Discovery of novel series of benzoic acid derivatives containing biphenyl ether moiety as potent and selective human beta(3)-adrenergic receptor agonists: Part IV

  • Bioorg Med Chem Lett. 2008 Sep 15;18(18):5037-40. doi: 10.1016/j.bmcl.2008.08.009.
Yutaka Nakajima  1 ,  Masashi Imanishi ,  Shinji Itou ,  Hitoshi Hamashima ,  Yasuyo Tomishima ,  Kenichi Washizuka ,  Minoru Sakurai ,  Shigeo Matsui ,  Emiko Imamura ,  Koji Ueshima ,  Takao Yamamoto ,  Nobuhiro Yamamoto ,  Hirofumi Ishikawa ,  Keiko Nakano ,  Naoko Unami ,  Kaori Hamada ,  Kouji Hattori
Affiliations
  • 1. Chemistry Research Laboratories, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan.
PMID: 18752946 DOI: 10.1016/j.bmcl.2008.08.009
Abstract

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.