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

  • Bioorg Med Chem Lett. 2008 Aug 1;18(15):4298-302. doi: 10.1016/j.bmcl.2008.06.088.
Zhili Xin  1 ,  Hongyu Zhao ,  Michael D Serby ,  Bo Liu ,  Mei Liu ,  Bruce G Szczepankiewicz ,  Lissa T J Nelson ,  Harriet T Smith ,  Tom S Suhar ,  Rich S Janis ,  Ning Cao ,  Heidi S Camp ,  Christine A Collins ,  Hing L Sham ,  Teresa K Surowy ,  Gang Liu
Affiliations
  • 1. Abbott Laboratories, Global Pharmaceutical Research and Development, 100 Abbott Road, Abbott Park, IL 60064, USA. [email protected]
PMID: 18632269 DOI: 10.1016/j.bmcl.2008.06.088
Abstract

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.

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