Design, synthesis and biological evaluation of substituted dioxodibenzothiazepines and dibenzocycloheptanes as farnesyltransferase inhibitors.
A new series of FTase inhibitors containing a tricyclic moiety--dioxodibenzothiazepine or dibenzocycloheptane--has been designed and synthesized. Among them, dioxodibenzothiazepine 18d displayed significant inhibitory FTase activity (IC(50)=17.3 nM) and antiproliferative properties.
Gilleron
Pauline
P
Institut de Chimie Pharmaceutique Albert Lespagnol, EA 2692, IFR 114, Université de Lille 2, 3 rue du Professeur Laguesse, BP 83, 59006 Lille, France.
Wlodarczyk
Nicolas
N
Houssin
Raymond
R
Farce
Amaury
A
Laconde
Guillaume
G
Goossens
Jean-François
JF
Lemoine
Amélie
A
Pommery
Nicole
N
Hénichart
Jean-Pierre
JP
Millet
Régis
R
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D007939:Leukemia L1210; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles