specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 440 (MN+)

Example 133

2 Isopropoxy-3-4-methoxy-3-[([4-active compounds]oxyimino)methyl]phenyl)propanoic acid

Using 4-ethylbenzylamine specified in the header with the unity was obtained by the same methodology, as described in example 127f).

MSm/e(ESI) 400 (MN+)

Example 134

2 Isopropoxy-3-4-methoxy-3-[([2-naphthyl]oxyimino)methyl]phenyl)propanoic acid

Using 2-bromethalin specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 422 (MN+)

Example 135

2 Isopropoxy-3-4-methoxy-3-[([2-phenylbenzyl]oxyimino)methyl]phenyl)propanoic acid

Using 2-phenylbenzoate specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 448 (MN+)

Example 136

2 Isopropoxy-3-4-methoxy-3-[([4-tert-butylbenzyl]oxyimino)methyl]phenyl)propanoic acid

Using 4-tert-butylbenzylamine specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 428 (MN+)

Example 137

2 Isopropoxy-3-4-methoxy-3-[([4-phenylbenzyl]oxyimino)methyl]phenyl)propanoic acid

Using 4-phenylbenzophenone specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 448 (MN+)

Example 138

2-is isopropoxy-3-4-methoxy-3-[([2,4-dichlorobenzyl]oxyimino)methyl]phenyl)propanoic acid

Using 2,4-DICHLOROSILANE specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 440 (MN+)

Example 139

2 Isopropoxy-3-4-methoxy-3-[([4-benzyloxybenzyl]oxyimino)methyl]phenyl)propanoic acid

Using 4-benzyloxybenzophenone specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 478 (MN+)

Example 140

2 Isopropoxy-3-[3-([2-(trifluoromethyl)benzyl]acetanilide)phenyl]propanoic acid

Using ethyl 3-(3-acetylphenyl)-2-isopropanol and 2-triftormetilfosfinov specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 424 (MN+)

Example 141

2 Isopropoxy-3-[3-([3-(trifluoromethyl)benzyl]acetanilide)phenyl]propanoic acid

Using 3-triftormetilfosfinov specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 424 (MN+)

Example 142

2 Isopropoxy-3-[3-([4-(trifluoromethyl)benzyl]acetanilide)phenyl]propanoic acid

Using 4-triftormetilfosfinov specified in the title compound was obtained by a similar procedure as described in example 127f).

1H-NMR (CDCl3) δ: 0,98 (d, J=6.0 Hz, 3H), 1.14 in (d, J=6.4 Hz, 3H), of 2.28 (s, 3H), 2,96 (DD, J=8,0, of 14.0 Hz, 1H), 3.15 in (DD, J=3,6, of 14.0 Hz, 1H), 3,52 (Sept, J=6,4 Hz, 1H), 4,13 (DD, J=4.0 a, and 8.4 Hz, 1H), from 5.29 (s, 2H), 7.23 percent-7,27 (m, 2H), 7,30 (t, J=7.2 Hz, 1H), 7,51 (d, J=7,6 Hz, 1H), 7,53 (d, J=6.0 Hz, 1H), 7.62mm (d, J=8.0 Hz, 1H)

MSm/e(ESI) 424 (MH+)

Example 143

2 Isopropoxy-3-[3-([3,4-(dichloro)benzyl]acetanilide)phenyl]propanoic acid

Using 3,4-dichlorobenzamide specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 424 (MN+)

Example 144

2 Isopropoxy-3-[3-([2,6-(dichloro)benzyl]acetanilide)phenyl]propanoic acid

Using 2,6-dichlorobenzamide specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 424 (MN+)

Example 145

2 Isopropoxy-3-[3-([2,4-(dichloro)benzyl]acetanilide)phenyl]propanoic acid

Using 2,4-DICHLOROSILANE specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 424 (MN+)

the example 146

2 Isopropoxy-3-[3-([4-bromo-2-terbisil]acetanilide)phenyl]propanoic acid

Using 4-bromo-2-florantyrone specified in the title compound was obtained by a similar procedure as described in example 127f).

MSm/e(ESI) 452 (MN+)

Example 147

3-[3-({[(Benzyloxy)carbonyl]amino}methyl)-4-methoxyphenyl]-2-isopropoxypropylamine acid

Example of getting a)

tert-Butyl N-(2-methoxybenzyl)carbamate

13,0 mg of 2-Methoxybenzylamine was dissolved in 80 ml of tetrahydrofuran and the solution was added 16 g of tert-BUTYLCARBAMATE in tetrahydrofuran (20 ml). After stirring at room temperature for 1 hour and the solvent evaporated. The residue was dissolved in ethyl acetate and sequentially washed with 1 N. hydrochloric acid and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated to obtain 19,0 g specified in the connection header.

1H-NMR (CDCl3) δ: 1,45 (s, 9H), of 3.84 (s, 3H), 4,27-to 4.33 (m, 2H), 5,01 (width, 1H), at 6.84 (d, J=8,8 Hz, 1H), 6,94 (t, J=8,8 Hz, 1H), 7.23 percent-7,29 (m, 2H)

Example of getting 147b)

tert-Butyl N-(5-bromo-2-methoxybenzyl)carbamate

6,04 g of tert-Butyl N-(2-methoxybenzyl)carbamate was dissolved in 50 ml acetone the sludge was added 4.6 g of N-bromosuccinimide. After stirring at room temperature for 3 hours the solvent evaporated. The residue was dissolved in ethyl acetate and washed successively with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue is washed with a mixed solution of methyl tert-butyl ether and hexane to obtain 6,97 g specified in the connection header.

1H-NMR (CDCl3) δ: 1,45 (s, N), 3,62 (s, 3H), 4.26 deaths (d, J=6,4 Hz, 2H), equal to 4.97 (width, 1H), 6,72 (d, J=8,8 Hz, 1H), 7,34 (DD, J=2,8, 11.2 Hz), 7,35 (s, 1H)

Example of getting s)

tert-Butyl N-(5-formyl-2-methoxybenzyl)carbamate

1,015 g of tert-Butyl N-(5-bromo-2-methoxybenzyl)carbamate, 45 mg dichlorobis(triphenylphosphine)palladium (II), 330 mg of sodium formiate and 17 mg of triphenylphosphine was dissolved in anhydrous N,N-dimethylformamide and the mixture was stirred at 110°C for 2 hours in an atmosphere of carbon monoxide. The reaction mixture was diluted with ethyl acetate and washed with water and saturated aqueous sodium bicarbonate. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 640 mg specified in the connection header in the fraction of hexane-ethyl acetate (3:1).

1H-NMR (CDCl3) δ: 1,45 (s, 9H), of 3.94 (s, 3H), 4,36 (d, J=,0 Hz, 2H), 5,00 (width, 1H), 6,98 (d, J=8,4 Hz, 1H), 7,80-7,83 (m, 2H), 9,88 (s, 1H)

Example of getting 147d)

Ethyl 3-(3-[tert-butoxycarbonylamino]methyl-4-methoxyphenyl)-3-hydroxy-2-isopropoxyphenol

In a nitrogen atmosphere to 80 ml hexamethyldisilazane sodium (1M solution in tetrahydrofuran) was diluted in 40 ml of tetrahydrofuran and the mixture was cooled to -78°C, after which the solution was added 11,68 g of ethyl 2-isopropoxyaniline in tetrahydrofuran (10 ml). After stirring for 30 minutes was added a solution containing of 10.73 g of tert-butyl N-(5-formyl-2-methoxybenzyl)carbamate in tetrahydrofuran (10 ml). After stirring for a further 1 hour was added 100 ml of a saturated aqueous solution of ammonium chloride. The reaction solution was poured into 400 ml of water and 500 ml of ethyl acetate to separate and the organic layer was dried over anhydrous magnesium sulfate. The solvent evaporated and the residue was purified by chromatography on a column of silica gel (eluting solvent: hexane-ethyl acetate) to give 12.8 g specified in the title compound (a mixture of Erythro forms, Treo) as a colourless oil.

1H-NMR (CDCl3) δ: 0,99 (d, J=6,1 Hz, 3H)and 1.15 (d, J=6,1 Hz, 3H), 1,19 (t, J=7,6 Hz, 3H), of 1.44 (s, 9H), 2.91 in (d, J=5,2 Hz, 1H), 3.43 points (Sept, J=6,1 Hz, 1H), 3,83 (s, 3H), a 4.03 (d, J=6.3 Hz, 1H), 4,12 (kV, J=7,6 Hz, 2H), 4,29 (d, J=6.6 Hz, 2H), a 4.86 (DD, J=5,2, 6.3 Hz, 1H), 4,99 (t, J=6,6 Hz, 1H), for 6.81 (d, J=8.7 Hz, 1H), 7.23 percent-7,29 (m, 2H)

1The NMR (CDCl 3) δ: 1,11 (t, J=6.9 Hz, 3H), of 1.17 (d, J=6,1 Hz, 3H), 1,19 (d, J=6,1 Hz, 3H), of 1.44 (s, 9H), of 3.00 (d, J=4.4 Hz, 1H), 3,63 (Sept, J=6,1 Hz, 1H), 3,83 (s, 3H), 3,95 (d, J=5,9 Hz, 1H), 4,08 (kV, J=6,9 Hz, 2H), 4,29 (d, J=6.6 Hz, 2H), 4,80 (DD, J=4,4, 5,9 Hz, 1H), 4,99 (t, J=6,6 Hz, 1H), for 6.81 (d, J=8.7 Hz, 1H), 7.23 percent-7,29 (m, 2H)

Example of getting a)

Ethyl 3-[3-(aminomethyl)-4-methoxyphenyl]-2-isopropoxyphenol

of 24.7 g of Ethyl 3-(3-[(tert-butoxycarbonyl)amino]methyl-4-methoxyphenyl)-3-hydroxy-2-isopropoxypropylamine (a mixture of Erythro forms, Treo) was dissolved in 400 ml triperoxonane acid, was added to 96 ml of triethylsilane and the mixture was stirred for 38 hours. The solvent is evaporated and the residue was dissolved in 300 ml of 3 N. hydrochloric acid and 200 ml of hexane. The aqueous layer was washed with 100 ml of hexane, was podslushivaet 5 N. solution of sodium hydroxide and was extracted with dichloromethane (200 ml x 4). The organic layers were combined and dried over anhydrous magnesium sulfate to obtain 13,0 g specified in the title compounds as a pale yellow oil.

1H-NMR (CDCl3) δas 0.96 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,25 (t, J=7.2 Hz, 3H), 2,88 (DD, J=8,8, to 13.6 Hz, 1H), 2,95 (DD, J=4,8, to 13.6 Hz, 1H), 3,50 (Sept, J=6.0 Hz, 1H), 3,84 (s, 3H), of 4.00 (DD, J=4,8, 8,8 Hz, 1H), 4,15-is 4.21 (m, 2H), 4,32 (s, 2H), 6,83 (d, J=8.0 Hz, 1H), 7,14 (d, J=2.0 Hz, 1H), 7, 20 (DD, J=2,0, 8.0 Hz, 1H)

Example 147f)

3-[3-({[(Benzyloxy)carbonyl]amino}methyl)-4-methoxyphenyl]-2-isopropoxypropylamine acid

4,327 g of Ethyl 3-[3-(aminomethyl)-4-methoxyphenyl]-2-isopropoxypropylamine was dissolved in 30 ml of ethyl acetate and 10 ml of water, was added 2 g of sodium bicarbonate and 2 ml of benzylchloride and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate, washed with water and saturated salt solution, dried over anhydrous magnesium sulfate, filtered and drove the solvent to obtain ethyl 3-[3-({[(benzyloxy)carbonyl]amino}methyl)-4-methoxyphenyl]-2-isopropoxypropylamine. The obtained product was dissolved in 60 ml of ethanol and 15 ml of 5 n sodium hydroxide solution and the mixture was stirred at room temperature for another 1 hour. The reaction mixture was acidified using 1 N. hydrochloric acid and was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and drove the solvent with the receipt of 4.75 g specified in the connection header.

MSm/e(ESI) 401 (MN+)

Example 148

2 Isopropoxy-3-(3-{[({[3-(trifluoromethyl)benzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Example of getting a)

tert-Butyl N-(3-bromobenzyl)carbamate

26,25 g of the hydrochloride of 3-bromobenzylamine suspended in 250 ml of dichloromethane and the mixture was cooled to 0°C. was Added a 33.5 g of N,N-diisopropylethylamine and 28.3 g of tert-buildi is arbonate. After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate. The solution was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate, filtered and drove the solvent to obtain 31,28 g specified in the connection header.

1H-NMR (CDCl3) δ: 1,45 (s, 9H), 4,28 (d, J=6.0 Hz, 2H), 4,87 (Sirs, 1H), 7,20 (m, 2H), 7,38 (m, 1H), 7,43 (Sirs, 1H)

Example of getting 148b)

tert-Butyl N-(3-formylmethyl)carbamate

8,58 g of tert-Butyl N-(3-bromobenzyl)carbamate was dissolved in 100 ml of tetrahydrofuran and the mixture was cooled to -78°C in nitrogen atmosphere. Added 41 ml utility (1,56M solution in hexane). After stirring for 30 minutes was added 6,91 g N-formylmorpholine. Continued stirring at -78°another 30 minutes, after which was added 1 N. hydrochloric acid and the mixture was extracted with ethyl acetate. The solution was dried over anhydrous magnesium sulfate, filtered, drove the solvent and the residue was purified by chromatography on a column of silica gel with getting 4,762 g specified in the connection header in the fraction of hexane-ethyl acetate (3:1 → 3:2).

1H-NMR (CDCl3) δ: of 1.44 (s, 9H), and 4.40 (d, J=6.0 Hz, 2H), 4, 95 (lat., 1H), 7,50 (m, 1H), 7,56-to 7.59 (m, 1H), 7,78-7,80 (m, 1H), 7,80 (s, 1H), 10,01 (s, 1H)

Example of getting s)

Ethyl (E,Z)-3-(3-{[(tert-butoxycarbonyl the l)amino]methyl}phenyl)-2-isopropoxy-2-propenoate

Using tert-butyl N-(3-formylmethyl)carbamate and ethyl 2-(diethoxyphosphoryl)-2-isopropoxyethanol specified in the title compound was obtained by a similar procedure as described in example obtaining 46a).

Example of getting 148d)

Ethyl 3-(3-{[(tert-butoxycarbonyl)amino]methyl}phenyl)-2-isopropoxyphenol

Using ethyl (E,Z)-3-(3-{[(tert-butoxycarbonyl)amino]methyl}phenyl)-2-isopropoxy-2-propenoate specified in the title compound was obtained by a similar procedure as described in example obtaining 46b).

1H-NMR (CDCl3) δ: of 0.95 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), of 1.46 (s, N), with 2.93 (DD, J=8,4, of 14.0 Hz, 1H), of 3.07 (DD, J=4,8, of 14.0 Hz, 1H), 3,49 (Sept, J=6,4 Hz, 1H), Android 4.04 (DD, J=4,8, and 8.4 Hz, 1H), 4,12-4,19 (m, 2H), 4,30 (d, J=5,2 Hz, 2H), 4,80 (width, 1H), 7,12-7,16 (m, 3H), of 7.23 (d, J=8.0 Hz, 1H)

Example of getting a)

Hydrochloride ethyl 3-[3-(ammoniated)phenyl]-2-isopropoxypropylamine

of 4.67 g of Ethyl 3-(3-{[(tert-butoxycarbonyl)amino]methyl}phenyl)-2-isopropoxypropylamine was dissolved in 50 ml triperoxonane acid and the mixture was stirred at room temperature overnight. Concentrated solvent was dried and added 10 ml of 4 n solution of the hydrochloride in ethyl acetate to obtain 6,931 g specified in the connection header.

1H-NMR (CDCl3) δ: 0,97 (who, J=6.0 Hz, 3H), 1,10 (d, J=6.0 Hz, 3H), 1,25 (t, J=7.2 Hz, 3H), 2,87 (m, 2H), 3,52 (m, 1H), 4,10 (t, J=6.0 Hz, 2H), 4,50 (kV, J=7.2 Hz, 2H), 7,20 (m, 2H), 7,34 (m, 1H)

Example 148f)

2 Isopropoxy-3-(3-{[({[3-(trifluoromethyl)benzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

20 mg of chloride ethyl 3-[3-(ammoniated)phenyl]-2-isopropoxypropylamine was dissolved in 0.5 ml N,N-dimethylformamide, which was previously saturated with carbon dioxide by adding dry ice, and added 150 mg of cesium carbonate and 200 mg tetrabutylammonium, after which the mixture was stirred at room temperature for 30 minutes. Added 40 mg of 3-triftormetilfosfinov and continued stirring at room temperature for 3 hours. To the reaction mixture were added ethyl acetate and the mixture washed with water. Concentrated solvent, the residue was treated with 0.4 ml of ethanol and 0.1 ml of 5 n sodium hydroxide solution and kept the mixture at room temperature for 30 minutes. The solution was neutralized 1 N. hydrochloric acid and was extracted with ethyl acetate. The solvent is kept off and the residue was purified by high-performance liquid chromatography with reversed phase, receiving 1,09 mg specified in the connection header.

MSm/e(ESI) 440 (MN+)

Example 149

2 Isopropoxy-3-(3-{[({[4-(trifluoromethyl)benzyl]oxy}carbonyl)amino]IU the Il}phenyl)propanoic acid

Using 4-triftormetilfosfinov specified in the title compound was obtained by a similar procedure as described in example 148f).

