Oxo-piperazine derivatives of N-arylpiperazinones as inhibitors of farnesyltransferase

C J Dinsmore; J M Bergman; D D Wei; C B Zartman; J P Davide; I B Greenberg; D Liu; T J O'Neill; J B Gibbs; K S Koblan; N E Kohl; R B Lobell; I W Chen; D A McLoughlin; T V Olah; S L Graham; G D Hartman; T M Williams

doi:10.1016/s0960-894x(00)00710-1

Oxo-piperazine derivatives of N-arylpiperazinones as inhibitors of farnesyltransferase

Bioorg Med Chem Lett. 2001 Feb 26;11(4):537-40. doi: 10.1016/s0960-894x(00)00710-1.

Authors

C J Dinsmore¹, J M Bergman, D D Wei, C B Zartman, J P Davide, I B Greenberg, D Liu, T J O'Neill, J B Gibbs, K S Koblan, N E Kohl, R B Lobell, I W Chen, D A McLoughlin, T V Olah, S L Graham, G D Hartman, T M Williams

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. christopher_dinsmore@merck.com

PMID: 11229765
DOI: 10.1016/s0960-894x(00)00710-1

Abstract

The evaluation of SAR associated with the insertion of carbonyl groups at various positions of N-arylpiperazinone farnesyltransferase inhibitors is described herein. 1-Aryl-2,3-diketopiperazine derivatives exhibited the best balance of potency and pharmacokinetic profile relative to the parent 1-aryl-2-piperazinones.

MeSH terms

Alkyl and Aryl Transferases / antagonists & inhibitors*
Animals
Dogs
Enzyme Inhibitors / pharmacokinetics
Enzyme Inhibitors / pharmacology*
Farnesyltranstransferase
Piperazines / pharmacology*
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Piperazines
Alkyl and Aryl Transferases
Farnesyltranstransferase