Pyrazoles as 11-beta-hsd-1 inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to pyrrole derivatives of formula (I): , where R1 denotes hydrogen; R2 denotes adamantine which is unsubstituted or substituted with a hydroxy group or halogen; R3 denotes trifluoromethyl, pyrazole, triazole, piperidine, pyrrolidine, hydroxymethylpiperidine, benzylpiperazine, hydroxypyrrolidine, tert-butylpyrrolidine, hydroxyethylpiperazine, hydroxypiperidine or thiomorpholyl group; R4 denotes cyclopropyl, tert-butyl, -CH(CH3)2CH2OH, methyl, -CF3 or -(CH2)nCF3 group, where n equals 1 or 2; R5 denotes hydrogen or lower alkyl which is unsubstituted or substituted with a halogen, as well as pharmaceutically acceptable salts thereof.

EFFECT: compounds and pharmaceutical compositions containing said compounds can inhibit 11β-hydroxysteroid dehydrogenase of the form 1 (11-BETA-HSD-1) and can be used to treat diseases such as type II sugar diabetes type and metabolic syndrome.

17 cl, 99 ex, 1 tbl

 

The text descriptions are given in facsimile form.

1. The compound of formula (I):
,
in which R1denotes hydrogen;
R2means adamantane, unsubstituted or substituted by a hydroxy-group or halogen;
R3means triptoreline, Prasolova, triazolone, piperidine, pyrolidine, hydroxyethylpiperazine, benzylpiperazine, hydroxypyrrolidine, tert-butylpyridinium, hydroxyethylpiperazine, hydroxypiperidine or thiomorpholine group;
R4denotes cyclopropyl, tert-butyl, -CH(CH3)2CH2OH, methyl, -CF3or a group -(CH2)nCF3where n is 1 or 2;
R5denotes hydrogen or nits. alkyl, unsubstituted or substituted with halogen;
and its pharmaceutically acceptable salts.

2. The compound according to claim 1, in which
R2denotes unsubstituted adamantane; and
R3means triptoreline, Prasolova, triazolone, piperidine, pyrolidine, hydroxyethylpiperazine, benzylpiperazine, hydroxypyrrolidine, tert-butylpyridinium, hydroxyethylpiperazine, hydroxypiperidine or thiomorpholine group.

3. The compound according to claim 1, in which
R2denotes the adamantane substituted hydroxy-group or halogen; and
R3means triptoreline, Prasolova, triazolone, piperidine, pyrolidine, hydroxyethylpiperazine, benzyl Persenbeug, hydroxypyrrolidine, tert-butylpyridinium, hydroxyethylpiperazine, hydroxypiperidine or thiomorpholine group.

4. The compound according to claim 1, in which
R2denotes unsubstituted adamantane; and
R4denotes cyclopropyl, tert-butyl, -CH(CH3)2CH2OH, methyl, -CF3or a group -(CH2)nCF3where n is 1 or 2.

5. The compound according to claim 1, in which
R2denotes the adamantane substituted hydroxy-group or halogen; and
R4denotes cyclopropyl, tert-butyl, -CH(CH3)2CH2OH, methyl, -CF3or a group -(CH2)nCF3where n is 1 or 2.

6. The compound according to claim 1, in which R2denotes TRANS-hydroxyadamantane.

7. The compound according to claim 1, in which R3means triptorelin group.

8. The compound according to claim 1, in which R3means Prasolova, triazolone, piperidine, pyrolidine, hydroxyethylpiperazine, benzylpiperazine, hydroxypyrrolidine, tert-butylpyridinium, hydroxyethylpiperazine, hydroxypiperidine or thiomorpholine group.