1H-NMR (CDCl3) δ: 1,01 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 2,95 (DD, J=8,0, 14.4 Hz, 1H), 3,12 (DD, J=1,6, or 14.8 Hz, 1H), 3,54 (Sept, J=6,4 Hz, 1H), 4,13 (DD, J=4,0, 8.0 Hz, 1H), to 4.38 (d, J=6,4 Hz, 2H), 5,11 (Shir., 1H), 5,19 (s, 2H), 7,15-7,19 (m, 3H), 7,25-7,30 (m, 1H), of 7.48 (d, J=8,8 Hz, 2H), 7.62mm (d, J=8,4 Hz, 2H)

Example 150

2 Isopropoxy-3-(3-{[({[2,4-dichlorobenzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 2,4-dichlorobenzamide specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 440 (MN+)

Example 151

2 Isopropoxy-3-(3-{[({[2,6-dichlorobenzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 2,6-dichlorobenzamide specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 440 (MN+)

Example 152

2 Isopropoxy-3-(3-{[({[3,4-dichlorobenzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 3,4-dichlorobenzamide specified in the title compound was obtained by a similar procedure as described in example 148f).

MS<> m/e(ESI) 440 (MN+)

Example 153

2 Isopropoxy-3-[4-methoxy-3-({[5-(2-methyl-1,3-thiazol-4-yl)-2-thienyl]sulfonyl}oxy)phenyl]propanoic acid

15 mg of Ethyl 3-(3-hydroxy-4-methoxyphenyl)-2-isopropoxypropylamine and 25 mg of 5-(2-methyl-1,3-thiazol-4-yl)-2-thiophenesulfonyl was dissolved in 0.4 ml of dichloromethane, was added 50 μl of triethylamine and the mixture was stirred at room temperature overnight. To the reaction mixture were added ethyl acetate and the mixture washed with water. Concentrated solvent and the residue was treated with 0.4 ml of ethanol and 0.1 ml of 5 n sodium hydroxide solution and kept the mixture at room temperature for 30 minutes. The reaction mixture was neutralized 1 N. hydrochloric acid and was extracted with ethyl acetate. Drove the solvent and the residue was purified by high-performance liquid chromatography with reversed phase, getting to 5.8 mg specified in the connection header.

MS m/e (ESI) 498 (MN+)

Example 154

2 Isopropoxy-3-[3-({[5-(3-isoxazolyl)-2-thienyl]sulfonyl}oxy)-4-methoxyphenyl]propanoic acid

Using 5-(3-isoxazolyl)-2-thiophenesulfonyl specified in the title compound was obtained by a similar procedure as described in example 153.

MS m/e (ESI) 468 (MN+)

Example 155

3-(3-{[(4-Butoxyphenyl)sulfo the yl]oxy}-4-methoxyphenyl)-2-isopropoxypropylamine acid

Using 4-butoxybenzaldehyde specified in the title compound was obtained by a similar procedure as described in example 153.

MS m/e (ESI) 467 (MN+)

Example 156

3-(3-[(4-Biphenylmethanol)oxy]-4-methoxyphenyl)-2-isopropoxypropylamine acid

Using 4-biphenylmethanol specified in the title compound was obtained by a similar procedure as described in example 153.

MS m/e (ESI) 471 (MN+)

Example 157

2 Isopropoxy-3-{3-[({[4-(trifluoromethyl)aniline]carbonyl}oxy)methyl]phenyl}propanoic acid

Example of getting a)

3-({[1-(tert-Butyl)-1,1-dimethylsilane]oxy}methyl)benzaldehyde

14 g of 3-Bromobenzylamine alcohol was dissolved in 200 ml of N,N-dimethylformamide was added 15 g of tert-butylcholinesterase and 10 g of imidazole. After stirring at room temperature overnight the solution was diluted with ethyl acetate and washed successively 1 N. hydrochloric acid and saturated salt solution. After drying the organic layer over anhydrous magnesium sulfate the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 21 g of [(3-bromobenzyl)oxy](tert-butyl)dimethylsilane in the fraction of hexane-ethyl acetate (4:1). Then 21 g of the obtained [(3-braben who yl)oxy](tert-butyl)dimethylsilane was dissolved in 300 ml of tetrahydrofuran and the mixture was cooled to -78° C in nitrogen atmosphere. Added 55 ml utility (1,52M solution in hexane) and the mixture was stirred for 30 minutes. Was added a solution of 11.5 g of 4-formylmorpholine in 20 ml of tetrahydrofuran. After stirring at -78°C for 1 hour was added 1 N. hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel with receipt of 14.7 g specified in the connection header in the fraction of hexane-ethyl acetate (4:1).

1H-NMR (CDCl3) δ: of 0.12 (s, 6H), of 0.93 (s, 9H), to 4.81(s, 2H), 7,49-7,53 (m, 1H), 7,60 to 7.62 (m, 1H), to 7.77 (d, J=7,6 Hz, 1H), 7,87 (s, 1H), 10,02 (s, 1H)

Example of getting 157b)

Ethyl 3-[3-(hydroxymethyl)phenyl]-2-isopropoxyphenol

600 mg of sodium Hydride suspended in 20 ml of tetrahydrofuran was added under ice cooling a solution of 4.2 g of diethyl 2-isopropoxyphenol in 25 ml of tetrahydrofuran. After stirring at room temperature for 30 minutes was added a solution of 3.0 g of 3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)benzaldehyde in 25 ml of tetrahydrofuran. After stirring at room temperature for 15 hours to the reaction mixture were added 1 N. hydrochloric acid and the mixture was extracted with ethyl acetate. the content of inorganic fillers layer was washed with water and saturated salt solution, was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 3.4 g of ethyl (E,Z)-3-[3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)phenyl]-2-isopropoxy-2-propenoate in the fraction of hexane-ethyl acetate (4:1). Then the obtained 3.4 g of ethyl (E,Z)-3-[3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)phenyl]-2-isopropoxy-2-propenoate was dissolved in 30 ml of tetrahydrofuran and added to 13.5 ml of tetrabutylammonium (1M solution in tetrahydrofuran). After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate, the organic layer was washed with water and saturated salt solution and dried over anhydrous magnesium sulfate. The solvent evaporated, and the resulting crude product was dissolved in 25 ml of ethanol, was added to 0.30 g of 10% palladium on coal and the mixture was stirred for 5 hours in an atmosphere of hydrogen. The catalyst was filtered and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 1.1 g specified in the connection header in the fraction of hexane-ethyl acetate (3:1).

1H-NMR (CDCl3) δ: of 0.95 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.4 Hz, 3H), 1,24 (t, J=6.8 Hz, 3H), 2,95 (DD, J=8,8, to 13.6 Hz, 1H), to 3.02 (DD, J=5,2, to 13.6 Hz, 1H), 3,50 (Sept, J=6,4 Hz, 1H), of 4.05 (DD, J=5,2, 8,8 Hz, 1H), 4,14-4,20 (m, 2H), 4,67(s, 2H), 7,17-7,30 (m, 4H)

Example of getting s)

Ethyl 2-isopropoxy-3-{3-[({[4-(trif ormetal)aniline]carbonyl}oxy)methyl]phenyl}propanoate

Suspension in tetrahydrofuran (2.0 ml)containing 100 mg of ethyl 3-[3-(hydroxymethyl)phenyl]-2-isopropoxypropylamine, 150 mg α,α,α-Cryptor-p-trilinoleate and 35 μl of pyridine, stirred at room temperature for 14 hours. Solvent was removed and the residue was treated with dichloromethane. After filtering off insoluble matters, the residue was purified by chromatography on a column of silica gel to obtain 149 mg specified in the connection header.

1H-NMR (CDCl3) δ: of 0.93 (d, J=6.0 Hz, 3H), 1.14 in (d, J=6.0 Hz, 3H), of 1.23 (t, J=7.2 Hz, 3H), 2,95 (DD, J=8,8, to 13.6 Hz, 1H), to 3.02 (DD, 4,8, to 13.6 Hz, 1H), 3,49 (Sept, J=6.0 Hz, 2H), 4,06 (DD, J=4,8, 8,8 Hz, 1H), 4,12-to 4.23 (m, 2H), 5,19 (s, 2H), 7,00 (Sirs, 1H), 7,22-to 7.32 (m, 4H), 7,51 (d, J=8,8 Hz, 2H), 7,56 (d, J=8,8 Hz, 2H)

Example 157d)

2 Isopropoxy-3-{3-[({[4-(trifluoromethyl)aniline]carbonyl}oxy)methyl]phenyl}propanoic acid

To 149 mg of ethyl 2-isopropoxy-3-{3-[({[4-(trifluoromethyl)aniline]carbonyl}oxy)methyl]phenyl}of propanoate was added 4 ml of ethanol and 1.0 ml of 5 N. aqueous sodium hydroxide solution and the mixture was stirred at room temperature for 20 hours. After diluting the reaction solution with water brought the pH to 5 by adding 5 N. hydrochloric acid and the solution was diluted with ethyl acetate and saturated aqueous ammonium chloride. The organic layer industry is Ali saturated aqueous ammonium chloride, was dried over anhydrous sodium sulfate and concentrated. The residue was purified by chromatography on a column of silica gel to obtain 26 mg specified in the connection header.

1H-NMR (CDCl3) δ: 1,02 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), 2,99 (DD, J=7,6, of 14.0 Hz, 1H), 3.15 in (DD, 4,0, of 14.0 Hz, 1H), 3,50-3,60 (m, 1H), 4,15 (DD, J=4,0, 7,6 Hz, 1H), 5,20 (s, 2H), 6,93 (Sirs, 1H), 7,16-7,35 (m, 4H), 7,51 (d, J=8,8 Hz, 2H), EUR 7.57 (d, J=8,8 Hz, 2H)

MSm/e(ESI) 426 (MH+)

Example 158

3-(3-{[(Anilinoacrolein)oxy]methyl}phenyl)-2-isopropoxypropylamine acid

Suspension in tetrahydrofuran (0.6 ml)containing 20 µl of ethyl 3-[3-(hydroxymethyl)phenyl]-2-isopropoxypropylamine, 20 μl of phenylisocyanate and 5 μl of pyridine, stirred at room temperature for 11 hours. Drove the solvent, the residue was treated with 0.4 ml of ethanol and 0.1 ml of 5 N. aqueous sodium hydroxide solution and the mixture was stirred at room temperature for 1.5 hours. The reaction solution was diluted with water and neutralized 5 N. hydrochloric acid. The mixture was extracted with ethyl acetate and concentrated. Then half of the total residue was purified HPLC using a column with reversed phase system water-acetonitrile-triperoxonane acid as an eluting solvent, getting 6,02 mg specified in the connection header.

MSm/e(ESI) 358 (MN+)

u> Example 159

3-[3-({[(4-Chloroanilino)carbonyl]oxy}methyl)phenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 392 (MN+)

Example 160

2 Isopropoxy-3-(3-{[(4-toluenesulfonyl)oxy]methyl}phenyl)propanoic acid

Using ethyl 3-[3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and p-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 372 (MN+)

Example 161

2 Isopropoxy-3-[3-({[(4-methoxyaniline)carbonyl]oxy}methyl)phenyl]propanoic acid

Using ethyl 3-[3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 4-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 388 (MN+)

Example 162

2 Isopropoxy-3-{3-[({[3-(trifluoromethyl)aniline]carbonyl}oxy)methyl]phenyl}propanoic acid

Using ethyl 3-[3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and α,α,α-Cryptor-m-that is ilization, specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 426 (MN+)

Example 163

3-[3-({[(2,4-Dichloraniline)carbonyl]oxy}methyl)phenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 2,4-dichlorophenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 426 (MN+)

Example 164

2 Isopropoxy-3-{3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid

Example of getting a)

3-(2-{[1-(tert-Butyl)-1,1-definiltely]oxy}ethyl)benzaldehyde

3-Bromophenethylamine alcohol was dissolved in 110 ml of N,N-dimethylformamide was added 16 ml of tert-butylchloroformate and 8.3 g of imidazole. After stirring at room temperature overnight the solution was diluted with ethyl acetate and washed successively 1 N. hydrochloric acid and saturated salt solution. After drying the organic layer over anhydrous magnesium sulfate the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 22.1 g of [(3-brominated)oxy](tert-butyl)diphenylsilane in the fraction of hexane-ethyl acetate (4:1). Then the obtained 22 g of [(3-brominated)oxy](tert-butyl)diphenylsilane was dissolved in 200 ml of tetrahydrofuran and the mixture was cooled to -78° C in nitrogen atmosphere. Added 37 ml utility (1,52M solution in hexane) and the mixture was stirred for 30 minutes, after which was added 10 ml of 4-formylmorpholine. After stirring at -78°C for 1 hour was added 1 N. hydrochloric acid and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 17 g specified in the connection header in the fraction of hexane-ethyl acetate (4:1).

1H-NMR (CDCl3) δ: of 0.12 (s, 6H), of 0.93 (s, 9H), to 4.81(s, 2H), 7,49-7,53 (m, 1H), 7,60 to 7.62 (m, 1H), to 7.77 (d, J=7,6 Hz, 1H), 7,87 (s, 1H), 10,02 (s, 1H)

Example of getting 164b)

Ethyl 3-[3-(2-hydroxyethyl)phenyl]-2-isopropoxyphenol

Using 3-(2-{[1-(tert-butyl)-1,1-definiltely]oxy}ethyl)benzaldehyde and diethyl 2-isopropoxyethanol specified in the title compound was obtained by a similar procedure as described in example obtaining 157b).

1H-NMR (CDCl3) δ: of 0.95 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.4 Hz, 3H), 1,24 (t, J=6.8 Hz, 3H), 2,84 (t, J=6.4 Hz, 2H), 2,93 (DD, J=8,4, of 14.0 Hz, 1H), 2,99 (DD, J=4,8, of 14.0 Hz, 1H), 3,50 (Sept, J=6,4 Hz, 1H), 3,84 (width, 2H), of 4.05 (DD, J=4,8, and 8.4 Hz, 1H), 4,14-4,20 (m, 2H), 7,08-7,13 (m, 3H), 7,22 (d, J=7,6 Hz, 1H)

Example 164 ° C.)

2 Isopropoxy-3-{3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}prop the new acid

Using ethyl 3-[3-(2-hydroxyethyl)phenyl]-2-isopropoxyphenol and α,α,α-Cryptor-p-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

1H-NMR (CDCl3) δ: of 1.18 (d, J=6.0 Hz, 3H), 1,21 (d, J=6.0 Hz, 3H), 2,87-2,99 (m, 1H), 3,09 (d, J=5,2 Hz, 2H), 3,76 (Sept, J=6.0 Hz, 1H), 4,14-to 4.23 (m, 1H), 4.26 deaths (t, J=5,2 Hz, 1H), 4,46-a 4.53 (m, 1H), 7,09-to 7.15 (m, 3H), 7,25 (t, J=7.2 Hz, 1H), 7,53 (d, J=9.0 Hz, 2H), 7,56 (d, J=9.0 Hz, 2H), to 7.67 (Sirs, 1H)

MSm/e(ESI) 440 (MH+)

Example 165

3-(3-{2-[(Anilinoacrolein)oxy]ethyl}phenyl)-2-isopropoxypropylamine acid

Using ethyl 3-[3-(2-hydroxyethyl)phenyl]-2-isopropoxyphenol and phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 372 (MN+)

Example 166

3-[3-(2-{[(4-Chloroanilino)carbonyl]oxy}ethyl)phenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(2-hydroxyethyl)phenyl]-2-isopropoxyphenol and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 406 (MN+)

Example 167

2 Isopropoxy-3-(3-{2-[(4-toluenesulfonyl)oxy]ethyl}phenyl)propanoic acid

Using ethyl 3-[3-(2-hydroxyethyl)phenyl]-2-isopropoxyphenol and p-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 386 (MN+)

Example 168

2 Isopropoxy-3-[3-(2-{[(4-methoxyaniline)carbonyl]oxy}ethyl)phenyl]propanoic acid

Using ethyl 3-[3-(2-hydroxyethyl)phenyl]-2-isopropoxyphenol and 4-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 402 (MN+)

Example 169

2 Isopropoxy-3-{3-[2-({[3-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid

Using ethyl 3-[3-(2-hydroxyethyl)phenyl]-2-isopropoxyphenol and α,α,α-Cryptor-m-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 440 (MN+)

Example 170

2 Ethoxy-3-{3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid

Example of getting a)

Ethyl 2-ethoxy-3-[3-(2-hydroxyethyl)phenyl]propanoate

Using 3-(2-{[1-(tert-butyl)-1,1-definiltely]oxy}ethyl)benzaldehyde and diethyl 2-ethoxypropionate specified the title compound was obtained according to a similar method, as described in the example of obtaining 157b).

1H-NMR (CDCl3) δ: of 1.13 (t, J=6.8 Hz, 3H), 1,22 (t, J=7.2 Hz, 3H), of 2.97 (t, J=6,8 Hz, 2H), 3,05 (DD, J=5,2, of 14.0 Hz, 1H), 3,11 (DD, J=8,4, of 14.0 Hz, 1H), 3,31 (DQC, J=6,8, 8,8 Hz, 1H), 3,59 (DQC, J=6,8, 8,8 Hz, 1H), a 3.87 (dt, J=1,6, 6,8 Hz, 2H), 4,06 (DD, J=5,2, and 8.4 Hz, 1H), 4,17 (kV, J=7.2 Hz, 2H), 7,16-7,25 (m, 4H)

Example 170b)

2 Ethoxy-3-{3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid

Suspension in tetrahydrofuran (0.6 ml)containing 14 mg of ethyl 2-ethoxy-3-[3-(2-hydroxyethyl)phenyl]propanoate, 20 µl α,α,α-triptoreline and 5 μl of pyridine, stirred at room temperature for 11 hours. Drove the solvent, the residue was treated with 0.4 ml of ethanol and 0.1 ml of 5 N. aqueous sodium hydroxide solution and the mixture was stirred at room temperature for 1.5 hours. The reaction solution was diluted with water and neutralized 5 N. hydrochloric acid. The mixture was extracted with ethyl acetate and concentrated. Then half of the total residue was purified HPLC using a column with reversed phase system water-acetonitrile-triperoxonane acid as an eluting solvent, getting 7.8 mg specified in the connection header.

