Heterocycle-containing inhibitors of farnesyl-protein transferas

Details Heterocycle-containing inhibitors of farnesyl-protein transferas Heterocycle-containing inhibitors of farnesyl-protein transferas

1995-09-21

1997-07-29

Higel, Floyd D.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

514397, 5483111, 5483154, 5483241, A61K 31415, C07D23302, C07D23304, C07D23354, C07D23330

Patent

active

056522576

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 the farnesylation of Ras. Furthermore, these CAAX analogues differ from those previously described as inhibitors of Ras farnesyl 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. Further contained in this invention are chemotherapeutic compositions containing these farnesyl transferase inhibitors and methods for their production.

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