9. The compound according to claim 1, in which R5means triptorelin group.

10. The compound according to claim 1, selected from the group comprising (5-hydroxyadamantane-2-yl)-amide methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid;
(5-hydroxy shall adamantan-2-yl)-amide, TRANS-1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 2'-methyl-2'H-[1,3']piperazinyl-4'-carboxylic acid;
adamantane-2-alamid methyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-chloro-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
amide, TRANS-1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
amide CIS-1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-methyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
adamantane-2-alamid 5-chloro-1-methyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-chloro-1,3-dimethyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid methyl-5-(4-methylpiperazin-1-yl)-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-(2-hydroxyethylamino)-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid methyl-5-[1,2,4]triazole-1-yl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid methyl-5-pyrrolidin-1-yl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-(3-hydroxypyrrolidine-1-yl)-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-(4-hydroxypiperidine-1-yl)-1-methyl-1H-pyrazole-4-carbon is acid;
adamantane-2-alamid 5-[(2-hydroxyethyl)-methylamino]-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-(2-hydroxypropylamino)-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid methyl-5-morpholine-4-yl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-(2-methoxyethylamine)-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-isopropylamino-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid methyl-5-piperidine-1-yl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-(4-hydroxyethylpiperazine-1-yl)-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-(4-benzylpiperazine-1-yl)-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-(R-3-hydroxypyrrolidine-1-yl)-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-diethylamino-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid tert-butyl-5-pyrrolidin-1-yl-1H-pyrazole-4-carboxylic acid;
adamantylamine 5-[4-(2-hydroxyethyl)-piperazine-1-yl]-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-[(2-methoxyethyl)-methylamino]-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 2'-tert-butyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-tert-butyl-2 N-[1,3']piperazinyl-4'-CT is about acid;
adamantane-2-alamid tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid tert-butyl-5-(3-hydroxypyrrolidine-1-yl)-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid tert-butyl-5-(4-hydroxypiperidine-1-yl)-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 5-azepin-1-yl-1-methyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid methyl-5-thiomorpholine-4-yl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid tert-butyl-5-piperidine-1-yl-1H-pyrazole-4-carboxylic acid;
(5-foredmonton-2-yl)-amide, TRANS-1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
TRANS-N-(4-aminoadamantana-1-yl)-ndimethylacetamide;
TRANS-N-(4-aminoadamantana-1-yl)-methanesulfonamide;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-methyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid;
(5-methanesulfonylaminoethyl-2-yl)-amide, TRANS-1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-methanesulfonylaminoethyl-2-yl)-amide, TRANS-1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-tert-butyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-methanesulfonylaminoethyl-2-yl)-amide, TRANS-2'-tert-butyl-'N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-1-methyl-5-piperidine-1-yl-1H-pyrazole-4-carboxylic acid;
(5-methanesulfonylaminoethyl-2-yl)-amide, TRANS-2'-methyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-tert-butyl-5-methyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-tert-butyl-5-ethoxymethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-1-tert-butyl-5-methoxymethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-medtrans-1-tert-butyl-5-(5-methylisoxazol-3-yl)-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-tert-butyl-5-(5-chlorzoxazone-3-yl)-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-5-chloro-1-cyclohexyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-medtrans-2'-cyclohexyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-5-chloro-1-cyclohexyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-cyclohexyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-(tetrahydropyran-4-yl)-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-5-chloro-1-cyclopentyl - 1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-cyclopentyl-'N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-cyclopentyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-5-chloro-1-(CIS-4-hydroxycyclohexyl)-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-(CIS-4-hydroxycyclohexyl)-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-cyclopentyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-cyclohexyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-(CIS-4-hydroxycyclohexyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-(TRANS-4-hydroxycyclohexyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-(2-methoxyethyl)-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-(2-methoxyethyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-alamid TRANS-2'-(2-methoxyethyl)-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-[2-(2-methoxyethoxy)-ethyl]-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-(2-tert-butoxyethyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-(3-methoxypropyl)-2 N-[1,3']Vipera is olil-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-(3-methoxypropyl)-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-5-chloro-1-cyclopropyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-cyclopropyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-4-chloro-2'-cyclopropyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-cyclopropylmethyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-(2-hydroxy-1,1-dimethylethyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-tert-butyl-5-cyclopropyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-cyclobutyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-1-cyclobutyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-5-chloro-1-cyclobutyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-cyclobutyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-tert-butyl-4-methyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide is Rance-2'-tert-butyl-4-chloro-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-4-bromo-2'-tert-butyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-tert-butyl-4-chloro-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-4-chloro-2'-cyclobutyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-cyclopropyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-4-chloro-2'-cyclopropyl-2 N-[1,3']piperazinyl-4'-carboxylic acid and
(5-acetylaminofluorene-2-yl)-amide, TRANS-4-chloro-2'-(2-methoxyethyl)-2 N-[1,3']piperazinyl-4'-carboxylic acid.

11. The compound according to claim 1, selected from the group including
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-tert-butyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 2'-methyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
adamantane-2-alamid 1-methyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide CIS-1-tert-butyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-methyl-2 N-1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide 1-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
adamantane-2-alamid 2'-tert-butyl-2 N-[1,3']piperazinyl-4'-carboxylic acid; and
(5-hydroxyadamantane-2-yl)-amide 1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid.

12. The compound according to claim 1 selected from the group including
(5-acetylaminofluorene-2-yl)-amide, TRANS-1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-tert-butyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-methanesulfonylaminoethyl-2-yl)-amide, TRANS-2'-tert-butyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-tert-butyl-5-ethoxymethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-1-tert-butyl-5-methoxymethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-1-tert-butyl-5-(5-methylisoxazol-3-yl)-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-tert-butyl-5-(5-chlorzoxazone-3-yl)-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-medtrans-2'-cyclohexyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-cyclohexyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-medtrans-2'-(tetrahydropyran-4-yl)-2 N-[1,3']piperazinyl-4'-Karanovo acid;
(5-hydroxide the'antan-2-yl)-medtrans-2'-checkpointer-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-cyclopentyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-(CIS-4-hydroxycyclohexyl)-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-(CIS-4-hydroxycyclohexyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-(TRANS-4-hydroxycyclohexyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-(2-methoxyethyl)-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-(2-methoxyethyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-(2-methoxyethyl)-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-(3-methoxypropyl)-2 N- [1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-(3-methoxypropyl)-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-cyclopropyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-5-chloro-1-cyclopropyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-medtrans-2'-cyclopropyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-4-chloro-2'-cyclopropyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-cyclopropylmethyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-(2-hydroxy-1,1-dimethylethyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-tert-butyl-5-cyclopropyl-1H-pyrazole-4-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-1-cyclobutyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-1-cyclobutyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-5-chloro-1-cyclobutyl-1H-pyrazole-4-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-cyclobutyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-tert-butyl-4-methyl-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-hydroxyadamantane-2-yl)-amide, TRANS-2'-tert-butyl-4-chloro-2 N-[1,3']piperazinyl-4'-carboxylic acid;
(5-acetylaminofluorene-2-yl)-amide, TRANS-2'-tert-butyl-4-chloro-2 N-[1,3']piperazinyl-4'-carboxylic acid; and
(5-acetylaminofluorene-2-yl)-amide, TRANS-4-chloro-2'-cyclobutyl-2 N-[1,3']piperazinyl-4'-carboxylic acid.

