Design, synthesis and biological evaluation of substituted dioxodibenzothiazepines and dibenzocycloheptanes as farnesyltransferase inhibitors

Pauline Gilleron; Nicolas Wlodarczyk; Raymond Houssin; Amaury Farce; Guillaume Laconde; Jean-François Goossens; Amélie Lemoine; Nicole Pommery; Jean-Pierre Hénichart; Régis Millet

doi:10.1016/j.bmcl.2007.07.002

Design, synthesis and biological evaluation of substituted dioxodibenzothiazepines and dibenzocycloheptanes as farnesyltransferase inhibitors

Bioorg Med Chem Lett. 2007 Oct 1;17(19):5465-71. doi: 10.1016/j.bmcl.2007.07.002. Epub 2007 Jul 7.

Authors

Pauline Gilleron¹, Nicolas Wlodarczyk, Raymond Houssin, Amaury Farce, Guillaume Laconde, Jean-François Goossens, Amélie Lemoine, Nicole Pommery, Jean-Pierre Hénichart, Régis Millet

Affiliation

¹ Institut de Chimie Pharmaceutique Albert Lespagnol, EA 2692, IFR 114, Université de Lille 2, 3 rue du Professeur Laguesse, BP 83, 59006 Lille, France.

PMID: 17827015
DOI: 10.1016/j.bmcl.2007.07.002

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation / drug effects
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Farnesyltranstransferase / antagonists & inhibitors*
Humans
Leukemia L1210
Models, Molecular
Molecular Conformation
Structure-Activity Relationship
Tetrazolium Salts
Thiazoles

Substances

Enzyme Inhibitors
Tetrazolium Salts
Thiazoles
Farnesyltranstransferase
thiazolyl blue