Gaba-ergic modulators

FIELD: medicine.

SUBSTANCE: invention is related to new derivatives of benzoindazole of formula I , where radicals A1, A2, A3, R1, R2, R3, R4 and n have values mentioned in formula of invention, and their pharmaceutically acceptable salts, and also to application of these compounds for production of medicinal agent intended for modulation of α2-subsort of GABA receptor, and pharmaceutical composition that contains it.

EFFECT: application of compounds for preparation of medicinal agent intended for treatment of depression, disorder in the form of anxiety, psychic disorder, disturbed ability to learning and cognition, sleep disturbance, disorder in the form of cramps or fits or pain.

16 cl, 5 tbl, 40 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula I, where

R1means CHRfRgWith2-C10quinil, halogen, cyano, -C(=Z)Ro, -NRfSO2Rsup> o,
-N=CRfNRjRk, -S(O)mRh, CONRiOthero,
R2means hydrogen, C1-C6alkyl, C3-C6cycloalkyl,3-C6cycloalkyl(C1-C3)alkyl, C1-C3alkoxycarbonyl(C1-C3)alkyl or phenyl(C1-C6)alkyl,
R3means phenyl or pyridyl, thienyl, furyl, benzothiazolyl, each of which is optionally substituted by one or more substituents independently selected from the group comprising C1-C6alkyl, C1-C6alkoxy, halogen, C1-C6halogenated,
Rfmeans hydrogen or C1-C10alkyl,
Rgmeans2-C10alkenyl, -NHNH2, cyano, -OC(=O)Rf, -S(O)mRhor-X2(C=O)X1Rf,
Rhmeans C1-C6alkyl or NRjRk,
Rimeans3-C6cycloalkyl or3-C6cycloalkyl(C1-C3)alkyl,
Rjand Rk(1) independently mean hydrogen, C1-C6alkyl, C1-C6heteroalkyl or (2) together with the nitrogen atom to which they are attached represent (CH2)2X1(CH2)2,
Romeans C1-C6alkyl,
X1and X2independently denote-O -, or-NRfl-,
Z denotes O or NORo,
m R the VNO integer from 0 to 2,
n is 0,
And1And2and3independently mean C or N, provided that at least one of the A1And2and3means CH,
and its pharmaceutically acceptable salts.

2. The compound according to claim 1, where
R1means CHRfRgWith2-C10quinil, halogen, cyano, -C(=Z)Ro, -NRfSO2Ro, -S(O)mRo, CONRiOthero,
R2means hydrogen, C1-C6alkyl, C3-C6cycloalkyl,3-C6cycloalkyl(C1-C3)alkyl, C1-C3alkoxycarbonyl(C1-C3)alkyl or phenyl(C1-C6)alkyl,
R3means phenyl or pyridyl, thienyl, furyl or benzothiazolyl, each of which is optionally substituted by one or more substituents independently selected from the group comprising C1-C6alkyl, C1-C6alkoxy, halogen, C1-C6halogenated,
Rfmeans hydrogen or C1-C10alkyl,
Rgmeans2-C10alkenyl,
Romeans C1-C6alkyl,
Rimeans3-C6cycloalkyl or3-C6cycloalkyl(C1-C3)alkyl,
Z denotes O or NORo,
m is an integer from 0 to 2,
n is 0,
And1And2and3independently mean C or N, provided that Myung is our least one And 1And2and3means CH.

3. The compound according to claim 1, where R1means CHRfRgWith2-C10quinil or halogen, R2means hydrogen or C1-C6alkyl, and R3means optionally substituted phenyl.

4. The compound according to claim 1, where R1means-S(O)mRh, R2means hydrogen or C1-C6alkyl, R3means optionally substituted phenyl, and m is 2.

5. The compound according to claim 1, where R1means CHRfRg, Rgmeans-X2C(=O)X1Rf, R2means hydrogen or C1-C6alkyl, and R3means optionally substituted phenyl.

6. The compound according to claim 1, selected from the group including:
3-allyl-7-(2,4-dichlorophenyl)-2-methyl-2H-indazol,
O-methyloxime 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carbaldehyde,
1-[2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol-3-yl]alanon,
3-chloro-2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol,
3-chloro-7-(2,4-dichlorophenyl)-2-methyl-2H-indazol,
the hydrochloride of 3-bromo-2-methyl-7-(2,4,6-trimetilfenil)-2H-indazole,
3-bromo-7-(2,4-dichlorophenyl)-2-methyl-2H-indazol,
[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]acetonitrile,
7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carbonitril,
7-(3,5-dichloropyridine-2-yl)-2,3-dimethyl-2H-indazol,
3-chloro-7-(3,5-dichloropyridine-2-yl)-2-methyl-2H-indazol,
3-bromo-7-(3,5-dichloropyridine-2-yl)-2-methyl-2H-indas is l,
the hydrochloride of 7-(2,4-dichlorophenyl)-2-methyl-2H-pyrazolo[3,4-C]pyridine,
7-(2,4-dichlorophenyl)-2-methyl-2H-pyrazolo[4,3-C]pyridine,
7-(2,4-dichlorophenyl)-2-methyl-2H-pyrazolo[4,3-b]pyridine,
N-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]-N-methylacetamide,
hydrochloride [7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]hydrazine,
hydrochloride N'-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]-N,N-dimethylformamidine,
hydrochloride methyl ester [7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]carbamino acid,
dimethoxyaniline-[2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol-3-yl]amine,
[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]amide morpholine-4-carboxylic acid,
methyl ether [7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]carbamino acid,
3-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]-1,1-dimethyloxetane,
[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]urea,
3-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]-1,1-dimethyloxetane,
3-econsultancy-2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol,
3-methanesulfonyl-2-methyl-7-(2,4-dichlorophenyl)-2H-indazol,
amide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonic acid,
2-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylsulphonyl]ethanol,
2-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonyl]ethanol,
(2-hydroxyethyl)amide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonic acid,
(2-methoxyethyl)amide 7-(2,4-dichlorophenyl)-2-ethyl-2H-indazol-3-sulfonic acid,
dimethylamide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonic acid,
methylamide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonic acid,
7-(2,4-dichlorophenyl)-2-methyl-3-(morpholine-4-sulfonyl)-2H-indazol,
7-(2,4-dichlorophenyl)-2-methyl-3-(4-methylpiperazin-1-sulfonyl)-2H-indazol,
bis-(2-hydroxyethyl)amide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonic acid,
7-(2,4-dichlorophenyl)-3-methanesulfonyl-2-methyl-2H-indazol,
7-(2,4-dichlorophenyl)-3-methanesulfonyl-2-methyl-2H-indazol,
N-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]methanesulfonamide,
1-[2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol-3-yl]ethanol,
7-(2,4-dichlorophenyl)-3-(2-methoxyethoxymethyl)-2-methyl-2H-indazol,
7-(2,4-dichlorophenyl)-3-methoxymethyl-2-methyl-2H-indazol,
[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]methyl ester acetic acid,
7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ymetray ether dimethylcarbinol acid, and
7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ymetray ether of carbamino acid.

