Discovery of a new class of glucosylceramide synthase inhibitors

  • Bioorg Med Chem Lett. 2011 Nov 15;21(22):6773-7. doi: 10.1016/j.bmcl.2011.09.037.
Elena Koltun  1 ,  Steven Richards ,  Vicky Chan ,  Jason Nachtigall ,  Hongwang Du ,  Kevin Noson ,  Adam Galan ,  Naing Aay ,  Art Hanel ,  Amanda Harrison ,  Jeff Zhang ,  Kwang-Ai Won ,  Danny Tam ,  Fawn Qian ,  Tao Wang ,  Patricia Finn ,  Kathleen Ogilvie ,  Jon Rosen ,  Raju Mohan ,  Christopher Larson ,  Peter Lamb ,  John Nuss ,  Patrick Kearney
Affiliations
  • 1. Exelixis, 210 E. Grand Avenue, South San Francisco, CA 94005, USA.
PMID: 21974949 DOI: 10.1016/j.bmcl.2011.09.037
Abstract

A novel series of potent inhibitors of glucosylceramide synthase are described. The optimization of biochemical and cellular potency as well as ADME properties led to compound 23c. Broad tissue distribution was obtained following oral administration to mice. Thus 23c could be another useful tool compound for studying the effects of GCS inhibition in vitro and in vivo.