Non-thiol farnesyltransferase inhibitors: the concept of benzophenone-based bisubstrate analogue farnesyltransferase inhibitors.

摘要: Replacement of the thiol in a benzophenone-based CAAX-peptidomimetic farnesyltransferase inhibitor by carboxylic acid moiety resulted marked drop inhibitory potency. Transformation these derivatives into bisubstrate analogues addition lipophilic alkyl chain, which should be able to occupy considerable portions farnesyl binding region farnesyltransferase's active site, regain activity. These represent new lead structures for non-thiol inhibitors.