MSm/e(ESI) 426 (MN+)

Example 171

3-(3-{2-[(Anilinoacrolein)oxy]ethyl}phenyl)-2-ethoxypropanol acid

Using ethyl 2-ethoxy-3-[3-(2-hydroxyethyl)phenyl]propanoate and phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 170b).

MSm/e(ESI) 358 (MN+)

Example 172

3-[3-(2-{[(4-Chloroanilino)carbonyl]oxy}ethyl)phenyl]-2-ethoxypropanol acid

Using ethyl 2-ethoxy-3-[3-(2-hydroxyethyl)phenyl]propanoate and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 170b).

MSm/e(ESI) 392 (MN+)

Example 173

2 Ethoxy-3-(3-{2-[(4-toluenesulfonyl)oxy]ethyl}phenyl)propanoic acid

Using ethyl 2-ethoxy-3-[3-(2-hydroxyethyl)phenyl]propanoate and p-tolerization specified in the title compound was obtained by a similar procedure as described in example 170b).

MSm/e(ESI) 372 (MN+)

Example 174

2 Ethoxy-3-[3-(2-{[(4-methoxyaniline)carbonyl]oxy}ethyl)phenyl]propanoic acid

Using ethyl 2-ethoxy-3-[3-(2-hydroxyethyl)phenyl]propanoate and 4-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 170b).

MSm/e(ESI) 388 (MN+)

Example 175

2 Amoxici-3-{3-[2-({[3-(trifluoromethyl)Anil is but]carbonyl}oxy)ethyl]phenyl}propanoic acid

Using ethyl 2-ethoxy-3-[3-(2-hydroxyethyl)phenyl]propanoate and α,α,α-Cryptor-m-tolerization specified in the title compound was obtained by a similar procedure as described in example 170b).

MSm/e(ESI) 426 (MN+)

Example 176

3-[3-(2-{[(2,4-Dichloraniline)carbonyl]oxy}ethyl)phenyl]-2-ethoxypropanol acid

Using ethyl 2-ethoxy-3-[3-(2-hydroxyethyl)phenyl]propanoate and 2,4-dichlorophenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 170b).

MSm/e(ESI) 426 (MN+)

Example 177

2 Ethoxy-3-{3-[2-({[methyl-4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid

To a solution of the other half of the residue in dimethylsulfoxide (0.5 ml) before HPLC purification in the synthesis of 2-ethoxy-3-{3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid was added 0.1 ml of methyliodide and 10 ml of sodium hydride in oil under ice cooling and the mixture was stirred for 12 hours with a gradual temperature increase to room. The reaction solution was diluted with water and extracted with ethyl acetate. The organic layer was concentrated, then the residue was treated with 0.4 ml of ethanol and 0.1 ml of 5 N. aqueous sodium hydroxide solution and mesh was stirred at room temperature for 1 hour. The reaction solution was diluted with water and neutralized 5 N. hydrochloric acid. After extraction with ethyl acetate and concentration the residue was purified HPLC using a column with reversed phase system water-acetonitrile-triperoxonane acid as an eluting solvent, gaining 3.4 mg specified in the connection header.

MSm/e(ESI) 440 (MN+)

Example 178

2 Ethoxy-3-[3-(2-{[(methylaniline)carbonyl]oxy}ethyl)phenyl]propanoic acid

Specified in the title compound was obtained by a similar procedure as described in example 177.

MSm/e(ESI) 372 (MN+)

Example 179

3-{3-[2-({[4-Chloro(methyl)aniline]carbonyl}oxy)ethyl]phenyl}-2-ethoxypropanol acid

Specified in the title compound was obtained by a similar procedure as described in example 177.

MS m/e (ESI) 406 (MN+)

Example 180

3-[3-(2-{[(N-methyl-4-methylaniline)carbonyl]oxy}ethyl)phenyl]-2-ethoxypropanol acid

Specified in the title compound was obtained by a similar procedure as described in example 177.

MS m/e (ESI) 386 (MN+)

Example 181

2 Ethoxy-3-{3-[2-({[4-methoxy(methyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid

is shown in the title compound was obtained according to a similar method, as described in example 177.

MS m/e (ESI) 402 (MN+)

Example 182

2 Ethoxy-3-{3-[2-({[methyl-3-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid

Specified in the title compound was obtained by a similar procedure as described in example 177.

MSm/e(ESI) 440 (MN+)

Example 183

3-{3-[2-({[2,4-Dichloro(methyl)aniline]carbonyl}oxy)ethyl]phenyl}-2-ethoxypropanol acid

Specified in the title compound was obtained by a similar procedure as described in example 177.

MSm/e(ESI) 440 (MN+)

Example 184

2 Isopropoxy-3-{4-methoxy-3-[({[4-(trifluoromethyl)aniline]carbonyl}oxy)methyl]phenyl}propanoic acid

Using ethyl 3-[3-(hydroxymethyl)-4-methoxyphenyl]-2-isopropoxyphenol and α,α,α-Cryptor-p-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 456 (MN+)

Example 185

3-(3-{[(Anilinoacrolein)oxy]methyl}-4-methoxyphenyl)-2-isopropoxypropylamine acid

Using ethyl 3-[3-(hydroxymethyl)-4-methoxyphenyl]-2-isopropoxyphenol and phenylisocyanate specified in the title compound was obtained according to a similar method, campisano in example 158.

MSm/e(ESI) 388 (MN+)

Example 186

3-[3-({[(4-Chloroanilino)carbonyl]oxy}methyl)-4-methoxyphenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(hydroxymethyl)-4-methoxyphenyl]-2-isopropoxyphenol and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 422 (MN+)

Example 187

2 Isopropoxy-3-[4-methoxy-3-({[(4-methoxyaniline)carbonyl]oxy}methyl)phenyl]propanoic acid

Using ethyl 3-[3-(hydroxymethyl)-4-methoxyphenyl]-2 - isopropoxyphenol and 4-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 158.

MS m/e (ESI) 418 (MN+)

Example 188

2 Isopropoxy-3-{4-methoxy-3-[({[3-(trifluoromethyl)aniline]carbonyl}oxy)methyl]phenyl}propanoic acid

Using ethyl 3-[3-(hydroxymethyl)-4-methoxyphenyl]-2-isopropoxyphenol and α,α,α-Cryptor-m-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

MS m/e (ESI) 456 (MN+)

Example 189

3-[3-({[(2,4-Dichloraniline)carbonyl]oxy}methyl)-4-methoxyphenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(hydroxymethyl)-4-methoxyphenyl]-2-isopropoxyphenol and 2,4-dichlorophenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 158.

MS m/e (ESI) 456 (MN+)

Example 190

2 Isopropoxy-3-[4-methoxy-3-(2-{[(3-methoxyaniline)carbonyl]oxy}ethyl)phenyl]propanoic acid

Example of getting 190A)

[(5-Bromo-2-methoxyphenyl)oxy](tert-butyl)dimethylsilane

Using 2-methoxyphenethylamine alcohol specified in the title compound was obtained by a similar procedure as described in example a).

1H-NMR (CDCl3) δ: of 0.07 (s, 6H), to 0.88 (s, 9H), 2,82 (t, J=6,8 Hz, 2H), 3,79 (t, J=6,8 Hz, 2H), 3,81 (s, 3H), 6.73 x (d, J=8,4 Hz, 1H), 7,26-7,30 (m, 1H)

Example of getting 190b)

3-(2-{[1-(tert-Butyl)-1,1-dimethylsilane]oxy}ethyl)-4-methoxybenzaldehyde

Using [(5-bromo-2-methoxyphenyl)oxy](tert-butyl)dimethylsilane specified in the title compound was obtained by a similar procedure as described in example obtaining 127b).

1H-NMR (CDCl3) δ: of 0.07 (s, 6H), to 0.88 (s, 9H), with 2.93 (t, J=6,8 Hz, 2H), 3,83 (t, J=6,8 Hz, 2H), of 3.94 (s, 3H), 6,98 (d, J=8,4 Hz, 1H), 7,74 (d, J=2.4 Hz, 1H), 7,78 (DD, J=2,4, and 8.4 Hz, 1H), 7,26-7,30 (m, 1H), 9,90 (s, 1H)

Example of getting 190s)

Ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol

Using 3-(2-{[1-(tert-butyl)-1,1-dimethylsilane]oxy}ethyl)-4-methoxybenzaldehyde and diethyl 2-isopropoxyethanol specified in the title compound was obtained by a similar procedure as described in example obtaining 157b).

1H-NMR (CDCl3) δ: 0,98 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,24 (t, J=6.8 Hz, 3H), 2,85-2,95 (m, 4H), 3,51 (Sept, J=6.0 Hz, 1H), 3,78-a-3.84 (m, 2H), 3,80 (s, 3H), 4,01 (DD, J=4,8, 8.0 Hz, 1H), 4,14-4,20 (m, 2H,), is 6.78 (d, J=8,4 Hz, 1H),? 7.04 baby mortality (d, J=2.0 Hz, 1H), was 7.08 (DD, J=2.0 a, and 8.4 Hz, 1H)

Example 190d)

2 Isopropoxy-3-[4-methoxy-3-(2-{[(3-methoxyaniline)carbonyl]oxy}ethyl)phenyl]propanoic acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and 3-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 432 (MN+)

Example 191

3-[3-(2-{[(2,4-Diptiranjan)carbonyl]oxy}ethyl)-4-methoxyphenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and 2,4-differentiational specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 438 (MN+)

Example 192

2 Isopropoxy-3-[4-methoxy-3-(2-{[(4-phenoxyimino)carbonyl]oxy}ethyl)phenyl]propanoic acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and 4-phenoxyphenylacetic specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 494 (MN+)

Example 193

3-[3-(2-{[(4-Foronline)carbonyl]oxy}ethyl)-4-methoxyphenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and 4-forgenerations specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 420 (MN+)

Example 194

2 Isopropoxy-3-{4-methoxy-3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and α,α,α-Cryptor-p-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 470 (MN+)

Example 195

3-[3-(2-{[(3-Chloroanilino)carbonyl]oxy}ethyl)-4-methoxyphenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and 3-chloronicotinate specified in sagola the ke compound was obtained according to a similar method, as described in example 158.

MSm/e(ESI) 436 (MN+)

Example 196

3-[3-(2-{[(2-Chloroanilino)carbonyl]oxy}ethyl)-4-methoxyphenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and 2-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 436 (MN+)

Example 197

3-(3-{2-[(Anilinoacrolein)oxy]ethyl}-4-methoxyphenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 402 (MN+)

Example 198

3-[3-(2-{[(4-Chloroanilino)carbonyl]oxy}ethyl)-4-methoxyphenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 436 (MN+)

Example 199

2 Isopropoxy-3-(4-methoxy-3-{2-[(4-toluenesulfonyl)oxy]ethyl}phenyl)propanoic acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and p-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 416 (MN+)

Example 200

2 Isopropoxy-3-[4-methoxy-3-(2-{[(4-methoxyaniline)carbonyl]oxy}ethyl)phenyl]propanoic acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and 4-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 432 (MN+)

Example 201

2 Isopropoxy-3-{4-methoxy-3-[2-({[3-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]phenyl}propanoic acid

Using ethyl 3-[3-(2-hydroxyethyl)-4-methoxyphenyl]-2-isopropoxyphenol and α,α,α-Cryptor-m-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 470 (MN+)

Example 202

Dimethyl 2-{3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)methyl]benzyl}malonate

Example of getting a)

Dimethyl 2-[3-(hydroxymethyl)benzyl]malonate

1.5 g of 3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)benzaldehyde and 1.6 g dimethylsilane is and was dissolved in 20 ml of toluene, added 90 μl of piperidine and 52 μl of acetic acid and the mixture is boiled under reflux, using a trap Dean-stark. After 9 hours, the solvent evaporated and the residue was purified by chromatography on a column of silica gel to obtain 5.8 g of dimethyl 2-{[3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)phenyl]methylene}malonate in the fraction of hexane-ethyl acetate (4:1). Then the obtained 5.8 g of dimethyl 2-{[3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)phenyl]methylene}malonate was dissolved in a mixture of 3 ml of methanol and 15 ml of 1,4-dioxane was added 0.20 g of 10% palladium on coal and the mixture was stirred for 5 hours in an atmosphere of hydrogen. The catalyst was filtered and the solvent evaporated. Then the obtained crude product was dissolved in 12 ml of tetrahydrofuran and the resulting solution was added to 8.0 ml of tetrabutylammonium (1M solution in tetrahydrofuran). After stirring at room temperature overnight, the reaction mixture was diluted with ethyl acetate and the organic layer was washed with water and saturated salt solution. After drying over anhydrous magnesium sulfate the solvent evaporated and the residue was purified by chromatography on a column of silica gel to obtain 0.95 g specified in the connection header in the fraction of hexane-ethyl acetate (2:1).

1H-NMR (CDCl3) δ: 3,23 (d, J=8.0 Hz, 2H), 3,68 (t, J=8.0 Hz, 1H), 3,70 (s, 6H), of 4.66 (d, J=4.4 Hz, 2H), 7,11-7,30 (m, 4H)

Example 202b)/u>

Dimethyl 2-{3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)methyl]benzyl}malonate

The suspension containing 63 mg of dimethyl 2-[3-(hydroxymethyl)benzyl]malonate, 47 mg α,α,α-Cryptor-p-trilinoleate and 30 μl of pyridine in tetrahydrofuran (2.0 ml), was stirred at room temperature for 19 hours. Drove the solvent and the residue was treated with dichloromethane. After filtering off insoluble substances and concentration of the filtrate the residue was purified HPLC using a column with reversed phase system water-acetonitrile-triperoxonane acid as an eluting solvent, receiving 71 mg specified in the connection header.

1H-NMR (CDCl3) δ: 3,24 (d, J=8.0 Hz, 2H), 3,68 (t, J=8.0 Hz, 1H), 3,70 (s, 6H), is 5.18 (s, 2H), 7,17-7,31 (m, 4H), 7,50-to 7.59 (m, 4H)

MSm/e(ESI) 440 (MH+)

Example 203

Dimethyl 2-(3-{[(anilinoacrolein)oxy]methyl}benzyl)malonate

Using dimethyl 2-[3-(hydroxymethyl)benzyl]malonate and phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 372 (MN+)

Example 204

Dimethyl 2-(3-{[(4-toluenesulfonyl)oxy]methyl}benzyl)malonate

Using dimethyl 2-[3-(hydroxymethyl)benzyl]Malon and p-tallization, specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 386 (MN+)

Example 205

Dimethyl 2-[3-({[(4-methoxyaniline)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)benzyl]malonate and 4-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 402 (MN+)

Example 206

Dimethyl 2-[3-({[(3-methoxyaniline)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)benzyl]malonate and 3-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 402 (MN+)

Example 207

Dimethyl 2-[3-({[(4-chloroanilino)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)benzyl]malonate and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 406 (MN+)

Example 208

Dimethyl 2-[3-({[(2,4-dichloraniline)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)benzyl]Malon and 2,4-dichlorophenylisocyanate, specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 440 (MN+)

Example 209

Dimethyl 2-[3-({[(2-chloroanilino)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)benzyl]malonate and 2-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 406 (MN+)

Example 210

Dimethyl 2-[3-({[(2,4-diptiranjan)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)benzyl]malonate and 2,4-differentiational specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 408 (MN+)

Example 211

Dimethyl 2-[3-({[(3-chloroanilino)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)benzyl]malonate and 3-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 406 (MN+)

Example 212

Dimethyl 2-{3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]benzyl}malonate

Example of getting a)

Dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate

Using 3-(2-{[1-(tert-butyl)-1,1-definiltely]oxy}ethyl)benzaldehyde and diethylmalonate specified in the title compound was obtained by a similar procedure as described in example a).

1H-NMR (CDCl3) δ: and 2.83 (t, J=6.4 Hz, 2H), 3,21 (d, J=8.0 Hz, 2H), to 3.67 (t, J=8.0 Hz, 1H), 3,70 (s, 6H), of 3.84 (t, J=6.4 Hz, 2H), 7,06-7,10 (m, 3H), 7,21-7,25 (m, 1H)

Example 212b)

Dimethyl 2-{3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]benzyl}malonate

Using dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate and α,α,α-Cryptor-p-tolerization specified in the title compound was obtained by a similar procedure as described in example 202b).

