Isoquinolinone derivatives as NK3 antagonists and their preparation, pharmaceutical compositions and use in the treatment of psychosis and schizophrenia.

Abstract

Isoquinolone derivs. of the general formula I, which are NK3 antagonists and useful for the treatment of e.g. psychosis and schizophrenia are provided. Compds. of formula I wherein A is N, CH and CR1; each R1 are independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, CO-C1-6 alkyl, etc.; X is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, CN, OH and derivs., etc.; R4 - R17 are independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, NH2 and derivs., OH, CN, etc.; and pharmaceutically acceptable salts thereof, are claimed. Example compd. II was prepd. by amination of 3-bromomethyl-1-oxo-2-phenyl-1,2-dihydroisoquinoline-4-carboxylic acid ((S)-1-phenylpropyl amide) with dimethylamine. All the invention compds. were evaluated for their NK3 antagonistic activity. From the assay, it was detd. that compd. II exhibited Ki values of 180 nM. [on SciFinder(R)]