8-substituted-9H-1,3-dioxolo[4,5-H],[2,3]benzodiazepine derivatives, as AMPA/kainate receptor inhibitors

摘要

A 8-substituted-9H-1,3-dioxolo-[4,5-H][2,3]-benzodiazepine derivative of the formula I wherein: X is a carbonyl group or a methylene group; R1 is a hydrogen atom, a hydroxy group, an alkoxy group, an alkanoyloxy group, a alkylsulfonyloxy group or a group of the formula -NR4R5; or X forms together with R1 a cyano group, a tetrazolyl group, -CHNOH, -COR6 R4 and R5 are independently, a hydrogen atom or an alkoxy group, an alkanoyl group or an alkyl group optionally substituted by a saturated or unsaturated heterocyclic group having 5 or 6 members and comprising one or two nitrogen atom(s) or a nitrogen atom and an oxygen atom as the heteroatom, or by an N-[phenyl-alky]-N-alkylamino group, wherein the phenyl group is optionally substituted by 1 to 3 alkoxy groups; or R4 and R5 form with the adjacent nitrogen atom and optionally with a further nitrogen atom or an oxygen atom, a saturated or unsaturated heterocyclic group having 5 to 10 members; R6 is a hydroxy group or an alkoxy group, a phenoxy group, a naphthyloxy group, or an amino group optionally substituted by an alkyl group; R2 is a nitro group, an amino group or a alkanoylamino group; R3 is a hydrogen atom, an alkyl group, or a group of the formula -COR7; R7 is a hydrogen atom, an alkyl group optionally substituted by 1 to 3 halo atoms, an alkoxy group, a phenoxy group, a pyridyl group, a phenyl group or a naphthyl group which two latter groups are optionally substituted by 1 to 3 substituents, or a group of the formula -(CH2)n-NR8R9; R8 and R9 are independently a hydrogen atom, an alkyl group optionally substituted by a phenyl group or a saturated heterocyclic group having 5 or 6 members and containing a nitrogen group or a nitrogen and an oxygen group, and said phenyl group is optionally substituted by 1 to 3 alkoxy groups; or R8 and R9 form, together with the adjacent nitrogen atom and optionally a further nitrogen or oxygen atom, a saturated or unsaturated heterocyclic group having 5 or 6 members optionally substituted by a phenyl group that is optionally substituted by 1 to 3 substituents selected from a halo atom or an alkoxy group; n is 0, 1 or 2; Y is a hydrogen atom, or a methyl group; or Y forms together with R3 a valence bond between the carbon atom in position 8 and the nitrogen atom in position 7; and pharmaceutically suitable acid addition salts and quaternary ammonium derivatives thereof. The compounds are useful for treating epilepsy, a neurodegenerative disease or post-stroke conditions.