7. The use of the compounds of formula I

where R1means-NRaRb, -CRcRdRe, CHRfRg, CO2Ra, -C(O)NRaRbhydrogen, C2-C10quinil, halogen, cyano, -C(=Z)Ro, NRfSO2Ro, -N=CRfNRjRk, -S(O)mRh, CONRiOthero,
R2snakecord, C1-C6alkyl, C3-C6cycloalkyl,3-C6cycloalkyl(C1-C3)alkyl, C1-C3alkoxycarbonyl(C1-C3)alkyl or phenyl(C1-C6)alkyl,
R3means phenyl, pyridyl, thienyl, furyl or benzothiazolyl, each of which is optionally substituted by one or more substituents independently selected from the group comprising C1-C6alkyl, C1-C6alkoxy, halogen, C1-C6halogenated, cyano,
R4means-NRaRbwhere Raand Rbeach independently selected from the group including hydrogen, C1-C9alkyl and C1-C9alkylsulphonyl,
Raand Rbeach independently selected from the group including hydrogen, C1-C9alkyl, C1-C10hydroxyalkyl, C1-C6alkoxyalkyl, C1-C10carboxyethyl,3-C6cycloalkyl,3-C6cycloalkyl(C1-C3)alkyl, or
Raand Rbtogether with the nitrogen atom to which they are attached, form heterocyclyl selected from the group comprising pyrrolidine, piperidine, homopiperazine, each of these cycles optionally substituted by one or more substituents selected from the group comprising C1-C6alkoxy, C1-C6alkoxyl is l,
Rcmeans hydrogen, hydroxy, C1-C6alkoxy or-NRa"'Rb"',
Rdand Reeach independently selected from the group including hydrogen, C1-C9alkyl,
Rfmeans hydrogen or C1-C10alkyl,
Rgmeans2-C10alkenyl, -NHNH2, cyano, -OC(=O)Rf, -S(O)mRhor-X2(C=O)X1Rf,
Rhmeans C1-C6alkyl, NRjRkC1-C10hydroxyalkyl,
Rimeans3-C6cycloalkyl or3-C6cycloalkyl(C1-C3)alkyl,
Rjand Rk(1) independently mean hydrogen, C1-C6alkyl, C1-C10hydroxyalkyl or (2) together with the nitrogen atom to which they are attached represent (CH2)2X1(CH2)2,
Romeans C1-C6alkyl,
X1and X2independently denote-O -, or-NRfl-and in each case, Rflmeans independently selected radical Rfor, if Rfand Rflattached to the same nitrogen atom, Rfand Rfltogether imply (CH2)2X1(CH2)2,
Z denotes O or NORo,
m is an integer from 0 to 2,
n is an integer from 0 to 1,
Ra"'and Rb"'each independently selected from the group including hydrogen, C1-C9alkyl, C1-C10hydroxyalkyl,1-C6alkoxyalkyl,
C1-C10carboxyethyl, acyl, C3-C6cycloalkyl,3-C6cycloalkyl(C1-C3)alkyl, or
Ra"'and Rb"'together with the nitrogen atom to which they are attached, form heterocyclyl cycle selected from the group comprising pyrrolidine, piperidine, homopiperazine, hexahydropirimidine series, pyrazolidine, piperazine, morpholine, each of these cycles optionally substituted by one or more C1-C10the alkyl,
And1And2and3independently mean C or N, provided that at least one of the A1And2and3means SN or CR4and its pharmaceutically acceptable salts for obtaining a medicinal product intended for the prevention or treatment of disorders, the symptoms are alleviated with the introduction of a positive allosteric modulator of the GABA receptorAnd.

