Diarylamine-containing compounds, compositions and use thereof as c-kit receptor modulators

FIELD: chemistry.

SUBSTANCE: invention relates to novel diarylamine-containing compounds of formula (I) or formula (4b), pharmaceutically acceptable salts thereof, which have c-kit inhibiting properties. In formulae (I) and (4b), each R1 independently denotes H, -C(O)OH and -L1-C1-6alkyl, where L1 denotes -O- or -C(O)O-, or any two neighbouring R1 groups can together form a 5-6-member heterocyclic ring containing a nitrogen atom or an oxygen atom as a heteroatom, a 6-member heterocyclic ring with one or two nitrogen atom s as heteroatoms, optionally substituted with a C1-4alkyl, and R5 denotes hydrogen or C1-C6alkyl; values of radicals Ar and Q are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds, and a method of treating diseases whose development is promoted by c-kit receptor activity.

EFFECT: more effective use of the compounds.

17 cl, 3 tbl, 9 ex

 

The text description is given in facsimile form.

1. The compound of structural formula (1) or structural formula (46)
,,
where Ar is selected from the group including
,,,,,,
,,,,
,,,
,,,
,,,,
,,,
,,,
,,,
,,,
,,,and

Q is selected from the group including
,,,,,
,,,,
,,,,
,,,,
,,,,
,,,,
,,, ,
,,,,
,,,
,,,
,,,
,,,
,,,,
,,,
,,,
,,
,,
,,,
,,,
,,,
,,,,
,, ,,,
,,,,,
,,,,
,,,,
,,,,,
,,,,
,,,
,,,,
,,,,,
,,,,,
,,,,
,,,
,,,,
,,,
,,,,,
,,,,
,,,,
,,,,
,,,,
,,,,
,,,,
,,,
,,,
, ,,,
,,,
,,,
,,,
,,,
,,,,,
,,,,,
,,,,,
,,,,
,,,,
,,,
,,,,,
,,,,
,,,,,
,,,,
,,,,,
,,,,,
,,,,,
,,,,,
,,,,,
,,,,
,,,,
,,,,
,,,
,,,
,,,
,,,
,,,
,,,
,,and;
each R1independently of the other represents H, -C(O)HE-L1-C1-6alkyl, where
L1represents-O - or-C(O)O-, or
any two adjacent groups R1together may form a 5-6-membered heterocyclic ring containing a nitrogen atom or an oxygen atom as a heteroatom, or 6-membered heterocyclic ring with one or two nitrogen atoms as heteroatoms, optionally substituted C1-4the alkyl, and
R5denotes hydrogen or C1-C6alkyl,
or its pharmaceutically acceptable salt.

2. Soy is inania according to claim 1, in which Q is selected from the group including
,,,,
,,,,,
,,,,,
,,,,,
,,,,,
,,,,,
,,,,
,,,,
,,,,,
, ,,,,
,,,,
and.

3. The compound according to claim 1, in which Q is selected from the group including
,,,,,,
,,,,,
,,,,,
,,,,,,,
,,,,
,,,,,
,, ,,,
,,,,,
,,,,,,
,,,,,
,,,,,
,,,,
,,,,
,,,,,
,,,,,,
,and

4. The connection according to one of claims 1 to 3, wherein the AG is selected from the group including
,,,,,
,,and.

5. The connection according to one of claims 1 to 4, in which each R1denotes N.

6. The connection according to one of claims 1 to 5, in which R5denotes N.

7. The compound according to claim 1, selected from the group including:
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-carboxylic acid,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)-2-perbenzoic)acetate,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)-2-forbindelsen)acetate,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)benzylamino)acetate,
2,2'-(2-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenoxy)-ethyl)ethandiyl)diethanol,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)-benzamido)acetate,
methyl-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-carboxylate,
N-(4-(2-(diethylamino)ethyl)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
1-(2-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenoxy)ethyl)piperidine-4-carboxylic acid,
N-(4-(2-(diethylamino)ethoxy)Fe who yl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
tert-butyl 2-(4-(2-(4-(2-morpholinoethoxy)phenylamino)pyrimidine-5-yl)-benzamido)acetate,
tert-butyl 2-(4-(2-(4-(2-(4-carbamoylbiphenyl-1-yl)ethoxy)-phenylamino)pyrimidine-5-yl)benzamido)acetate,
4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)phenyl acetate,
ethyl-2-(2-(diethylamino)ethoxy)-5-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoate,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl-4-methylpiperazin-1-carboxylate,
5-(4-methoxyphenyl)-N-(4-(2-(methyl(pyridin-2-yl)amino)ethoxy)phenyl)pyrimidine-2-amine,
methyl-4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)benzoate,
N-(4-(2-(diethylamino)ethoxy)phenyl)-5-(3-fluoro-4-methoxyphenyl)pyrimidine-2-amine,
2-(2-(diethylamino)ethoxy)-4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoic acid
methyl-2-(2-(diethylamino)ethoxy)-4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoate,
N-(3-(2-(diethylamino)ethoxy)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
N-(3-(2-(diethylamino)ethyl)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-4-carboxamide,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-3-carboxamide,
tert-butyl 3-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-benzylamino)propanoate,
5-(4-methoxyphenyl)-N-(4-(piperazine-1-ylmethyl)phenyl)pyrimidine-2-amine,
1-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)Etalon,
(4-(4-(5-(4-methoxyphenyl)pyrimido the-2-ylamino)benzyl)piperazine-1-yl)(tetrahydrofuran-2-yl)methanon,
1-(3-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzylamino)propyl)-pyrrolidin-2-it,
(S)-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)pyrrolidin-2-yl)methanol,
(R)-N-(4-((2-(methoxymethyl)pyrrolidin-1-yl)methyl)phenyl)-5-(4-methoxyphenyl)-pyrimidine-2-amine,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)pyrrolidin-3-ol,
methyl-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzylamino)-cyclopentanecarboxylic,
4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)-2-methylpiperazin-1-carboxylic acid
3-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)propionic acid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-3-carboxylic acid
ethyl-2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)acetate,
2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)acetic acid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)pyrrolidin-3-carboxylic acid
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenylmorpholine-4-carboxylate,
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl-4-methylpiperazin-1-carboxylate,
3-(5-(4-((2-tert-butoxy-2-oxoethylidene)methyl)phenyl)pyrimidine-2-ylamino)-phenyl-4-methylpiperazin-1-carboxylate,
methyl-4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperazine-1-carboxylate,
4-(5-(4-((2-tert-butoxy-2-oxoethylidene)methyl)phenyl)pyrimidine-2-ylamino)-phenyl-4-methylpiperid the zine-1-carboxylate,
N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-4-methylpiperazin-1-carboxamid,
2-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-1-(4-methylpiperazin-1-yl)Etalon,
N1-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)piperidine-1,4-dicarboxamide,
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl-4-methylpiperazin-1-carboxylate,
4-hydroxy-N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)piperidine-1-carboxamide,
N-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-4-methylpiperazin-1-carboxamid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-carboxamide,
furan-2-yl-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperazine-1-yl)methanon,
5-(4-methoxyphenyl)-N-(4-(2-(piperazine-1-yl)ethyl)phenyl)pyrimidine-2-amine,
N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-N,4-dimethylpiperidin-1-carboxamid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-3-carboxamide,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-3-carboxylic acid
methyl-4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperazine-1-carboxylate,
2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-yl)acetic acid,
methyl-2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-yl)acetate,
(3-(hydroxymethyl)piperidine-1-yl)(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-phenyl)methanon,
(3-hydroxypyrrolidine-1-yl)(4-(5-(4-methox is phenyl)pyrimidine-2-ylamino)-phenyl)methanon,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperidine-4-carboxamide,
3-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperazine-1-yl)propionic acid,
(S)-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)pyrrolidine-2-carboxylic acid,
4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethylamine)-cyclohexanecarbonyl acid,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzamide,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperidine-3-carboxamide,
N-(3-carbamoylmethyl)-4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzamide,
1,4'-bipiperidine-1'-yl-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-phenyl)methanon,
(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(4-(pyrrolidin-1-yl)-piperidine-1-yl)methanon,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(2-(pyridin-2-yl)ethyl)benzamide,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(1,3,5-trimethyl-1H-pyrazole-4-yl)-benzamid,
(4-(furan-2-carbonyl)piperazine-1-yl)(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)methanon,
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(1,3,5-trimethyl-1H-pyrazole-4-yl)-benzamid,
(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(4-(1-methylpiperidin-4-yl)-piperazine-1-yl)methanon,
1-(4-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperazine-1-yl)Etalon,
(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(4-(pyrrolidin-1-yl)-piperidine-1-yl)methanon,
1,4'-beeper the DIN-1'-yl(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)methanon,
1-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperidine-3-carboxamide,
N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-4-(1-methylpiperidin-4-yl)-piperazine-1-carboxamide,
methyl-4-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenylcarbamoyl)piperazine-1-carboxylate,
(R)-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-3-carboxylic acid
(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(piperazine-1-yl)methanon,
4-acetyl-N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)piperazine-1-carboxamide and
(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(piperazine-1-yl)methanon.

