Central & Peripheral Nervous System: Benzothiazepine and benzoxazepine derivatives as cholecystokinin receptor antagonists

Abstract

Novel benzothiazepine and benzoxazepine derivatives are disclosed as cholecystokinin (CCK) antagonists. These novel CCK_b receptor antagonists are claimed to have potential therapeutic utility in the treatment of pain and gastrointestinal disorders as well as CNS disorders.

The current Pfizer patent under review includes experimental details for 220 compounds including their intermediates. H NMR data are provided for each example, and detailed descriptions of general synthetic approaches towards target compounds as well as key references for their synthesis are provided. Although a detailed description of the receptor binding assay and the claim for cholecystokinin antagonist activity and potential therapeutic utility thereof are included, no receptor binding data are provided for the claimed compounds. The patent genetically discloses a large number of benzothiazepine and benzoxazepine derivatives, but only 15 compounds are specifically claimed which includes enantiomeric pairs. One of the compounds claimed is (S)-1-[3,4-dihydro-4-oxo-3-[[(3-methylphenylamino)carbonyl]amino]-1,5-benzothiaz epine-5(2H)-acetyl-3,3-dimethyl piperidine (1) which is representative of this class of compounds.