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 published the artcile< Design, Synthesis, and Biological Activity of 4-[(4-Cyano-2-arylbenzyloxy)-(3-methyl-3H-imidazol-4-yl)methyl]benzonitriles as Potent and Selective Farnesyltransferase(FTase) Inhibitors>, Recommanded Product: Methyl 5-cyano-2-methylbenzoate, the main research area is farnesylation Ras protein cyano aryl benzyloxy methylimidazolylmethyl benzonitrile preparation; benzamide cyano cyanophenyl methylimidazolylmethoxymethyl preparation farnesyltransferase inhibitor; farnesyltransferase inhibitor cyano aryl benzyloxy methylimidazolylmethyl benzonitrile preparation; pharmacophore farnesyltransferase inhibitor cyano aryl benzyloxy methylimidazolylmethyl benzonitrile preparation; crystal structure cyanophenyl methylimidazolylmethoxymethyl biphenylcarbonitrile farnesyltransferase complex preparation; mol structure cyanophenyl methylimidazolylmethoxymethyl biphenylcarbonitrile farnesyltransferase complex preparation.
A novel series of 4-[(4-cyano-2-arylbenzyloxy)-(3-methyl-3H-imidazol-4-yl)methyl]benzonitriles have been synthesized as selective farnesyltransferase inhibitors using a structure-based design. X-ray cocrystal structures of compound 6-[[(1R)-(4-cyanophenyl)(1-methyl-1H-imidazol-5-yl)methoxy]methyl]-3′-methoxy[1,1′-biphenyl]-3-carbonitrile-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 the improved selectivity for this new series of FTase inhibitors. Medicinal chem. efforts led to the discovery of 3-cyano-6-[[(4-cyanophenyl)(1-methyl-1H-imidazol-5-yl)methoxy]methyl]-N-phenylbenzamide (I) with potent cellular activity (EC50 = 3.5 nM) and outstanding pharmacokinetic profiles in dog (96% bioavailable, 18.4 h oral t1/2, and 0.19 L/(h·kg) plasma clearance).
Journal of Medicinal Chemistry published new progress about Crystal structure. 103261-68-3 belongs to class nitriles-buliding-blocks, and the molecular formula is C10H9NO2, Recommanded Product: Methyl 5-cyano-2-methylbenzoate.
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts