TETRACYCLIC IMIDAZO-BENZODIAZEPINES AS GABA RECEPTORS MODULATORS

摘要

The present invention is concerned with substituted imidazo [1,5-a] [1,2,4] triazolo [1,5-d] [1,4]benzodiazepine derivatives of the following formula (I) wherein R' is hydrogen, halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy, lower alkoxy substituted by halogen, nitro, cycloalkyl, -O(CH<SUB>2</SUB>)<SUB>m</SUB>O(CH<SUB>2</SUB>)<SUB>m</SUB>OH or -C=C-R'; R<SUP>2</SUP> is hydrogen or methyl; R<SUP>3</SUP> is lower alkyl, lower alkyl substituted by halogen, lower alkenyl, lower alkenyl substituted by halogen, lower alkynyl, -(CH<SUB>2</SUB>)<SUB>n</SUB>-cycloalkyl, -(CR'R")<SUB>m </SUB>CH<SUB>3</SUB>, or is phenyl, unsubstituted or substituted by halogen, or is pyridinyl or thienyl, unsubstituted or substituted by lower alkyl, or is -(CH<SUB>2</SUB>)<SUB>n</SUB>-NH-cycloalkyl, lower alkenyl-cycloalkyl, lower alkynyl-(CR'R")<SUB>m</SUB>OH, or is lower alkynyl-phenyl, wherein the phenyl ring is unsubstituited or substituted by halogen, CF<SUB>3</SUB>, lower alkyl or lower alkoxy; R' is hydrogen or lower alkyl; R" is hydrogen, hydroxy or lower alkyl; n is 0, 1 or 2; m is 1, 2 or 3; o is 1 or 2; and with their pharmaceutically acceptable acid addition salts. It has been found that this class of compounds show high affinity and selectivity for GABA A a 5 receptor binding sites and might be useful as cognitive enhancer or for the treatment of cognitive disorders like Alzheimer's disease.