Synthesis routes towards the farnesyl protein transferase inhibitor ZARNESTRA™

The discovery that post-translational farnesylation of Ras oncoprotein was an essential step in exercising its biological effect led to the design of farnesyl protein transferase inhibitors (FTIs) in order to control growth of tumors bearing Ras mutations. Pre-clinical studies on murine models have confirmed their inhibitory effect on tumor growth and enabled clinical development. R115777 (ZARNESTRA(TM)) is currently undergoing clinical evaluation and recent studies have confirmed its antitumor potential and low toxicity. We wish to describe here the chemical synthesis routes that our group have developed to access ZARNESTRA(TM). ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).