Conversion of systemically-distributed triazole-based stearoyl-CoA desaturase (SCD) uHTS hits into liver-targeted SCD inhibitors

被引：12

作者：

Leclerc, Jean-Philippe ^{[1
]}

Falgueyret, Jean-Pierre ^{[2
]}

Girardin, Melina ^{[3
]}

Guay, Jocelyne ^{[2
]}

Guiral, Sebastien ^{[2
]}

Huang, Zheng ^{[2
]}

Li, Chun Sing ^{[1
]}

Oballa, Renata ^{[1
]}

Ramtohul, Yeeman K. ^{[1
]}

Skorey, Kathryn ^{[2
]}

Tawa, Paul ^{[2
]}

Wang, Hao ^{[2
]}

Zhang, Lei ^{[2
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Dept Med Chem, Kirkland, PQ H9H 3L1, Canada

[2] Merck Frosst Ctr Therapeut Res, Dept Biochem & Mol Biol, Kirkland, PQ H9H 3L1, Canada

[3] Merck Frosst Ctr Therapeut Res, Dept Proc Res, Kirkland, PQ H9H 3L1, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 21期

关键词：

Stearoyl-CoA desaturase inhibitors; SCD inhibitors; Triazoles; Liver-targeted; MK-8245; OBESITY; IDENTIFICATION; DEFICIENCY; MICE;

D O I：

10.1016/j.bmcl.2011.08.073

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

It has been demonstrated that once-a-day dosing of systemically-distributed SCD inhibitors leads to adverse events in eye and skin. Herein, we describe our efforts to convert a novel class of systemically-distributed potent triazole-based uHTS hits into liver-targeted SCD inhibitors as a means to circumvent chronic toxicity. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：6505 / 6509

页数：5

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