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

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

Affiliation

  • 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.

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