INHIBITORS OF PROTEASES DECOMPOSING AFTER PROLINE Russian patent published in 2009 - IPC C07D207/16 C07D277/04 C07D295/18 C07D211/16 C07D417/12 C07D401/12 A61K31/401 A61K31/426 A61K31/4427 A61K31/53 A61K31/54 A61K31/541 A61K31/445 A61K31/4709 A61P3/10 

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to compounds of formula 1 and their pharmaceutically acceptable salts as inhibitors of post-proline aminopepdidases, as well as to pharmaceutical composition based on them and application for manufacturing such composition, and to method of inhibition with their application. Compounds can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose. In general formula 1 ,

either G¹ represents -CH₂-X²-(CH₂)_a-G³, and G² represents H, or G² represents -CH₂-(CH₂)_a-G³, and G¹ represents H; G³ is selected from group according to general formula 2 ,

group according to general formula 3

and group according to general formula 4 ;

a is 0, 1 or 2; b is 1 or 2; X¹ is selected from CH₂, S, CF₂, CHF and O; X² is selected from CH₂; X³, X⁴ and X⁵ are selected from N; X⁶ is selected from NH; X⁷ is selected from NH; R¹ is selected from H and CN; R² represents H; R³ is selected from H, Cl, OH, NH₂, NH-C₁-C₁₀alkyl and N(C₁-C₁₀alkyl)₂; R⁴, R⁵, R⁶, R⁷ and R⁸ are independently selected from H, Br, Cl, F, OH, NO₂; R⁹ represents H; R¹⁰, R¹¹, R¹², R¹³ and R¹⁴ are independently selected from H, Cl and CF₃; R¹⁵ and R¹⁶ are independently selected from H, C₁-C₁₀alkyl, C₁-C₁₀alkenyl, C₃-C₁₀cycloalkyl, C₃-C₁₀cycloalkenyl, quinoline, naphtyl and -CH₂-L-R¹⁷; R¹⁷ is selected from C₁-C₁₀alkyl, phenyl, naphtyl, quinolinyl and indolyl; L is selected from covalent bond, CH=CH and -C₆H₄-; on condition that when R¹⁵ and R¹⁶ both represent H, and b is 1, then X¹ does not represent S or CH₂.

EFFECT: obtaining compounds that can be applied for treatment of diseases mediated by activity of post-proline aminopeptidases, such as type II diabetes and disturbed tolerance to glucose.

58 cl, 10 tbl, 1705 ex