Macrocyclic piperazinones as potent dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I

  • Bioorg Med Chem Lett. 2004 Feb 9;14(3):639-43. doi: 10.1016/j.bmcl.2003.11.051.
Christopher J Dinsmore  1 ,  C Blair Zartman ,  Jeffrey M Bergman ,  Marc T Abrams ,  Carolyn A Buser ,  J Christopher Culberson ,  Joseph P Davide ,  Michelle Ellis-Hutchings ,  Christine Fernandes ,  Samuel L Graham ,  George D Hartman ,  Hans E Huber ,  Robert B Lobell ,  Scott D Mosser ,  Ronald G Robinson ,  Theresa M Williams
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. [email protected]
PMID: 14741259 DOI: 10.1016/j.bmcl.2003.11.051
Abstract

A series of macrocyclic piperazinone compounds with dual farnesyltransferase/geranylgeranyltransferase-I inhibitory activity was prepared. These compounds were found to be potent inhibitors of protein prenylation in Cell Culture. A hypothesis for the binding mode of compound 3o in FPTase is proposed.