Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors

被引：68
作者：
Xin, Zhili [1 ]
Zhao, Hongyu [1 ]
Serby, Michael D. [1 ]
Liu, Bo [1 ]
Liu, Mei [1 ]
Szczepankiewicz, Bruce G. [1 ]
Nelson, Lissa T. J. [1 ]
Smith, Harriet T. [1 ]
Suhar, Tom S. [1 ]
Janis, Rich S. [1 ]
Cao, Ning [1 ]
Camp, Heidi S. [1 ]
Collins, Christine A. [1 ]
Sham, Hing L. [1 ]
Surowy, Teresa K. [1 ]
Liu, Gang [1 ]
机构：
[1] Abbott Labs, Global Pharmaceut Res & Dev, Abbott Pk, IL 60064 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 15期
关键词：
SCD1; inhibitors; desaturation index;
D O I：
10.1016/j.bmcl.2008.06.088
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of structurally novel stearoyl-CoA desaturase1 (SCD1) inhibitors has been identified via molecular scaffold manipulation. Preliminary structure-activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(methyl carbamoyl)phenyl]piperidine-1-carboxamide 4c exhibited robust in vivo activity with dose-dependent desaturation index lowering effects. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4298 / 4302
页数：5
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