Synthesis and evaluation of a novel series of farnesyl protein transferase inhibitors as non-peptidic CAAX tetrapeptide analogues.
A novel series of compounds, derived from 4-amino-phenyl piperazine, has been designed to selectively inhibit farnesyl protein transferase (FPTase) as CAAX tetrapeptide analogues. Certain of these compounds were shown to possess low nanomolar inhibitory activity both against the isolated enzyme and in cultured cells.
Perez
Michel
M
Department of Medicinal Chemistry 4, Centre de Recherche Pierre Fabre, 17, Avenue Jean Moulin, 81106 Cedex, Castres, France. michel.perez@pierre-fabre.com
Maraval
Catherine
C
Dumond
Stephan
S
Lamothe
Marie
M
Schambel
Philippe
P
Etiévant
Chantal
C
Hill
Bridget
B
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017368:Protein Prenylation / Q000187:drug effects; D013329:Structure-Activity Relationship; D014166:Transferases / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D009842:Oligopeptides; D010879:Piperazines; C109563:RTL8C protein, human; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C064911:p21(ras) farnesyl-protein transferase; D018631:ras Proteins