1H-NMR (CDCl3) δ: of 2.93 (t, J=6.4 Hz, 2H), 3,23 (d, J=7,6 Hz, 2H), 3,69 (t, J=7,6 Hz, 1H), 3,70 (s, 6H), 4,35 (t, J=6.4 Hz, 2H), 7,06-7,11 (m, 3H), 7,25 (t, J=7.2 Hz, 1H), 7,52-7,56 (m, 4H)

MSm/e(ESI) 454 (MH+)

Example 213

Dimethyl 2-(3-{2-[(anilinoacrolein)oxy]ethyl}benzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate and phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 386 (MN+)

Example 214

Dimethyl 2-(3-{2-[(4-toluenesulfonyl)oxy]ethyl}benzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate and p-t is limitational, specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 400 (MN+)

Example 215

Dimethyl 2-(3-{2-[(4-methoxyaniline)oxy]ethyl}benzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate and 4-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 416 (MN+)

Example 216

Dimethyl 2-(3-{2-[(3-methoxyaniline)oxy]ethyl}benzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate and 3-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 416 (MN+)

Example 217

Dimethyl 2-(3-{2-[(4-chloraniline)oxy]ethyl}benzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 420 (MN+)

Example 218

Dimethyl 2-(3-{2-[(2,4-dichloraniline)oxy]ethyl}benzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate and 2-dichlorophenylisocyanate, specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 454 (MN+)

Example 219

Dimethyl 2-(3-{2-[(2-chloraniline)oxy]ethyl}benzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate and 2-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 420 (MN+)

Example 220

Dimethyl 2-(3-{2-[(2,4-differencesnational)oxy]ethyl}benzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate and 2,4-differentiational specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 422 (MN+)

Example 221

Dimethyl 2-(3-{2-[(3-chloraniline)oxy]ethyl}benzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)benzyl]malonate and 3-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 420 (MN+)

Example 222

Dimethyl 2-(3-{[(anilinoacrolein)oxy]methyl}-4-methoxybenzyl)malonate

Example of getting a)

Dimethyl 2-[3-(hydroxymethyl)-4-methoxybenzyl]malonate

Using 3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)-4-methoxybenzaldehyde and diethylmalonate specified in the title compound was obtained by a similar procedure as described in example a).

1H-NMR (CDCl3) δ: and 3.16 (d, J=8.0 Hz, 2H), 3,68 (t, J=8.0 Hz, 1H), 3,70 (s, 6H), of 3.84 (s, 3H), with 4.64 (d, J=6.0 Hz, 2H), 6,79 (d, J=9,2 Hz, 1H), 7,09-7,11 (m, 2H)

Example 222b)

Dimethyl 2-(3-{[(anilinoacrolein)oxy]methyl}-4-methoxybenzyl)malonate

Using dimethyl 2-[3-(hydroxymethyl)-4-methoxybenzyl]malonate and phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 402 (MN+)

Example 223

Dimethyl 2-(4-methoxy-3-{[(4-toluenesulfonyl)oxy]methyl}benzyl)malonate

Using dimethyl 2-[3-(hydroxymethyl)-4-methoxybenzyl]malonate and p-tolerization specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 416 (MN+)

Example 224

Dimethyl 2-[4-methoxy-3-({[(4-methoxyaniline)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)-4-methoxybenzyl]malonate and 4-methoxyphenylalanine specified in the title compound was obtained according to a similar method as described in point is the iMER 202b).

MSm/e(ESI) 432 (MN+)

Example 225

Dimethyl 2-[4-methoxy-3-({[(3-methoxyaniline)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)-4-methoxybenzyl]malonate and 3-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 432 (MN+)

Example 226

Dimethyl 2-[3-({[(4-chloroanilino)carbonyl]oxy}methyl)-4-methoxybenzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)-4-methoxybenzyl]malonate and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 436 (MN+)

Example 227

Dimethyl 2-[3-({[(2,4-dichloraniline)carbonyl]oxy}methyl)-4-methoxybenzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)-4-methoxybenzyl]malonate and 2,4-dichlorophenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 470 (MN+)

Example 228

Dimethyl 2-[3-({[(2-chloroanilino)carbonyl]oxy}methyl)-4-methoxybenzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)-4-methoxybenzyl]malonate and 2-chloronicotinate specified in the title compound was obtained according to a similar method, as described in example 202b).

MS m/e (ESI) 436 (MN+)

Example 229

Dimethyl 2-[3-({[(2,4-diptiranjan)carbonyl]oxy}methyl)-4-methoxybenzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)-4-methoxybenzyl]malonate and 2,4-differentiational specified in the title compound was obtained by a similar procedure as described in example 202b).

MS m/e (ESI) 438 (MN+)

Example 230

Dimethyl 2-[3-({[(4-triptoreline)carbonyl]oxy}methyl)-4-methoxybenzyl]malonate

Using dimethyl 2-[3-(hydroxymethyl)-4-methoxybenzyl]malonate and α,α,α-Cryptor-p-tolerization specified in the title compound was obtained by a similar procedure as described in example 202b).

MS m/e (ESI) 470 (MN+)

Example 231

Dimethyl 2-(3-{-2-[(anilinoacrolein)oxy]ethyl}-4-methoxybenzyl)malonate

Example of getting a)

Dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]malonate

Using 3-(2-{[1-(tert-butyl)-1,1-dimethylsilane]oxy}ethyl)-4-methoxybenzaldehyde and diethylmalonate specified in the title compound was obtained by a similar procedure as described in example a).

1H-NMR (CDCl3) δ: of 2.86 (t, J=6.4 Hz, 2H), 3,14 (d, J=8.0 Hz, 2H), 3,62 (t, J=8.0 Hz, 1H), 3,70 (s, 6H), of 3.80 (s, 3H), 3,81 (t, J=6.4 Hz, 2H), 6,77 (d, J=8,4 Hz, 1H), 6,98 (d, J=2.4 Hz, 1H),? 7.04 baby mortality (DD, J=Hz 2,4,8,4, 1H)

Example 231b)

Dimethyl 2-(3-{2-[(anilinoacrolein)oxy]ethyl}-4-methoxybenzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]malonate and phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 416 (MN+)

Example 232

Dimethyl 2-(4-methoxy-3-{2-[(4-toluenesulfonyl)oxy]ethyl}benzyl)malonate

Using dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]malonate and p-tolerization specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 430 (MN+)

Example 233

Dimethyl 2-[4-methoxy-3-(2-{[(4-methoxyaniline)carbonyl]oxy}ethyl)benzyl]malonate

Using dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]malonate and 4-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 446 (MN+)

Example 234

Dimethyl 2-[4-methoxy-3-(2-{[(3-methoxyaniline)carbonyl]oxy}ethyl)benzyl]malonate

Using dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]malonate and 3-methoxyphenylalanine specified in the title compound was obtained p the same methodology, as described in example 202b).

MSm/e(ESI) 446 (MN+)

Example 235

Dimethyl 2-[3-(2-{[(4-chloroanilino)carbonyl]oxy}ethyl)-4-methoxybenzyl]malonate

Using dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]malonate and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 450 (MN+)

Example 236

Dimethyl 2-[3-(2-{[(2,4-dichloraniline)carbonyl]oxy}ethyl)-4-methoxybenzyl]malonate

Using dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]malonate and 2,4-dichlorophenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 484 (MN+)

Example 237

Dimethyl 2-[3-(2-{[(2-chloroanilino)carbonyl]oxy}ethyl)-4-methoxybenzyl]malonate

Using dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]malonate and 2-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 450 (MN+)

Example 238

Dimethyl 2-[3-(2-{[(2,4-diptiranjan)carbonyl]oxy}ethyl)-4-methoxybenzyl]malonate

Using dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]Malon and 2,4-differentiational, specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 452 (MN+)

Example 239

Dimethyl 2-{4-methoxy-3-[2-({[4-(trifluoromethyl)aniline]carbonyl}oxy)ethyl]benzyl}malonate

Using dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]malonate and α,α,α-Cryptor-p-tolerization specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 484 (MN+)

Example 240

Dimethyl 2-(3-{[(anilinoacrolein)oxy]methyl}-4-ethoxybenzyl)malonate

Example of getting a)

3-({[1-tert-Butyl-1,1-dimethylallyl]oxy}methyl)-4-ethoxybenzaldehyde

Using 2-ethoxybenzyl alcohol specified in the title compound was obtained by a similar procedure as described in example obtaining a) and then in the example of obtaining 127b).

1H-NMR (CDCl3) δ: of 0.12 (s, 6H), of 0.93 (s, 9H), of 1.40 (t, J=6.8 Hz, 3H), 4,11 (kV, J=6,8 Hz, 2H), 4,74 (s, 2H), make 6.90 (d, J=8,4 Hz, 1H), 7,76 (DD, J=1,6, and 8.4 Hz, 1H), of 7.97 (d, J=1.6 Hz, 1H), 9,86 (s, 1H)

Example of getting 240b)

Dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate

Using 3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)-4-ethoxybenzaldehyde and diethylmalonate specified in the header of the link is received by the same methodology, as described in example a).

1H-NMR (CDCl3) δ: of 1.42 (d, J=6.8 Hz, 3H)and 3.15 (d, J=8.0 Hz, 2H), 3,63 (t, J=8.0 Hz, 1H), 3,70 (s, 6H), of 4.05 (q, J=6,8 Hz, 2H)and 4.65 (d, J=6,4 Hz, 2H), 6,77 (d, J=8,4 Hz, 1H), 7,06-to 7.09 (m, 2H)

Example C)

Dimethyl 2-(3-{[(anilinoacrolein)oxy]methyl}-4-ethoxybenzyl)malonate

Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate and phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 416 (MN+)

Example 241

Dimethyl 2-(4-ethoxy-3-{[(4-toluenesulfonyl)oxy]methyl}benzyl)malonate

Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate and p-tolerization specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 430 (MN+)

Example 242

Dimethyl 2-[4-ethoxy-3-({[(4-methoxyaniline)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate and 4-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 446 (MN+)

Example 243

Dimethyl 2-[4-ethoxy-3-({[(3-methoxyaniline)carbonyl]oxy}methyl)benzyl]malonate

Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate and 3-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 446 (MN+)

Example 244

Dimethyl 2-[3-({[(4-chloroanilino)carbonyl]oxy}methyl)-4-ethoxybenzyl]malonate

Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 450 (MN+)

Example 245

Dimethyl 2-[3-({[(2,4-dichloraniline)carbonyl]oxy}methyl)-4-ethoxybenzyl]malonate

Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate and 2,4-dichlorophenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 484 (MN+)

Example 246

Dimethyl 2-[3-({[(2-chloroanilino)carbonyl]oxy}methyl)-4-ethoxybenzyl]malonate

Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate and 2-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 450 (MN+)

Example 247

Dimethyl 2-[3-({[(2,4-gift is anilino)carbonyl]oxy}methyl)-4-ethoxybenzyl]malonate

Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate and 2,4-differentiational specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 452 (MN+)

Example 248

Dimethyl 2-{4-ethoxy-3-[({[4-(trifluoromethyl)aniline]carbonyl}oxy)methyl]benzyl}malonate

Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate and α,α,α-Cryptor-p-tolerization specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 484 (MN+)

Example 249

Dimethyl 2-[3-({[(3-chloroanilino)carbonyl]oxy}methyl)-4-ethoxybenzyl]malonate

Using dimethyl 2-[4-ethoxy-3-(hydroxymethyl)benzyl]malonate and 3-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 202b).

MSm/e(ESI) 450 (MN+)

Example 250

Ethyl 2-isopropoxy-3-[3-({[4-(trifluoromethyl)aniline]carbonyl}oxy)phenyl]propanoate

Using ethyl 3-(3-hydroxyphenyl)-2-isopropoxyphenol and α,α,α-Cryptor-p-tolerization specified in the title compound was obtained by a similar procedure as described in example 02b).

MSm/e(ESI) 484 (MN+)

Example 251

3-[3-({[(2,4-Dichlorophenyl)sulfonyl]amino}methyl)-4-methoxyphenyl]-2-isopropoxypropylamine acid

To a solution of 33 mg of ethyl [3-(aminomethyl)-4-methoxyphenyl]-2-isopropoxypropylamine and 25 mg of 2,4-dichlorobenzenesulfonyl in 0.8 ml dichloromethane was added 40 μl of pyridine under ice cooling and the mixture was stirred at room temperature for 4 hours. After removal of solvent the residue was added 1.0 ml of ethanol and 0.3 ml of 2 N. aqueous sodium hydroxide solution and the mixture was stirred at room temperature for 2 hours. The reaction solution was diluted with water and neutralized 2 N. hydrochloric acid. The mixture was extracted with ethyl acetate and concentrated. Then the residue was purified HPLC using a column with reversed phase system water-acetonitrile-triperoxonane acid as an eluting solvent, receiving 2.0 mg specified in the connection header.

MSm/e(ESI) 476 (MN+)

Example 252

3-{3-[3-(3,4-Dimethylphenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 3,4-dimethylphenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 425 (MNa+)

Example 253

3-{3-[3-(4-Bromophenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 4-bromophenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 475 (MNa+)

Example 254

3-{3-[2-Hydroxy-3-(2-methoxy-5-methylphenoxy)propoxy]phenyl}-2-isopropoxypropylamine acid

Using 2-methoxy-5-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example 1C).

MS m/e (ESI) 441 (MNa+)

Example 255

3-{3-[3-(3-Chlorophenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 3-chlorophenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MS m/e (ESI) 431 (MNa+)

Example 256

3-[3-(2-Hydroxy-3-p-tolylenediamine)phenyl]-2-isopropoxypropylamine acid

Using 4-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example 1C).

MS m/e (ESI) 411 (MNa+)

Example 257

3-{3-[3-(2,4-Dimethylphenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 2,4-dimethylphenol specified in the agolove compound was obtained according to a similar method, as described in example 1C).

MSm/e(ESI) 425 (MNa+)

Example 258

3-[3-(2-Hydroxy-3-m-tolylenediamine)phenyl]-2-isopropoxypropylamine acid

Using 3-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 411 (MNa+)

Example 259

3-{3-[3-(3-Ethylenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 3-ethylphenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 425 (MNa+)

Example 260

3-{3-[3-(2,6-Divergence)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 2,6-diferena specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 433 (MNa+)

Example 261

3-{3-[3-(2-Chloro-5-triptoreline)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 2-chloro-5-cryptomaterial specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 499 (MNa+)

Example 262

3-{3-[3-(3,4-Dichlorophenoxy)-2-hydrox is propoxy]phenyl}-2-isopropoxypropylamine acid

Using 3,4-dichlorophenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 465 (MNa+)

Example 263

3-{3-[3-(4-Chloro-3-methylphenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 4-chloro-3-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 445 (MNa+)

Example 264

3-{3-[3-(4-Cyanomethylene)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 4-cyanomethylene specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 435 (MNa+)

Example 265

3-{3-[3-(3-Chloro-4-pertenece)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 3-chloro-4-terfenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 449 (MNa+)

Example 266

3-{3-[3-(4-Chlorophenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 4-chlorophenol, specified in the header of connection produces and on the same methodology, as described in example 1C).

MSm/e(ESI) 431 (MNa+)

Example 267

3-{3-[2-Hydroxy-3-(2-piperidino-1 elfenix)propoxy]phenyl}-2-isopropoxypropylamine acid

Using 2-piperidinophenyl specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 480 (MNa+)

Example 268

3-{3-[3-(4-Pertenece)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 4-terfenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 415 (MNa+)

Example 269

3-{3-[3-(4-Ethylenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 4-ethylphenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 425 (MNa+)

Example 270

3-{3-[3-(5-Chloro-2-methylphenoxy)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 2-methyl-3-chlorophenol, specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 445 (MNa+)

Example 271

3-{3-[2-Hydroxy-3-(3-methoxy-5-methylphen the XI)propoxy]phenyl}-2-isopropoxypropylamine acid

Using 3-methyl-5-methoxyphenol specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 441 (MNa+)

Example 272

3-{3-[3-(3-Ethynylene)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 3-ethynylphenyl specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 421 (MNa+)

Example 273

3-{3-[2-Hydroxy-3-(1H-indol-4-yloxy)propoxy]phenyl}-2-isopropoxypropylamine acid

Using 4-hydroxyindole specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 435 (MNa+)

Example 274

3-{3-[3-(4-Chloro-2-cianfrocca)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 4-chloro-2-cyanoprop specified in the title compound was obtained by a similar procedure as described in example 1C).

MSm/e(ESI) 456 (MNa+)

Example 275

3-{3-[3-(4-Bromo-2-cianfrocca)-2-hydroxypropoxy]phenyl}-2-isopropoxypropylamine acid

Using 4-bromo-2-cyanoprop specified in the header soedineniya on the same methodology, as described in example 1C).

MSm/e(ESI) 500 (MNa+)

Example 276

2 Isopropoxy-3-(3-{[({[4-Chlorobenzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 4-Chlorobenzilate specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 428 (MN+)

Example 277

2 Isopropoxy-3-(3-{[({[3-Chlorobenzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 3-chlorobenzylamino specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 428 (MN+)

Example 278

2 Isopropoxy-3-(3-{[({[2-Chlorobenzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 2-chlorobenzylamino specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 428 (MN+)

Example 279

2 Isopropoxy-3-(3-{[({[4-terbisil]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 4-florantyrone specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 412 (MN+)

Example 280

2-Isopr is poxi-3-(3-{[({[3-terbisil]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 3-florantyrone specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 412 (MN+)

Example 281

2 Isopropoxy-3-(3-{[({[4-cyanobenzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 4-cyanobenzeneboronic specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 419 (MN+)

Example 282

2 Isopropoxy-3-(3-{[({[3-cyanobenzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 3-cyanobenzeneboronic specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 419 (MN+)

Example 283

2 Isopropoxy-3-(3-{[({[2,4-diferensial]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 2,4-differenziale specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 430 (MN+)

Example 284

2 Isopropoxy-3-(3-{[({[4-methoxybenzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 4-methoxybenzylamine specified in the title compound was obtained according to a similar method, as described in example 148f).

MSm/e(ESI) 424 (MN+)

Example 285

2 Isopropoxy-3-(3-{[({[2-fluoro-4-trifloromethyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 2-fluoro-4-triftormetilfosfinov specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 480 (MN+)

Example 286

2 Isopropoxy-3-(3-{[({[2-chloro-4-propoxyphenyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 2-chloro-4-propoxybenzaldehyde specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 486 (MN+)

Example 287

2 Isopropoxy-3-(3-{[({[2-fluoro-4-Chlorobenzyl]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 2-fluoro-4-Chlorobenzilate specified in the title compound was obtained by a similar procedure as described in example 148f).

