Synthesis and biological activity of a potent and orally bioavailable SCD inhibitor (MF-438)

被引：55

作者：

Leger, Serge ^{[1
]}

Black, W. Cameron ^{[1
]}

Deschenes, Denis ^{[1
]}

Dolman, Sarah ^{[1
]}

Falgueyret, Jean-Pierre ^{[1
]}

Gagnon, Marc ^{[1
]}

Guiral, Sebastien ^{[1
]}

Huang, Zheng ^{[1
]}

Guay, Jocelyne ^{[1
]}

Leblanc, Yves ^{[1
]}

Li, Chun-Sing ^{[1
]}

Masse, Frederic ^{[1
]}

Oballa, Renata ^{[1
]}

Zhang, Lei ^{[1
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Pointe Claire, PQ H9R 4P8, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 02期

关键词：

SCD inhibitor; Stearoyl-CoA; Pyridazine; Thiadiazole; Bioavailable; STEAROYL-COA DESATURASE; COENZYME-A DESATURASE; PART I; DEFICIENCY; MICROSOMES; DISCOVERY; ENZYME; MICE;

D O I：

10.1016/j.bmcl.2009.11.111

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of stearoyl-CoA desaturase 1 (SCD1) inhibitors were developed. Investigations of enzyme potency and metabolism led to the identification of the thiadiazole-pyridazine derivative MF-438 as a potent SCD1 inhibitor. MF-438 exhibits good pharmacokinetics and metabolic stability, thereby serving as a valuable tool for further understanding the role of SCD inhibition in biological and pharmacological models of diseases related to metabolic disorders. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：499 / 502

页数：4

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