8. The use according to claim 7, where in the compound of the formula I
R1means-NRaRb, -CRcRdRe, CHRfRg, CO2Ra, -C(O)NRaRbhydrogen, C2-C10quinil, halogen, cyano, -C(=Z)Ro, -NRfSO2Ro, -S(O)mRo, CONRiOthero,
R2oznachaet is hydrogen, C1-C6alkyl, C3-C6cycloalkyl,3-C6cycloalkyl(C1-C3)alkyl or phenyl(C1-C6)alkyl,
R3means phenyl, pyridyl, thienyl, furyl or benzothiazolyl, each of which is optionally substituted by one or more substituents independently selected from the group comprising C1-C6alkyl, C1-C6alkoxy, halogen, C1-C6halogenated, cyano,
R4means-NRaRbwhere Raand Rbeach independently selected from the group including hydrogen, C1-C9alkyl and C1-C9alkylsulphonyl,
Raand Rbeach independently selected from the group including hydrogen, C1-C9alkyl, C1-C10hydroxyalkyl, C1-C6alkoxyalkyl, C1-C10carboxyethyl, acyl, C3-C6cycloalkyl,3-C6cycloalkyl(C1-C3)alkyl, or
Raand Rbtogether with the nitrogen atom to which they are attached, form heterocyclyl or heteroaryl selected from the group comprising pyrrolidine, piperidine, homopiperazine, each of these cycles optionally substituted by one or more substituents selected from the group comprising C1-C6alkoxy, C1-C6alkoxyalkyl,
Rcmeans hydrogen, hydroc and, C1-C6alkoxy or-NRa"'Rb"',
Rdand Reeach independently selected from the group including hydrogen, C1-C9alkyl,
Rfmeans hydrogen or C1-C10alkyl,
Rgmeans2-C10alkenyl,
Romeans C1-C6alkyl,
Rimeans3-C6cycloalkyl or3-C6cycloalkyl(C1-C3)alkyl,
Z denotes O or NORo,
m is an integer from 0 to 2,
n is an integer from 0 to 1,
Ra"'and Rb"'each independently selected from the group including hydrogen, C1-C9alkyl, C1-C10hydroxyalkyl,1-C6alkoxyalkyl,
C1-C10carboxyethyl, acyl, or
Ra"'and Rb"'together with the nitrogen atom to which they are attached, form heterocyclyl cycle selected from the group comprising pyrrolidine, piperidine, homopiperazine, hexahydropirimidine series, pyrazolidine, piperazine, morpholine, each of these cycles optionally substituted by one or more C1-C6the alkyl,
And1And2and3independently mean C or N, provided that at least one of the A1And2and3means SN or CR4.

9. The use of claim 8, where in the compound of the formula I
R1mean CRc/sup> RdRe, CHRfRg, CO2Ra, -C(O)NRaRbhydrogen, C2-C10quinil, halogen, cyano, -C(=Z)Ro, -NRfSO2Ro, -S(O)mRo, CONRiOthero,
Rcmeans hydrogen, hydroxy, C1-C6alkoxy, or-NRa"'Rb"',
Rdand Reeach independently selected from the group including hydrogen, C1-C9alkyl.

10. The use according to claim 7, where in the compound of the formula I R1means-S(O)mRhX2means O or NRflwhere Rflmeans independently selected radical Rf, R2means hydrogen or C1-C6alkyl, R3means optionally substituted phenyl, a m is 2.

11. The use according to claim 7, where in the compound of the formula I R1means CHRfRg, Rgmeans X2C(=O)XlRfR2means hydrogen or C1-C6alkyl, R3means optionally substituted phenyl.

