N-Methylbenzanilide derivatives as a novel class of selective V(1A) receptor antagonists.
During our efforts to develop a novel class of selective V(1A) receptor antagonists, the N-methylbenzanilide structure was applied to a 4,4-difluoro-1-benzazepine derivative, 4, which is a selective V(1A) receptor antagonist. Further structural modifications gave 16a with high V(1A) affinity and V(2)/V(1A) selectivity (K(i)=5.71 nM, V(2)/V(1A)=140) and potent V(1A) receptor antagonist activity (ID(50)=0.0080 mg/kg iv).
Kakefuda
Akio
A
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., 21Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. kakefuda@yamanouchi.co.jp
Tsukada
Junko
J
Kusayama
Toshiyuki
T
Tahara
Atsuo
A
Tsukamoto
Shin-ichi
S
D000813:Anilides / Q000737:chemistry / Q000494:pharmacology*; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000378:metabolism; D015394:Molecular Structure; D017483:Receptors, Vasopressin / Q000378:metabolism
D000813:Anilides; D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C034595:benzanilide