MSm/e(ESI) 446 (MN+)

Example 288

2 Isopropoxy-3-(3-{[({[4-cryptomaterial]oxy}carbonyl)amino]methyl}phenyl)propanoic acid

Using 4-cryptomaterial specified in the title compound was obtained according to a similar method as described is example 148f).

MS m/e (ESI) 478 (MN+)

Example 289

3-{3-[3-(2,4-Dichlorophenoxy)-2(S)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acid

Example of getting a)

4(S)-Benzyl-3-(2-isopropoxyphenyl)oxazolidin-2-he

A solution containing 98 g of 2-isopropoxyethanol acid and 360 ml of triethylamine in tetrahydrofuran (4 l)was cooled to -25°C. was Added dropwise 92 ml of 2,2-dimethylpropanolamine, after which the reaction solution was stirred at -20°C for 5 hours. Then added successively 50 g of anhydrous lithium chloride and 120 g of (4S)-4-benzyl-1,3-oxazolidin-2-it and continued stirring at room temperature over night. Then the reaction solution was filtered and evaporated. The residue was dissolved in 2 l of ethyl acetate, washed with saturated aqueous sodium bicarbonate and then dried over anhydrous magnesium sulfate. The solvent evaporated and the residue was purified by chromatography on a column of silica gel (eluting solvent: hexane-ethyl acetate) to obtain the 106,6 g of (4S)-4-benzyl-3-(2-isopropoxyphenyl)-1,3-oxazolidin-2-it is in the form of a colorless oil.

1H-NMR (CDCl3) δ: 1,17 (d, J=6.0 Hz, 6H), of 2.81 (DD, J=9,5, a 13.4 Hz, 1H), 3,35 (DD, J=3.2, and the 13.4 Hz, 1H), 3,74 (Sept, J=6.0 Hz, 1H), 4,24 (DD, J=3,5, and 9.3 Hz), the 4.29 (t, J=9,3 Hz, 1H)and 4.65 (d, J=19,5 Hz, 1H), 4,69 (m, 1H), 4,70 (d, J=19,5 Hz, 1H), 7,22 (d, J=7.2 Hz, 2H), 7,30 was 7.45 (m, 3H)

Sample of what I 289b)

4(S)-Benzyl-3-[3-(3-benzyloxyphenyl)-3-hydroxy-2(S)-isopropoxyphenyl]oxazolidin-2-he

After cooling the solution containing 8.1 g of (4S)-4-benzyl-3-(2-isopropoxyphenyl)-1,3-oxazolidin-2-she in toluene (120 ml) to -75°C, was added 5.0 ml of triethylamine. Was added dropwise to 30.5 ml dibutylphtalate (1M solution in dichloromethane) with such speed that the internal temperature did not exceed -70°C. Upon completion of adding dropwise, the mixture was stirred for 50 minutes. Then, the inner temperature was raised to 0°and the mixture was stirred for another 50 minutes and again cooled to -75°C. To the reaction solution via a cannula was added a solution containing 5.2 g of 3-benzyloxybenzaldehyde in dichloromethane (25 ml)and continued stirring at -75°C for 30 minutes. Then the temperature of the reaction mass was raised to 0°for about 1 hour, 10°With in 10 minutes. After cooling to -75°again added to the solution containing 2.0 g of 3-benzyloxybenzaldehyde in dichloromethane (10 ml). The temperature was gradually raised to room temperature and stirred the mixture at room temperature for 3 days. The reaction solution was poured into a mixed solution of 150 ml of methanol, 100 ml of buffer with pH 7 (mixture of disodium hydrogen phosphate-citric acid) and 30 ml of hydrogen peroxide (30% aqueous solution) and was extracted with ethyl acetate. The PR is anceschi layer was washed with saturated salt solution, was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel with receipt of 13.1 g of 4(S)-benzyl-3-[3-(3-benzyloxyphenyl)-3-hydroxy-2(S)-isopropoxyphenyl]oxazolidin-2-it is in the form of a colorless oil in the fraction of hexane-ethyl acetate (2:1 → 3:2).

1H-NMR (CDCl3) δ: 1,11 (d, J=6.0 Hz, 3H), 1,19 (d, J=6.0 Hz, 3H), of 2.75 (DD, J=9,6, 13,2 Hz, 1H), is 3.08 (d, J=5.6 Hz, 1H), 3,26 (DD, J=3.2, and up to 13.2 Hz, 1H), 3,60 at 3.69 (m, 2H), 3,99 (DD, J=1,6, 8,8 Hz, 1H), 4,27-to 4.33 (m, 1H), 4,84 (t, J=5.6 Hz, 1H), 5,07 (s, 2H), 5,44 (d, J=5,2 Hz, 1H), 6,88-of 6.90 (m, 1H), 7,00 (d, J=7,6 Hz, 1H), to 7.09 (t, J=2.0 Hz, 1H), 7,16-7,24 (m, 3H), 7,28-7,35 (m, 6H), 7,39-the 7.43 (m, 2H)

Example of getting s)

4(S)-Benzyl-3-[3-(3-hydroxyphenyl)-2(S)-isopropoxyphenyl]oxazolidin-2-he

of 12.9 g of 4-Benzyl-3-[3-(3-benzyloxyphenyl)-3-hydroxy-2-isopropoxyphenyl]oxazolidin-2-it was dissolved in 30 ml of pyridine was added dropwise under ice cooling to 3.06 ml methanesulfonanilide. After stirring at room temperature for 2 hours, the reaction solution was diluted with ethyl acetate and washed successively 1 N. hydrochloric acid and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated solvent to obtain 3-(4(S)-benzyl-2-oxoacridine-3-yl)-1-(3-benzyloxyphenyl)-2(S)-isopropoxy-3-occupationaltherapy product was then dissolved in 300 ml of ethanol, added 2 g of 10% palladium on coal and the mixture was stirred overnight in a hydrogen atmosphere at room temperature. The reaction solution was filtered and the filtrate was concentrated. The residue was diluted with ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel with getting by 5.87 g specified in the title compounds as colorless oils in the fraction of hexane-ethyl acetate (2:1 → 3:2).

1H-NMR (CDCl3) δ: 1,04 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), 2,78 (DD, J=9,6, 13,2 Hz, 1H), 2,86-2,96 (m, 2H), and 3.31 (DD, J=2,4, of 13.6 Hz, 1H), 3,53 (Sept, J=6.0 Hz, 1H), 4,01 (t, J=8.0 Hz, 1H), 4,13 (DD, J=2,4, 9,2 Hz, 1H), 4,50-4,55 (m, 1H), 5,22 (s, 1H), 5,39 (DD, J=5,2, and 8.4 Hz, 1H), of 6.71 (DD, J=2,4, 8.0 Hz, 1H), PC 6.82 (t, J=2.0 Hz, 1H), 6.87 in (d, J=7,6 Hz, 1H), 7,14 (t, J=8.0 Hz, 1H), 7.18 in-of 7.23 (m, 2H), 7,27-7,35 (m, 3H)

Example of getting 289d)

Ethyl ester of 3-(3-hydroxyphenyl)-2(S)-isopropoxypropylamine acid

1,535 g 4(S)-Benzyl-3-[3-(3-hydroxyphenyl)-2(S)-isopropoxyphenyl]oxazolidin-2-it was dissolved in 40 ml of tetrahydrofuran, was sequentially added under ice cooling and 3.3 ml of 30% aqueous hydrogen peroxide solution and 12 ml of 1 N. aqueous solution of lithium hydroxide and the mixture was stirred at room temperature overnight. After adding to the reaction is Oh a mixture of water the mixture was extracted with dichloromethane and the aqueous layer was acidified to 1 N. hydrochloric acid. After extraction (3 times) with ethyl acetate the organic layer was dried over anhydrous magnesium sulfate and drove away under reduced pressure, the solvent is getting 847 mg of 3-(3-hydroxyphenyl)-2(S)-isopropoxypropylamine acid. The resulting product was then dissolved in 10 ml of N,N-dimethylformamide were added successively 400 mg of potassium bicarbonate and 0.32 ml of atunited and the mixture was stirred at room temperature for 3 days. The reaction solution was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel with getting 567 mg specified in the title compounds as colorless oils in the fraction of hexane-ethyl acetate (3:1).

1H-NMR (CDCl3) δ: 0,98 (d, J=6.4 Hz, 3H), of 1.16 (d, J=6.4 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), 2,89 (DD, J=8,8, of 14.0 Hz, 1H), 2,97 (DD, J=4,8, to 13.6 Hz, 1H), 3,52 (Sept, J=6.0 Hz, 1H), of 4.05 (DD, J=4,8, 8,8 Hz, 1H), 4,12-4,19 (m, 2H), 5,01 (width, 1H), 6,09-6,72 (m, 1H), for 6.81-6,83 (m, 1H), 6.75 in (t, J=1.6 Hz, 1H), 7,15 (t, J=7,6 Hz, 1H)

Example of getting a)

Ethyl ester of 2(S)-isopropoxy-3-(3(R)-oxiranylmethyl)propanoic acid

127 mg of Ethyl ester of 3-(3-hydroxyphenyl)-2(S)-isopropoxypropylamine acid was dissolved in 1.7 ml of N,N-dimethylformamide, were added 83 mg of potassium carbonate, 15 mg of fluoride is Asia and 156 mg (R)-glycidylmethacrylate and the mixture was stirred at room temperature overnight. The reaction solution was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel with 100 mg specified in the title compounds as colorless oils in the fraction of hexane-ethyl acetate (4:1).

1H-NMR (CDCl3) δas 0.96 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), was 2.76 (DD, J=2,8, 4.8 Hz, 1H), 2,87-of 2.93 (m, 2H), 2,98 (DD, J=4,8, of 14.0 Hz, 1H), 3.33 and-3,37 (m, 1H), 3,50 (Sept, J=6.0 Hz, 1H), of 3.95 (DD, J=6,0, 11.2 Hz, 1H), Android 4.04 (DD, J=4,8, and 9.2 Hz, 1H), 4,14-4,22 (m, 3H), 6,78 (DD, J=2,8, and 8.4 Hz, 1H), 6,83 (d, J=2.0 Hz, 1H), 6,86 (d, J=7,6 Hz, 1H), 7,19 (t, J=8,4 Hz, 1H)

Example of getting 289f)

Ethyl ester of 3-{3-[3-(2,4-dichlorophenoxy)-2(S)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acid

126 mg of Ethyl ester of 2-isopropoxy-3-(3-oxiranylmethyl)propanoic acid was diluted in ethanol, was added 130 mg of 2,4-dichlorophenol and 17 mg of potassium carbonate and the mixture was stirred at 50°C for 1.5 days. The reaction solution was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 177 mg specified in the title compounds as colorless oils in the fraction of hexane-ethyl acetate (3:1).

Example 289g)

3-{3-[3-(2,4-Dichlorophenoxy)-2(S)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acid

220 mg of Ethyl ester of 3-{3-[3-(2,4-dichlorophenoxy)-2(S)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acid was diluted in 4 ml of ethanol, followed by adding 1 ml of 1 n sodium hydroxide. Allowing the solution to stand at room temperature for 4 hours, neutralized 1 N. hydrochloric acid and was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 200 mg indicated in the title compounds as colorless oils in the fraction of hexane-ethyl acetate (3:2 → 2:3).

MSm/e(ESI) 465 (MNa+)

Example 290

3-{3-[3-(4-Chloro-2-cianfrocca)-2(S)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-cyanoprop specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

MSm/e(ESI) 456 (MNa+)

Example 291

3-(3-{2(S)-Hydroxy-3-[3-(1-hydroxy-1-methylethyl)phenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 3-(1-hydroxy-1-methylethyl)phenol specified in sagola the ke compound was obtained according to a similar method, as described in the example of obtaining 289f) and example 289g).

1H-NMR (CDCl3) δ: 1,04 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 1.57 (s, 6H), of 2.92 (DD, J=7,6, of 14.0 Hz, 1H), 3,10 (DD, J=3.2, and to 13.6 Hz, 1H), 3,55 (Sept, J=6.0 Hz, 1H), 4,11-4,12 (m, 5H), to 4.38 (Sept, J=5,2 Hz, 1H), 6,80-to 6.88 (m, 4H), 7,06 (d, J=7.2 Hz, 1H), 7,12 (t, J=2.4 Hz, 1H), 7,21 (DD, J=7,6, 8.0 Hz, 1H), 7,24 (m, 1H)

MSm/e(ESI) 453 (MNa+)

Example 292

3-(3-{2(R)-Hydroxy-3-[4-chlorophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-chlorophenol specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 2.92 (DD, J=7,2, to 13.6 Hz, 1H), 3,11 (DD, J=3,6, to 13.6 Hz, 1H), 3,53 (Sept, J=6.0 Hz, 1H), 4.09 to-4,17 (m, 5H), to 4.38 (Sept, J=5.6 Hz, 1H), 6,80-6,89 (m, 4H), 7,20-7,26 (m, 4H)

MSm/e(ESI) 431 (MNa+)

Example 293

3-(3-{2(S)-Hydroxy-3-[3,4-dichlorophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 3,4-dichlorophenol specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

1H-NMR (CDCl3) δ: 1,04 (d, J=6.4 Hz, 3H), of 1.17 (d, J=6.0 Hz, 3H), of 2.93 (DD, J=7,6, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, to 13.6 Hz, 1H), of 3.56 (Sept, J=6.0 Hz, 1H), 4.09 to to 4.16 (m, 5H), to 4.38 (Sept, J=6,4 Hz, 1H), 6,80 (DD, J=2,8, 8,8 Hz, 1H), 6,83 (Sirs, 2H), 6.87 in (d, J=7,6 Hz, 1H), 7,05 (d, J=2,8 Hz, 1H), 7,22 (DD, J=7,6, 8,8 is C, 1H), 7,34 (l, 8,8 Hz, 1H)

MSm/e(ESI) 465 (MNa+)

Example 294

3-(3-{2(R)-Hydroxy-3-[4-methylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), to 2.29 (s, 3H), 2.91 in (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=3,6, to 13.6 Hz, 1H), 3,54 (Sept, J=6,4 Hz, 1H), 4.09 to-4,17 (m, 5H), 4,37 (Sept, J=6,4 Hz, 1H), 6,80-6,87 (m, 5H), to 7.09 (d, J=8,4 Hz, 2H), 7,21 (DD, J=7,6, and 9.2 Hz, 1H)

MSm/e(ESI) 411 (MNa+)

Example 295

3-(3-{2(S)-Hydroxy-3-[2,4-dimethylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2,4-dimethylphenol specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), of 2.20 (s, 3H), and 2.26 (s, 3H), 2.91 in (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, of 14.0 Hz, 1H), 3,54 (Sept, J=6.0 Hz, 1H), 4,10-4,20 (m, 5H), 4,39 (Sept, J=5,2 Hz, 1H), 6.75 in (d, J=7,6 Hz, 1H), for 6.81-6.87 in (m, 3H), 6,93-6,97 (m, 2H), 7,22 (DD, J=8.0 a, 8,8 Hz, 1H)

MSm/e(ESI) 425 (MNa+)

Example 296

3-(3-{2(S)-Hydroxy-3-[4-chloro-2-methylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-METHYLPHENOL, ukazannoi the title compound was obtained according to a similar method, as described in the example of obtaining 289f) and example 289g).

MSm/e(ESI) 445 (MNa+)

Example 297

3-(3-{2(S)-Hydroxy-3-[4-chloro-2-fervency]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-terfenol specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

MSm/e(ESI) 449 (MNa+)

Example 298

3-(3-{2(S)-Hydroxy-3-[4-chloro-3-fervency]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-chloro-3-terfenol specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

MSm/e(ESI) 449 (MNa+)

Example 299

3-(3-{2(S)-Hydroxy-3-[2,4,6-trimethylphenol]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2,4,6-trimethylphenol specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

MSm/e(ESI) 439 (MNa+)

Example 300

3-(3-{2(S)-Hydroxy-3-[4-fluoro-2-methylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-fluoro-2-METHYLPHENOL specified in the title compound was obtained by analogues of the Neu methodology, as described in the example of obtaining 289f) and example 289g).

MSm/e(ESI) 429 (MNa+)

Example 301

3-(3-{2(S)-Hydroxy-3-[2-bromo-4-methylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2-bromo-4-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

MSm/e(ESI) 489 (MNa+)

Example 302

3-(3-{2(S)-Hydroxy-3-[2-acetyl-4-chlorophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2-acetyl-4-chlorophenol, specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

MSm/e(ESI) 473 (MNa+)

Example 303

3-(3-{2(S)-Hydroxy-3-[2,5-dimethylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2.5-dimethylphenol specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

MSm/e(ESI) 425 (MNa+)

Example 304

3-(3-{2(S)-Hydroxy-3-[2,5-dichlorophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2.5-dichlorphenol specified in the title compound was obtained by similar m is todica, as described in the example of obtaining 289f) and example 289g).

MSm/e(ESI) 465 (MNa+)

Example 305

3-(3-{2(S)-Hydroxy-3-[2-fluoro-5-triptoreline]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2-fluoro-5-cryptomaterial specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

MSm/e(ESI) 483 (MNa+)

Example 306

3-(3-{2(S)-Hydroxy-3-[5-fluoro-2-triptoreline]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 5-fluoro-2-cryptomaterial specified in the title compound was obtained by a similar procedure as described in example obtaining 289f) and example 289g).

MSm/e(ESI) 483 (MNa+)

Example 307

3-(3-{2(R)-Hydroxy-3-[2,4-dichlorophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Example of getting a)

Ethyl ester of 2(S)-isopropoxy-3-(3-(S)-oxiranylmethyl)propanoic acid

Using (S)-glycidylether specified in the title compound was obtained by a similar procedure as described in example obtaining e).