12. The use according to claim 7 where the compound is selected from the group including:
the hydrochloride of 7-(2,4-dichlorophenyl)-2-methyl-2H-indazole,
triptorelin 2-benzyl-7-(2,4-dichlorophenyl)-2H-indazole,
triptorelin ethyl ester [7-(2,4-dichlorophenyl)indazol-2-yl]acetic acid,
2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol,
3-methyl-4-(2-methyl-2H-indazol-7-yl)benzonitrile,
5,7-dimethyl-4-(2-methyl-2 is-indazol-7-yl)-benzo[1,2,5]thiadiazole,
7-(3-chloropyridin-2-yl)-2-methyl-2H-indazol,
triptorelin 2-methyl-7-phenyl-2H-indazole,
7-(3-chloro-5-triptorelin-2-yl)-2-methyl-2H-indazol,
triptorelin 7-(6-methoxy-2-methylpyridin-3-yl)-2-methyl-2H-indazole,
2-(2-methyl-2H-indazol-7-yl)-nicotinamide,
hydrochloride 7-(3,5-dichloropyridine-2-yl)-2-methyl-2H-indazole,
the hydrochloride of 7-(2,4-dichlorophenyl)-2,3-dimethyl-2H-indazole,
hydrochloride of 2,3-dimethyl-7-(2,4,6-trimetilfenil)-2H-indazole,
triptorelin 7-(2,4-dichlorophenyl)-2-ethyl-2H-indazole,
7-(2,4-dichlorophenyl)-2-methyl-3-vinyl-2H-indazol,
2-methyl-7-(2,4,6-trimetilfenil)-3-vinyl-2H-indazol,
the hydrochloride of 7-(2,4-dichlorophenyl)-2-methyl-3-((E)-1-propilot-1-enyl)-2H-indazole,
7-(2,4-dichlorophenyl)-3-ethinyl-2-methyl-2H-indazol,
3-allyl-7-(2,4-dichlorophenyl)-2-methyl-2H-indazol,
O-methyloxime 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carbaldehyde,
1-[2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol-3-yl]alanon,
3-chloro-2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol,
3-chloro-7-(2,4-dichlorophenyl)-2-methyl-2H-indazol,
the hydrochloride of 3-bromo-2-methyl-7-(2,4,6-trimetilfenil)-2H-indazole,
3-bromo-7-(2,4-dichlorophenyl)-2-methyl-2H-indazol,
[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]acetonitrile,
7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carbonitril,
7-(3,5-dichloropyridine-2-yl)-2,3-dimethyl-2H-indazol,
3-chloro-7-(3,5-dichloropyridine-2-yl)-2-methyl-2H-indazol,
3-bromo-7-(3,5-dichloropyridine-2-yl)-2-methyl-2H-indazol,
the hydrochloride of 7-(4-dichlorophenyl)-2-methyl-2H-pyrazolo [3,4-C]pyridine,
7-(2,4-dichlorophenyl)-2-methyl-2H-pyrazolo[4,3-C]pyridine,
7-(2,4-dichlorophenyl)-2-methyl-2H-pyrazolo[4,3-b]pyridine,
hydrochloride methyl ester [7-(2,4-dichlorophenyl)-2,3-dimethyl-2H-indazol-5-yl]carbamino acid,
methyl ester of 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carboxylic acid,
methyl ester of 7-(2,4-dichlorophenyl)-2-ethyl-2H-indazol-3-carboxylic acid,
triptorelin methyl ester 7-(3-methoxyphenyl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin methyl ester of 2-methyl-7-(2-phenoxyphenyl)-2H-indazol-3-carboxylic acid,
triptorelin methyl ester of 2-methyl-7-meta-tolyl-2H-indazol-3-carboxylic acid,
triptorelin methyl ester 7-(3, 5dimethylphenyl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin methyl ester 7-(4-methoxy-2-methyl-pyridin-3-yl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin methyl ester 7-(2,5-acid)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin methyl ester of 2-methyl-7-(4-phenoxyphenyl)-2H-indazol-3-carboxylic acid,
triptorelin methyl ester of 2-methyl-7-thiophene-3-yl-2H-indazol-3-carboxylic acid,
triptorelin methyl ester 7-furan-3-yl-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin methyl ester 7-(2,4-acid)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin methyl ester 7-(4-isopropylphenyl)-2-m is Teal-2H-indazol-3-carboxylic acid,
triptorelin methyl ester 7-(2,5-dichlorophenyl)-2-methyl-2H-indazol-3-carboxylic acid,
the hydrochloride of 7-(2,4-dichlorophenyl)-2-methyl-2H-pyrazolo[3,4-C]pyridine,
triptorelin N-cyclopropylmethyl-N'-acylhydrazides 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin of ethylpropylamine 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin of dipropylamine 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin bis-(2-methoxyethyl)amide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin of diethylamide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin ethyl-(2-methoxyethyl)amide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin of dimethylamide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin [7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]-((S)-2-methoxymethyl-pyrrolidin-1-yl)-methanone,
methylamide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-carboxylic acid,
triptorelin cyclopropylmethyl[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]Propylamine,
methylamide 7-(2,4-dichlorophenyl)-2-ethyl-2H-indazol-3-carboxylic acid,
hydrochloride [7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]dipropylamine,
hydrochloride [7-(4-methoxy-2-were)-2-methyl-2H-indazol-3-yl]dimethylamine,
[7-(2,4-dichlorophenyl)-2-methyl-2 is-indazol-3-ylmethyl]dimethylamine,
hydrochloride [7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]methylamine,
hydrochloride dimethyl[2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol-3-yl]amine
N-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]-N-methylacetamide,
hydrochloride [7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]hydrazine,
hydrochloride N'-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]-N,N-dimethylformamidine,
hydrochloride methyl ester [7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]carbamino acid,
dimethoxyaniline-[2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol-3-yl]amine,
[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]amide morpholine-4-carboxylic acid,
methyl ether [7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]carbamino acid,
3-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylmethyl]-1,1-dimethyloxetane,
[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]urea,
3-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]-1,1-dimethyloxetane,
3-econsultancy-2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol,
3-methanesulfonyl-2-methyl-7-(2,4-dichlorophenyl)-2H-indazol,
amide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonic acid,
2-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ylsulphonyl]ethanol,
2-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonyl]ethanol,
(2-hydroxyethyl)amide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonic acid,
(2-methoxyethyl)amide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulf the new acid,
dimethylamide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonic acid,
methylamide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonic acid,
7-(2,4-dichlorophenyl)-2-methyl-3-(morpholine-4-sulfonyl)-2H-indazol,
7-(2,4-dichlorophenyl)-2-methyl-3-(4-methylpiperazin-1-sulfonyl)-2H-indazol,
bis-(2-hydroxyethyl)amide 7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-sulfonic acid,
7-(2,4-dichlorophenyl)-3-methanesulfonyl-2-methyl-2H-indazol,
7-(2,4-dichlorophenyl)-3-methanesulfonyl-2-methyl-2H-indazol,
N-[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]methanesulfonamide,
1-[2-methyl-7-(2,4,6-trimetilfenil)-2H-indazol-3-yl]ethanol,
7-(2,4-dichlorophenyl)-3-(2-methoxyethoxymethyl)-2-methyl-2H-indazol,
7-(2,4-dichlorophenyl)-3-methoxymethyl-2-methyl-2H-indazol,
7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]methanol,
[7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-yl]methyl ester acetic acid,
7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ymetray ether dimethylcarbinol acid, and
7-(2,4-dichlorophenyl)-2-methyl-2H-indazol-3-ymetray ether of carbamino acid.

13. The use according to claim 7, where the specified disorder means depression, anxiety, mental disorder, impaired learning ability and cognitive functioning, sleep disturbance, disorder in the form of convulsions, or seizures, or pain.

14. The use according to claim 7, where the specified positive allosterically modulator of the receptor, the GABA Andit is a selective modulator of subspecies α2compared to the subspecies α1.

15. Pharmaceutical composition for prevention or treatment of disorders, the symptoms are alleviated with the introduction of a positive allosteric modulator of the GABA receptorAndmoreover , this composition includes a therapeutically effective amount of a compound according to claim 1 in a mixture of at least one diluent, excipient or the media.

