Non-thiol 3-aminomethylbenzamide inhibitors of farnesyl-protein transferase

T M Ciccarone; S C MacTough; T M Williams; C J Dinsmore; T J O'Neill; D Shah; J C Culberson; K S Koblan; N E Kohl; J B Gibbs; A I Oliff; S L Graham; G D Hartman

doi:10.1016/s0960-894x(99)00323-6

Non-thiol 3-aminomethylbenzamide inhibitors of farnesyl-protein transferase

Bioorg Med Chem Lett. 1999 Jul 19;9(14):1991-6. doi: 10.1016/s0960-894x(99)00323-6.

Authors

T M Ciccarone¹, S C MacTough, T M Williams, C J Dinsmore, T J O'Neill, D Shah, J C Culberson, 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: 10450968
DOI: 10.1016/s0960-894x(99)00323-6

Abstract

The design and syntheses of non-thiol inhibitors of farnesyl-protein transferase are described. Substitutions on an imidazolylmethyl-AMBA-methionine template gave a highly potent and cell-active inhibitor.

MeSH terms

Alkyl and Aryl Transferases / antagonists & inhibitors*
Alkyl and Aryl Transferases / chemistry
Alkyl and Aryl Transferases / metabolism
Animals
Benzamides / chemistry*
Benzamides / metabolism
Benzamides / pharmacology*
Binding Sites
Cell Division / drug effects
Drug Design
Drug Evaluation, Preclinical
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Imidazoles / chemistry
Inhibitory Concentration 50
Models, Molecular
Molecular Structure
Protein Conformation
Rats
Structure-Activity Relationship
Sulfhydryl Compounds / chemistry
Sulfhydryl Compounds / pharmacology

Substances

Benzamides
Enzyme Inhibitors
Imidazoles
Sulfhydryl Compounds
imidazole
Alkyl and Aryl Transferases
p21(ras) farnesyl-protein transferase