8. The compound according to claim 1, having the structure

9. Pharmaceutical composition having the properties of an inhibitor of the receptor c-kit, containing a compound of structural formula (1) or structural formula (46):
,
where Ar is selected from the group including
,,,,,
,,,,
,,,
,, ,
,,,
,,,
,,,
,,
,,
,,,
,,,
,and;
Q is selected from the group including
,,,,
,,,,
,,,,
,,,,
,,,,
,, ,,
,,,,
,,,,
,,,
,,,
,,,
,,,
,,,,
,,,
,,
,,
,,
,,
,,,
,,,
,,,
,,,,
,,,,,
,,,,,
,,,,
,,,,
,,,,,
,,,,
,,,
,,,,
,,,,,
,,, ,,
,,,,
,,,
,,,,
,,,
,,,,,
,,,,
,,,,
,,,,
,,,,
,,,,
,,,,
, ,,
,,,
,,,,
,,,
,,,
,,,
,,,
,,,,,
,,,,,
,,,,,
,,,,
,,,,
,, ,
,,,,,
,,,,
,,,,,
,,,,
,,,,,
,,,,,
,,,,,
,,,,,
,,,,,
,, ,,
,,,,,
,,,,
,,,
,,,
,,,
,,,
,,,
,,,
,,and;
each R1independently of the other represents H, -C(O)HE-L1-C1-6alkyl, where
L1represents-O - or-C(O)O-, or
any two adjacent groups R1together may form a 5-6-membered heterocyclic ring containing a nitrogen atom or an oxygen atom as a heteroatom, or 6-membered heterocyclic ring with one or two nitrogen atoms as is heteroatoms, optionally substituted C1-4the alkyl, and
R5denotes hydrogen or C1-C6alkyl,
the effective amount or its pharmaceutically acceptable salt and also containing one or more auxiliary substances.

10. The pharmaceutical composition according to claim 9, which is contained in the compound selected from the group including
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-carboxylic acid,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)-2-perbenzoic)acetate,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)-2-forbindelsen)acetate,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)benzylamino)acetate,
2,2'-(2-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenoxy)-ethyl)ethandiyl)diethanol,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)-benzamido)acetate,
methyl-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-carboxylate,
N-(4-(2-(diethylamino)ethyl)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
1-(2-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenoxy)ethyl)piperidine-4-carboxylic acid,
N-(4-(2-(diethylamino)ethoxy)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
tert-butyl 2-(4-(2-(4-(2-morpholinoethoxy)phenylamino)pyrimidine-5-yl)-benzamido)acetate,
tert-butyl 2-(4-(2-(4-(2-(4-carbamoylbiphenyl-1-yl)ethoxy)-Fenelon the but)pyrimidine-5-yl)benzamido)acetate,
4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)phenyl acetate,
ethyl-2-(2-(diethylamino)ethoxy)-5-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoate,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl-4-methylpiperazin-1-carboxylate,
5-(4-methoxyphenyl)-N-(4-(2-(methyl(pyridin-2-yl)amino)ethoxy)phenyl)pyrimidine-2-amine,
methyl-4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)benzoate,
N-(4-(2-(diethylamino)ethoxy)phenyl)-5-(3-fluoro-4-methoxyphenyl)pyrimidine-2-amine,
2-(2-(diethylamino)ethoxy)-4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoic acid
methyl-2-(2-(diethylamino)ethoxy)-4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoate,
N-(3-(2-(diethylamino)ethoxy)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
N-(3-(2-(diethylamino)ethyl)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-4-carboxamide,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-3-carboxamide,
tert-butyl 3-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-benzylamino)propanoate,
5-(4-methoxyphenyl)-N-(4-(piperazine-1-ylmethyl)phenyl)pyrimidine-2-amine,
1-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)Etalon,
(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)(tetrahydrofuran-2-yl)methanon,
1-(3-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzylamino)propyl)-pyrrolidin-2-it,
(S)-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-yl) - Rev. Mino)benzyl)pyrrolidin-2-yl)methanol,
(R)-N-(4-((2-(methoxymethyl)pyrrolidin-1-yl)methyl)phenyl)-5-(4-methoxyphenyl)-pyrimidine-2-amine,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)pyrrolidin-3-ol,
methyl-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzylamino)-cyclopentanecarboxylic,
4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)-2-methylpiperazin-1-carboxylic acid
3-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)propionic acid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-3-carboxylic acid
ethyl-2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)acetate,
2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)acetic acid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)pyrrolidin-3-carboxylic acid
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenylmorpholine-4-carboxylate,
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl-4-methylpiperazin-1-carboxylate,
3-(5-(4-((2-tert-butoxy-2-oxoethylidene)methyl)phenyl)pyrimidine-2-ylamino)-phenyl-4-methylpiperazin-1-carboxylate,
methyl-4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperazine-1-carboxylate,
4-(5-(4-((2-tert-butoxy-2-oxoethylidene)methyl)phenyl)pyrimidine-2-ylamino)-phenyl-4-methylpiperazin-1-carboxylate,
N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-4-methylpiperazin-1-carboxamid,
2-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-1-(4-methyl who piperazin-1-yl)Etalon,
N1-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)piperidine-1,4-dicarboxamide,
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl-4-methylpiperazin-1-carboxylate,
4-hydroxy-N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)piperidine-1-carboxamide,
N-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-4-methylpiperazin-1-carboxamid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-carboxamide,
furan-2-yl-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperazine-1-yl)methanon,
5-(4-methoxyphenyl)-N-(4-(2-(piperazine-1-yl)ethyl)phenyl)pyrimidine-2-amine,
N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-N,4-dimethylpiperidin-1-carboxamid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-3-carboxamide,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-3-carboxylic acid
methyl-4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperazine-1-carboxylate,
2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-yl)acetic acid,
methyl-2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-yl)acetate,
(3-(hydroxymethyl)piperidine-1-yl)(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-phenyl)methanon,
(3-hydroxypyrrolidine-1-yl)(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-phenyl)methanon,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperidine-4-carboxamide,
3-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-silts is about)phenethyl)piperazine-1-yl)propionic acid,
(S)-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)pyrrolidine-2-carboxylic acid,
4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethylamine)-cyclohexanecarbonyl acid,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzamide,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperidine-3-carboxamide,
N-(3-carbamoylmethyl)-4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzamide,
1,4'-bipiperidine-1'-yl-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-phenyl)methanon,
(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(4-(pyrrolidin-1-yl)-piperidine-1-yl)methanon,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(2-(pyridin-2-yl)ethyl)benzamide,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(1,3,5-trimethyl-1H-pyrazole-4-yl)-benzamid,
(4-(furan-2-carbonyl)piperazine-1-yl)(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)methanon,
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(1,3,5-trimethyl-1H-pyrazole-4-yl)-benzamid,
(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(4-(1-methylpiperidin-4-yl)-piperazine-1-yl)methanon,
1-(4-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperazine-1-yl)Etalon,
(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(4-(pyrrolidin-1-yl)-piperidine-1-yl)methanon,
1,4'-bipiperidine-1'-yl(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)methanon,
1-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperidine-3-carboxamide,
N-(3-(5-(4-methoxyphenyl)PIR is midin-2-ylamino)phenyl)-4-(1-methylpiperidin-4-yl)-piperazine-1-carboxamide,
methyl-4-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenylcarbamoyl)piperazine-1-carboxylate,
(R)-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-3-carboxylic acid
(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(piperazine-1-yl)methanon,
4-acetyl-N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)piperazine-1-carboxamide and
(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(piperazine-1-yl)methanon.