16. Pharmaceutical composition for prevention or treatment of disorders, the symptoms are alleviated with the introduction of a positive allosteric modulator of the GABA receptorAndmoreover , this composition includes a therapeutically effective amount of a compound according to claim 2 in a mixture of at least one diluent, excipient or carrier.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention is related to antagonists of serotonin 5-HT6 receptors of common formula 1 and their pharmaceutically acceptable salts and/or hydrates, pharmaceutical compositions, dosage forms and methods of production. Invention also includes new compounds of formula 1.1. In formulae 1 and 1.1 , Ar represents aryl, selected from unnecessarily substituted phenyl or unnecessarily substituted 5-6-member heteroaryl, which contains atom of nitrogen or atom of sulfur and heteroatom; R1 represents atom of hydrogen, unnecessarily substituted C1-C5 alkyl; Ar represents aryl, selected from unnecessarily substituted phenyl or unnecessarily substituted 5-6-member heteroaryl, which contains atom of nitrogen or atom of sulfur as heteroatom; R1 represents atom of hydrogen, which is unnecessarily substituted C1-C5 alkyl; R21,R22, R31, R32 independently from each other represent atom of hydrogen or substituent of aminogroup, selected from unnecessarily substituted C1-C4 alkyl, unnecessarily substituted phenyl, or R31 and R32 together with atom of nitrogen, to which they are bound, create unnecessarily substituted saturated 6-member heterocycle, possibly containing atom of nitrogen in cycle; or R1 together with atom of nitrogen, to which it is bound, and R21 and R22 together with atom of nitrogen, to which they are bound, create substituted pyrimidine cycle. In formula 1.1 R4, R5 and R6 independently from each other represent atom of hydrogen, unnecessarily substituted C1-C3 alkyl or phenyl.

EFFECT: compounds of invention may find application for treatment and prevention of development of conditions and disorders of central nervous system.

13 cl, 11 dwg, 4 tbl, 11 ex

FIELD: medicine.

SUBSTANCE: there are described new p38 kinase inhibitors that are compounds of general formula (I) (radical values are presented in the patent claim), their pharmaceutically acceptable salts and solvates, a pharmaceutical composition containing thereof, and method for treating inflammatory diseases.

EFFECT: new compounds have effective biological activity.

24 cl, 311 ex

FIELD: medicine.

SUBSTANCE: there are described new isoindole derivatives of general formula (1), wherein A1, A2 and A4 stands for CH, and A3 means N or C-OH; n is equal to 2; R1 represents O; R2-stands for H; and a pharmaceutical composition containing thereof.

EFFECT: new compounds are inhibitors of chaperone protein Hsp90 activity and can be used in chemotherapy of cancerous diseases.

6 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new 2-alkylsufanyl-3-arylsufonyl-cycloalkano[e]pyrazolol[1,5-a]pyrimidines of general formula 1 or 2-alkylsufanyl-3-arylsufonyl-cycloalkano[d]pyrazolo[1,5-a]pyrimidines of general formula 2, which are antagonist of 5-HT6 receptors. In compounds of formula 1

and 2 ,

R1 is a hydrogen atom or C1-C3 alkyl; R2 is C1-C3 alkyl; R3 is a hydrogen atom, one or two optionally identical halogen atoms, C1-C3 alkyl or hydroxyl, optionally substituted with C1-C3 alkyl; n is an integer equal to 1, 2 or 3.

EFFECT: compounds can be used in preventing and treating diseases of the central nervous system, anxiolytics and as compounds with nootropic effect and suitable for enhancing memory.

12 cl, 1 dwg, 4 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a cyclic bioisostere of purine system derivatives, with general structural formula given below , where R = , Li, Na or K, R1 = -H, -NH2, -Br, -Cl, -OH, -COOH; A = -N- for B=-N=, Z = -CH-; A = -CH= for B = -N=, Z = -CH-; A = -CH= for B = -N=, Z = -N=; A = -CH= for B = -CH=, Z - -CH=; A = -CH= for B = -CH=, Z = -N=, except compounds in which A = -CH= for B = -CH=, Z = -CH=, R= Li, Na or K and R1= -NH2 in the 5th position of the benzo[d]-3H-pyridazine-1,4-dione nucleus, and its pharmacologically acceptable salts, with normalising effect on intracellular processes.

EFFECT: obtaining compounds which can be used for normalising intracellular processes in therapy of disorders, caused by intracellular acidosis and/or oxygen deficiency and/or excess formation of free radicals and/or excess formation of free radical forms of oxygen and/or high thrombocyte aggregation and/or erythrocytes and/or adverse effects and/or nitrergic cell mechanism disorder.

17 cl, 14 tbl, 15 dwg

FIELD: chemistry.

SUBSTANCE: new pyrrolotriazine derivatives of general formula (I) are described, where R1 is possibly substituted piperidinyl or piperazinyl; R2 is possibly substituted phenyl; R3 is hydrogen; X is -NH-; Y is -CH2-; as well as their pharmaceutically acceptable salts or steroisomers, and pharmaceutical compositions containing said compounds.

EFFECT: given compounds are kinase inhibitors and can be used in medicine, for example as anticancer agents.

9 cl, 267 ex, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of imidazo[1,2-c]pyrimidinyl acetic acid of formula (I) or to its salts: , where R1 is ,, in which n is an integer ranging from 0 to 6; Y is aryl, where the said aryl is optionally substituted at a substitutable position with one or more substitutes selected from a group which consists of halogen or C1-6alkyl, optionally substituted with mono-, di- or trihalogen; R2 is hydrogen; R3 is hydrogen or halogen; and R4 is hydrogen. The invention also relates to derivatives of imidazo[1,2-c]pyrimidinyl acetic acid of formula (I-i) or to its salts, to a drug, to use of compounds in paragraph 1, as well as to a drug in form of a standard single dosage.

EFFECT: obtaining new biologically active compounds, which are active towards CRTH2.

