3-cyanoindole-based inhibitors of inosine monophosphate dehydrogenase: synthesis and initial structure-activity relationships

  • Bioorg Med Chem Lett. 2003 Oct 20;13(20):3557-60. doi: 10.1016/s0960-894x(03)00757-1.
T G Murali Dhar  1 ,  Zhongqi Shen ,  Henry H Gu ,  Ping Chen ,  Derek Norris ,  Scott H Watterson ,  Shelley K Ballentine ,  Catherine A Fleener ,  Katherine A Rouleau ,  Joel C Barrish ,  Robert Townsend ,  Diane L Hollenbaugh ,  Edwin J Iwanowicz
Affiliations
  • 1. Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. [email protected]
PMID: 14505670 DOI: 10.1016/s0960-894x(03)00757-1
Abstract

A series of novel small molecule inhibitors of Inosine monophosphate dehydrogenase (IMPDH), based upon a 3-cyanoindole core, were explored. IMPDH catalyzes the rate determining step in Guanine Nucleotide biosynthesis and is a target for Anticancer, immunosuppressive and Antiviral therapy. The synthesis and the structure-activity relationships (SAR), derived from in vitro studies, for this new series of inhibitors is given.