N-Methylbenzanilide derivatives as a novel class of selective V1A receptor antagonists

During our efforts to develop a novel class of selective V1A receptor antagonists, the N-methylbenzanilide structure was applied to a 4,4-difluoro-1-benzazepine derivative, 4, which is a selective V1A receptor antagonist. Further structural modifications gave 16a with high V1A affinity and V2/V1A selectivity (Ki=5.71 nM, V2/V1A=140) and potent V1A receptor antagonist activity (ID50=0.0080 mg/kg iv).