Design, Synthesis, and Biological Activity of 4-[(4-Cyano-2-arylbenzyloxy)-(3-methyl-3 H-imidazol-4-yl) methyl] benzonitriles as Potent and Selective …

…, Y Tong, G Sullivan, D Park, NM Leonard…

Index: Wang, Le; Wang, Gary T.; Wang, Xilu; Tong, Yunsong; Sullivan, Gerry; Park, David; Leonard, Nicholas M.; Li, Qun; Cohen, Jerry; Gu, Wen-Zhen; Zhang, Haiying; Bauch, Joy L.; Jakob, Clarissa G.; Hutchins, Charles W.; Stoll, Vincent S.; Marsh, Kennan; Rosenberg, Saul H.; Sham, Hing L.; Lin, Nan-Horng Journal of Medicinal Chemistry, 2004 , vol. 47, # 3 p. 612 - 626

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Citation Number: 40

Abstract

A novel series of 4-[(4-cyano-2-arylbenzyloxy)-(3-methyl-3 H-imidazol-4-yl) methyl] benzonitriles have been synthesized as selective farnesyltransferase inhibitors using structure-based design. X-ray cocrystal structures of compound 20-FTase-HFP and A313326-FTase-HFP confirmed our initial design. The decreased interaction between the aryl groups and Ser 48 in GGTase-I binding site could be one possible reason to explain ...