11. The pharmaceutical composition according to claim 9, which contains a compound having the structure:

12. The method of treatment of the disease, the development of which contributes to the activity of the receptor c-kit, comprising introducing a therapeutically effective amount of a compound of structural formula (1) or structural formula (46)
,
where Ar is selected from the group including
,,,,,
,,,,
,,,
,,,
, ,,
,,,
,,,
,,
,,
,,,
,,,
,and;
Q is selected from the group including
,,,,,
,,,,
,,,,
,,,,
,,,,
,,, ,
,,,,
,,,,
,,,
,,,
,,,
,,,
,,,,
,,,
,,,
,,
,,
,,,
,,,
,,,
,, ,,
,,,,,
,,,,,
,,,,
,,,,
,,,,,
,,,,
,,,
,,,,
,,,,,
,,,,,
,,,,
,,,
,,,,
,,,
,,,,,
,,,,
,,,,
,,,,
,,,,
,,,,
,,,,
,,,
,,,
,,,,
,,,
,,,
,,,
,,,
,,,,,
,,,,,
,,,,,
,,,,
,,,,
,,,
, ,,,,
,,,,
,,,,,
,,,,
,,,,,
,,,,,
,,,,,
,,,,,
,,,,,
,,,,
,,,,,
,,,,
,,,
,,,
,,,
,,,
,,,
,,,
,,and;
each R1independently of the other represents H, -C(O)HE-L1-C1-6alkyl, where
L1represents-O - or-C(O)O-, or
any two adjacent groups R1together may form a 5-6-membered heterocyclic ring containing a nitrogen atom or an oxygen atom as a heteroatom, or 6-membered heterocyclic ring with one or two nitrogen atoms as heteroatoms, optionally substituted C1-4the alkyl,and
R5denotes hydrogen or C1-C6alkyl,
or its pharmaceutically acceptable salt.

13. The method according to item 12, in which Q is selected from the group including
,,,,,
,,,,,
,,,,,
,,,,,
,,,,,
,,,,,
,,,,
,,,,
,, ,,,
,,,,,
,,,,
and.

14. The method according to item 12, in which Q is selected from the group including,
,,,,,,
,,,,,
,,,,,,
,,,,,,
,,,,,
, ,,,,
,,,,
,,,,,
,,,,,
,,,,,
,,,,,,
,,,,
,,,,
,,,,,
,,,, ,
,and.

15. The method according to any of PP-14, in which Ar is selected from the group including,,,,
,,,
and.

16. The method according to item 12, in which the compound is selected from the group including
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-carboxylic acid,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)-2-perbenzoic)acetate,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)-2-forbindelsen)acetate,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)benzylamino)acetate,
2,2'-(2-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenoxy)-ethyl)ethandiyl)diethanol,
tert-butyl 2-(4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)-benzamido)acetate,
methyl-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-carboxylate,
N-(4-(2-(diethylamino)ethyl)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
1-(2-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenoxy)ethyl)piperidine-4-carboxylic acid,
N-(4-(2-(diethylamino)ethoxy)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,br/> tert-butyl 2-(4-(2-(4-(2-morpholinoethoxy)phenylamino)pyrimidine-5-yl)-benzamido)acetate,
tert-butyl 2-(4-(2-(4-(2-(4-carbamoylbiphenyl-1-yl)ethoxy)-phenylamino)pyrimidine-5-yl)benzamido)acetate,
4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)phenyl acetate,
ethyl-2-(2-(diethylamino)ethoxy)-5-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoate,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl-4-methylpiperazin-1-carboxylate,
5-(4-methoxyphenyl)-N-(4-(2-(methyl(pyridin-2-yl)amino)ethoxy)phenyl)pyrimidine-2-amine,
methyl-4-(2-(4-(2-(diethylamino)ethoxy)phenylamino)pyrimidine-5-yl)benzoate,
N-(4-(2-(diethylamino)ethoxy)phenyl)-5-(3-fluoro-4-methoxyphenyl)pyrimidine-2-amine,
2-(2-(diethylamino)ethoxy)-4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoic acid
methyl-2-(2-(diethylamino)ethoxy)-4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoate,
N-(3-(2-(diethylamino)ethoxy)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
N-(3-(2-(diethylamino)ethyl)phenyl)-5-(4-methoxyphenyl)pyrimidine-2-amine,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-4-carboxamide,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-3-carboxamide,
tert-butyl 3-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-benzylamino)propanoate,
5-(4-methoxyphenyl)-N-(4-(piperazine-1-ylmethyl)phenyl)pyrimidine-2-amine,
1-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)Etalon,
(4-(4-(5-(4-methoxyphenyl)pyrimido the-2-ylamino)benzyl)piperazine-1-yl)(tetrahydrofuran-2-yl)methanon,
1-(3-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzylamino)propyl)-pyrrolidin-2-it,
(S)-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)pyrrolidin-2-yl)methanol,
(R)-N-(4-((2-(methoxymethyl)pyrrolidin-1-yl)methyl)phenyl)-5-(4-methoxyphenyl)-pyrimidine-2-amine,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)pyrrolidin-3-ol,
methyl-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzylamino)-cyclopentanecarboxylic,
4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)-2-methylpiperazin-1-carboxylic acid
3-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperazine-1-yl)propionic acid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-3-carboxylic acid
ethyl-2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)acetate,
2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperidine-4-yl)acetic acid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)pyrrolidin-3-carboxylic acid
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenylmorpholine-4-carboxylate,
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl-4-methylpiperazin-1-carboxylate,
3-(5-(4-((2-tert-butoxy-2-oxoethylidene)methyl)phenyl)pyrimidine-2-ylamino)-phenyl-4-methylpiperazin-1-carboxylate,
methyl-4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl)piperazine-1-carboxylate,
4-(5-(4-((2-tert-butoxy-2-oxoethylidene)methyl)phenyl)pyrimidine-2-ylamino)-phenyl-4-methylpiperid the zine-1-carboxylate,
N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-4-methylpiperazin-1-carboxamid,
2-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-1-(4-methylpiperazin-1-yl)Etalon,
N1-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)piperidine-1,4-dicarboxamide,
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzyl-4-methylpiperazin-1-carboxylate,
4-hydroxy-N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)piperidine-1-carboxamide,
N-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-4-methylpiperazin-1-carboxamid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-carboxamide,
furan-2-yl-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperazine-1-yl)methanon,
5-(4-methoxyphenyl)-N-(4-(2-(piperazine-1-yl)ethyl)phenyl)pyrimidine-2-amine,
N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-N,4-dimethylpiperidin-1-carboxamid,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-3-carboxamide,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-3-carboxylic acid
methyl-4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperazine-1-carboxylate,
2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-yl)acetic acid,
methyl-2-(1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-4-yl)acetate,
(3-(hydroxymethyl)piperidine-1-yl)(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-phenyl)methanon,
(3-hydroxypyrrolidine-1-yl)(4-(5-(4-methox is phenyl)pyrimidine-2-ylamino)-phenyl)methanon,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperidine-4-carboxamide,
3-(4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperazine-1-yl)propionic acid,
(S)-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)pyrrolidine-2-carboxylic acid,
4-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethylamine)-cyclohexanecarbonyl acid,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzamide,
1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperidine-3-carboxamide,
N-(3-carbamoylmethyl)-4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzamide,
1,4'-bipiperidine-1'-yl-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-phenyl)methanon,
(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(4-(pyrrolidin-1-yl)-piperidine-1-yl)methanon,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(2-(pyridin-2-yl)ethyl)benzamide,
4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(1,3,5-trimethyl-1H-pyrazole-4-yl)-benzamid,
(4-(furan-2-carbonyl)piperazine-1-yl)(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)methanon,
3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)-N-(1,3,5-trimethyl-1H-pyrazole-4-yl)benzamid,
(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(4-(1-methylpiperidin-4-yl)piperazine-1-yl)methanon,
1-(4-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperazine-1-yl)Etalon,
(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(4-(pyrrolidin-1-yl)piperidine-1-yl)methanon,
1,4'-ipipiri the Jn-1'-yl-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)methanon,
1-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)benzoyl)piperidine-3-carboxamide,
N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-4-(1-methylpiperidin-4-yl)piperazine-1-carboxamide,
methyl-4-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenylcarbamoyl)-piperazine-1-carboxylate,
(R)-1-(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenethyl)piperidine-3-carboxylic acid
(4-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(piperazine-1-yl)methanon,
4-acetyl-N-(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)-piperazine-1-carboxamide and
(3-(5-(4-methoxyphenyl)pyrimidine-2-ylamino)phenyl)(piperazine-1-yl)methanon.