23 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: in compounds of formula (I) , Q is: (IIa) or (IIb) , R1 is chosen from a group which consists of carboxylic aryl and carboxylic aryl which is substituted with substitute(s) independently chosen from a group which consists of halogen, cyano, nitro, C1-10alkyl, C1-10alkyl which is substituted with substitute(s) independently chosen from a group which consists of halogen, C1-9alkoxy, C1-9alkoxy which is substituted with substitute(s) independently chosen from a group which consists of halogen, mono-C1-5alkylamino, and heterocyclyl or heterocyclyl which is substituted with substitute(s) independently chosen from a group which consists of halogen, C1-5alkyl; R2 is C1-5alkyl, C1-5alkyl which is substituted with halogen, C1-5alkyl which is substituted with carboxylic aryl, C1-5alkoxy, -N(R2a)(R2b); where R2a and R2b are each independently hydrogen, C1-5alkyl or C1-5alkyl, substituted with substitute(s) independently chosen from a group which consists of hydroxyl, carboxylic aryl; L represents formula (IIIa); , where R3 and R4 are each hydrogen; A is a single bond, and B is a single bond or -CH2-; Z1, Z3, and Z4 are each independently hydrogen, halogen, C1-5alkyl, C1-5alkyl, substituted with carboxylic aryl, C1-5alkoxy, mono-C1-5alkylamino, di-C1-5alkylamino, carboxylic aryl, heterocyclyl or substituted heterocyclyl; Z2 is hydrogen, C1-5alkyl, C1-5alkyl which is substituted with carboxylic aryl, C1-5alkoxy, mono-C1-5alkylamino, di-C1-5alkylamino, carboxylic aryl, heterocyclyl or substituted heterocyclyl; Y is -C(O)NH-, -C(O)-, -C(S)NH-, -C(O)O- or -CH2-; where carboxylic aryl is phenyl; heterocyclyl is 1H-indolyl, 9H- xanthenyl, benzo[1,3]dioxolyl, furyl, imidazolyl, isoxazolyl, morpholinyl, piperazinyl, pyridyl, pyrrolidyl; halogen is fluorine, chlorine, bromine or iodine. The invention also relates to a pharmaceutical composition.

EFFECT: compounds can be used for treating central nervous system diseases, and for improving memory functioning, sleep, awakening, diabetes.

16 cl, 8 dwg, 4 tbl, 525 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a tetrazole compound with general formula I , where X3 and X4 are independently N and C, where one of X3 and X4 is certainly C; P is phenyl; m equals 1 or 2, where if m equals 1, R1 is bonded to P through a carbon atom on ring P in the meta-position of ring P relative the point at which P is bonded to X3, and if m equals 2, R1 is bonded to P through a carbon atom on ring P in positions 2 and 5 of ring P; R1 is halogen, C1-6alkyl, OC1-6alkyl or cyano group; X1 is C2-3alkyl, C2-3alkenyl, NR3, O, S, CR3R4, SO, SO2; X2 is a bond, CR3R4, O, S, NR3, SO, SO2; R3 and R4 are independently chosen from a group which consists of hydrogen, hydroxy, C1-6alkyl; Q is triazolyl, piperazinyl, or triazole or imidazole ring, condensed with a 6- or 7-member heterocyclic ring with one or two N atoms as heteroatoms; R is C1-6alkyl, C3-6cycloalkyl, pyridinyl, which can be substituted with a nitro, cyano, halogen or OC1-4alkyl group; phenyl, which can be substituted with a halogen, C1-4alkyl, OC1-4alkyl group; (CO)OC1-4alkyl; pyrimidinyl, which can be substituted with a OC1-4alkyl group; p equals 0, 1 or 2, or pharmaceutically acceptable salt or hydrate thereof.

EFFECT: invention also relates to method of inhibiting activity of mGluR5 receptors.

11 cl, 44 ex

FIELD: pharmacology.

SUBSTANCE: invention concerns novel compounds of formula (1a), formula (1b), formula (1c) and formula (1d), as well as pharmaceutical composition based on them and their application in medicine obtainment. R1-R4, G, W, X, X1, U, V, a, b are defined in the invention claim.

EFFECT: compound with antagonistic effect on vasopressin V1A receptor.

73 cl, 133 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treatment and prevention of diseases associated with activity of specified enzyme, such as diabetes, obesity, diseases associated with food intake, dyslipidemia and hypertension. In general formula (I) , R1 represents methyl, ethyl, cyclopropyl, cyclobutyl, isopropyl, tert-butyl, methoxymethyl, cyclopropyl methoxymethyl, 2-methyl thiazolyl, morpholinyl methyl or phenyl; R2 represents hydrogen, C1-4alkyl or phenyl; R3 represents hydrogen, C1-4alkyl or phenyl; R4 represents phenyl, naphthyl, thiophenyl, quinolyl or piperidyl where phenyl, naphthyl, thiophenyl, quinolyl and piperidyl are optionally substituted with one to three substitutes independently chosen of C1-4alkyl, halogen, C1-4alkoxy, cyano, trifluoromethyl, phenyl, phenyls C1-4alkyl, phenyloxy, oxasolyl and pyridinyl; R5 represents hydrogen, C1-4alkyl, phenyl-C1-4alkyl, C3-6dicloalkyl-C1-4alkyl or aminocarbonylC1-4alkyl.

EFFECT: higher clinical effectiveness.

