2. Academic Validation
  3. Novel, potent, selective, and metabolically stable stearoyl-CoA desaturase (SCD) inhibitors

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

Affiliation

  • 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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