17. The method according to item 12, which selects the connection having the structure:



 

Same patents:

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of bicyclic imdazo-3-lylamines of general formula and corresponding physiologically transportable salts thereof, where A1 denotes a nitrogen atom or a C-R1a-group, A2 denotes a nitrogen atom or a C-R1b-group, A3 denotes a C-R1c-group, A4 denotes a nitrogen atom or a C-R1d-group, R1a, R1b, R1c, R1d independently denote hydrogen, halogen, -C(=O)-OR12, -OR16, a straight or branched, saturated, unsubstituted or halogen-tri-substituted C1-10-aliphatic residue, or an unsubstituted phenyl residue which can be bonded through a straight or branched C1-5-alkylene group, or R1b and R1c or R1c and R1d together with a C-C-bridge bonded to them optionally form an unsubstituted annelated phenyl residue, R2 and R3 independently denote hydrogen, -C(=O)-R2b, (CH2)q -C(=O)-R21, where q equals 1, -(CH2)r- C(=O)-O-R22, where r equals 1, a straight or branched, saturated unsubstituted C1-16-aliphatic residue, saturated, unsubstituted C4-8-cycloaliphatic residue which can be bonded through a straight or branched C1-5-alkylene group, or an unsubstituted or at least mono-substituted phenyl or heteroaryl residue which can be bonded through a straight or branched C1-5-alkylene group, or R2 and R3 together with the nitrogen atom with which they are bonded to as a ring member form a saturated heterocycloaliphatic residue which is piperidine or pyrrolidine, R12, R16, R20, R21 and R22 independently denote hydrogen, straight or branched, saturated C1-4-aliphatic residue or an unsubstituted or at least mono-substituted phenyl residue, which can be bonded through a straight or branched C1-5-alkylene group, M1 denotes a phenyl or heteroaryl residue which can be substituted with an additional substitute which is methyl or -CH2-CN, M2 denotes an unsubstituted or at least mono-substituted phenyl or heteroaryl residue, wherein the heteroaryl is selected from a group consisting of the following residues: furyl (furanyl), thienyl (thiophenyl), imidazolyl, thiazolyl, pyrrolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl and quinolyl, the expression "at least mono-substituted" in association with "phenyl" or "heteroaryl" relates to a phenyl or heteroaryl residue which can be substituted with 1 or 2 substitutes independently selected from a group comprising halogen, , -CN, -NO2, -OH, -NH2, -CH2-NH2, -C(=O)-OH, C1-C5alkyl, -CH2-O-C1-C5alkyl, -C2-C5alkenyl, -S-C1-C5alkyl, -O-C1-C5alkyl, -CF3, -O-CF3, -NH-C1-C5alkyl, -N-(C1-C5alkyl)2, -C(=O)-O-C1-C5alkyl, -C(=O)-H, -C(=O)-C1-C5alkyl, -NH-S(=O)2-C1-C5alkyl, -NH-C(O)-C1-C5alkyl, -S(=O)2-NH2,-S(=O)2-NH-C1-C5alkyl, -CH2OH, -C(=O)-NH2, -Si(phenyl)2[C1-C5alkyl], (1,3)-dioxolanyl, phenyl and pyrrolyl. The invention also relates to methods of producing compounds of formula I, a medicinal agent based on compounds of formula I, use of compounds of formula I to prepare the medicinal agent.

EFFECT: obtaining novel derivatives of bicyclic imidazo-3-ylamines of general formula I, used to regulate the mGluR5-receptor.

30 cl, 3 tbl, 365 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula (I): or its pharmaceutically acceptable salt where Q is 2,6-pyrimidyl; where Q is optionally substituted by 1-5 substitutes JQ; Z is a link or NH; R1 is H; R2 is H; R3 is halogen or -(U)m-X where m is equal to 0; X is H or halogen; JQ is halogen, OCF3, -(Vn)-R", -(Vn)-CN or -(Vn)-(C1-4 halogenaliphatic group) where JQ is not H; V is C1-10aliphatic group where up to three methylene groups are substituted by GV where Gv is selected from -NH-, -NR-, -O-, -S-, -CO2-, -C(O)CO-, -C(O), -C(O)NH-, -C(O)NR-, -C(=N-CN)-, -NHCO-, -NRCO-, -NHSO2-, -NRSO2-, -NHC(O)NH-, -NRC(O)NH-, -NHC(O)NR-, -NRC(O)NR or -SO2-; and where V is optionally substituted by 1-6 substitutes JV; R" is H or an optionally substituted group selected from C1-6aliphatic group, C3-10cycloaliphatic group, C6-10aryl, 5-10-member heteroaryl or 5-10-member heterocyclyl; or two R" groups on the same substitute or various substitutes together with atom (s) whereto each group R" is attached, form optionally substituted 3-8-member heterocyclyl; where each optionally substituted R" group is independently and optionally substituted by 1-6 substitutes JR; R is an optionally substituted group selected from C1-6aliphatic group and C6-10aryl where each group R is independently and optionally substituted by 1-4 substitutes JR; each Jv and JR are independently selected from halogen, L, - (Ln)-R', - (Ln)-N(R')2, -(Ln)-OR', C1-4haloalkyl, -(Ln)-CN, - (Ln)-OH, -CO2R', -CO2H or -COR'; or two Jv, JR groups on the same substitute or various substitutes together with atom (s) whereto each group JV and JR is attached, form a 5-7-member saturated, unsaturated or partially saturated ring; R' is H or C1-6aliphatic group; L is C1-6aliphatic group where up to three methylene units are substituted by -C(O)-; each n is independently equal to 0 or 1. Besides, an invention refers to of a pharmaceutical composition for ROCK or JAK kinase inhibition on the basis of the given compounds, to a method of ROCK or JAK kinase activity inhibition, and also to application of the compounds of formula I, for preparing a drug where Q, Z, R1, R2 and R3 are those as described in cl. 1 of the patent claim, effective as protein kinase inhibitors, especially JAK and ROCK families kinase inhibitors.

EFFECT: there are prepared and described new compounds which can find the application in medicine.

42 cl, 6 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: described is a compound of general formula: [1], where R1 denotes an optionally substituted C2-C12 alkyl, aryl or heterocyclic group which can be a mono- or bicyclic 5-11-member radical, where the heteroatoms can be nitrogen, oxygen or sulphur; X1 denotes C2-C4 an alkylene group; X2 denotes a bond; X3 denotes a group of general formula NR3 or CR4R5NR3 (where R3 denotes a hydrogen atom, optionally substituted lower alkyl group or imino-protective group) and R4 and R5 are identical or different, and each denotes a hydrogen atom or a lower alkyl group or bond; X4 denotes a lower alkylene or lower alkenylene or lower alkynylene group, which can be substituted with one or more oxo groups or a bond; X5 denotes a sulphur atom or bond; Y1 denotes an optionally substituted divalent 4-, 5- or 6-member alicyclic hydrocarbon residue or an optionally subsituted divalent 5- or 6-member alicyclic amine residue, where the heteroatoms can be nitrogen or oxygen; Z1, Z2, Z3, Z4, Z5 and Z6 are identical or different, and each denotes a nitrogen atom or a group of general formula CR7 (where R7 denotes a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, an optionally substituted amino group, or an amino group substituted with one or more C1-6 alkyl groups, a lower alkyl group, a cycloalkyl, a lower alkoxy group or a monocyclic 5-member heterocyclic group which can be substituted with one or more halogen atoms, where the heteroatoms can be nitrogen, acid or sulphur or a group of general formula Q1CO2R10 (where R10 denotes a carboxyl-protective group and Q1 denotes a lower alkenylene group), provided that at least one of Z3, Z4, Z5 and Z6 denotes a nitrogen atom, or salt thereof. The invention also describes an antimicrobial agent based on said compound.

