| 摘要 |
The present invention comprises analogs of the CA1A2X motif of the protein Ras that is modified by farnesylation in vivo. These CA1A2X analogs inhibit the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, these CA1A2X analogs differ from those previously described as inhibitors of farnesyl-protein transferase in that they do 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 compounds of the instant invention also incorporate a cyclic amine moiety in the A2 position of the motif. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production. |
