2. Academic Validation
  3. Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors

Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors

  • J Med Chem. 2007 Jun 28;50(13):3086-100. doi: 10.1021/jm070219p.
Gang Liu 1,  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
Affiliations

Affiliation

  • 1 Metabolic Disease Research, Drug Metabolism, Advanced Technology, Exploratory Pharmacokinetics, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois 60064-6101, USA. liugx@gmail.com
PMID: 17530838 DOI: 10.1021/jm070219p
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.

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