Author/Authors :
Yutaka Nakajima، نويسنده , , Masashi Imanishi، نويسنده , , Shinji Itou، نويسنده , , Hitoshi Hamashima، نويسنده , , Yasuyo Tomishima، نويسنده , , Kenichi Washizuka، نويسنده , , Minoru Sakurai، نويسنده , , Shigeo Matsui، نويسنده , , Emiko Imamura، نويسنده , , Koji Ueshima، نويسنده , , Pedro Takao Yamamoto، نويسنده , , Nobuhiro Yamamoto، نويسنده , , Hirofumi Ishikawa، نويسنده , , Keiko Nakano، نويسنده , , Naoko Unami، نويسنده , , Kaori Hamada، نويسنده , , Kouji Hattori، نويسنده ,
Abstract :
Identification and SAR study of novel series of β3-AR agonists with benzoic acid are described. Conversion of ether linkage position of phenoxybenzoic acid derivative 2b led to compound 7b with moderate β3-AR activity. Further modification in right, center and left parts of compound 7b was investigated to improve the β3-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 β3-AR agonists. In addition, in vivo efficacy of compounds 7g and 7k was exhibited on dog OAB model.