Example of getting 307b)

Ethyl ester of 3-{3-[3-(2,4-dichlorophenoxy)-2(R)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine sour is you

Using the ethyl ester of 2(S)-isopropoxy-3-(3-(S)-oxiranylmethyl)propanoic acid specified in the title compound was obtained by a similar procedure as described in example obtaining 289f).

Example C)

3-{3-[3-(2,4-Dichlorophenoxy)-2(R)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acid

Using the ethyl ester of 3-{3-[3-(2,4-dichlorophenoxy)-2(R)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acid specified in the title compound was obtained by a similar procedure as described in example 289g).

MSm/e(ESI) 465 (MNa+)

Example 308

3-{3-[3-(4-Chloro-2-cianfrocca)-2(R)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-cyanoprop specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

MSm/e(ESI) 458 (MNa+)

Example 309

3-(3-{2(R)-Hydroxy-3-[3-(1-hydroxy-1-methylethyl)phenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 3-dimetilgidrozinom specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

1H-NMR (CDCl3) δ: 1,04 (d,J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 1.57 (s, 6H), of 2.92 (DD, J=8,0, of 14.0 Hz, 1H), 3,10 (DD, J=3,6, to 13.6 Hz, 1H), 3,55 (Sept, J=6.0 Hz, 1H), 4.09 to is 4.21 (m, 5H), 4,39 (Sept, J=5,2 Hz, 1H), 6,80-to 6.88 (m, 4H), 7,05-7,07 (m, 1H), for 7.12 (t, J=2.4 Hz, 1H), 7,21 (DD, J=7,6, 8.0 Hz, 1H), 7.24 to 7,28 (m, 1H)

MSm/e(ESI) 453 (MNa+)

Example 310

3-(3-{2(S)-Hydroxy-3-[4-chlorophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-chlorophenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 2.92 (DD, J=8,0, to 13.6 Hz, 1H), 3,11 (DD, J=4,0, to 13.6 Hz, 1H), 3,55 (Sept, J=6.0 Hz, 1H), 4,08-4,17 (m, 5H), to 4.38 (Sept, J=4,8 Hz, 1H), 6,80-6,89 (m, 4H), 7,20-7,26 (m, 4H)

MSm/e(ESI) 431 (MNa+)

Example 311

3-(3-{2(R)-Hydroxy-3-[3,4-dichlorophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 3,4-dichlorophenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.4 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 2.93 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=6,0, of 14.0 Hz, 1H), of 3.56 (Sept, J=6,4 Hz, 1H), 4.09 to to 4.16 (m, 5H), 4,37 (Sept, J=6,4 Hz, 1H), 6,78-6,84 (m, 3H), 6,87 (d, J=7,6 Hz, 1H),? 7.04 baby mortality (d, J=2,8 Hz, 1H), 7,22 (t, J=7,6 Hz, 1H), 7,33 (l, 8,8 Hz, 1H)

MSm/e(ESI) 465 (MNa+)

Example 312

3-(3-{2(S)-Hydroxy-3-[4-methylphenoxy]propoxy}f the Nile)-2(S)-isopropoxypropylamine acid

Using 4-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6,4 Hz, 3H), of 1.16 (d, J=6,0 Hz, 3H), to 2.29 (s, 3H), 2.91 in (DD, J=8,0, 13,Hz, 1H), 3,11 (DD, J=4,0, 14,0 Hz, 1H), 3,54 (Sept, J=6,4 Hz, 1H), 4.09 to-4,17 (m, 5H), 4,37 (Sept, J=5,2Hz, 1H), 6,80-to 6.88 (m, 5H), to 7.09 (d, J=8,4 Hz, 2H), 7,21 (DD, J=7,6, 9,2 Hz, 1H)

MSm/e(ESI) 411 (MNa+)

Example 313

3-(3-{2(R)-Hydroxy-3-[2,4-dimethylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2,4-dimethylphenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

1H-NMR (CDCl3) δ: 1,02 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 2.20 (s, 3H), and 2.26 (s, 3H), 2.91 in (DD, J=8,0, to 13.6 Hz, 1H), 3,11 (DD, J=3,6, to 13.6 Hz, 1H), 3,54 (Sept, J=6.0 Hz, 1H), 4.09 to-4,20 (m, 5H), 4,39 (Sept, J=5,2 Hz, 1H), 6.75 in (d, J=8.0 Hz, 1H), 6,80-6,87 (m, 3H), 6,93-6,97 (m, 2H), 7,22 (DD, J=8.0 a, 8,8 Hz, 1H)

MSm/e(ESI) 425 (MNa+)

Example 314

3-(3-{2(S)-Hydroxy-3-[4-bromophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-bromophenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

1H-NMR (CDCl3) δ: 1,04 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), 2,9 (DD, J=7,6, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, to 13.6 Hz, 1H), 3,55 (Sept, J=6.0 Hz, 1H), 4,08-4,17 (m, 5H), to 4.38 (Sept, J=4,8 Hz, 1H), 6,80-6,84 (m, 4H), 6.87 in (d, J=7,6 Hz, 1H), 7,22 (DD, J=7,6, 8,8 Hz, 1H), 7,39 (d, J=8,8 Hz, 1H)

MSm/e(ESI) 475 (MNa+)

Example 315

3-(3-{2(S)-Hydroxy-3-[4-ethylenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-ethylphenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 1.20 (t, J=7.2 Hz, 3H), 2,59 (kV, J=7,6 Hz, 2H), 2.91 in (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=3,6, to 13.6 Hz, 1H), 3,54 (Sept, J=6.0 Hz, 1H), 4,10-4,17 (m, 5H), to 4.38 (Sept, J=5,2 Hz, 1H), 6,83 (t, J=6,8 Hz, 2H), 6,86 (d, J=8,4 Hz, 3H), 7,12 (d, J=8,4 Hz, 2H), 7,21 (DD, J=7,2, and 9.2 Hz, 1H)

MSm/e(ESI) 425 (MNa+)

Example 316

3-(3-{2(S)-Hydroxy-3-[4-chloro-3-methylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-chloro-3-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.4 Hz, 3H), of 2.92 (DD, J=7,6, to 13.6 Hz, 1H), 3,11 (DD, J=3,6, to 13.6 Hz, 1H), 3,55 (Sept, J=6.0 Hz, 1H), 4,08-4,16 (m, 5H), 4,37 (Sept, J=5,2 Hz, 1H), of 6.71 (DD, J=2,8, 8,8 Hz, 1H), 6,80-6,84 (m, 3H), 6.87 in (d, J=7.2 Hz, 1H), 7,19-7,24 (m, 2H)

MSm/e(ESI) 445 (MNa+)

Example 317

3-(3-{2(R)-Hydroxy-3-[3-PI is the p-4 fervency]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 3-chloro-4-terfenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

1H-NMR (CDCl3) δ: 1,04 (d, J=6.0 Hz, 3H), of 1.17 (d, J=6.0 Hz, 3H), of 2.93 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, of 14.0 Hz, 1H), of 3.56 (Sept, J=6,4 Hz, 1H), 4,07-4,16 (m, 5H), 4,37 (Sept, J=4,8 Hz, 1H), 6,77-6,84 (m, 3H), 6,87 (d, J=7,6 Hz, 1H), 6,98 (DD, J=3.2, and 6.0 Hz, 1H), 7,06 (t, J=8,8 Hz, 1H), 7,22 (DD, J=7,6, and 9.2 Hz, 1H)

MSm/e(ESI) 449 (MNa+)

Example 318

3-(3-{2(R)-Hydroxy-3-[4-chloro-2-methylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

MSm/e(ESI) 445 (MNa+)

Example 319

3-(3-{2(R)-Hydroxy-3-[4-chloro-2-fervency]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-terfenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

MSm/e(ESI) 449 (MNa+)

Example 320

3-(3-{2(R)-Hydroxy-3-[4-chloro-3-fervency]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-chloro-3-terfenol specified in segaloviciene received the same methodology, as described in the example of a 307b) and example 307c).

MSm/e(ESI) 449 (MNa+)

Example 321

3-(3-{2(R)-Hydroxy-3-[4-acetyl-2-methylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-acetyl-2-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

MSm/e(ESI) 453 (MNa+)

Example 322

3-(3-{2(R)-Hydroxy-3-[2,4,6-trimethylphenol]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2,4,6-trimethylphenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

MSm/e(ESI) 439 (MNa+)

Example 323

3-(3-{2(R)-Hydroxy-3-[4-fluoro-2-methylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-fluoro-2-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

MSm/e(ESI) 429 (MNa+)

Example 324

3-(3-{2(R)-Hydroxy-3-[2-bromo-4-methylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2-bromo-4-METHYLPHENOL specified in the title compound was obtained paralogical method as described in the example of a 307b) and example 307c).

MSm/e(ESI) 489 (MNa+)

Example 325

3-(3-{2(R)-Hydroxy-3-[2-acetyl-4-chlorophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2-acetyl-4-chlorophenol, specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

MSm/e(ESI) 473 (MNa+)

Example 326

3-(3-{2(R)-Hydroxy-3-[2,5-dimethylphenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2.5-dimethylphenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

MSm/e(ESI) 425 (MNa+)

Example 327

3-(3-{2(R)-Hydroxy-3-[2,5-dichlorophenoxy]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2.5-dichlorphenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

MSm/e(ESI) 465 (MNa+)

Example 328

3-(3-{2(R)-Hydroxy-3-[2-fluoro-5-triptoreline]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 2-fluoro-5-cryptomaterial specified in the title compound was obtained p the same methodology, as described in the example of a 307b) and example 307c).

MSm/e(ESI) 483 (MNa+)

Example 329

3-(3-{2(R)-Hydroxy-3-[5-fluoro-2-triptoreline]propoxy}phenyl)-2(S)-isopropoxypropylamine acid

Using 5-fluoro-2-cryptomaterial specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 307c).

MSm/e(ESI) 483 (MNa+)

Example 330

3-{3-[3-(2,4-Dichlorophenoxy)-2(R)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

174 mg of ethyl ester of 3-{3-[3-(2,4-dichlorophenoxy)-2(S)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acid (example obtaining e)) was dissolved in 5 ml of dichloromethane and the mixture was cooled to -78°C. To the solution was added 0.15 ml TRIFLUORIDE (diethylamino)sulfur and the mixture was stirred at room temperature for 2 days. Added water and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and solvent was removed. The residue was purified by chromatography on a column of silica gel to obtain 79 mg of ethyl ester of 3-{3-[3-(2,4-dichlorophenoxy)-2(R)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid in the fraction of hexane-ethyl acetate (7:1 → 5:1). The obtained product was dissolved in 4 ml of ethanol and 0.5 ml tetrahydrofuran is a, added 0.5 ml of 1 n lithium hydroxide and stirred overnight at room temperature. The solution was acidified using 1 N. hydrochloric acid and was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and solvent was removed. The residue was purified by chromatography on a column of silica gel to obtain 61 mg specified in the connection header in the fraction of hexane-ethyl acetate (3:1 → 1:1).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.4 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 2.92 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=3,6, of 14.0 Hz, 1H), 3,54 (Sept, J=6,4 Hz, 1H), 4,13 (kV, J=4.0 Hz, 1H), 4,28-4,39 (m, 4H), 5,18 (dt, J=4,0, 46,8 Hz, 1H), 6,82-6,92 (m, 4H), 7,19-7,29 (m, 3H)

MSm/e(ESI) 467 (MNa+)

Example 331

3-{3-[3-(4-Chlorophenoxy)-2(S)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

Using 4-chlorophenol specified in the title compound was obtained by a similar procedure as described in example obtaining e) and example 329.

1H-NMR (CDCl3) δ: 1,02 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.0 Hz, 3H), of 2.92 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=3,6, of 14.0 Hz, 1H), 3,55 (Sept, J=6.0 Hz, 1H), 4,13 (kV, J=3,6 Hz, 1H), 4.26 deaths (d, J=4.4 Hz, 2H), or 4.31 (d, J=4,8 Hz, 2H), 5,14 (Sept, J=4,8, or 47.2 Hz, 1H), 6,80-of 6.90 (m, 5H), 7,20-7,26 (m, 3H)

MSm/e(ESI) 433 (MNa+)

Example 332

3-{3-[3-(3,4-Dichlorophenoxy)-2(R)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

Using 3,4-dichlorophenol, specified in the title compound was obtained by a similar procedure as described in example obtaining e) and example 330.

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.4 Hz, 3H), of 1.17 (d, J=6.4 Hz, 3H), of 2.93 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, of 14.0 Hz, 1H), 3,55 (Sept, J=6,4 Hz, 1H), 4,14 (kV, J=3,6 Hz, 1H), 4.26 deaths (d, J=4.4 Hz, 2H), or 4.31 (t, J=4,8 Hz, 2H), 5,13 (Sept, J=4,8 and 46.8 Hz, 1H), 6,79-6,84 (m, 3H), to 6.88 (d, J=7,6 Hz, 1H), 7,05 (d, J=2,8 Hz, 1H), 7.23 percent (dt, J=1,2, 7,6 Hz, 1H), 7,34 (d, J=8,8 Hz, 1H)

MSm/e(ESI) 467 (MNa+)

Example 333

3-{3-[3-(4-Chloro-2-cianfrocca)-2(R)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-cyanoprop specified in the title compound was obtained by a similar procedure as described in example obtaining e) and example 330.

1H-NMR (CDCl3) δ: 1,04 (d, J=6.0 Hz, 3H), of 1.17 (d, J=6.0 Hz, 3H), equal to 2.94 (DD, J=7,6, to 13.6 Hz, 1H), 3,10 (DD, J=4,0, to 13.6 Hz, 1H), only 3.57 (Sept, J=6.0 Hz, 1H), 4,14 (kV, J=4.0 Hz, 1H), 4,28-4,50 (m, 4H), 5,20 (Sept, J=4,4, 46,4 Hz, 1H), 6,80-6,85 (m, 2H), to 6.88 (d, J=7,6 Hz, 1H), 6,98 (d, J=8,8 Hz, 1H), 7,22 (dt, J=0,8 and 7.6 Hz, 1H), 7,49-to 7.64 (m, 2H)

MSm/e(ESI) 458 (MNa+)

Example 334

3-{3-[3-(2,4-Dimethylphenoxy)-2(R)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

Using 2,4-dimethylphenol specified in the title compound was obtained by a similar procedure as described in example obtaining e) and example 330.

1H-NMR (CDCl3) δ: 1,01 (d, J=6,4 Hz, 3H), of 1.16 (d, J=6.4 Hz, 3H), of 2.20 (s, 3H), and 2.26 (s, 3H), 2.91 in (DD, J=8,4, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, to 13.6 Hz, 1H), 3,53 (Sept, J=6.0 Hz, 1H), 4,13 (kV, J=4.0 Hz, 1H), 4,21 is 4.35 (m, 4H), 5,16 (Sept, J=4,4, 47,6 Hz, 1H), 6,74 (d, J=8.0 Hz, 1H), 6,80-6,84 (m, 2H), 6.87 in (d, J=7,6 Hz, 1H), 6,93-6,97 (m, 2H), 7,22 (dt, J=0,6 and 7.6 Hz, 1H)

MSm/e(ESI) 458 (MNa+)

Example 335

3-{3-[3-(4-Chloro-2-methylphenoxy)-2(R)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example obtaining e) and example 330.

MSm/e(ESI) 447 (MNa+)

Example 336

3-{3-[3-(2,4-Dichlorophenoxy)-2(S)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

174 mg of ethyl ester of 3-{3-[3-(2,4-dichlorophenoxy)-2(R)-hydroxypropoxy]phenyl}-2(S)-isopropoxypropylamine acid (example obtaining 307b)) was dissolved in 5 ml of dichloromethane and the mixture was cooled to -78°C. To the solution was added 0.15 ml TRIFLUORIDE (diethylamino)sulfur and stirred at room temperature for 2 days. Added water and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and solvent was removed. The residue was purified by chromatography on a column of silica gel to obtain 87 mg of ethyl ester of 3-{3-[3-(2,4-dichlorophenoxy)-2(S)-forproperty]phenyl}-2(S)-isopro is oxopropanoic acid in the fraction of hexane-ethyl acetate (7:1 → 5:1). The obtained product was dissolved in 4 ml of ethanol and 0.5 ml of tetrahydrofuran, was added 0.5 ml of 1 n lithium hydroxide and the mixture was stirred over night at room temperature. The solution was acidified using 1 N. hydrochloric acid and was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and solvent was removed. The residue was purified by chromatography on a column of silica gel to obtain 83 mg specified in the connection header in the fraction of hexane-ethyl acetate (3:1 → 1:1).

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.4 Hz, 3H), of 1.16 (d, J=6.4 Hz, 3H), of 2.92 (DD, J=7,6, to 13.6 Hz, 1H), 3,11 (DD, J=3,6, to 13.6 Hz, 1H), 3,55 (Sept, J=6.0 Hz, 1H), 4,13 (kV, J=4.0 Hz, 1H), 4,29-4,39 (m, 4H), 5,18 (dt, J=4,4, 46,8 Hz, 1H), 6,82-6,92 (m, 4H), 7.18 in-7,26 (m, 3H)

MSm/e(ESI) 467 (MNa+)

Example 337

3-{3-[3-(4-Chlorophenoxy)-2(R)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

Using 4-chlorophenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 336.

