Impact on farnesyltransferase inhibition of 4-chlorophenyl moiety replacement in the Zarnestra® series

Based on the structure of R115777 (tipifarnib, Zarnestra®), a series of farnesyltransferase inhibitors have been synthesized by modification of the 2-quinolinone motif and transposition of the 4-chlorophenyl ring to the imidazole or its replacement by 5-membered rings. This has yielded a novel series of potent farnesyltransferase inhibitors.

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