EFFECT: novel compounds which can be used as antimicrobial agents are obtained and described.

25 cl, 176 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (1) (lb) in which A denotes a benzene ring; Ar denotes naphthalenyl which optionally contains 1-3 substitutes independently selected from a group comprising C1-C6alkyl, C3-C7cycloalkyl, C3-C7cycloalkyl-C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, hydroxy group, C1-C6alkoxy group, halogen, heteroalkyl, heteroalkoxy group, nitro group, cyano group, amino- and mono- or di- C1-C6alkyl-substuted amino group; R1 denotes hydrogen, halogen, C1-C6alkyl, C1-C6alkoxy group, carboxy group, heteroalkyl, hydroxy group optionally substituted with heterocyclylcarbonyl-C1-C6alkyl or R1 denotes N(R')(R")-C1-C6alkyl or N(R')(R")-carbonyl- C1-C6alkyl-, in which R' and R" are independently selected from a group comprising hydrogen, C1-C6alkyl, C3-C7cycloalkyl, C3-C7cycloalkyl-C1-C6alkyl, heteroalkyl, phenyl-C1-C6alkyl; or R1 denotes R'-CO-N(R")-C1-C6alkyl, R'-O-CO-N(R")- C1-C6alkyl- or R'-SO2-N(R")- C1-C6alkyl-, in which R' and R" are independently selected from a group comprising hydrogen, C1-C6alkyl, C3-C7cyclalkyl, C3-C7cycloalkyl- C1-C6alkyl or optionally substituted phenyl; R2, R2' and R2" independently denote hydrogen, halogen, cyano group, C1-C6alkyl, halogenated C1-C6alkyl or C1-C6alkoxy group; n equals 1; and pharmaceutically acceptable salts thereof. The invention also relates to use of compounds in any of claims 1-9, as well as to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds with chymase inhibiting activity.

14 cl, 128 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I), in which X denotes N or CR3, M denotes (CH2)m; m equals 0 or 1, R1 denotes H or lower alkyl which can be substituted with a group selected from a group consisting of mono- or di-lower alkylamino and -O-lower alkyl, R2 denotes H or lower alkyl, R3 denotes H or lower alkyl substituted with a group selected from a group consisting of halogen, mono- or di-lower alkylamino and cyclic amino, R41 denotes H or pyridine which can be substituted with a cyano group, R42 denotes a bridged polycyclic hydrocarbon or a bridged azacyclic hydrocarbon, each of which can be substituted, R5 denotes a group selected from a group consisting of halogen, cyano, lower alkyl-carbonyl, lower alkyl-oxycarbonyl, hydroxycarbonyl, formyl, amidinooxycarbonyl, guanidinooxycarbonyl, guanidino, carbamoyl, -C(=O)-5- or -6-member heterocycloalkyl, -C(=O)-5- or -6-member heteroaryl, lower alkyl, lower alkenyl, -O-lower alkyl, 5- or 6-member heterocycloalkyl and 5-member heteroaryl, each of which can be substituted, provided that when R5 denotes a 5-member heteroaryl, X denotes -CR3; or R41 and R15 can be bonded through a defined functional group to form divalent groups shown below: (I-A) (I-B) or (I-C), in which RA denotes H or acyl, which can be substituted, provided that the term "substituted" with respect to R4 and/or R5 denotes substitution with one or more substitutes selected from a group comprising the following substitutes: (a). halogen; (b) -OH, -O-R2, -O-phenyl, -OCO-RZ-OCONH-RZ oxo (=O); (c) -SH, -S-R2, -S-phenyl, -S-heteroaryl, -SO-R2, -SO-phenyl, -SO-heteroaryl, -SO3H, -SO2-RZ, -SO2-phenyl, - SO2-heteroaryl, sulphamoyl, which can be substituted with one or two RZ groups; (d) amino, which can be substituted with one or two RZ groups, -NHCO-RZ, -NHCO-phenyl, -NHCO2-RZ, -NHCONH2, -NHCONH-RZ, -NHSO2-R0, -NHSO2-phenyl, -NHSO2NH2, -NO2, =N-O-RZ; (e) -CHO, -CO-RZ, -CO2H, -CO2-RZ, carbamoyl, which can be substituted with one or two RZ groups, -CO-cyclic amino, -COCO-RZ, cyano; (f) RZ; (g) phenyl, which can be substituted with one or more groups selected from substitutes described above in paragraphs from (a) to (f), a 5- or 6-member heterocycloalkyl, a 5- or 6-member heteroaryl, a 5- or 6-member heterocycloaryl; or pharmaceutically acceptable salts thereof. The invention also relates to a method of producing compounds of formula II, a pharmaceutical composition based on said compounds which is a Janus kinase 3 inhibitor, a method of treating and/or preventing different immunopathological diseases, including autoimmune diseases, inflammatory diseases and allergic diseases.

EFFECT: novel compounds are obtained and described, which can be used as an active ingredient of an agent for treating or preventing diseases caused by undesirable cytokine signal transmission or diseases caused by pathological cytokine signal transmission.

14 cl, 579 ex, 72 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to RSV replication inhibitors of formula (I) or salts thereof or stereochemically isomeric forms, where R is a radical of formula (a) or (b) . Q is hydrogen or C1-6alkyl substituted with a heterocycle selected from oxazolidine, morpholinyl and hexahydrooxazepine. Alk denotes C1-6alkanediyl. X is O; -a1=a2-a3=a4 - is -N=CH-CH=CH-, -CH=N-CH=CH-, -CH=CH-N=CH- or -CH=CH-CH=N-; R1 is selected from optionally substituted pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl and pyrrolyl. R2 is C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, Ar-C1-6alkyloxyC1-6alkyl, C3-7cycloalkyl, Ar-C1-6alkyl. R3 is cyano. Ar is phenyl o substituted phenyl. The invention also relates to pharmaceutical compositions containing compounds (I) and a method of producing compounds (I).

EFFECT: high efficiency of the compositions.

9 cl, 20 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (IC-2), to their pharmaceutically acceptable salts, N- oxides or solvates. In formula (IC-2) Z represents carbomoyl group, which can be replaced with C1-4 alkyl or hydroxy; R1 represents C1-8 alkyl or C1-8 alkoxy; R4 and R4-1 each independently represent hydrogen atom or C1-8 alkyl; m represents integer number from 1 to 5, when m equals 2 or larger number, all R1 can have same or different values. Invention also relates to compounds, representing 1-({6-[(2-methoxy-4-propylbenzyl)oxy]-1-methyl-3,4-dihydro-2-napthlenyl}methyl)-3-azetidinecarbonic acid, 1-({6-[(4-isobutyl-2-methoxybenzyl)oxy]-1-methyl-3,4-dihydro-2-naphthalinyl}methyl)-3- azetidinecarbonic acid and other, given in formula of claimed invention.

EFFECT: obtaining pharmaceutical composition, which has agonistic activity with respect to EDG-1, EDG-6 and/or EDG-8, containing as active component invention compound, to method of prevention and/or treatment of disease, conditioned by EDG-1, EDG-6 and/or EDG-8 invention compounds, to method of prevention and/or treatment of disseminated sclerosis and method of immune reaction suppression and/or induction of lymphopenia, to application of invention compounds for obtaining medication for prevention and/or treatment of disease, conditioned by EDG-1, EDG-6 and/or EDG-8, to application of compounds for obtaining medication for prevention and/or treatment of disseminated sclerosis, to application of compounds for obtaining immunodepresant and/or medication inducing lymphopenia and to crystal forms of some individual compounds.