17 cl, 2 dwg, 72 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new substituted phenoxy-aceitic acids (I), in which: X is halogen, cyano, nitro or C1-4alkyl, which is substituted with one or more halogen atoms; Y is chosen from hydrogen, halogen or C1-C6alkyl, Z is phenyl, naphthyl or ring A, where A is a six-member heterocyclic aromatic ring containing one or two nitrogen atoms, or can be 6,6- or 6,5-condensed bicycle which contains one O, N or S atoms, or can be 6,5-condensed bicycle which contains two O atoms, where phenyl, naphthyl or ring A can all be substituted with one or more substitutes, independently chosen from halogen, CN, OH, nitro, COR9, CO2R6, SO2R9, OR9, SR9, SO2NR10R11, CONR10R11, NR10R11, NHSO2R9, NR9SO2R9, NR6CO2R6, NR9COR9, NR6CONR4R5, NR6SO2NR4R5, phenyl or C1-6alkyl, where the last group can possibly be substituted with one or more substitutes, independently chosen from halogen; R1 and R2 independently represent a hydrogen atom or C1-6alkyl group, R4 and R5 independently represent hydrogen, C3-C7cycloalkyl or C1-6alkyl, R6 is a hydrogen atom of C1-6alkyl; R8 is C1-4alkyl; R9 is C1-6alkyl, possibly substituted with one or more substitutes, independently chosen from halogen or phenyl; R10 and R11 independently represent phenyl, 5-member aromatic ring which contains two heteroatoms, chosen from N or S, hydrogen, C3-C7cycloalkyl or C1-6alkyl, where the last two groups are possibly substituted with one or more substitutes, independently chosen from halogen or phenyl; or R10 and R11 together with the nitrogen atom to which they are bonded, can form a 3- to 8-member saturated heterocyclic ring, which possibly contains one or more atoms chosen from O, S(O)n (where n= 0, 1 or 2), NR8.

EFFECT: invention relates to a method of modulating activity of CRTh2 receptors, involving administration of therapeutically effective amount of formula compound or its pharmaceutically acceptable salt to a patient.

9 cl, 170 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 2-heteroaryl derivatives of benzothiazole and benzoxazole of formula by boiling amine with general formula with acid chloride of general formula , where R=2-furyl or 2-thienyl, X = S or O, in 1-methyl-2-pyrrolidone.

EFFECT: method increases output of product to 78 to 90% and environmental friendliness of the process.

1 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula (I-a), where R1 and R2, each independently, represent -COORA (where RA is hydrogen or C1-8 alkyl), -CONRBSO2RC (where RB is hydrogen or C1-8 alkyl, RC is C1-8 hydrocarbon), -D-R1 is -CO-(CH2)2-R1, -CO-(CH2)3-R1, -CO-(CH2)4-R1 or C1-4alkylene-R1; E is a bond or C1-4alkylene; ring formula represents a 3,4-dihydro-2H-1,4-benzoxazine or 1H-indole ring; V is , where R110 is hydrogen or C1-8 alkyl, and the arrow shows that it is bonded to ring A; the group with formula is a phenyl group, which can contain a group with formula , where ring 2 is a C5-10 mono- or bicyclic aromatic carbocyclic ring, which can be partially or completely saturated, spirobicyclic carbocyclic ring, or a carbocyclic ring bonded by a bridge bond; where W is -O-CH2-, -O-(CH2)2, -O-(CH2)3, -O-(CH2)4, -O-(CH2)5, -CH2-O, -(CH2)2-O-, -(CH2)3-O-, -(CH2)4-O-, -(CH2)5-O-, -O-(CH2)3-O-, -O-(CH2)4-O-, -O-(CH2)5-O-, C1-6 alkylene, its N-oxide, its salt or its solvate. The invention also relates to a pharmaceutical composition based on formula I-a compound and its use.

EFFECT: obtaining new derivatives of benzoxazine and indole, with antagonistic effect on cysLT2 and which are useful for preventing and/or curing respiratory diseases, such as bronchial asthma, chronic obstructive lung diseases.

8 cl, 57 tbl, 261 ex

FIELD: medicine.

SUBSTANCE: invention covers thaizole derivatives of formula (I) and to their pharmaceutically acceptable salts. In formula I: X1 and X2 differ from each other and represent sulphur atom or carbon atom; R1 represents phenyl group; phenyl group substituted by 1-2 members chosen from the group including halogen atoms, alkoxygroup with 1-6 carbon atoms, hydroxygroup, phenylalkoxygroup with 7-12 carbon atoms; phenyl group fused with 5-7-membered heteroaromatic or nonaromatic ring with at least one heteroatom consisting of N, O and S; pyridyl group; R2 represents hydrogen atom, halogen atom, alkyl group with 1-6 carbon atoms, alkyl group with 1-6 carbon atoms substituted by 1-5 halogen atoms, alkoxygroup with 1-6 carbon atoms, or hydroxyalkyl group with 1-5 carbon atoms; A represents group which is presented by formula or . Also, the invention concerns ALK5 inhibitor containing compound of the invention as an active component, stimulators of hair follicles proliferation and hair growth, and also to thiazole derivative of formula where A1 represents .

EFFECT: higher efficiency.

12 cl, 2 tbl, 50 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: new 5-sulphanyl-4H-1,2,4-triazole derivatives of general formula I (meaning of radicals R1-R3 are indicated in the description of the invention), methods of their preparation by liquid-phase parallel synthesis and pharmaceutical composition are claimed.

EFFECT: claimed compounds display high affinity to some subtypes of somostatin receptors of the SST2 and SST5 subtypes and possibility of their usage for treatment of pathological states or diseases involving one or more of the given somostatin receptors

9 cl, 708 ex

FIELD: chemistry.

