Diaryl ether inhibitors of farnesyl-protein transferase

S C Mactough; S J Desolms; A W Shaw; M T Abrams; T M Ciccarone; J P Davide; K A Hamilton; J H Hutchinson; K S Koblan; N E Kohl; R B Lobell; R G Robinson; S L Graham

doi:10.1016/s0960-894x(01)00162-7

Diaryl ether inhibitors of farnesyl-protein transferase

Bioorg Med Chem Lett. 2001 May 21;11(10):1257-60. doi: 10.1016/s0960-894x(01)00162-7.

Authors

S C Mactough¹, S J Desolms, A W Shaw, M T Abrams, T M Ciccarone, J P Davide, K A Hamilton, J H Hutchinson, K S Koblan, N E Kohl, R B Lobell, R G Robinson, S L Graham

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486. USA. [email protected]

PMID: 11392531
DOI: 10.1016/s0960-894x(01)00162-7

Abstract

Imidazolemethyl diaryl ethers are potent inhibitors of farnesyl-protein transferase. The SNAr displacement reaction used to prepare these diaryl ethers was amenable to rapid parallel synthesis of FPTase inhibitors. The use of a broad range of commercially available phenols quickly identified compounds which proved active in cells.

MeSH terms

Alkyl and Aryl Transferases / antagonists & inhibitors*
Alkyl and Aryl Transferases / metabolism
Animals
Binding, Competitive
Cell Line
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Imidazoles / chemistry
Inhibitory Concentration 50
Peptide Library
Phenyl Ethers / chemical synthesis
Phenyl Ethers / pharmacology*
Rats
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Imidazoles
Peptide Library
Phenyl Ethers
Alkyl and Aryl Transferases
geranylgeranyltransferase type-I
p21(ras) farnesyl-protein transferase