Potent and Selective Non-Cysteine-Containing Inhibitors of Protein Farnesyltransferase
- 19 September 1998
- journal article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 41 (22) , 4288-4300
- https://doi.org/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.Keywords
This publication has 22 references indexed in Scilit:
- Inhibitors of Farnesyl Protein Transferase. 4-Amido, 4-Carbamoyl, and 4-Carboxamido Derivatives of 1-(8-Chloro-6,11-dihydro-5H-benzo[5,6]- cyclohepta[1,2-b]pyridin-11-yl)piperazine and 1-(3-Bromo-8-chloro-6,11- dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazineJournal of Medicinal Chemistry, 1998
- Glycine receptorsTrends in Pharmacological Sciences, 1997
- Structure−Activity Relationship of 3-Substituted N-(Pyridinylacetyl)-4- (8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)- piperidine Inhibitors of Farnesyl-Protein Transferase: Design and Synthesis of in Vivo Active Antitumor CompoundsJournal of Medicinal Chemistry, 1997
- THE POTENTIAL OF FARNESYLTRANSFERASE INHIBITORS AS CANCER CHEMOTHERAPEUTICSAnnual Review of Pharmacology and Toxicology, 1997
- Section Review Oncologic, Endocrine & Metabolic: Farnesyl-protein transferase inhibitors in early developmentExpert Opinion on Investigational Drugs, 1996
- Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeuticCell, 1994
- PROTEIN PRENYLATION: GENES, ENZYMES, TARGETS, AND FUNCTIONSAnnual Review of Genetics, 1992
- p21ras is modified by a farnesyl isoprenoid.Proceedings of the National Academy of Sciences, 1989
- All ras proteins are polyisoprenylated but only some are palmitoylatedCell, 1989
- ras GENESAnnual Review of Biochemistry, 1987