Inhibitor of farnesyl-protein transferase

Details Inhibitor of farnesyl-protein transferase Inhibitor of farnesyl-protein transferase

1996-10-10

1997-12-30

Higel, Floyd D.

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

514397, A61K 31415, C07D40302

Patent

active

057032416

ABSTRACT:
The present invention comprises an analog of the CA.sub.1 A.sub.2 X motif of the protein Ras that is modified by farnesylation in vivo. This CA.sub.1 A.sub.2 X analog inhibits the farnesyl-protein transferase and the farnesylation of certain proteins. Furthermore, this CA.sub.1 A.sub.2 X analog differs from most compounds previously described as inhibitors of farnesyl-protein transferase in that it does 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 compound of the instant invention also incorporates a cyclic amine moiety in the A.sup.1 position of the motif. Further contained in this invention are chemotherapeutic compositions containing this farnesyl transferase inhibitor and methods for its production.

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