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Discovery of 3-aryl-3-ethoxypropanoic acids as orally active GPR40 agonists.
Takano, Rieko; Yoshida, Masao; Inoue, Masahiro; Honda, Takeshi; Nakashima, Ryutaro; Matsumoto, Koji; Yano, Tatsuya; Ogata, Tsuneaki; Watanabe, Nobuaki; Toda, Narihiro.
Affiliation
  • Takano R; R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • Yoshida M; R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • Inoue M; R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • Honda T; R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • Nakashima R; R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • Matsumoto K; R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • Yano T; R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • Ogata T; R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • Watanabe N; R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • Toda N; R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: toda.narihiro.jw@daiichisankyo.co.jp.
Bioorg Med Chem Lett ; 24(13): 2949-53, 2014 Jul 01.
Article in En | MEDLINE | ID: mdl-24835985
ABSTRACT
The G protein-coupled receptor 40 (GPR40) mediates enhancement of glucose-stimulated insulin secretion in pancreatic ß cells. The GPR40 agonist has been attracting attention as a novel insulin secretagogue with glucose dependency for the treatment of type 2 diabetes. The optimization study of compound 1 led to a potent and bioavailable GPR40 agonist 24, which showed insulin secretion and glucose lowering effects in rat OGTT. Compound 24 is a potential lead compound for a novel insulin secretagogue with a low risk of hypoglycemia.
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Full text: 1 Database: MEDLINE Main subject: Propionates / Receptors, G-Protein-Coupled / Drug Discovery Limits: Animals / Humans Language: En Journal: Bioorg Med Chem Lett Journal subject: BIOQUIMICA / QUIMICA Year: 2014 Type: Article Affiliation country: Japan
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Full text: 1 Database: MEDLINE Main subject: Propionates / Receptors, G-Protein-Coupled / Drug Discovery Limits: Animals / Humans Language: En Journal: Bioorg Med Chem Lett Journal subject: BIOQUIMICA / QUIMICA Year: 2014 Type: Article Affiliation country: Japan