17 cl, 10 dwg, 5 tbl, 251 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel bicyclic derivatives of general formula (I)

(values of radicals are given in the description) and a pharmaceutical composition containing said derivatives, as well as use of said novel compounds to treat or inhibit symptomatic diseases where CEPT is involved, and a method of treating said diseases.

EFFECT: high efficiency of using compounds when treating diseases.

14 cl, 34 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I or pharmaceutically acceptable salts thereof, which have receptor tyrosine kinase type I inhibiting properties and can be used in treating hyperproliferative disorders in mammals. In general formula

,

A is O or S; G is N; B is a 6-member aryl or 5-6-member heteroaryl ring containing a sulphur atom as a heteroatom; E is

, , , , , X is N or CH; D1, D2 and D3 independently denote N or CR19; D4 and D5 independently denote N or CR19 and D6 is O, S or NR20, where at least one of D4 and D5 is CR19; D7, D8, D9 and D10 independently denote N or CR19, where at least one of D7, D8, D9 and D10 is N; R1 is H or C1-C6 alkyl; each R2 independently denotes halogen, cyano, nitro etc, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, -SR18, -OR15, -C(O)R15, -C(O)OR15, -NR14C(O)OR18, -OC(O)R15, -NR14SO2R18, -SO2NR15R14, -NR14C(O)R15, -C(O)NR15R14, -NR15C(O)NR15R14, -NR13C(NCN)NR15R14, -NR15R14, C1-C12alkyl, C2-C12 alkenyl, alkynyl, saturated or partially unsaturated C3-C10cycloalkyl, C3-C10cycloalkyl-C1-C12alkyl, -S(O)p(C1-C6alkyl), -S(O)p(CR13R14)q-phenyl, phenyl, phenyl-C1-3-alkyl, 5-6-member heteroaryl, 5-6-member heteroaryl-C1-C3-alkyl, saturated or partially unsaturated 3-8-member heterocyclyl, 5-6-member heterocyclyl-C1-C3-alkyl, -O(CR13R14)q-phenyl, NR15(CR13R14)q-phenyl, O(CR13R14)q-(5-6-member heteroaryl), NR13(CR13R14)q-(5-6-member heteroaryl, -O(CR13R14)q-(3-8-member heterocyclyl) or -NR15(CR13R14)q-3-8-member heterocyclyl), each R3 denotes Z, where Z is selected from and , W is O or S; W2 is O or S;V is CR8R9, R8b is H or C1-C6alkyl; each of R6, R8, R8a and R9 independently denotes hydrogen, trifluoromethyl, C1-C12alkyl etc.

EFFECT: improved properties and high efficiency of using the compounds.

25 cl, 13 dwg, 1 tbl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) in free form or in form of a pharmaceutically acceptable salt, where A is independently selected from CH and at least one nitrogen atom; D denotes CR3; R1 and R2 denote H, R3 denotes C1-C8-alkyl, R5 denotes , R5j and R5k are independently selected from H, C1-C8-alkyl and C3-C15-carbocyclic group, or R5j and R5k together with the nitrogen atom to which they are bonded form an optionally substituted 4-14-member heterocyclic group; R6 denotes H; W denotes a C6-C15-aromatic carbocyclic group; X denotes -CH2-; n assumes values from 0 to 3, a pharmaceutical composition based on said compounds and having CRTh2 receptor modulating activity, as well as a method for synthesis of compounds of formula I.

EFFECT: novel compounds which can be used as anti-inflammatory agents are obtained and described.

9 cl, 1 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula where R denotes a thiazolyl group of formula R2 and R3 are selected from: hydrogen, C1-C3linear alkyl; R4 is selected from: C1-C3linear or C3cyclic alkyl, phenyl and thiophenyl; Z denotes a group of formula: -(L)n-R1; R1 is selected from: i) C1-C3linear or branched alkyl, optionally substituted with C1-C4alkoxycarbonyl, halogen; ii) substituted phenyl or substituted with one or two substitutes selected from halogen, methoxy- or hydroxy group, C1-C4alkoxycarbonyl; iii) dioxopiperazinyl and 2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl, substituted with C1-C3alkyl; or iv) heteroaryl rings containing 5-10 atoms selected from thiazole, triazole, 1H-imidazole, thiadiazole, oxazole, isoxazole, oxadiazole, benzodioxole, benzo(1,4)dioxepanyl, pyridine, pyrimidine, 1H-indole, 2,3-dihydrobenzo[b][1,4]dioxynil, which can be substituted with oine or two substitutes selected from: a) hydroxy; b) C1-C3alkyl (which can be substituted with one more two substitutes selected from: ) phenyl; ii) C1-C4alkoxycarbonyl; iii) naphthalenyl; iv) 2-methylthiazolyl) ; c) NHC(O)C1-C3alkyl; d) C1-C4alkoxycarbonyl; e) 1 -(tert-butoxycarbonyl)-2-phenylethyl; f) methoxybenzyl; g) phenyl which can be substuted with C1-C4alkoxy, halogen, methoxycarbonyl or >NHC(O)CH3; h) (methoxy-2-oxoethyl)carbamoyl; L denotes a group selected from: i) C(O)NH[C(R5aR5b)]w-; ii) -C(O)[C(R6aR6b)]x-; iii) -C(O)[C(R7aR7b)]yC(O)-; iv) -SO2[C(R8aR8b)]z-; R5a, R5b, R6a, R6b, R7a, R7b, R8a and R8b, each independently denotes: i) hydrogen; ii) C1-C3 linear alkyl which can be substituted with 1 or 2 halogen atoms; iii) phenyl which can be substituted with 1-2 substitutes selected from halogen and lower alkoxy; iv) heteroaryl rings selected from imidazolyl, imidazolyl substituted with methyl, benzo(1,4)oxazinyl, oxadiazolyl substituted with methyl; index n equals 0 or 1; indices w, x, y and z are each independently equal to a number from 1 to 3. The invention also relates to pharmaceutically acceptable salts of compounds of formula (I) and use of compounds of formula (I) to prepare a medicinal agent for treating protein tyrosine phosphatase beta-mediated conditions.

EFFECT: obtaining compounds of formula (I) as human protein tyrosine phosphatase beta (HPTP-β) inhibitors.

15 cl, 17 dwg, 13 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an isoxazoline-substituted benzamide derivative of formula or salt thereof, where A1 denotes a carbon or nitrogen atom, A2 and A3 independently denote a carbon atom, G denotes a benzene ring, W denotes an oxygen or sulphur atom, X denotes a halogen atom or C1-C6alkyl, arbitrarily substituted with a radical R4, Y denotes a halogen atom, cyano, nitro, C1-C6alkyl, C1-C6alkyl arbitrarily substituted with radical R4, -OR5, -N(R7)R6, phenyl, D-41, when n equals 2, each Y can be identical or different from each other, R1 denotes -C(R1b)=NOR1a, M-5, -C(O)OR1c, -C(O)SR1c, -C(S)OR1c, -C(S)SR1c, -C(O)N(R1e)R1d, -C(S)N(R1e)R1d, -C(R1d)=NN(R1e)R1lf, phenyl, phehnyl substituted with (Z)p1, or D-3, D-8, D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59, R2 denotes C1-C6alkyl, -CH2R14a, E-5, C3-C6alkynyl, -C(O)R15, -C(O)OR15, -C(O)C(O)OR15 or -SR15, where, when R1 denotes -C(R1b)=NOR1a, M-5, or -C(R1b)=NN(R1e)R1f, R2 can denote a hydrogen atom, when R1 denotes -C(O)OR1c, -C(O)SR1c, -C(S)OR1c or -C(S)SR1c, R2 can denote hydrogen, when R denotes -C(O)N(R1e)R1d or -C(S)N(R1c)R1d, R2 can denote a hydrogen atom, when R1 denotes phenyl, phenyl substituted with (Z)p1, or D-3, D-8, -D-13-D-15, D-21, D-35, D-52-D-55 or D-57-D-59 R2 can denote C1-C6halogenalkyl, C1-C6alkyl arbitrarily substituted with a radical R14a, C3-C6alkenyl, -C(O)NH2, -C(O)N(R16)R15, or R2 together with R1 can form =C(R2b)R2a, R3 denotes C1-C6alkyl arbitrarily substituted with radical R4, D-1, D-3, D-8, D-13-D-15, D-21, D-35, D-41, D-52-D-55, D-57-D-59 denote aromatic heterocyclic rings, m equals an integer from 2 to 3, n equals an integer from 0 to 2.

