Inhibitors of farnesyl-protein transferase

Details Inhibitors of farnesyl-protein transferase Inhibitors of farnesyl-protein transferase

1996-02-13

1997-05-06

Northington Davis, Zinna

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

5483385, C07D40106, A61K 31415

Patent

active

056272022

ABSTRACT:
The present invention comprises analogs of the CA.sup.1 A.sup.2 X motif of the protein Ras that is modified by farnesylation in vivo. These CA.sup.1 A.sup.2 X analogs inhibit the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, these CA.sup.1 A.sup.2 X 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 A.sup.2 position of the motif. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

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