Inhibitors of farnesyl-protein transferase

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

1994-09-29

1996-06-04

Killos, Paul J.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acid esters

562427, 548495, C07C31702, C07C31744

Patent

active

055234569

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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