EFFECT: isoxazoline-substituted benzamide derivative and salt thereof are used in pest control, against harmful arthropods in agriculture and horticulture or in livestock farming and in the field of hygiene.

12 cl, 18 tbl, 73 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 1,7-bis[4(5)-methyl-1,3-thiazol-2-yl]-3,5-dithia-1,7-diazaheptanes of general formula (1), which can be used in organic synthesis to produce macro-heterocyclic rings, as well as sorbents and extraction agents for precious and rare-earth metals. The method is realised by reacting hydrogen sulphide-saturated aqueous formaldehyde solution (37%) with 2-amino-4(5)-methylthiazole with molar ratio of initial reagents 2-amino-4(5)-methylthiazole: formaldehyde: hydrogen sulphide equal to 20:30:20, at temperature -5-5°C and atmospheric pressure for 8-12 hours.

EFFECT: improved method.

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula

, where R is a group selected from: i) hydrogen; ii) phenyl and iii) thiophenyl; Z is a substituted or unsubstituted [1,3,4]thiadiazol-2-yl group, R1 is selected from: i) hydrogen; ii) straight C1-C6alkyl; iii) C6 or C10 aryl; iv) C(O)OR5; and v) 2-methylthiazol-4-yl; R5 denotes a straight or branched C1-C6alkyl; and index x equals 0 or 1. The invention also relates to use of compounds of formula (I) to prepare a medicinal agent having human protein tyrosine phosphatase beta (HPTP-β) inhibiting action and use in treatment.

EFFECT: compounds can be used as human protein tyrosine phosphatase beta inhibitors.

11 cl, 1 dwg, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a use of N-(2-thiazolyl)amide derivatives of formula

,

where R1 and R2 are independently selected from H, -NO2, halogen, C1-C6 alkyl with a straight chain, where at least one of R1 and R2 is different from H; m equals 0, 1, 2 or 3; X is selected from a group consisting of: indole of formula (A) bound in position 2, indole of formula (B) bound in position 3 and indazole of formula (C) bound in position 3:

, , ,

where R3 is selected from H and C1-C6 alkyl with a straight chain; R4, R5, R6 and R7 are independently selected from H and C1-C6 alkoxy group; R8 is selected from H and C1-C6 alkyl, or any of its pharmaceutically acceptable salts to obtain a medicinal agent for treating or preventing diseases or conditions mediated by GSK-3, especially neurodegenerative diseases such as Alzheimer's disease or insulin-independent sugar diabetes. The invention also relates to a compound of formula (I), a pharmaceutical composition based on said compound and synthesis method thereof.

EFFECT: high efficiency of using said derivatives.

30 cl, 3 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I or pharmaceutically acceptable salts thereof, which have receptor tyrosine kinase type I inhibiting properties and can be used in treating hyperproliferative disorders in mammals. In general formula

,

A is O or S; G is N; B is a 6-member aryl or 5-6-member heteroaryl ring containing a sulphur atom as a heteroatom; E is

, , , , , X is N or CH; D1, D2 and D3 independently denote N or CR19; D4 and D5 independently denote N or CR19 and D6 is O, S or NR20, where at least one of D4 and D5 is CR19; D7, D8, D9 and D10 independently denote N or CR19, where at least one of D7, D8, D9 and D10 is N; R1 is H or C1-C6 alkyl; each R2 independently denotes halogen, cyano, nitro etc, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, -SR18, -OR15, -C(O)R15, -C(O)OR15, -NR14C(O)OR18, -OC(O)R15, -NR14SO2R18, -SO2NR15R14, -NR14C(O)R15, -C(O)NR15R14, -NR15C(O)NR15R14, -NR13C(NCN)NR15R14, -NR15R14, C1-C12alkyl, C2-C12 alkenyl, alkynyl, saturated or partially unsaturated C3-C10cycloalkyl, C3-C10cycloalkyl-C1-C12alkyl, -S(O)p(C1-C6alkyl), -S(O)p(CR13R14)q-phenyl, phenyl, phenyl-C1-3-alkyl, 5-6-member heteroaryl, 5-6-member heteroaryl-C1-C3-alkyl, saturated or partially unsaturated 3-8-member heterocyclyl, 5-6-member heterocyclyl-C1-C3-alkyl, -O(CR13R14)q-phenyl, NR15(CR13R14)q-phenyl, O(CR13R14)q-(5-6-member heteroaryl), NR13(CR13R14)q-(5-6-member heteroaryl, -O(CR13R14)q-(3-8-member heterocyclyl) or -NR15(CR13R14)q-3-8-member heterocyclyl), each R3 denotes Z, where Z is selected from and , W is O or S; W2 is O or S;V is CR8R9, R8b is H or C1-C6alkyl; each of R6, R8, R8a and R9 independently denotes hydrogen, trifluoromethyl, C1-C12alkyl etc.

EFFECT: improved properties and high efficiency of using the compounds.

25 cl, 13 dwg, 1 tbl, 36 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (11) given below and pharmaceutically acceptable salts thereof: chemical formula 1

in which: each of G1, G2, G3 and G8 independently denotes -N=, -CR1= or -C(-G9-X)=; one of G1, G2, G3 and G8 is-C(-G9-X)=; X is C1-6 alkyl (where C1-6 can be optionally substituted with a group selected from a halogen atom, hydroxy, cyano and -NR56R57), aryl, heterocycle (where the heterocycle denotes a 5-9-member saturated or unsaturated cyclic group containing one or more heteroatoms selected from nitrogen, oxygen and sulphur atoms, and can be a monocycle or condensed ring, and can be optionally substituted with a halogen atom, C1-6 alkyl; C1-6 alkoxy, R33R34NCS-, R3R4NCO-); G9 denotes a single bond, an oxygen atom, a sulphur atom, ring G6 denotes a divalent aryl group or divalent pyridyl group (where the divalent pyridyl group can be optionally substituted with a halogen atom); A is a group of formula (2) given below, or a group of formula (3) given below. Chemical formula 2