13. The compound according to claim 1, which represents (5-hydroxyadamantane-2-yl)amide, TRANS-2'-tert-butyl-2 N-[1,3']piperazinyl-4'-carboxylic acid.

14. Pharmaceutical composition having inhibitory activity against 11β-hydroxysteroiddehydrogenase form 1, comprising a therapeutically effective amount with the organisations according to claim 1 or its pharmaceutically acceptable salts and pharmaceutically acceptable carrier.

15. Compounds according to claim 1, intended for use as therapeutically active substances.

16. Compounds according to claim 1, intended for the preparation of drugs intended for the treatment of metabolic disorders.

17. The use of compounds according to claim 1 for the preparation of drugs intended for the treatment of diabetes, obesity or metabolic syndrome.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compounds of formula I: and their pharmaceutically acceptable salts, in which R1-R4 have values, given in item 1 of invention formula. Said compounds possess inhibiting activity with respect to 11-beta-hydroxysteroid-dehydrogenase and can be applied for production of medications, intended for treatment and prevention of diabetes, especially, diabetes of II type, obesity, malnutrition and hypertension.

EFFECT: development of efficient method of obtaining formula I compounds and based on them pharmaceutical composition.

25 cl, 1 tbl, 149 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) in form of base or a pharmaceutically acceptable addition salt with an acid. The disclosed compounds have β-amyloid peptide(β-A4) formation inhibiting properties. In formula (I), R1 denotes: C1-6-alkyl or phenyl; where said phenyl groups are substituted with two substitutes selected from halogen atoms; R1 and R2' independently denote a hydrogen atom or a hydroxy group; R3 denotes C1-6-alkyl; one or another of radicals R4 and R5 is a group Z and one or another of radicals R4 and R5 is a -C(X)R6 group; G denotes a single bond; Y denotes a single bond, an oxygen atom, a sulphur atom, a C1-4-alkylene group; A and B independently denote a hydrogen atom, a halogen, trifluoromethyl, trifluoromethoxy group; provided that if Y denotes a single bond or an oxygen atom and if group Z is a type group, A does not denote a hydrogen atom; X denotes an oxygen atom; R6 denotes a C1-6alkoxy group. The invention also relates to a method for synthesis of formula (I) compounds, to a medicinal agent and a pharmaceutical composition based on said compounds, and to use of formula (I) compounds in preparing the medicinal agent.

EFFECT: increased effectiveness of using said derivatives.

6 cl, 1 tbl, 31 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula

, in which A is a counter ion, a=1-3, b=0-3, X=1-6C alkyl, R1=1-6C alkyl, one or R2 and R3 is 1-6C alkyl and the other is XN+Hb(R1)3-b, or R2 and R3 form a methylenedioxy group, one or R4 and R5 is a halogen and the other is a halogen-substituted 1-6C alkyl, or R4 and R5 are bonded to form a 6-10C aromatic ring or a substituted 6-10C aromatic ring in which the substitute is selected from 1-6C alkoxy, halogen and halogen-substituted 1-6C alkyl. The invention also relates to a method of measuring content of analysed substance capable of ensuring proportional colour change as a result of a reaction in a biological fluid, involving the following steps: ensuring availability of the disclosed tetrazolium salt as an indicator and determination of concentration of the said analysed substance in the biological fluid using the said tetrazolium salt which is used as an indicator.

EFFECT: agents are highly effective.

24 cl, 7 dwg, 1 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of general formula I and to their pharmaceutically acceptable acid addition salts. The compounds of the present invention exhibit the properties of glycine carrier 1 (GlyT-1) inhibitors. In formula I , R1 represents -OR1', -SR1' or morpholinyl; R1' represents lower alkyl, halogen-substituted lower alkyl, or represents -(CH2)n-lower cycloalkyl; R2 represents -S(O)2-lower alkyl, -S(O)2NH-lower alkyl, NO2 or CN; X1 represents CR3 or N; X2 represents CR3' or N; R3/R3' independently represent hydrogen, halogen, lower alkyl, CN, NO2, -S(O)2-phenyl, -S(O)2-lower alkyl, -S(O)2-pyridine-2, 3 or 4-yl, phenyl optionally substituted with one or two substitutes specified from the group consisting of NO2 or halogen, or represent halogen-substituted lower alkyl, or represent -C(O)-lower alkyl; n has a value of 0, 1 or 2. The invention also concerns a drug containing one or more compounds of the invention and pharmaceutically appropriate excipients.

EFFECT: preparation of the compounds exhibiting the properties of glycine carrier inhibitors.

