title: Nonpeptide arginine vasopressin antagonists for both V1A and V2 receptors: synthesis and pharmacological properties of 2-phenyl-4'-[(2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]benzanil ide derivatives.
abstract: A series of compounds structurally related to 4'-[(2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]benzanili de was synthesized and demonstrated to have arginine vasopressin (AVP) antagonist activity for both V1A and V2 receptors. The introduction of a phenyl or a 4-substituted phenyl group into the ortho position of the benzoyl moiety resulted in an increase in both binding affinity and antagonistic activity. The 2-(4-methylphenyl) derivative (1g) exhibited high antagonistic activities for both V1A (8.6-fold) and V2 (38-fold) receptors and high oral activity (8.6-fold) compared with the 2-methyl lead compound (1a). Detail of the synthesis and the pharmacological properties of this series are presented.
authors.affiliation: Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Matsuhisa
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Shimada
authors.forename: T
authors.initials: T
authors.lastname: Yatsu
authors.forename: I
authors.initials: I
authors.lastname: Yanagisawa
mesh_terms: D000813:Anilides / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001552:Benzazepines / Q000138:chemical synthesis* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D014563:Urodynamics / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D000813:Anilides; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin