Structure-Activity Relationship Studies of 3-or 4-Pyridine Derivatives of DS-6930

被引：4

作者：

Shinozuka, Tsuyoshi ^{[1
]}

Tsukada, Tomoharu ^{[1
]}

Fujii, Kunihiko ^{[1
]}

Tokumaru, Eri ^{[1
]}

Matsui, Yumi ^{[2
]}

Wakimoto, Satoko ^{[1
]}

Ogata, Tsuneaki ^{[1
]}

Araki, Kazushi ^{[1
]}

Sawamura, Ryoko ^{[1
]}

Watanabe, Nobuaki ^{[1
]}

Mori, Makoto ^{[1
]}

Tanaka, Jun ^{[1
]}

机构：

[1] Daiichi Sankyo Co Ltd, R&D Div, Shinagawa Ku, 1-2-58 Hiromachi, Tokyo 1408710, Japan

[2] Daiichi Sankyo RD Novare Co Ltd, R&D Div, Edogawa Ku, 1-16-13 Kitakasai, Tokyo 1348630, Japan

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2019年 / 10卷 / 03期

关键词：

DS-6930; benzoic acid; benzimidazole; PPAR gamma; partial agonist;

D O I：

10.1021/acsmedchemlett.8b00645

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Derivatization efforts were continued to discover backups for a potent selective PPAR gamma modulator, DS-6930. In this Letter, the replacement of 2-pyridine ring in DS-6930 with 3- or 4-pyridyl group is reported. As the introduction of substituents on the pyridine ring did not provide potent partial agonists, modifications of benzimidazole ring were explored to discover potent intermediate agonists. 4'-Alkoxy substituted benzimidazoles failed to show potent efficacy in vivo, whereas 7'-fluoro benzimidazole 3g (DS19161384) was found to result in robust plasma glucose reductions with excellent DMPK profiles.

引用

页码：358 / 362

页数：9

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