20 cl, 1 tbl, 133 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) , where R1 is selected from group, including: phenyl, unsubstituted or mono-, di- or tri-substituted independently with lower alkyl, lower alkoxy group, halogen or lower halogenalkyl; naphtyl; tetrahydronaphtyl; C3-7cycloalkyl; -(CHR3)m-phenyl, where m stands for 1, 2, or 3; and phenyl is unsubstituted or mono-, di- or tri-substituted with lower alkoxy group, and where R3 is independently selected from hydrogen and lower alkyl; -(CH2)n-heteroaryl, where n stands for 1, 2 or 3; term "heteroaryl" relates to aromatic 5- or 6- member ring or bicyclic 9-member aromatic groups, which can include 1, 2 or 3 atoms, selected from nitrogen and/or sulphur; -(CH2)n-heteroaryl, where n stands for 1, 2 or 3; term "heteroaryl" relates to aromatic 5- or 6- member ring or bicyclic 9-member aromatic groups, which can include 1, 2 or 3 atoms, selected from nitrogen and/or sulphur, and heteroaryl is mono-, di- or tri-substituted independently with lower alkoxy group; and R2 is selected from group including: n-butyl; phenyl, unsubstituted or mono-, di- or tri-substituted independently with lower alkyl, halogen or lower alkoxy group; heteroaryl, where term "heteroaryl" relates to aromatic 5-member ring, which can include 1, 2 or 3 atoms, selected from nitrogen and/or sulphur; unsubstituted or mono-, di- or tri-substituted independently with lower alkoxy group; -C(O)-NR4R5; where R4 and R5 stand for lower alkyl or together with nitrogen atom, to which they are bound, form 5-member heterocycle, which can additionally contain heteroatom, selected from N or S, and to their pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds, able to inhibit DPP-IV.

13 cl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel benzothiazinone derivatives of formula (I) and their use as antibacterial agents in infectious diseases caused by bacteria, especially mycobacterium tuberculosis (TB) and leprosy, in which R1 and R2 independently denote NO2, CN, CONR7R8, COOR9 CHO, halogen, SO2NR7R8, OCF3, trifluromethyl; R3 and R4 independently denote H or methyl; R5 and R6 independently denote a straight or branched aliphatic radical having 1-8 members in the chain, or R5 and R6 together denote a divalent radical -(CR92)m- or R5 and R6 together denote a divalent radical: R7, R8 and R9 independently denote H or a straight or branched aliphatic radical having 1-7 members in the chain, or phenyl.

EFFECT: design of an efficient method of obtaining benzothiazinone derivatives, a pharmaceutical composition having anti-mycobacterial activity.

12 cl, 6 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where the carbon atom denoted * is in R- or S-configuration; X is a concentrated bicyclic carbocycle or heterocycle selected from a group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, indazolyl, indolyl, benzooxazolyl, benzothiazolyl, indenyl, indanyl, dihydrobenzocycloheptenyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, quinoxalinyl, 2H-chromenyl, imidazo[1.2-a]pyridinyl, pyrazolo[1.5-a]pyridinyl, and condensed bicyclic carbocycle or condensed bicyclic heterocycle, optionally substituted with substitutes (1 to 4) which are defined below for R14; R1 is H, C1-C6-alkyl, C3-C6-cyclalkyl, C1-C3-alkyl, substituted OR11, -NR9R10 or -CN; R2 is H, C1-C6-alkyl, or gem-dimethyl; R3 is H, -OR11, C1-C6-alkyl or halogen; R4 is H, halogen, -OR11, -CN, C1-C6-alkyl, C1-C6-alkyl, substituted -NR9R10, C3-C6-cycloalkyl, substituted -NR9R10, C(O)R12; or R4 is morpholinyl, piperidinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, isoxazolyl, pyrrolidinyl, piperazinyl, 2-oxo-2H-pyridinyl, [1.2.4]triazolo[4.3-a]pyridinyl, 3-oxo-[1.2.4]triazolo[4.3-a]pyridinyl, quinoxalinyl, which are optionally substituted with substitutes (1 to 4) which are defined below for R14; R5 is H or C1-C6-alkyl; R6 is H, C1-C6-alkyl, or -OR11; R7 is H; R8 is H, -OR9, C1-C6-alkyl, -CN; R9 is H or C1-C4-alkyl; R10 is H or C1-C4-alkyl; or R9 and R10 taken together with the nitrogen atom to which they are bonded form morpholine; R11 is H, C1-C4-alkyl; R12 is C1-C6-alkyl; R14 in each case is independently selected from a substitute selected from a group consisting of halogen, -OR11, -NR11R12, C1-C6-alkyl, which is optionally substituted with 1-3 substitutes, in each case independently selected from a group consisting of C1-C3-alkyl, aryl; or to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, to a method of obtaining formula (I) compounds, as well as to a method of treating disorders.

EFFECT: obtaining new biological active compounds having norepinephrine, dopamine and serotonin reuptake selective inhibitory activity.

