Design and synthesis of o-trifluoromethylbiphenyl substituted 2-amino-nicotinonitriles as inhibitors of farnesyltransferase

…, CW Hutchins, S O'Conner, R Gentiles, T Sowin…

Index: Wang, Gary T.; Wang, Xilu; Wang, Weibo; Hasvold, Lisa A.; Sullivan, Gerry; Hutchins, Charles W.; O'Conner, Steve; Gentiles, Robert; Sowin, Thomas; Cohen, Jerry; Gu, Wen-Zhen; Zhang, Haiying; Rosenberg, Saul H.; Sham, Hing L. Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 1 p. 153 - 158

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Citation Number: 20

Abstract

A non-methionine FT inhibitor lead structure (1) was designed through computer modeling of the peptidomimetic FT inhibitor ABT839. Optimization of this lead resulted in compounds 2e and 2g, with FT IC50 values of 1.3 and 1.8 nM, GGT IC50 of 1400nM, and EC50 (Ras processing) values of 13 and 11nM, respectively.