, chemical formula 3 , G4 is an oxygen atom or sulphur atom; G5 is an oxygen atom or sulphur atom; G7 is an oxygen atom, -CR42R43-, -CONR44-, -NR44CO, -NR45-, CR42R43NR45-, -S-, -NR44S(=O)2-; R1 is a hydrogen atom, a halogen atom, cyano, C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a halogen atom), carbamoyl or C2-7 alkynyl (where C2-7 alkynyl can be optionally substituted with C1-4 acyl); when G2 or G3 denotes -CR1=, then G8 is -C(-G9-X)=, and X is R3R4NCO-, R33R34NCS-; when G8 is -CR1=, then G3 denotes -C(-G9-X)=, and X is R3R4NCO, or R33R34NCS-; when G1 or G8 denotes -CR4 then G2 is -C(-G9-X)=, and X denotes R3R4NCO-, or R33R34NCS-; or when G2 is -CR1=, then G1 denotes -C(-G9-X)=, and X denotes R3R4NCO-, or R33R34NCS-; R1 can form a single bond or -CH2- with R4 or R34; R2 denotes hydroxy or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from a halogen atom, hydroxy, C1-6 alkoxy, formyl and -CO2R50); R3, R4, R9 and R10 each independently denotes a hydrogen atom, C3-8 cycloalkyl or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from cyano, a halogen atom, hydroxy, C1-6 alkoxy, -NR13R14, and CONR28R29); R6 and R7 each independently denotes a hydrogen atom, C1-6 alkoxy, C3-8 cycloalkyl or C1-6 alkyl (where C1-6 alkyl can be optionally substituted with a group selected from cyano, halogen atom, hydroxy, C1-6 alkoxy, -NR13R14, and CONR28R29); R33 and R34 each independently denotes a hydrogen atom, C1-6 alkyl, the combination of R3 and R4 together with a nitrogen atom to which they are bonded can form a 5-6-member heterocyclic group containing at least one nitrogen atom (where the 5-6-member heterocyclic group which contains at least one nitrogen atom is a saturated or unsaturated heterocyclic group containing 5-6 atoms in the ring and which, in addition to one or more nitrogen atoms, can contain one or more heteroatoms selected from oxygen and sulphur atoms (where the 5-6-member heterocyclic group can be optionally condensed with a benzene ring); and which can be optionally substituted with a halogen atom or C1-6 alkyl; the combination of R6 and R7 together with the nitrogen atom to which they are bonded can form a 5-6-member heterocyclic group containing at least one nitrogen atom (where the 5-6-member heterocyclic group which contains at least one nitrogen atom is a saturated or unsaturated heterocyclic group containing 5-6 atoms in the ring and which, in addition to one or more nitrogen atoms, can contain one or more heteroatoms selected from oxygen and sulphur atoms (where the 5-6-member heterocyclic group can be optionally condensed with a benzene ring); and which can be optionally substituted with a halogen atom, C1-6 alkyl or an oxo group; R45 is a hydrogen atom, R13 and R14 each independently denotes a hydrogen atom, C1-6 alkyl or COR32; R56 and R57 each independently denotes a hydrogen atom or C1-6 alkyl, and R5, R8, R28, R29, R32, R42, R43, R44, and R50 each independently denotes a hydrogen atom or C1-6 alkyl. The invention also relates to a pharmaceutical composition, as well as to a medicinal agent for treating cell proliferative disorder.

EFFECT: obtaining novel biologically active compounds having inhibitory effect on cell proliferation.

15 cl, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In formula (I) Y is C-R4 and Z is CH; or Y is C-R4 and Z is N; or Y is N and Z is CH; R1 is a 5- or 6-member ring of formula (II) or (III): R2 is H, C1-C7-alkyl; R3 is phenyl, pyrazolyl, isoxazolyl, pyridinyl, pyrimidinyl or pyrazinyl, which can possibly be substituted with one, two or three substitutes selected from a group consisting of: CN, CI, F, Br, CF3, CHF2, C1-C7-alkyl, -O-C1-C7-alkyl, -(CH2)m-Rc, -O-CH2F, -O-CHF2, -O-CF3, -S(O)2-Rd; R4 is H, C1-C7-alkyl; R5 is H, CI, F, Br, CN, CF3, CHF2, C1-C7-alkyl, -C3-C6-cycloalkyl, -(CH2)m-Re or -(CO)-NRiRj; R6 is C1-C7-alkyl; R7 is H, CI, F, CN or C1-C7-alkyl; Rc is -OH; Rd is C1-C7-alkyl; Re is -CH2F, -CHF2, -CF3, CN, C1-C7-alkoxy; Ri, Rj independently denote H or C1-C7-alkyl; m equals 1-4. The invention also relates to a medicinal agent having mGluR5a receptor antagonist properties, containing one or more of the disclosed compounds as an active component.

EFFECT: high efficiency of the medicinal agent.

24 cl, 208 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazole derivatives of general formula I and pharmaceutically acceptable salts thereof, where R1 is selected from a group comprising aryl and alkyl, optionally substituted hydroxy; R2 is selected from a group comprising hydrogen and alkyl; R3 is selected from a group comprising hydrogen and -X-A, where X is selected from a group comprising -C(O)- and -S(O)2-; and A is selected from a group comprising hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycle and optionally substituted cycloalkyl, where the optionally substituted groups are substituted with 1-2 substitutes selected from a group comprising alkyl, substituted alkyl, alkoxy, substituted amine which is a -NRR group, substituted aryloxy, heteroaryl, heterocycle, halogen, hydroxy and -S(O)2-R9, where R9 is an alkyl; or R1 and R3 together with a carbon atom bonded to R1 and a nitrogen atom bonded to R3 form a heterocyclic or substituted heterocyclic group; R4 is selected from a group comprising hydrogen, linear alkyl, -alkylene-aminoacyl-, -alkylene-hydroxy-, -[alkylene]p-nitrogen-containing heterocycle, -[alkylene]p-nitrogen-containing substituted heterocycle, -[alkylene]p-nitrogen-containing heteroaryl, -[alkylene]p-nitrogen-containing substituted heteroaryl and -[alkylene]p-NR10R11, where p equals 0 or 1, the alkylene contains 1-5 carbon atoms and can have 1 or 2 substitutes selected from a group comprising amine, hydroxy and halogen, aminoacyl relates to a group -C(O)NRR, where each R is independently selected from a group comprising hydrogen and alkyl, R10 and R11 are independently selected from a group comprising hydrogen, alkyl, substituted alkyl, -S(O)2-alkyl, substituted aryl, substituted heteroaryl, cycloalkyl, or when R10 is hydrogen, R11 is hydroxy, alkoxy or substituted alkoxy; or when R1 and R3 together with carbon and nitrogen atoms respectively bonded to them do not form a heterocyclic or a substituted heterocyclic group, R3 and R4 together with a nitrogen atom to which they are bonded form a spiro-condensed heterocyclic group; R5 is selected from a group comprising L-A1, where L is selected from a group comprising C1-C5alkylene, where the alkylene is defined above; and A1 is selected from a group comprising aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle; and one of R6 or R7 is selected from a group comprising aryl and heteroaryl, each of which can optionally be substituted with -(R8)m, where m equals a whole number from 1 to 2, and the other of R6 or R7 is selected from a group comprising hydrogen, halogen and alkyl; or R6 as well as R7 denotes hydrogen; R8 is selected from a group comprising cyano, alkyl, -CF3, alkoxy, halogen, where alkyl, aryl, aryloxy, cycloalkyl, heterocycle, heteraryl and substituted alkyl, aryl, aryloxy, cycloalkyl, heterocycle and heteroaryl are described in claim 1. The invention also relates to specific compounds, a pharmaceutical composition based on the compound of formula I, a method of inhibiting KSP and use of the composition to prepare a medicinal agent.

EFFECT: novel imidazole derivatives are useful as kinesin spindle protein inhibitors for treating cancer.

25 cl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula as well as separate enantiomers, diastereomers, racemic mixures and pharmaceutically acceptable salts thereof, having mitotic kinesin KSP inhibiting activity, as well as inhibitory action on tumour cells, use thereof in preparing a medicinal agent and a pharmaceutical composition based on said compounds. In said formula, R denotes Z-NR2R3, Z-OH, Ar1 and Ar2 independently denote a phenyl which, if needed, is substituted with one or more groups independently selected from: F, CI, Br, I, OH, Z denotes an alkylene having 1-6 carbon atoms which, if needed, is substituted with C1-6alkyl, and R1 assumes values given in the claim.

EFFECT: improved method.

16 cl, 3 dwg, 124 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula in which R1 means hydrogen or alkyl with 1-4 carbon atoms, R2 means hydrogen and L means an alkandiyl group with 1-4 carbon atoms, one CH2-group in which can be substituted by with oxygen atom or a group of formula: or in which * means a conjunction with nitrogen atom, R3 means hydrogen, methyl, propane-2-yl, propane-1-yl, imidazol-4-ylmethyl, hydroxymethryl or 4-aminobutan-4-yl, or R3 is connected with R1 together with which forms (CH2)3- or (CH2)4- -group, R4 means hydrogen or methyl, R5 means alkyl with 1-4 carbon atoms, and R6 means hydrogen or alkyl with 1-4 carbon atoms, and also to its salt and to a method of preparing it.

EFFECT: there are prepared new compounds which can find application in medicine for treating and/or preventing diseases, first of all thromboembolic diseases.

5 cl, 4 tbl, 23 ex

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