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

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. (C) 2003 Elsevier Ltd. All rights reserved.