title: Synthesis and structure-activity relationships of amide derivatives of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetic acid as selective arginine vasopressin V2 receptor agonists.
abstract: A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives was synthesized, and their structure-activity relationships were examined in order to identify potent and selective arginine vasopressin V(2) receptor agonists. Attempts to substitute other chemical groups in place of the 2-pyridilmethyl moiety of 1a led to the discovery that potent V(2) binding affinity could be obtained with a wide range of functional groups. This structural tolerance allowed for the manipulation of other attributes, such as selectivity against V(1a) receptor affinity or avoidance of the undesirable inhibition of cytochrome P450 (CYP), without losing potent affinity for the V(2) receptor. Some representative compounds obtained in this study were also found to decrease urine volume in awake rats.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Tsukamoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koshio
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kuramochi
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: Yoshiaki
authors.initials: Y
authors.lastname: Shimada
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsukamoto