| Literature DB >> 17530838 |
Gang Liu1, John K Lynch, Jennifer Freeman, Bo Liu, Zhili Xin, Hongyu Zhao, Michael D Serby, Philip R Kym, Tom S Suhar, Harriet T Smith, Ning Cao, Ruojing Yang, Rich S Janis, Joel A Krauser, Steven P Cepa, David W A Beno, Hing L Sham, Christine A Collins, Teresa K Surowy, Heidi S Camp.
Abstract
Stearoyl-CoA desaturase 1 (SCD1) catalyzes the committed step in the biosynthesis of monounsaturated fatty acids from saturated, long-chain fatty acids. Studies with SCD1 knockout mice have established that these animals are lean and protected from leptin deficiency-induced and diet-induced obesity, with greater whole body insulin sensitivity than wild-type animals. In this work, we have discovered a series of potent, selective, orally bioavailable SCD1 inhibitors based on a known pyridazine carboxamide template. The representative lead inhibitor 28c also demonstrates excellent cellular activity in blocking the conversion of saturated long-chain fatty acid-CoAs (LCFA-CoAs) to monounsaturated LCFA-CoAs in HepG2 cells.Entities:
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Year: 2007 PMID： 17530838 DOI： 10.1021/jm070219p
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446