Aryloxy substituted N-arylpiperazinones as dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I

J M Bergman; M T Abrams; J P Davide; I B Greenberg; R G Robinson; C A Buser; H E Huber; K S Koblan; N E Kohl; R B Lobell; S L Graham; G D Hartman; T M Williams; C J Dinsmore

doi:10.1016/s0960-894x(01)00240-2

Aryloxy substituted N-arylpiperazinones as dual inhibitors of farnesyltransferase and geranylgeranyltransferase-I

Bioorg Med Chem Lett. 2001 Jun 4;11(11):1411-5. doi: 10.1016/s0960-894x(01)00240-2.

Authors

J M Bergman¹, M T Abrams, J P Davide, I B Greenberg, R G Robinson, C A Buser, H E Huber, K S Koblan, N E Kohl, R B Lobell, S L Graham, G D Hartman, T M Williams, C J Dinsmore

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.

PMID: 11378366
DOI: 10.1016/s0960-894x(01)00240-2

Abstract

A series of aryloxy substituted piperazinones with dual farnesyltransferase/geranylgeranyltransferase-I inhibitory activity was prepared. These compounds were found to have potent inhibitory activity in vitro and are promising agents for the inhibition of Ki-Ras signaling.

MeSH terms

Alkyl and Aryl Transferases / antagonists & inhibitors*
Drug Design
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Farnesyltranstransferase
Genes, ras / drug effects
Piperazines / chemistry
Piperazines / pharmacology*
Polymers / chemistry
Signal Transduction / drug effects
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Piperazines
Polymers
arylox
Alkyl and Aryl Transferases
geranylgeranyltransferase type-I
Farnesyltranstransferase