Discovery of novel series of benzoic acid derivatives containing biphenyl ether moiety as potent and selective human beta(3)-adrenergic receptor agonists: Part IV.
Identification and SAR study of novel series of beta(3)-AR agonists with benzoic acid are described. Conversion of ether linkage position of phenoxybenzoic acid derivative 2b led to compound 7b with moderate beta(3)-AR activity. Further modification in right, center and left parts of compound 7b was investigated to improve the beta(3)-AR potency and selectivity. Compounds 7g and 7k, with the bulky aliphatic-substituted group at 2-position of benzoic acid moiety, were identified as potent and selective beta(3)-AR agonists. In addition, in vivo efficacy of compounds 7g and 7k was exhibited on dog OAB model.
Nakajima
Yutaka
Y
Chemistry Research Laboratories, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.
Imanishi
Masashi
M
Itou
Shinji
S
Hamashima
Hitoshi
H
Tomishima
Yasuyo
Y
Washizuka
Kenichi
K
Sakurai
Minoru
M
Matsui
Shigeo
S
Imamura
Emiko
E
Ueshima
Koji
K
Yamamoto
Takao
T
Yamamoto
Nobuhiro
N
Ishikawa
Hirofumi
H
Nakano
Keiko
K
Unami
Naoko
N
Hamada
Kaori
K
Hattori
Kouji
K