Potent and selective non-cysteine-containing inhibitors of protein farnesyltransferase

J Med Chem. 1998 Oct 22;41(22):4288-300. doi: 10.1021/jm980298s.

D J Augeri ¹, S J O'Connor, D Janowick, B Szczepankiewicz, G Sullivan, J Larsen, D Kalvin, J Cohen, E Devine, H Zhang, S Cherian, B Saeed, S C Ng, S Rosenberg

Affiliations

Affiliation

1 Departments of Cancer Research, D-47B, and Combinatorial Chemistry, D-4CP, Abbott Laboratories, Abbott Park, Illinois 60064-3500, USA.

PMID: 9784104 DOI: 10.1021/jm980298s

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.