Inhibitor of farnesyl-protein transferase

摘要

The present invention comprises an analog of the CA1A2X motif of the protein Ras that is modified by farnesylation in vivo. This CA1A2X analog inhibits the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, this CA1A2X analog differs from most compounds previously described as inhibitors of farnesyl-protein transferase in that it does not have a thiol moiety. The lack of the thiol offers unique advantages in terms of improved pharmacokinetic behavior in animals, prevention of thiol-dependent chemical reactions, such as rapid autoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. The compound of the instant invention also incorporates a cyclic amine moiety in the A1 position of the motif. Further contained in this invention are chemotherapeutic compositions containing this farnesyl transferase inhibitor and methods for its production.