Synthesis and biological evaluation of 4-[(3-methyl-3H-imidazol-4-yl)-(2-phenylethynyl-benzyloxy)-methyl]-benzonitrile as novel farnesyltransferase inhibitor.
Farnesyltransferase inhibitors (FTIs) have emerged as a novel class of anticancer agents. Analogues of the potent FTI, 4-[3-biphenyl-1-hydroxy-1-(3-methyl-3H-imidazol-4-yl)-prop-2-ynyl]-1-yl-benzonitrile, were synthesized and tested in vitro for their inhibitory activities. The most promising compound identified from this series is analogue 11 that possesses potent enzymatic and cellular activities.
Lin
Nan-Horng
NH
Cancer Research, R-47B, Global Pharmaceutical Products Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-3500, USA. nanhorng.lin@abbott.com
Wang
Le
L
Cohen
Jerry
J
Gu
Wen-Zhen
WZ
Frost
David
D
Zhang
Haiying
H
Rosenberg
Saul
S
Sham
Hing
H
D016475:3T3 Cells; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D051379:Mice; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D005723:gamma-Glutamyltransferase / Q000037:antagonists & inhibitors
C486842:4-((3-methyl-3H-imidazol-4-yl)-(2-phenylethynyl-benzyloxy)-methyl)-benzonitrile; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007202:Indicators and Reagents; D009570:Nitriles; D005723:gamma-Glutamyltransferase; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase