Inhibitors of farnesyl-protein transferase

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

1995-09-14

1997-08-26

Raymond, Richard L.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

514307, 514314, 514343, 514397, 514414, 514422, 514423, 514428, 546147, 546167, 546175, 546208, 5462681, 5462764, 5462784, 5462791, 548236, 5483147, 548465, 548517, 548518, 548536, 548537, 548540, 548568, 548572, A61K 3140, A61K 31415, C07D20716, C07D40106

Patent

active

056611617

ABSTRACT:
The present invention comprises analogs of the CAAX motif of the protein Ras that is modified by farnesylation in vivo. These CAAX analogs inhibit farnesyl-protein transferase. Furthermore, these CAAX analogues 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 antoxidation and disulfide formation with endogenous thiols, and reduced systemic toxicity. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

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