Discovery of novel pyrrole derivatives as potent agonists for the niacin receptor GPR109A

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:30

Article

Miyazawa, Yuriko¹  Yamaguchi, Takahiro²  Yamaguchi, Mitsuhiro³  Tago, Keiko⁴  Tamura, Akihiro⁵  Sugiyama, Daisuke⁶  Aburatani, Takahide²  Nishizawa, Tomohiro¹  Kurikawa, Nobuya⁷  Kono, Keita⁸ 

[1] Daiichi Sankyo Co Ltd, External Affairs Dept, Chuo Ku, Tokyo 1038426, Japan

[2] Daiichi Sankyo Co Ltd, Modal Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

[3] Daiichi Sankyo Co Ltd, R&D Planning & Management Dept, Shinagawa Ku, Tokyo 1408710, Japan

[4] Daiichi Sankyo RD Novare Co Ltd, Med Chem Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

[5] Daiichi Sankyo RD Novare Co Ltd, Organ Synth Dept, Edogawa Ku, Tokyo 1348630, Japan

[6] Daiichi Sankyo Co Ltd, Drug Metab & Pharmacokinet Res Labs, Shinagawa Ku, Tokyo 1408710, Japan

[7] Daiichi Sankyo Co Ltd, Specialty Med Res Labs 2, Shinagawa Ku, Tokyo 1408710, Japan

[8] Daiichi Sankyo Co Ltd, Specialty Med Res Labs 1, Shinagawa Ku, Tokyo 1408710, Japan

关键词: GPR109A;    Niacin;    Pyrrole;    Lipolysis;    Non-esterified fatty acid;   

DOI  :  10.1016/j.bmcl.2020.127105

来源: Elsevier

【 摘 要 】

Novel pyrrole derivatives were discovered as potent agonists of the niacin receptor, GPR109A. During the derivatization, compound 16 was found to be effective both in vitro and in vivo. The compound 16 exhibited a significant reduction of the non-esterified fatty acid in human GPR109A transgenic rats, and the duration of its in vivo efficacy was much longer than niacin.

【 授权许可】

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