1H-NMR (CDCl3) δ: 1,02 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.4 Hz, 3H), of 2.93 (DD, J=8,4, of 14.0 Hz, 1H), 3,10 (DD, J=4,0, of 14.0 Hz, 1H), 3,55 (Sept, J=6.0 Hz, 1H), 4,13 (kV, J=4.0 Hz, 1H), 4.26 deaths (d, J=4.4 Hz, 2H), or 4.31 (d, J=4,8 Hz, 2H), 5,11 (Sept, J=4,8, to 47.4 Hz, 1H), 6,80-of 6.90 (m, 5H), 7,20-7,26 (m, 3H)

MSm/e(ESI) 433 (MNa+)

Example 338

3-{3-[3-(3,4-Dichlorophenoxy)-2(S)-forproperty]the dryer is l}-2(S)-isopropoxypropylamine acid

Using 3,4-dichlorophenol specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 336.

1H-NMR (CDCl3) δ: of 1.03 (d, J=6.0 Hz, 3H), of 1.17 (d, J=6.4 Hz, 3H), of 2.93 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=3,6, of 14.0 Hz, 1H), of 3.56 (Sept, J=6.0 Hz, 1H), 4,14 (kV, J=4.0 Hz, 1H), 4.26 deaths (d, J=4.4 Hz, 2H), or 4.31 (t, J=a 4.4 Hz, 2H), 5,13 (Sept, J=4,8, or 47.2 Hz, 1H), 6,79-6,85 (m, 3H), to 6.88 (d, J=7,6 Hz, 1H), 7,05 (d, J=2,8 Hz, 1H), 7.23 percent (dt, J=7,6, 8,8 Hz, 1H), 7,34 (d, J=8,8 Hz, 1H)

MSm/e(ESI) 467 (MNa+)

Example 339

3-{3-[3-(4-Chloro-2-cianfrocca)-2(S)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-cyanoprop specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 336.

1H-NMR (CDCl3) δ: 1,04 (d, J=6.4 Hz, 3H), of 1.17 (d, J=6.0 Hz, 3H), equal to 2.94 (DD, J=8,0, to 13.6 Hz, 1H), 3,10 (DD, J=3,6, 13,2 Hz, 1H), only 3.57 (Sept, J=4.0 Hz, 1H), 4,15 (width, 1H), 4,29-4,50 (m, 4H), 5,20 (Sept, J=4,4, 46.4 Hz, 1H), for 6.81-6,85 (m, 2H), to 6.88 (d, J=7,6 Hz, 1H), 6,98 (d, J=8,8 Hz, 1H), 7,22 (dt, J=8.0 a, and 9.2 Hz, 1H), 7,50-rate of 7.54 (m, 2H)

MSm/e(ESI) 458 (MNa+)

Example 340

3-{3-[3-(2,4-Dimethylphenoxy)-2(S)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

Using 2,4-dimethylphenol specified in the title compound was obtained by a similar procedure as described in example 307b) and example 336.

1H-NMR (CDCl3) δ: 1,02 (d, J=6.4 Hz, 3H), of 1.16 (d, J=6.4 Hz, 3H), of 2.20 (s, 3H), and 2.26 (s, 3H), 2.91 in (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, of 14.0 Hz, 1H), 3,54 (Sept, J=6.0 Hz, 1H), 4,13 (kV, J=4.0 Hz, 1H), 4,24-4,35 (m, 4H), 5,16 (Sept, J=4,8, or 47.6 Hz, 1H), 6,74 (d, J=8.0 Hz, 1H), for 6.81-6.89 in (m, 3H), 6,93-6,97 (m, 2H), 7,22 (dt, J=7,6, 8,8 Hz, 1H)

MS m/e (ESI) 458 (MNa+)

Example 341

3-{3-[3-(4-Chloro-2-methylphenoxy)-2(S)-forproperty]phenyl}-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-METHYLPHENOL specified in the title compound was obtained by a similar procedure as described in example obtaining 307b) and example 336.

MS m/e (ESI) 447 (MNa+)

Example 342

2(S)-Isopropoxy-3-{3-[(4-triftoratsetilatsetonom)methyl]phenyl}propanoic acid

Example of getting a)

tert-Butyl ether {3-[3-(4(S)-benzyl-2-oxoacridine-3-yl)-1(R)-hydroxy-2(S)-isopropoxy-3-oxopropyl]benzyl}carbamino acid

A solution of 15.3 g of (4S)-4-benzyl-3-(2-isopropoxyphenyl)-1,3-oxazolidin-2-she in toluene (250 ml) was cooled to -75°and was added to 9.0 ml of triethylamine. Was added dropwise 55 ml dibutylphtalate (1M solution in dichloromethane) with such speed that the temperature of the reaction mixture did not exceed -70°C. Upon completion of adding dropwise, the mixture was stirred for 50 minutes and then the temperature of the reaction mass was raised to 0°C. the Mixture was stirred E. the e 50 minutes and again cooled to -75° C. To the resulting reaction solution under a layer of liquid was added to the solution containing 9.6 g of tert-butyl N-(3-formylmethyl)carbamate in dichloromethane (40 ml) and the mixture was stirred at -75°C for 30 minutes. Then the temperature was raised to 0°for about 1 hour, 10°With in 10 minutes. The temperature was gradually raised to room temperature and stirred the mixture at room temperature over night. The reaction solution was poured into a mixed solution of 200 ml of methanol, 200 ml of buffer with pH 7 (mixture of disodium hydrogen phosphate-citric acid) and 60 ml of hydrogen peroxide (30% aqueous solution) and was extracted with ethyl acetate. The organic layer was washed with saturated salt solution, dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 19.2 g specified in the title compounds as colorless oils in the fraction of hexane-ethyl acetate (1:1).

1H-NMR (CDCl3) δ: of 1.12 (d, J=6.0 Hz, 3H), 1,19 (d, J=6.0 Hz, 3H), of 1.44 (s, 9H), to 2.75 (DD, J=10,0, to 13.6 Hz, 1H), 3,25 (DD, J=2,4, of 13.6 Hz, 1H), 3,65 (Sept, J=6.0 Hz, 1H), and 3.72 (t, J=8.0 Hz, 1H), was 4.02 (d, J=8,4 Hz, 1H), the 4.29 (d, J=6.0 Hz, 1H), 4,37-4,43 (m, 1H), 4,85 (t, J=4,8 Hz, 1H), 4,91 (m, 1H), 5,43 (d, J=5.6 Hz, 1H), 7,12-7,73 (m, 8H), 7,63 (s, 1H)

Example of getting 342b)

tert-Butyl ether {3-[3-(4(S)-benzyl-2-oxoacridine-3-yl)-2(S)-isopropoxy-3-oxopropyl]benzyl}carbamino acid

19.2 g of tert-Butyl methyl ether {3-[3-(4(S)-benzyl-2-oxoacridine-3-yl)-1(R)-hydroxy-2(S)-isopropoxy-3-oxopropyl]benzyl}carbamino acid was dissolved in 100 ml of pyridine and added dropwise 4,35 ml methanesulfonanilide while cooling with ice. After stirring for 2 hours under ice cooling and for 3 hours at room temperature the reaction solution was diluted with ethyl acetate and washed successively 1 N. hydrochloric acid and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated solvent to obtain 1(R)-(3-aminomethylphenol)-3-(4(S)-benzyl-2-oxoacridine-3-yl-2(S)-isopropoxy-3-oxopropionate ether methanesulfonate acid. The obtained product was dissolved in 500 ml of ethanol, was added 10 g of 10% palladium on coal and 5 g of potassium acetate and the mixture was stirred over night at room temperature in a hydrogen atmosphere. The reaction solution was filtered and the filtrate was concentrated. The residue was diluted with ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 15.3 g specified in the title compounds as white solids in the fraction of hexane-ethyl acetate (:1 → 3:2).

1H-NMR (CDCl3) δ: 1,02 (d, J=6.0 Hz, 3H), of 1.16 (d, J=6.4 Hz, 3H), 1,45 (s, 9H), 2,78 (DD, J=9,6, to 13.6 Hz, 1H), 2.93 which are 2.98 (m, 2H), 3,30 (DD, J=2,4, 13,2 Hz, 1H), 3,51 (Sept, J=6.0 Hz, 1H), a 3.87-4,01 (m, 1H), 4,08-4,12 (m, 1H), 4,28 (d, J=6.0 Hz, 2H), to 4.52-4,59 (m, 1H), 4.80 to 4,88 (m, 1H), 5,34-of 5.40 (m, 1H), 7,12-7,35 (m, 9H)

Example of getting s)

Methyl ester of 3-[3-(tert-butoxycarbonylamino)phenyl]-2(S)-isopropoxypropylamine acid

15.3 g of tert-butyl methyl ether {3-[3-(4(S)-benzyl-2-oxoacridine-3-yl)-2(S)-isopropoxy-3-oxopropyl]benzyl}carbamino acid was dissolved in 300 ml of tetrahydrofuran, was added sequentially 15 ml of 30% aqueous hydrogen peroxide solution and 75 ml of 1 N. aqueous solution of lithium hydroxide under ice cooling and the mixture was stirred at room temperature overnight. The reaction solution was treated with water, was extracted with dichloromethane and the aqueous layer was acidified using 1 N. hydrochloric acid. The mixture was extracted (3 times) with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated to obtain 16,68 g of 3-[3-(tert-butoxycarbonylamino)phenyl]-2(S)-isopropoxypropylamine acid. The obtained product was dissolved in 100 ml of N,N-dimethylformamide were added successively 7 g of potassium bicarbonate and 3.5 ml of iodomethane and the mixture was stirred over night at room temperature. The reaction R is the target was diluted with ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel with getting 8,58 g specified in the title compounds as white solids in the fraction of hexane-ethyl acetate (4:1).

1H-NMR (CDCl3) δ: of 0.94 (d, J=6.0 Hz, 3H), 1.14 in (d, J=6.4 Hz, 3H), of 1.46 (s, 9H), of 2.92 (DD, J=9,2, of 14.0 Hz, 1H), 2,99 (DD, J=5,2, of 14.0 Hz, 1H), 3,48 (Sept, J=6.0 Hz, 1H), 4,06 (DD, J=4,8, 8,8 Hz, 1H), 4,29 (sird, J=6.0 Hz, 2H), 4,80 (width, 1H), 7,13-to 7.15 (m, 3H), 7,24 (t, J=7,6 Hz, 1H)

Example of getting 342d)

Methyl ester 2(S)-isopropoxy-3-{3-[(4-triftoratsetilatsetonom)methyl]phenyl}propanoic acid

234 mg of Methyl ester of 3-[3-(tert-butoxycarbonylamino)phenyl]-2(S)-isopropoxypropylamine acid was dissolved in 10 ml of 1,4-dioxane and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated and the residue was treated with 320 mg of 4-triftormetilfosfinov, 500 mg tetrabutylammonium and 650 mg of cesium carbonate and dissolved in 7 ml of N,N-dimethylformamide. Slowly adding dry ice, the solution was stirred over night at room temperature. The reaction solution was dissolved in ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on to what the PMC with silica gel to obtain 173 mg specified in the connection header in the fraction of hexane-ethyl acetate (3:1).

Example e)

2(S)-Isopropoxy-3-{3-[(4-triftoratsetilatsetonom)methyl]phenyl}propanoic acid

173 mg of Methyl ester 2(S)-isopropoxy-3-{3-[(4-triftoratsetilatsetonom)methyl]phenyl}propanoic acid was dissolved in 4 ml of ethanol was added 1 ml of 1 n lithium hydroxide and the mixture was stirred at room temperature for 3 hours. The reaction solution was acidified using 1 N. hydrochloric acid, was extracted with ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 168 mg specified in the connection header in the fraction of hexane-ethyl acetate (3:2).

1H-NMR (CDCl3) δ: 1,00 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 2,95 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=2,4, of 13.6 Hz, 1H), 3,54 (Sept, J=6,4 Hz, 1H), 4,13 (kV, J=4.0 Hz, 1H), 4,37 (d, J=6.0 Hz, 2H), 5,12 (width, 1H), 5,19 (s, 2H), 7,15-7,19 (m, 3H), 7,25-7,27 (m, 1H), of 7.48 (d, J=8.0 Hz, 1H), 7.62mm (t, J=8.0 Hz, 1H)

MSm/e(ESI) 462 (MNa+)

Example 343

2(S)-Isopropoxy-3-{3-[(3-triftoratsetilatsetonom)methyl]phenyl}propanoic acid

Using 3-triftormetilfosfinov specified in the title compound was obtained by a similar procedure as described in example I).

1H-NMR (CDCl3)δ : 0,99 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.4 Hz, 3H), equal to 2.94 (DD, J=8,4, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, of 14.0 Hz, 1H), 3,53 (Sept, J=6,4 Hz, 1H), 4,12 (kV, J=4.0 Hz, 1H), to 4.38 (d, J=6,4 Hz, 2H), 5,13 (width, 1H), 5,19 (s, 2H), 7,11-to 7.18 (m, 3H), 7.24 to 7,29 (m, 1H), of 7.48 (t, J=7.2 Hz, 1H), 7,53-to 7.64 (m, 2H)

MSm/e(ESI) 462 (MNa+)

Example 344

2(S)-Isopropoxy-3-{3-[(4-chlorobenzenesulphonamide)methyl]phenyl}propanoic acid

Using 4-chlorobenzylchloride specified in the title compound was obtained by a similar procedure as described in example I).

1H-NMR (CDCl3) δ: 1,00 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), equal to 2.94 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, of 14.0 Hz, 1H), 3,53 (Sept, J=6.0 Hz, 1H), 4,12 (kV, J=4.0 Hz, 1H), 4,36 (d, J=6.0 Hz, 2H), 5,07 (width, 1H), 5,09 (s, 2H), 7,11-to 7.18 (m, 3H), 7.24 to 7,34 (m, 5H)

MSm/e(ESI) 428 (MNa+)

Example 345

2(S)-Isopropoxy-3-{3-[(4-triftormetilfullerenov)methyl]phenyl}propanoic acid

Using 4-cryptomaterial specified in the title compound was obtained by a similar procedure as described in example I).

1H-NMR (CDCl3) δ: 0,99 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), equal to 2.94 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=3,6, of 14.0 Hz, 1H), 3,53 (Sept, J=6.0 Hz, 1H), 4,12 (kV, J=4.0 Hz, 1H), 4,37 (d, J=6.0 Hz, 2H), 5,09 (width, 1H), 5,13 (s, 2H), 7,12-to 7.18 (m, 3H), 7.24 to 7,28 (m, 1H), 7,40 (d, J=8.0 Hz, 2H)

MSm/e(ESI) 478 (MNa+)

Example 346

3-(3-{[4-(1-Hydroxy-1-methylethyl)basiliximab is ylamino]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 1-hydroxy-1-methylethylbenzene specified in the title compound was obtained by a similar procedure as described in example I).

1H-NMR (CDCl3) δ: 1,00 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.4 Hz, 3H), 1,58 (s, 6H), of 2.93 (DD, J=7,2, to 12.8 Hz, 1H), 3,06-of 3.12 (m, 1H), 3,52 (Sept, J=6.0 Hz, 1H), 4,11 (t, J=7.2 Hz, 1H), 4,37 (d, J=5.6 Hz, 2H), 5,07 (Shir., 1H), 5,13 (s, 2H), 7,14-7,17 (m, 3H), 7.24 to 7,27 (m, 1H), 7,35 (d, J=8,4 Hz, 2H), 7,49 (d, J=8.0 Hz, 2H)

MSm/e(ESI) 452 (MNa+)

Example 347

3-{3-[(2,5-Dichlorobenzonitrile)methyl]phenyl}-2(S)-isopropoxypropylamine acid

Example of getting a)

Methyl ester 3-(3-aminomethylphenol)-2(S)-isopropoxypropylamine acid

to 1.034 g of Methyl ester of 3-[3-(tert-butoxycarbonylamino)phenyl)]-2(S)-isopropoxypropylamine acid was dissolved in 20 ml of hydrochloride of 1,4-dioxane and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated, the residue was dissolved in ethyl acetate and washed with saturated aqueous solution of sodium bicarbonate. The organic layer was dried over anhydrous magnesium sulfate and the solvent evaporated to obtain 653 mg specified in the title compounds as colorless oils.

Example 347b)

3-{3-[(2,5-Dichlorobenzonitrile)methyl]phenyl}-2(S)-isopropoxypropylamine acids is

305 mg of Methyl ester of 3-(3-aminomethylphenol)-2(S)-isopropoxypropylamine acid was dissolved in 3 ml dichloromethane was added under ice cooling a solution of 0.05 ml of pyridine and 180 mg triphosgene in dichloromethane (4 ml). Added 0.5 ml of triethylamine and the mixture was stirred at room temperature for 30 minutes. The solution was filtered and diluted to a total of 5 ml To the received 0.5 ml of a solution (containing about 13 mg of isocyanate methyl ester 3-(3-aminomethylphenol)-2(S)-isopropoxypropylamine acid) was added 20 mg of 2,5-amyl-metacresol. The reaction solution was concentrated, added 0.4 ml of tetrahydrofuran and the mixture was stirred at room temperature for 30 minutes. Added 0.5 ml of ethanol and 0.1 ml of 1 n sodium hydroxide and continued stirring overnight. The reaction solution was acidified using 1 N. hydrochloric acid and was extracted with ethyl acetate. Concentrated solvent and the residue was purified by high-performance liquid chromatography with reversed phase with obtaining 10,27 mg specified in the connection header.

MSm/e(ESI) 462 (MNa+)

Example 348

3-(3-{[3,5-Dichlorobenzonitrile]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 3,5-dichlorobenzoyl alcohol specified in the title the connection information received by the same methodology, as described in example 347b).

