HETEROARYL-SUBSTITUTED AMIDES CONTAINING SATURATED BINDING GROUP AND USE THEREOF AS PHARMACEUTICAL AGENTS Russian patent published in 2011 - IPC C07D401/06 C07D417/06 C07D401/12 C07D277/42 C07D213/63 C07D213/36 A61K31/4439 A61K31/444 A61P9/08 

FIELD: chemistry.

SUBSTANCE: invention relates to N-alkylamides of formula I

, where A is selected from such groups as -CH₂-CH₂-, -CH₂-CH₂-CH₂- and -Y-CH₂-CH₂-, where Y is selected from O, S and NR¹¹ and Y is bonded to a Het group; Het denotes a 5-member or 6-member monocyclic aromatic group which contains one or two identical or different heterocyclic ring elements selected from N, NR¹³ and S, and which can be substituted with one or more identical or different substitutes R⁵; X denotes a single bond; R¹ and R² together with a N-CO group which contains them, form a 4-10-member monocyclic or bicyclic saturated or unsaturated ring which, besides a nitrogen ring atom which is part of the N-CO group, can contain one or two additional heterocyclic ring elements selected from N, NR¹², O and S, which can be identical or different, provided that two ring elements from O and S cannot be in neighbouring positions in the ring, where the ring, formed by R¹ and R² and the N-CO group containing them, can be substituted with one or more identical or different substitutes R⁸; R³ is selected from phenyl, naphthalinyl and heteroaryl, which all can be substituted with one or more identical or different substitutes selected from a halogen atom, (C₁-C₄)alkyl, (C₁-C₄)alkyloxy group, which can be substituted with one or more fluorine atoms, (C₁-C₄)alkylamino, di((C₁-C₄)alkyl)amino, ((C₁-C₄)alkyl)-CONH-, CONH₂, CN, CF₃, H₂NSO₂- and (C₁-C₄)alkyl-SO₂-; R⁵ is selected from a halogen atom and (C₁-C₄)alkyl; R⁸ is selected from a halogen atom, (C₁-C₄)alkyl and an oxo-group; R¹¹ denotes a hydrogen atom; R¹² is selected from a hydrogen atom and (C₁-C₄)alkyl; R¹³ is selected from a hydrogen atom and (C₁-C₄)alkyl; heteraryl is a 5-member or 6-member monocyclic aromatic group which contains one, two or three identical or different heterocyclic ring elements selected from N, NR¹³, O and S; in any of its stereoisomeric forms or mixture of stereoisomeric forms in any ratio, or its physiologically acceptable salt; provided that the -N(R²)-CO-R¹ group cannot be an unsubstituted 2-oxopyrrolidin-1-yl group or unsubstituted 2-oxoimidazolin-1-yl group if the -N(R²)-CO-R¹ group simultaneously denotes a group of formula

,

in which the bond through which the group is bonded to group A, is denoted by a line starting from position 2 of the pyridine ring, and in which R⁹⁰ is selected from imidazol-1-yl, isoxazol-5-yl, isothiazol-5-yl, 1,2,4-thiazol-1-yl, pyrazin-2-yl and pyrazol-3-yl, which can all be substituted with (C1-C4)alkyl and which can be substituted in the pyridine ring with at most four substitutes selected from (C₁-C₄)alkyl and a halogen atom; and provided that the -N(R²)-CO-R¹ cannot be a 1,3-dioxoisoindol-2-yl group of formula

in which the bond through which the group is bonded to group A is denoted by a line beginning from the nitrogen atom. The invention also relates to a method of producing said compounds, a pharmaceutical composition for stimulating endothelia NO synthase, as well as to use thereof in preparing a medicinal agent.

EFFECT: novel compounds which can be used in conditions where high expression of the said enzyme, high content of NO or normalisation of low content of NO is desired are obtained and described.

18 cl, 87 ex, 1 tbl