90 cl, 162 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) and to their pharmaceutically acceptable salts, optical isomers or their mixture as glucokinase activators. In general formula (I) where R1 is C3-8-cycloalkyl, C3-8-cycloalkenyl, a 6-member heterocyclyl with 1 nitrogen atom, condensed phenyl-C3-8-cycloalkyl, each of which is possibly substituted with one or two substitutes R3, R4, R5 and R6; R2 is C3-8-cycloalkyl, a 5-6-member heterocyclyl with 1-2 heteroatoms selected from N, O, or S, each of which can be substituted with one or two substitutes R30, R31, R32 and R33, and R3, R4, R5, R6, R30, R31, R32 and R33 are independently selected from a group consisting of halogen, hydroxy, oxo, -CF3; or -NR10R12; or C1-6-alkyl, phenyl, C1-6-alkoxy, C1-6-alkyl-C(O)-O-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; or -C(O)-R27, -S(O)2-R27; or two substitutes selected from R3, R4, R5 and R6 or R30, R31, R32 and R33, bonded to the same atom or to neighbouring atoms, together form a -O-(CH2)2-O- radical; R10 and R11 independently represent hydrogen, C1-6-alkyl, -C(O)-C1-6-alkyl, -C(O)-O- C1-6-alkyl, -S(O)2- C1-6-alkyl; R27 is C1-6-alkyl, C1-6-alkoxy, C3-8-cycloalkyl, C3-8-cycloalkyl-C1-6-alkyl, phenyl, phenyl-C1-6-alkyl, a 5-6-member heteroaryl with 1-2 heteroatoms selected from N or S, a 6-member heteroaryl-C1-6-alkyl with 1 nitrogen atom, a 6-member heterocyclyl-C1-6-alkyl with 1-2 heteroatoms selected from N or O, R10R11-N- C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R12; R12 is a halogen, CF3, C1-6-alkoxy, -NR10R11; A is a 5-9-member heteroaryl with 1-3 heteroatoms selected from N, O or S, which is possibly substituted with one or two substitutes independently selected from R7, R8 and R9; R7, R8 and R9 are independently selected from halogen, cyano, -CF3; or C1-6-alkyl, C2-6-alkenyl, C1-6-alkoxy, C1-6-alkylthio, -C(O)-O-C1-6-alkyl, formyl, - C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-O-C(O)-C1-6-alkyl or hydroxy-C1-6-alkyl, each of which is possibly substituted with a substitute independently selected from R16; or phenyl, 5-member heteroaryl-C1-6-alkylthio with 2-4 nitrogen atoms, phenylthio, 5-6-member heteroarylthio with 1-2 nitrogen atoms, each of which is possibly substituted on the aryl or heteroaryl part with one or two substitutes independently selected from R17; or C3-8-cycloalkyl; or a 6-member heterocyclyl with 2 nitrogen atoms, 5-7-member heterocyclyl-C1-6-alkylthio with 1-2 heteroatoms selected from N or O, each of which is possibly substituted with one substitute independently selected from R16; or C1-6-alkyl-NR19R20, -S(O)2-R21 or -S(O)2-NR19R20; or -C(O)NR22R23; R16, R17 and R18 independently represent C1-6-alkyl, carboxy, -C(O)-O-C1-6-alkyl, -NR19R20, -C(O)NR19R20; R19 and R20 independently represent hydrogen, C1-6-alkyl, phenyl, 5-member heteroaryl with 2 heteroatoms selected from N or S, 6-member heterocyclyl with 1 nitrogen atom, -C(O)-O-C1-6-alkyl or -S(O)2-C1-6-alkyl, each of which is possibly substituted with one substitute independently selected from R24; or R19 and R20 together with a nitrogen atom to which they are bonded form a 5-7-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring possibly contains one additional heteroatom selected from nitrogen, oxygen and sulphur, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R21 is selected from C2-6-alkenyl; or R22 and R23 are independently selected from hydrogen, -C1-6-alkyl-C(O)-O-C1-6-alkyl, -C1-6-alkyl-S(O)2-C1-6-alkyl, C3-8-cycloalkyl; or R22 and R23 together with a nitrogen atom to which they are bonded form a 6-member heterocyclic ring with the said nitrogen atom, where this heterocyclic ring is possibly substituted with one substitute independently selected from R24; R24 is oxo, C1-6-alkyl, carboxy- C1-6-alkyl, a 6-member heterocyclyl with 1 nitrogen atom, -NH-S(O)2R28 or -S(O)2R28, where each cyclic group is possibly substituted with one substitute independently selected from R29; R28 is C1-6-alkyl, -C1-6-alkyl-C(O)-O- C1-6-alkyl or -N(CH3)2; R29 is C1-6-alkyl.

EFFECT: obtaining compounds which can be used for treating and preventing diseases mediated by low glucokinase activity.

21 cl, 1 dwg, 608 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (XXI) where values of R1, Y, Ra and Rb are given in subparagraphs 1 and 2 of the formula of invention, as phosphatidylinositol-3-kinase inhibitors, a pharmaceutical composition based on said compounds and their use.

EFFECT: compounds can be used for treating and preventing diseases mediated by phosphatidylinositol-3-kinase.

5 cl, 5 tbl, 146 ex

FIELD: medicine.

SUBSTANCE: there is described thiomorpholine compound presented by formula (I) wherein the ring A represents benzene ring; the ring B represents benzene ring; R1 represents hydrogen atom, R2 represents C1-6-alkyl group; R3a and R3b are identical or different, each representing hydrogen atom or C1-6-alkyl group, and n represents an integer equal to 2, or its pharmaceutically acceptable salt. There is also described method for making the compound of formula (1), a pharmaceutical composition and application of the compound of formula (1) for making a medical product used for treatment and prevention of the disease chosen from inflammation, allergic diseases, pain, migraine, neuralgia, itch, cough, central nervous system diseases, alimentary organ diseases, nausea, vomiting and urological disorders.