MSm/e(ESI) 462 (MNa+)

Example 349

3-(3-{[3,4-Diferenzierbaren]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 3,4-differentialy alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 432 (MNa+)

Example 350

3-(3-{[4-Methylbenzyloxycarbonyl]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-methylbenzylamine alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

1H-NMR (CDCl3) δ: 0,99 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), of 2.35 (s, 3H), of 2.93 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=3,6, of 14.0 Hz, 1H), 3,52 (Sept, J=6,4 Hz, 1H), 4,11 (kV, J=4.0 Hz, 1H), 4,36 (d, J=5.6 Hz, 2H), of 5.05 (width, 1H), 5,09 (s, 2H), 7,14-to 7.18 (m, 5H), 7.23 percent-7,28 (m, 3H)

MSm/e(ESI) 408 (MNa+)

Example 351

3-(3-{[4-Ethylbenzyltoluidines]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-ethylbenzylamine alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

1H-NMR (CDCl3) δ: 0,99 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), of 1.23 (t, J=7.2 Hz, 3H), 2,65 (kV, J=7,6 Hz, 2H), 2,93 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, of 14.0 Hz, 1H), 3,52 (Sept, J=6,4 Hz, 1H), 4,11 kV, J=4.0 Hz, 1H), 4,36 (d, J=6.0 Hz, 2H), of 5.05 (width, 1H), 5,10 (s, 2H), 7,14-7,21 (m, 5H), 7.23 percent-7,31 (m, 3H)

MSm/e(ESI) 422 (MNa+)

Example 352

3-(3-{[3,4-Dimethylbenzenesulfonamide]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 3,4-dimethylbenzylamine alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

1H-NMR (CDCl3) δ: 0,99 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), and 2.26 (s, 6H), of 2.93 (DD, J=8,0, to 13.6 Hz, 1H), 3,10 (DD, J=3,6, of 14.0 Hz, 1H), 3,52 (Sept, J=6.0 Hz, 1H), 4,11 (kV, J=4.0 Hz, 1H), 4,36 (d, J=5.6 Hz, 2H), 5,07 (Sirs, 3H), 7,09-to 7.18 (m, 6H), 7,26-7,28 (m, 1H)

MSm/e(ESI) 422 (MNa+)

Example 353

3-(3-{[4-Ethoxymethyleneamino]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-ethoxybenzyl alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 438 (MNa+)

Example 354

3-(3-{[3-Triftormetilfullerenov]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 3-cryptomaterial alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

1H-NMR (CDCl3) δ: 0,99 (d, J=6.4 Hz, 3H)and 1.15 (d, J=6.4 Hz, 3H), equal to 2.94 (DD, J=8,0, of 14.0 Hz, 1H), 3,11 (DD, J=4,0, 14,0 Hz, 1H), 3,53 (Sept, J=6.0 Hz, 1H), 4,12 (kV, J=4.0 Hz, 1H), to 4.38 (d, J=6.0 Hz, 2H), 5,13 (Sirs, 1H), further 5.15 (s, 2H), 7,14-7,20 (m, 4H), 7,21-7,30 (m, 3H), 7,38 (t, J=8.0 Hz, 1H)

MSm/e(ESI) 478 (MNa+)

Example 355

3-{3-[(Benzo(1,3]dioxol-5-ylmethoxycarbonyl)methyl]phenyl}-2(S)-isopropoxypropylamine acid

Using peperonity alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

1H-NMR (CDCl3) δ: 0,99 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.4 Hz, 3H), of 2.93 (DD, J=8,4, of 14.0 Hz, 1H), 3,11 (DD, J=3,6, of 14.0 Hz, 1H), 3,52 (Sept, J=6.0 Hz, 1H), 4,11 (kV, J=3,6 Hz, 1H), 4,36 (d, J=5.6 Hz, 2H), 5,03 (s, 3H), 5,96 (s, 2H), 6,76-6,89 (m, 3H), 7,12-to 7.18 (m, 3H), 7, 23-7,28 (m, 1H)

MSm/e(ESI) 438 (MNa+)

Example 356

2(S)-Isopropoxy-3-{3-[(6-methylpyridin-2-ylmethoxycarbonyl)methyl]phenyl}propanoic acid

Using (6-methylpyridin-2-yl)methanol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 409 (MNa+)

Example 357

2(S)-Isopropoxy-3-{3-[(6-methylpyridin-3-ylmethoxycarbonyl)methyl]phenyl}propanoic acid

Using (6-methylpyridin-3-yl)methanol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 409 (MNa+)

Example 38

2(S)-Isopropoxy-3-{3-[(4-methoxy-3,5-dimethylpyridin-2-ylmethoxycarbonyl)methyl]phenyl}propanoic acid

Using (4-methoxy-3,5-dimethylpyridin-2-yl)methanol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 453 (MNa+)

Example 359

3-{3-[(6-tert-Butoxycarbonylamino-3-ylmethoxycarbonyl)methyl]phenyl}-2(S)-isopropoxypropylamine acid

Using tert-butyl ester (5-hydroxymethyluracil-2-yl)carbamino acid specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 510 (MNa+)

Example 360

3-{3-[(6-Aminopyridine-3-ylmethoxycarbonyl)methyl]phenyl}-2(S)-isopropoxypropylamine acid

3-{3-[(6-tert-Butoxycarbonylamino-3-ylmethoxycarbonyl)methyl]phenyl}-2(S)-isopropoxyphenol acid was dissolved in triperoxonane acid and the mixture was concentrated. The residue was purified by high-performance liquid chromatography with reversed phase with obtaining specified in the connection header.

MSm/e(ESI) 510 (MNa+)

Example 361

3-{3-[(1H-Benzimidazole-2-ylmethoxycarbonyl)methyl]phenyl}-2(S)-isopropoxide the new acid

Using (1H-benzimidazole-2-yl)methanol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 434 (MNa+)

Example 362

2(S)-Isopropoxy-3-{3-[(3-methyl-3H-benzimidazole-5-ylmethoxycarbonyl)methyl]phenyl}propanoic acid

Using (3-methyl-3H-benzimidazole-5-yl)methanol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 449 (MNa+)

Example 363

3-(3-{[2-(4-Chlorophenyl)ethoxycarbonyl]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-chloro-2-finitely alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 442 (MNa+)

Example 364

3-(3-{[2-(3-Chlorophenyl)ethoxycarbonyl]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 3-chloro-2-finitely alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 442 (MNa+)

Example 365

3-(3-{[2-(4-Bromophenyl)ethoxycarbonyl]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 4-bromo-2-finitely alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 486 (MNa+)

Example 366

3-(3-{[2-(2,4-Dichlorophenyl)ethoxycarbonyl]methyl}phenyl)-2(S)-isopropoxypropylamine acid

Using 2,4-dichloro-2-finitely alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 476 (MNa+)

Example 367

2(S)-Isopropoxy-3-{3-[(quinoline-2-ylmethoxycarbonyl)methyl]phenyl}propanoic acid

Using quinoline-2-ylmethanol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 445 (MNa+)

Example 368

2(S)-Isopropoxy-3-{3-[(quinoline-4-ylmethoxycarbonyl)methyl]phenyl}propanoic acid

Using quinoline-4-ylmethanol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 445 (MNa+)

Example 369

2(S)-Isopropoxy-3-{3-[(4-propoxybenzaldehyde)methyl]phenyl}propanoic acid

Using 4-propoxybenzene alcohol specified in zag is lowke compound was obtained according to a similar method, as described in example 347b).

MSm/e(ESI) 452 (MNa+)

Example 370

2(S)-Isopropoxy-3-{3-[(4-isopropoxybenzonitrile)methyl]phenyl}propanoic acid

Using 4-isopropoxybenzoic alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 452 (MNa+)

Example 371

2(S)-Isopropoxy-3-{3-[(2-chloro-4-propoxybenzaldehyde)methyl]phenyl}propanoic acid

Using 2-chloro-4-propoxybenzene alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 486 (MNa+)

Example 372

2(S)-Isopropoxy-3-{3-[(4-isopropylaminocarbonyl)methyl]phenyl}propanoic acid

Using 4-isopropylbenzylamine alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 436 (MNa+)

Example 373

2(S)-Isopropoxy-3-{3-[(4-butylbenzenesulfonamide)methyl]phenyl}propanoic acid

Using 4-butylbenzyl alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

M is m/e(ESI) 450 (MNa+)

Example 374

2(S)-Isopropoxy-3-{3-[(2-fluoro-4-triftoratsetilatsetonom)methyl]phenyl}propanoic acid

Using 2-fluoro-4-tripterocalyx alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 480 (MNa+)

Example 375

2(S)-Isopropoxy-3-{3-[(3-fluoro-4-triftoratsetilatsetonom)methyl]phenyl}propanoic acid

Using 3-fluoro-4-tripterocalyx alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 480 (MNa+)

Example 376

2(S)-Isopropoxy-3-{3-[(4-fluoro-3-triftoratsetilatsetonom)methyl]phenyl}propanoic acid

Using 4-fluoro-3-tripterocalyx alcohol specified in the title compound was obtained by a similar procedure as described in example 347b).

MSm/e(ESI) 480 (MNa+)

MSm/e(ESI) 440 (MN+)

Example 377

3-[(4-Ethoxy-3-phenylcarbamoyloxy)phenyl]-2-isopropoxypropylamine acid

Example of getting a)

Ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol

400 mg of sodium Hydride su who was Bandarawela in 10 ml of tetrahydrofuran was added under ice cooling, 15 ml of a solution of 2.8 g of diethyl 2-isopropoxyphenol in tetrahydrofuran. The solution was stirred at room temperature for 30 minutes and was added 25 ml of a solution of 2.4 g of 3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)-4-ethoxybenzaldehyde in tetrahydrofuran. After stirring over night at room temperature the reaction solution was treated with 1 N. hydrochloric acid and was extracted with ethyl acetate. The organic layer was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain ethyl (E,Z)-3-[3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)-4-ethoxyphenyl]-2-isopropoxy-2-propenoate in the fraction of hexane-ethyl acetate (4:1). Then the obtained ethyl (E,Z)-3-[3-({[1-(tert-butyl)-1,1-dimethylsilane]oxy}methyl)-4-ethoxyphenyl]-2-isopropoxy-2-propenoate was dissolved in 25 ml of tetrahydrofuran and the resulting solution was added 10 ml of tetrabutylammonium (1M solution in tetrahydrofuran). After stirring at room temperature for 7 hours, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with water and saturated salt solution, dried over anhydrous magnesium sulfate and the solvent evaporated. Then the obtained crude product was dissolved in 25 ml of ethanol, the mixture was treated with 0.40 g of rhodium on aluminium oxide and stirred overnight in an atmosphere of water is kind. The catalyst was filtered and the solvent evaporated, then the residue was purified by chromatography on a column of silica gel to obtain 0.96 g specified in the connection header in the fraction of hexane-ethyl acetate (3:1).

1H-NMR (CDCl3) δ: 0,97 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), USD 1.43 (t, J=6.8 Hz, 3H), 2,87 (DD, J=8,4, of 14.0 Hz, 1H), equal to 2.94 (DD, J=5,2, of 14.0 Hz, 1H), 3,50 (Sept, J=6.0 Hz, 1H), 4,00 (DD, J=5,2, and 8.4 Hz, 1H), 4,07 (kV, J=6,8 Hz, 2H), 4,14-4,20 (m, 2H), of 4.66 (s, 2H), 6,78 (d, J=8.0 Hz, 1H), 7,13 (d, J=8.0 Hz, 1H), 7,14 (s, 1H)

Example of getting 377b)

3-[(4-Ethoxy-3-phenylcarbamoyloxy)phenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 402 (MN+)

Example 378

3-[(4-Ethoxy-3-p-taylorslolemail)phenyl]-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and p-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 416 (MN+)

Example 379

3-{[4-Ethoxy-3-(4-methoxyphenyl)carbamoyloxymethyl]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 4-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 432 (MN+)

Example 380

3-{[3-(4-Chlorophenyl)carbamoyloxymethyl-4-ethoxy]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 4-chloronicotinate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 436 (MN+)

Example 381

3-{[3-(2,4-Dichlorophenyl)carbamoyloxymethyl-4-ethoxy]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 2,4-dichlorophenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 470 (MN+)

Example 382

3-({4-Ethoxy-3-[4-(trifluoromethyl)phenyl]carbamoyloxymethyl}phenyl)-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and α,α,α-Cryptor-p-tolerization specified in the title compound was obtained by similar is eodice, as described in example 158.

MSm/e(ESI) 470 (MN+)

Example 383

3-{[3-(2,4-Acid)carbamoyloxymethyl-4-ethoxy]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 2,4-dimethoxyphenylacetic specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 462 (MN+)

Example 384

3-{[3-(4-Dimethylaminophenyl)carbamoyloxymethyl-4-ethoxy]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 4-dimethylaminopyridine specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 445 (MN+)

Example 385

3-{[3-(3,4-Acid)carbamoyloxymethyl-4-ethoxy]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 3,4-dimethoxyphenylacetone specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 462 (MN+)

Example 386

3-({3-[5-(Benzo[1,3]dioxole)]carbamoyloxymethyl-4-ethoxy}phenyl)-2-isopropoxypyridine the Wai acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 3,4-(methylendioxy)phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 446 (MN+)

Example 387

3-{[3-(2,4-Differenl)carbamoyloxymethyl-4-ethoxy]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 2,4-differentiational specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 438 (MN+)

Example 388

3-{[4-Ethoxy-3-(3-methoxyphenyl)carbamoyloxymethyl]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 3-methoxyphenylalanine specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 432 (MN+)

Example 389

3-{[3-(3-Chlorophenyl)carbamoyloxymethyl-4-ethoxy]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 3-chloronicotinate specified in the title compound, polucheniya the same methodology, as described in example 158.

MSm/e(ESI) 436 (MN+)

Example 390

3-{[4-Ethoxy-3-(4-ethoxyphenyl)carbamoyloxymethyl]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 4-ethoxyphenylurea specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 446 (MN+)

Example 391

3-({4-Ethoxy-3-[4-(triptoreline)phenyl]carbamoyloxymethyl}phenyl)-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 4-(triptoreline)phenylisocyanate specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 486 (MN+)

Example 392

3-{[4-Ethoxy-3-(4-forfinal)carbamoyloxymethyl]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 4-forgenerations specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 420 (MN+)

Example 393

3-{[3-(4-Cyanophenyl)carbamoyloxymethyl-4-ethoxy]phenyl}-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and 4-cyanophenylacetic specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 427 (MN+)

Example 394

3-({4-Ethoxy-3-[3-(trifluoromethyl)phenyl]carbamoyloxymethyl}phenyl)-2-isopropoxypropylamine acid

Using ethyl 3-[4-ethoxy-3-(hydroxymethyl)phenyl]-2-isopropoxyphenol and α,α,α-Cryptor-m-tolerization specified in the title compound was obtained by a similar procedure as described in example 158.

MSm/e(ESI) 470 (MN+)

Example 395

3-{4-Ethoxy-3-[2-(phenylcarbamoyloxy)ethyl]phenyl}-2-isopropoxypropylamine acid

Example of getting a)

2-(2-Ethoxyphenyl)ethanol

4.4 g of 2-Hydroxyphenethyl alcohol was dissolved in 80 ml of N,N-dimethylformamide was added 15.3 g ethyliodide and 4.7 g of potassium carbonate. After stirring at 70°overnight the solution was diluted with ethyl acetate and washed successively with water and saturated salt solution. The organic layer was dried over anhydrous magnesium sulfate and then the solvent evaporated. The residue was purified by chromatography on a column of silica gel to obtain 3.2 g specified in the connection header in fracc and hexane-ethyl acetate (4:1).

1H-NMR (CDCl3) δ: of 1.43 (t, J=6.8 Hz, 3H), of 2.92 (t, J=6.0 Hz, 2H), 3,85 (width, 2H), 4,05 (kV, J=6,8 Hz, 2H), 6,85-6,91 (m, 2H), 7,15-7,22 (m, 1H)

Example of getting 395b)

3-[2-(tert-Butyldimethylsilyloxy)ethyl]-4-ethoxybenzaldehyde

Using 2-(2-ethoxyphenyl)ethanol, specified in the title compound was obtained by a similar procedure as described in example obtaining a) and then in the example of obtaining 127b).

1H-NMR (CDCl3) δ: 0,00 (s, 6H), to 0.88 (s, 9H), to 1.48 (t, J=6.8 Hz, 3H), of 2.92 (t, J=7.2 Hz, 2H), 3,83 (t, J=7.2 Hz, 2H), 4,15 (kV, J=6,8 Hz, 2H), 6,94 (d, J=8,4 Hz, 1H), 7,72 (s, 1H), of 7.75 (d, J=8,4 Hz, 1H), 9,87 (s, 1H)

Example of getting s)

Ethyl 3-[4-ethoxy-3-(2-hydroxyethyl)phenyl]-2-isopropoxyphenol

Using 3-[2-(tert-butyldimethylsilyloxy)ethyl]-4-ethoxybenzaldehyde and triethyl 2-isopropoxyethanol specified in the title compound was obtained by a similar procedure as described in example obtaining 157b).

1H-NMR (CDCl3) δ: 0,97 (d, J=6.0 Hz, 3H)and 1.15 (d, J=6.0 Hz, 3H), 1,24 (t, J=7.2 Hz, 3H), of 1.41 (t, J=6.8 Hz, 3H), of 2.86 (DD, J=8,4, of 14.0 Hz, 1H), 2,88 (t, J=6.4 Hz, 2H), 2,92 (DD, J=5,2, of 14.0 Hz, 1H), 3,50 (Sept, J=6,0 Hz, 1H), 3,82 (t, J=6.4 Hz, 2H), 3,99-of 4.05 (m, 3H), 4,14-4,20 (m, 2H), 6,76 (d, J=8,4 Hz, 1H),? 7.04 baby mortality-7,07 (m, 2H)

Example of getting 395d)

3-{4-Ethoxy-3-[2-(phenylcarbamoyloxy)ethyl]phenyl}-2-isopropoxypropylamine acid