SUBSTANCE: in new compounds with general formula (I): , R1 stands for a naphthyl group, which can be substituted with a halogen atom, W represents a bond, a equals 0, 1 or 2, X1 represents C1-4alkylene, which can be substituted with a hydroxy group, Y1 represents -C(O)-,A represents a piperazine ring or piperidine ring, X2 represents a bond, Y2 represents -C(O)-, -S(O)2- or -C(=NR7)- (where R7 represents a hydrogen atom), X3 represents C1-4alkylene, which can be substituted with a hydroxyl group, oxo group or C1-6alkyl group; or C2-4alkylene, which can be substituted with a C1-6alkyl group, where two alkyl groups can be bonded to each other forming, together with carbon atoms to which they are bonded, an aryl ring when X3 represents C2-4alkylene, substituted with two alkyl groups, Z3 represents -N(R4)- or a bond (where R4 represents a hydrogen atom, C1-6alkyl group, which can be substituted with a hydroxy group or methoxy group, or acyl group), represents a single or double bond, where if represents a single bond, then Z1 represents -C(R2)(R2')-, -N(R2)- or -O- and Z2 represents C(R3)(R3')-, -N(R3)-, -O- or a bond (under the condition that, when Z2 represents -O-, then Z is different from -O-), and when represents a double bond, then Z1 represents -C(R3)= or a nitrogen atom and Z2 represents =C(R3)- or a nitrogen atom, each of R2, R2', R3 and R3' represents a hydrogen atom or C1-6alkylene. The invention also relates to salts of the given new compounds. The invention also relates to compounds, chosen from the group, to pharmaceutical compositions, to use of compounds in sub-paragraph 1 or 2, to prevention or treatment methods, as well as to the method of obtaining compounds in paragraph 1.

EFFECT: obtaining new biologically active compounds, which inhibit activated factor X of blood clotting and have anticoagulation activity and antithrombotic activity.

33 cl, 46 ex, 1 tbl

FIELD: chemistry; medicine.

SUBSTANCE: in novel triazole derivatives of general formula I or their pharmaceutically acceptable salts R4 is hydrogen; X is selected from group, consisting of single bond, NH- and groups: , values of R1-R3 radicals are given in description, pharmaceutical composition containing them, and application of novel compounds for obtaining medication for treating hyperglycemia, insulin-resistance, type 2 diabetes, fat exchange derangements, obesity, atheroslerosis and metabolic syndrome.

EFFECT: medications possess higher efficiency.

26 cl, 8 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: claimed invention relates to compounds of formula (I), their obtaining and application as elastase inhibitors, and can be applied in medicine, where Y = CH; R№ represents H or alkyl; RІ represents phenyl or 5-6-memner heteroaryl, G1 represents phenyl; R5 represents H, halogen, alkyl, CN or fluorinated alkyl; n=1-3; R4 = H; L represents bond, O, NR29 or alkyl; or R4 and L are bound together in such way that group -NR4L- represents 5-7-member asacyclic ring; G2 represents phenyl, 5-6-member heteroaryl, cycloalkyl, C4-7-heterocycle, bicycle from two condensed, bound with direct bond or separated with O atom rings, selected from phenyl, 5-6-member heteroaryl, cycloalkyl or C4-7-heterocycle; or when L does not represent bond, G2 represents H; s = 0-2; R25 represents H, alkyl or cycloalkyl; R29 represents H or alkyl.

EFFECT: obtaining novel biologically active compounds.

10 cl, 95 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to benzothiazol derivatives of general formula (I) and to their pharmaceutically acceptable acid-additive salts as adenosine receptor ligands and to based medicinal agent. In general formula (I) , R1 represents 1,4-dioxepanyl or tetrahydropyran-4-yl; R2 represents -N(R)-(CH2)n-5- or 6-merous nonaromatic heterocycle containing 1-2 nitrogen heteroatoms optionally substituted with one-two substitutes chosen from group, consisting of C1-C6alkyl or -NR2, or represents -(CH2)n-5- or 6-merous nonaromatic heterocycle containing 1-2 heteroatoms chosen of N, S or O, optionally substituted with group -(CH2)n-OH, C1-C6alkyl, C1-C6alkoxy, or represents -(CH2)n-5-or 6-merous aromatic heterocycle containing 1-2 nitrogen heteroatoms optionally substituted with the following group: C1-C6alkyl, C1-C6alkoxy, halogen, halogen-(C1-C6alkyl), -CH2N(R)(CH2)2OCH3, -N(R)(CH2)2OCH3, - CH2-morpholinyl or -CH2-pyrrolidinyl or represents (CH2)n-C3-C6cycloalkyl optionally substituted with group hydroxy, or represents -N(R)-C3-C6cycloalkyl optionally substituted with group hydroxy or C1-C6alkyl, or represents phenyl optionally substituted with group C1-C6alkoxy, halogen, halogen-(C1-C6alkyl), C1-C6alkyl, -CH2-pyrrolidine-1-yl, CH2N(R)(CH2)2OCH3 or -CH2-N(R)C(O)-(C1-C6alkyl), or represents 1,4-dioxa-8-azaspiro[4,5]decane, or 2-oxa-5-azabicyclo[2,2,1]heptane, or 1-oxa-8-azaspiro[4,5]decane, or -N(R)-7-oxabicyclo[2,2,1]hept-2-yl, or 2-azabicyclo[2,2,2]octane; R represents hydrogen or C1-C6alkyl; n stands for 0 or 1.

EFFECT: compounds can be applied for treatment and prevention of diseases mediated by adenosine A2A and A1 receptors, eg Alzheimer's disease, some depressions, toxicomania, Parkinson's disease.

8 cl, 3 dwg, 61 ex

FIELD: medicine.

SUBSTANCE: invention is related to compounds with common formulae I , III , IV and V , value of radicals such as given in formula of invention. Also suggested invention is related to pharmaceutical composition in the basis of above-mentioned compounds, to their use, and also to method of frequent urination treatment, enuresis and increased activity of urinary bladder.

EFFECT: increased efficiency of diseases treatment, in particular for treatment of frequent urination and enuresis, increased activity of urinary bladder and pain.

16 cl, 406 ex, 73 tbl

V:

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