Potent and Selective Non-Cysteine-Containing Inhibitors of Protein Farnesyltransferase
Journal of Medicinal Chemistry1998Vol. 41(22), pp. 4288–4300
Citations Over TimeTop 12% of 1998 papers
David J. Augeri, Stephen J. O’Connor, Dave Janowick, Bruce G. Szczepankiewicz, Gerry Sullivan, John J. Larsen, Douglas Kalvin, Jerry D. Cohen, Edward M. Devine, Haichao Zhang, Sajeev Cherian, Badr Saeed, Shi‐Chung Ng, Saul H. Rosenberg
Abstract
Potent and selective non-thiol-containing inhibitors of protein farnesyltransferase are described. FTI-276 (1) was transformed into pyridyl ether analogue 19. The potency of pyridyl ether 19 was improved by modification of the biphenyl core to that of an o-tolyl substituted biphenyl core to give 29. In addition to 0.4 nM in vitro potency, 29 displayed 350 nM potency in whole cells as the parent carboxylic acid. The o-tolyl biphenyl core dramatically and unexpectedly enhanced the potency of other compounds as exemplified by 46, 47, 48, and 49.
Related Papers
- → Roles of Farnesyl-Diphosphate Farnesyltransferase 1 in Tumour and Tumour Microenvironments(2020)63 cited
- → Probing the hydrophobic pocket of farnesyltransferase: aromatic substitution of CAAX peptidomimetics leads to highly potent inhibitors(1999)29 cited
- → J-104,871, a Novel Farnesyltransferase Inhibitor, Blocks Ras Farnesylation In Vivo in a Farnesyl Pyrophosphate-Competitive Manner(1998)37 cited
- → Non-thiol farnesyltransferase inhibitors: structure–activity relationships of benzophenone-based bisubstrate analogue farnesyltransferase inhibitors(2002)17 cited
- → Synthesis and biological activity of semipeptoid farnesyltransferase inhibitors(1997)14 cited