Imidazole-containing diarylether and diarylsulfone inhibitors of farnesyl-protein transferase

C J Dinsmore; T M Williams; T J O'Neill; D Liu; E Rands; J C Culberson; R B Lobell; K S Koblan; N E Kohl; J B Gibbs; A I Oliff; S L Graham; G D Hartman

doi:10.1016/s0960-894x(99)00605-8

Imidazole-containing diarylether and diarylsulfone inhibitors of farnesyl-protein transferase

Bioorg Med Chem Lett. 1999 Dec 6;9(23):3301-6. doi: 10.1016/s0960-894x(99)00605-8.

Authors

C J Dinsmore¹, T M Williams, T J O'Neill, D Liu, E Rands, J C Culberson, R B Lobell, K S Koblan, N E Kohl, J B Gibbs, A I Oliff, S L Graham, G D Hartman

Affiliation

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

PMID: 10612589
DOI: 10.1016/s0960-894x(99)00605-8

Abstract

The design and syntheses of non-thiol inhibitors of farnesyl-protein transferase are described. Optimization of cysteine-substituted diarylethers led to highly potent imidazole-containing diarylethers and diarylsulfones. Polar diaryl linkers dramatically improved potency and gave highly cell active compounds.

MeSH terms

Alkyl and Aryl Transferases / antagonists & inhibitors*
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Ethers / chemistry
Humans
Imidazoles / chemistry*
Imidazoles / pharmacology
Magnetic Resonance Spectroscopy
Molecular Structure
Sulfones / chemistry

Substances

Enzyme Inhibitors
Ethers
Imidazoles
Sulfones
Alkyl and Aryl Transferases
p21(ras) farnesyl-protein transferase