EFFECT: compounds exhibits affinity to neurokinine-1 receptor.

6 cl, 4 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is described a compound of formula [I]: where A cycle represents a benzene cycle optionally having substitute(s) different from R1, R1 represents a group of formula RaSO2NH-, RaSO2NH-CH2- or (Rb)(Rc)NSO2-, Ra represents C1-C6 alkyl group, C3-C10cycloalkyl group, an amino group, 6-10-member monocyclic or bicyclic aryl group or 5-10-member monocyclic or bicyclic heteroaryl group containing 1-2 heteroatoms, chosen from oxygen, sulphur and nitrogen atoms, Rb and Rc are identical or different, and each represents hydrogen atom, C1-C6alkyl group or C3-C10cycloalkyl group, one of R2 and R3 represents hydrogen atom, halogen atom or C1-C6alkyl group, and the other represents hydrogen atom, C1-C6alkyl group, C1-C6alkoxycarbonyl group or phenyl group, or both are combined with each other together with the neighbouring carbon atom to form C3-C10cycloalkyl group, X represents oxygen atom, sulphur atom, or formula group of -NR4-; Y represents a group of formula -C(=O)-, -C(=S)- or CH(R5)-; Ar represents optionally substituted 6-10-member monocyclic or bicyclic aryl group or 5-10-member monocyclic or bicyclic group; Q represents a simple bond, C1-C6alkylene group or C2-C6alkenylene group, or its pharmaceutically acceptable salts There are described specific compounds of formula [I], and also intermediate compounds.

EFFECT: presented compounds exhibit affinity to mineralocorticoid receptor (MR) and are applicable for prevention or treatment of various diseases or diseased states associated with such receptor.

11 cl, 54 tbl, 410 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) , where X is C(R8R9), NR10, O, S; R1 is phenyl which is substituted with 1-3 substitutes selected from a group which includes halogen, hydroxy group, lower alkyl, hydroxy-lower alkyl and CN; R2 is hydrogenor lower alkyl; R3 and R4 are hydrogen; R5 and R6 are hydrogen; R7 is oxadiazolyl or triazolyl, where oxadiazolyl or triazolyl is substituted with R11; R8 and R9 denote hydrogen; R10 denotes hydrogen, lower alkyl, lower alkyl-carbonyl or lower alkyl-sulfonyl, R11 denotes aryl or hetearyl, selected from a group comprising pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl, indazolyl, 1,3-dihydrobenzimidazol-2-one, 1,3-dihydroindol-2-one, benzotriazolyl, imidazopyridinyl, triazolepyridinyl, tetrazolepyridinyl, benzimidazolyl, 2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidin-2,4-one, benzoxazin-3-one, 1,4-dihydrobenzoxazin-2-one, indolyl, thiophenyl, oxazolyl, benzooxazin-2-one; 3,4-dihydroquinazolin-2-one, pyridazinyl, quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl, cinnolinyl, 1,4-dihydroquinoxalin-2,3-dione and 1,2-dihydroindazol-3-one, where the aryl or heteroaryl is optionally substituted with 1-3 substitutes selected from a group which includes lower alkyl, hydroxy group, B(OH)2, carboxy-lower alkoxy group, carbamoyl-lower alkoxy group, cyano group, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxy group, halogen, S(O2)R13, C(O)R14, NO2, NR15R16, phenyl-lower alkoxy group, [1,3,4]oxadiazol-2-one, oxadiazolyl, triazolyl and isoxazolyl, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, where imidazolyl is optionally substituted with lower alkyl, and where isoxazolyl is substituted with lower alkyl; R12 denotes hydrogen or lower alkyl; R13 denotes lower alkyl, NR17R18 or fluoro-lower alkyl; R14 denotes NR19 R20, lower alkoxy group, lower alkenyl-oxy group or lower alkyl; R15 and R16 independently denote hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO2, lower alkenyl-oxycarbonyl and lower alkyl-NH-carbonyl; or NR15R16 denotes heterocyclyl selected from a group which includes morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, piperidinyl, piperidin-2-one, piperazin-2-one, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl, pyrrolidinyl, 1,1-dioxoisothiazolidinyl, pyrrolidin-2-one, imidazolidine-1,4-dione, 2,4-dihydro[1.2.4]triazol-3-one, pyrrolidine-2,5-dione, azetidin-2-one and 1,3-dihydroimidazol-2-one, where the heterocycle is optionally substituted with hydroxy-lower alkyl or lower alkyl-carbonyl; R17 and R18 independently denote hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl; or NR17 R18 denotes morpholinyl; R19 and R20 independently denote hydrogen, lower alkyl, cycloalkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl or cyano-lower alkyl; or NR19 R20 denotes heterocyclyl selected from a group which includes morpholinyl, pyrrolidinyl, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl, thiomorpholinyl, 1,3,8-triaza-spiro[4.5]decane-2,4-dione and spiro(1- phthalan)piperidin-4-yl, where the heterocyclyl is optionally substituted with a hydroxy group, lower alkyl-(SO2), lower alkyl, lower alkyl-carbonyl or lower alkoxy group, carboxyl group, carbamoyl, cyano group and phenyl; and to their pharmaceutically acceptable salts. Invention also pertains to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds which inhibit hepatic carnitine palmitoyltransferase 1 (L-CPT1).

