QUINUCLIDINE DERIVATIVES AND USE THEREOF AS M3 MUSCARINIC RECEPTOR ANTAGONISTS Russian patent published in 2010 - IPC C07D453/02 A61K31/439 A61P11/00 A61P29/00 

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I

in form of a salt, where R¹ and R² each independently denotes phenyl, where one or both R¹ and R² are substituted in one, two or three positions by the following groups: halogen, C₁-C₈alkyl or C₁-C₈alkoxy, and R³ is hydroxy, or R¹ and R² each denotes an unsubstituted phenyl, and R is hydrogen, C₁-C₈alkyl, C₁-C₈alkoxy or C₁-C₈alkylthio, or R¹ is C₃-C₈cycloalkyl and R² is phenyl or a 5-member heterocycle containing at least one heteroatom in the ring selected from a group which includes oxygen and sulphur, and R³ is hydroxy, or -CR¹R²R³ denotes 9-hydroxy- 9H-fluoren-9-yl or 9-hydroxy-9H-xanthen-9-yl, and R⁴ is C₁-C₈alkyl substituted in one, two or three positions by a -CO-N(R⁵)R⁶ group, where R⁵ is hydrogen and R⁶ is a 5-member heterocycle containing at least one heteroatom in the ring selected from a group which includes nitrogen and oxygen, optionally substituted with phenyl, or R¹ and R² each denotes an unsubstituted phenyl, and R³ is hydroxy and R⁴ is C₁-C₈alkyl substituted in one, two or three positions by a -CO-N(R⁵)R⁶ group, where R⁵ is hydrogen and R⁶ is 5-methyl-3-isoxazolyl or R¹ and R² each denote unsubstituted phenyl, and R³ is hydroxy and R⁴ is 1-ethyl substituted in one, two or three positions by a -CO-N(R⁵)R⁶ group, where R⁵ is hydrogen, R⁶ is a 5-member heterocycle containing at least one heteroatom in the ring selected from a group which includes nitrogen and oxygen, provided that the formula I compound is not (R)-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-(pyrazin-2-ylcarbamoylmethy)-1-azoniumbicyclo[2.2.2]octane, (R)-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-(isoxazol-3-ylcarbamoylmethyl)-1-azoniumbicyclo [2.2.2]octane bromide or (R)-3-(2-hydroxy-2,2-dithiophen-2-ylacetoxy)-1-(pyrimidin-4-ylcarbamoylmethyl)-1-azoniumbicyclo [2.2.2]octane bromide. The invention also relates to a pharmaceutical composition, to use of compounds in any of claims 1-8, as well as to methods for synthesis of formula I compounds.

EFFECT: obtaining new biologically active compounds which have M3 muscarinic receptor mediated activity.

14 cl, 254 ex, 1 tbl