POTENT AND SELECTIVE NON-CYSTEINE-CONTAINING INHIBITORS OF PROTEIN FARNESYLTRANSFERASE

Potent and selective non-thiol-containing inhibitors of protein farnes yltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by mod ification of the biphenyl core to that of an o-tolyl substituted biphe nyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displa yed 350 nM potency in whole cells as the parent carboxylic acid. The o -tolyl biphenyl core dramatically and unexpectedly enhanced the potenc y of other compounds as exemplified by 46, 47, 48, and 49.