35 cl, 565 ex, 10 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel salt form of 5-[(2R,5S)-5-methyl-4-propylmorpholin-2-yl]piridine-2-amine (I): , and specifically to 5-[2R,5S)-5-methyl-4-propylmorpholin-2-yl]pyridine-2-amine di-(1S)-camphorsulphonate (di-S-camsylate), to a pharmaceutical composition having effect on dopamine D3 receptor, as well use of the given compound in preparing a medicinal agent for treating sexual dysfunction and neuropsychiatric disorders and a method of obtaining the said compound and an intermediate compound.

EFFECT: novel salt form of a dopamine agonist which has advantages, specifically is not hygroscopic, has a crystalline form and has high melting point is obtained and described.

11 cl, 9 ex, 2 tbl, 6 dwg

FIELD: chemistry.

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

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

17 cl, 56 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to phenylalanine derivatives and their pharmaceutically acceptable salts. In formula (1) R11 is a hydroxyl group, an alkoxyl group having 1-6 carbon atoms, which can be substituted with a methoxy group, cycloalkoxyl group having 3-6 carbon atoms, or a benzyloxy group; R12 and R13 each independently represents a hydrogen atom, alkyl group having 1-6 carbon atoms, cycloalkyl group having 3-6 carbon atoms, acetyl group or methyloxycarbonyl group, or N(R12)R13 is a 1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group; R14 is a methyl group; R1' is a hydrogen atom, fluorine atom; X1 is -CH(R1a)-, -CH(R1a)CH(R1b)-, -CH(R1a)CH(R1b)CH(R1c)-, -N(R1a)CH(R1b)CH(R1c)-, -OCH(R1a)CH(R1b)-, -OCH(R1a)CH(R1b)CH(R1c)- or 1,3-pyrrolidinylene, where R1a, R1b, each independently represents a hydrogen atom or a methyl group, and R1c is a hydrogen atom; Y11 and Y12 represent any of the combinations (CI, Cl), (CI, Me), (CI, F). Invention also relates to phenylalanine derivatives of formulae (2)-(14), given in the formula of invention.

EFFECT: obtaining a pharmaceutical composition having antagonistic effect on α4-integrin, containing a phenylalanine derivative as an active ingredient, a α4-integrin antagonist and a therapeutic agent.

65 cl, 51 tbl, 244 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where the carbon atom denoted * is in R- or S-configuration; X is a concentrated bicyclic carbocycle or heterocycle selected from a group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, indazolyl, indolyl, benzooxazolyl, benzothiazolyl, indenyl, indanyl, dihydrobenzocycloheptenyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, quinoxalinyl, 2H-chromenyl, imidazo[1.2-a]pyridinyl, pyrazolo[1.5-a]pyridinyl, and condensed bicyclic carbocycle or condensed bicyclic heterocycle, optionally substituted with substitutes (1 to 4) which are defined below for R14; R1 is H, C1-C6-alkyl, C3-C6-cyclalkyl, C1-C3-alkyl, substituted OR11, -NR9R10 or -CN; R2 is H, C1-C6-alkyl, or gem-dimethyl; R3 is H, -OR11, C1-C6-alkyl or halogen; R4 is H, halogen, -OR11, -CN, C1-C6-alkyl, C1-C6-alkyl, substituted -NR9R10, C3-C6-cycloalkyl, substituted -NR9R10, C(O)R12; or R4 is morpholinyl, piperidinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, isoxazolyl, pyrrolidinyl, piperazinyl, 2-oxo-2H-pyridinyl, [1.2.4]triazolo[4.3-a]pyridinyl, 3-oxo-[1.2.4]triazolo[4.3-a]pyridinyl, quinoxalinyl, which are optionally substituted with substitutes (1 to 4) which are defined below for R14; R5 is H or C1-C6-alkyl; R6 is H, C1-C6-alkyl, or -OR11; R7 is H; R8 is H, -OR9, C1-C6-alkyl, -CN; R9 is H or C1-C4-alkyl; R10 is H or C1-C4-alkyl; or R9 and R10 taken together with the nitrogen atom to which they are bonded form morpholine; R11 is H, C1-C4-alkyl; R12 is C1-C6-alkyl; R14 in each case is independently selected from a substitute selected from a group consisting of halogen, -OR11, -NR11R12, C1-C6-alkyl, which is optionally substituted with 1-3 substitutes, in each case independently selected from a group consisting of C1-C3-alkyl, aryl; or to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, to a method of obtaining formula (I) compounds, as well as to a method of treating disorders.

EFFECT: obtaining new biological active compounds having norepinephrine, dopamine and serotonin reuptake selective inhibitory activity.

90 cl, 162 ex, 2 tbl

Mif inhibitors // 2383541

FIELD: chemistry.

SUBSTANCE: there is described compound of formula 1

where R1 represents unsubstituted or substituted (C3-C8)cycloalkyl(C1-C4)alkyl, phenyl(C1-C4)alkyl, (C3-C8)cycloalkyl, phenyl, naphthyl, phenyl condensed with 18-(crown)-6, where substitutes include phenyl, halogen, hydroxy, aminosulfonyloxy, (C1-C4)alkoxy, tri(C1-C6)alkylsilyloxy, halogen(C1-C4)alkyl or halogen(C1-C4)alkoxy, R2 represents hydrogen, hydroxyl, aminosulfonyloxy, (C1-C4)alkoxy, tri(C1-C6)alkylsilyloxy or halogen(C1-C4)alkoxy. Also described is use of the compound for making a medicinal agent and a pharmaceutical composition.

