Discovery of novel nonpeptide tricyclic inhibitors of Ras farnesyl protein transferase

F G Njoroge; R J Doll; B Vibulbhan; C S Alvarez; W R Bishop; J Petrin; P Kirschmeier; N I Carruthers; J K Wong; M M Albanese; J J Piwinski; J Catino; V Girijavallabhan; A K Ganguly

doi:10.1016/s0968-0896(96)00206-4

Discovery of novel nonpeptide tricyclic inhibitors of Ras farnesyl protein transferase

Bioorg Med Chem. 1997 Jan;5(1):101-13. doi: 10.1016/s0968-0896(96)00206-4.

Authors

F G Njoroge¹, R J Doll, B Vibulbhan, C S Alvarez, W R Bishop, J Petrin, P Kirschmeier, N I Carruthers, J K Wong, M M Albanese, J J Piwinski, J Catino, V Girijavallabhan, A K Ganguly

Affiliation

¹ Schering-Plough Research Institute, Department of Chemistry, Kenilworth, NI 07033, USA.

PMID: 9043662
DOI: 10.1016/s0968-0896(96)00206-4

Abstract

A comprehensive structure-activity relationship (SAR) study of novel tricyclic amides has been undertaken. The discovery of compounds that are potent FPT inhibitors in the nanomolar range has been achieved. These compounds are nonpeptidic and do not contain sulfhydryl groups. They selectively inhibit farnesyl protein transferase (FPT) and not geranylgeranyl protein transferase-1 (GGPT-1). They also inhibit H-Ras processing in Cos monkey kidney cells.

MeSH terms

Alkyl and Aryl Transferases*
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Magnetic Resonance Spectroscopy
Spectrometry, Mass, Fast Atom Bombardment
Structure-Activity Relationship
Transferases / antagonists & inhibitors*

Substances

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