title: Optimization of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives as arginine vasopressin V2 receptor agonists and discussion of their binding modes.
abstract: A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives were optimized to achieve potent agonistic activity, both in vitro and in vivo, for the arginine vasopressin V(2) receptor, resulting in the eventual discovery of compound 1g. Molecular modeling of compound 1g with V(2) receptor was also examined to evaluate the binding mode of this series of compounds.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc, Tsukuba-shi, Ibaraki 305-8585, Japan. issei.tsukamoto@jp.astellas.com
authors.forename: Issei
authors.initials: I
authors.lastname: Tsukamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koshio
authors.forename: Masaya
authors.initials: M
authors.lastname: Orita
authors.forename: Chikashi
authors.initials: C
authors.lastname: Saitoh
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yanai-Inamura
authors.forename: Chika
authors.initials: C
authors.lastname: Kitada-Nozawa
authors.forename: Eisaku
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Yatsu
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsukamoto
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C030686:acetamide; D001120:Arginine