EFFECT: disclosed compounds have macrophage migration inhibitory factor activity (MIF).

8 cl, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

where R1 is hydrogen, alkyl, cycloalkyl, hydroxy group, hydroxyalkyl, alkoxy group, alkoxyalkyl, aminoalkyl, aryl, heterocyclyl, alkylsulfonyl, alkylsulfanyl, alkylcarbonylalkyl, alkylcarbonyloxyalkyl, aminocarbonylalkyl, heterocyclylcarbonylalkyl, alkoxycarbonylalkyl, alkoxyalkylaminocarbonylalkyl, cycloalkylalkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, haloidalkyl, haloidalkoxy group or haloidalkoxyalkyl, R2 is hydrogen, alkyl, cycloalkylalkoxyalkyl, alkoxyalkyl, arylalkoxyalkyl, haloidalkoxyalkyl, pyrrolidyl, morpholinyl, thiomorpholinyl, arylalkyl, arylalkoxy group, aryloxy group or heterocyclylalkyl, R3 is hydrogen or alkyl, R4 is hydrogen, alkyl or haloid, R5 is phenyl, naphthyl, piperidyl or 1,2,3,4-tetrahydroisoquinolinyl optionally substituted with one or more substitutes independently selected from alkyl, cycloalkyl, haloid, alkoxy group, nitro group, trifluoromethyl, trifluoromethoxy group, trifluoromethylcarbonyl group, aryl, aryloxy group, alkoxycarbonylalkoxy group and alkylsulfonyl, R6 is hydrogen or alkyl, and their pharmaceutically acceptable salts and esters, under the condition that N-(6-(1,1-dimethylethyl)-2-pyridinyl)-4-methylbenzenesulfamide is excluded, and in cases when R1 is hydrogen or methyl, R2 is not hydrogen or methyl, as well as a pharceutical composition based on these compounds.

EFFECT: novel chemical compounds which can be used in treating and preventing diabetes, obesity and eating disorders are obtained and described.

15 cl, 192 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula ; or their pharmaceutically acceptable salts, where A is phenyl, X is CH2- or C=O; Y is O; k equals 1; m equals 0; R2 and R3 each independently represents hydrogen or alkyl, R4 is a group of formula or . Disclosed compounds have selective affinity to 5-HT6 and 5-HT2A receptors. Also described is a pharmaceutical composition containing said compounds and use of the said compounds in making a medicinal agent for treating diseased conditions of the central nervous system.

EFFECT: more effective treatment.

49 cl, 1 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) which are protein tyrosine kinase 1B(PTP-1B) inhibitors and can be used in medicinal preparations for treating and preventing diseases related to high concentration of glucose in blood, for example diabetes and obesity. In formula (I) X is a X-1 group or X-2: , where R1 and R2 are each independently selected from a group consisting of hydrogen, lower alkyl, alkoxy-lower alkyl and hydroxyl-lower alkyl, under the condition that, R1 and R2 both represent hydrogen; R3, R4, R6 and R7 are each independently selected from a group consisting of hydrogen, lower alkyl; lower alkyl substituted with halogen or hydroxy; lower alkoxy; lower alkoxy substituted with halogen, hydroxy or lower alkoxy; hydroxyl, halogen, lower alkylthio, lower alkylsufanyl, lower alkylsufanyl, aminosufonyl, cyano, nitro, carbamoyl, lower mono- or dialkylcarbamoyl, lower alkanoyl, benzoyl, phenyl, phenyl substituted with halogen, phenyloxy, lower mono- or dialkylamino, hydroxy-substituted lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, heterocycloalkyl, hydroxy-substituted heterocycloalkyl, heterocyclyloxy, heterocyclylcarbonyl; where each heterocycloalkyl in the said values represents a 5-6-membr ring containing 1-2 heteroatoms selected from nitrogen and oxygen, and which can be substituted with lower alkyl or phenyl-lower alkyl; carboxyl, lower alkoxycarbonyl and a substitute of formula: ; R8 is selected from a group consisting of hydrogen, lower alkylthio, halogen, alkoxy-lower alkoxy, lower alkoxy, halogen-lower alkyl, hydroxy-lower alkyl; represents a 5-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of hydrogen, sulphur and nitrogen; R8 and R9 each independently represents hydrogen or lower alkyl.

EFFECT: novel compounds have useful biological properties.

31 cl, 7 dwg, 152 ex

FIELD: chemistry.

SUBSTANCE: invention describes a compound of formula I or its pharmaceutically acceptable salt , where R, R9, Z, X, Q and Y are defined in the formula of invention. The compounds are chemokine receptor 2 and chemokine receptor 5 antagonists and can be used as a medicinal agent for preventing, relieving or treating autoimmune or inflammatory diseases or conditions.

EFFECT: obtaining a formula (I) compound, a pharmaceutical composition based on the formula (I) compound, use of the compound in paragraph 1 to prepare a medicinal agent for treating an autoimmune or inflammatory disease or condition, as well as use of the compound in paragraph 1 to prepare a medicinal agent for treating HIV infection or AIDS.

11 cl, 181 ex

Up!