Preparation of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives as novel arginine vasopressin V2 receptor agonists

The present work describes the discovery of novel series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives as arginine vasopressin (AVP) V2 receptor agonists. By replacing the amide juncture in YM-35278 with a direct ring connection gave compound 10a, which acts as a V2 receptor agonist. These studies provided the potent, orally active non-peptidic V2 receptor agonists 10a and 10j.

A novel series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives were prepared, and their binding affinity for V2 receptor and intrinsic activity were evaluated. Synthesis and structure–activity relationships including in vivo evaluation are described.Figure optionsDownload as PowerPoint slide