Discovery of BI 99179, a potent and selective inhibitor of type I fatty acid synthase with central exposure

  • Bioorg Med Chem Lett. 2011 Oct 1;21(19):5924-7. doi: 10.1016/j.bmcl.2011.07.083.
Jörg T Kley  1 ,  Jürgen Mack ,  Bradford Hamilton ,  Stefan Scheuerer ,  Norbert Redemann
Affiliations
  • 1. Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, D-88397 Biberach, Germany. [email protected],
PMID: 21873051 DOI: 10.1016/j.bmcl.2011.07.083
Abstract

Based on a high-throughput screen, cyclopentanecarboxanilides were identified as a new chemotype of non-covalent inhibitors of type I fatty acid synthase (FAS). Starting from initial hits we aimed at generating a tool compound suitable for the in vivo validation of FAS as a therapeutic target. Optimisation yielded BI 99179 which is characterised by high potency, remarkably high selectivity and significant exposure (both peripheral and central) upon oral administration in rats.

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