Novel, potent, selective, and metabolically stable stearoyl-CoA desaturase (SCD) inhibitors

  • Bioorg Med Chem Lett. 2009 Apr 1;19(7):2048-52. doi: 10.1016/j.bmcl.2009.02.019.
Dmitry O Koltun  1 ,  Eric Q Parkhill ,  Natalya I Vasilevich ,  Andrei I Glushkov ,  Timur M Zilbershtein ,  Alexei V Ivanov ,  Andrew G Cole ,  Ian Henderson ,  Nathan A Zautke ,  Sandra A Brunn ,  Nevena Mollova ,  Kwan Leung ,  Jeffrey W Chisholm ,  Jeff Zablocki
Affiliations
  • 1. Department of Medicinal Chemistry, CV Therapeutics, Inc., Palo Alto, CA 94304, USA. [email protected]
PMID: 19249203 DOI: 10.1016/j.bmcl.2009.02.019
Abstract

We identified a series of structurally novel SCD (Delta9 desaturase) inhibitors via high-throughput screening and follow-up SAR studies. Modification of the central bicyclic scaffold has proven key to our potency optimization effort. The most potent analog (8g) had IC(50) value of 50 pM in a HEPG2 SCD assay and has been shown to be metabolically stable and selective against Delta5 and Delta6 desaturases.

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