Modulators of multi-drug resistances

C - Chemistry – Metallurgy – 07 – D

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C07D 233/64 (2006.01) A61K 31/415 (2006.01) C07D 409/04 (2006.01)

Patent

CA 2207753

The present invention relates to imidazole derivatives having formula 1 (see fig. I) wherein: R1 is selected from the group consisting of: mono-,di-,and tri-substituted phenyl or thienyl, the substituents are selected from the group consisting of: (i) substituted C1-6 alkyl, substituted C2-6 alkyloxy, wherein the substituents are selected from the group consisting of hydrogen or C1-6 alkoxy; (ii) C1-11 CO2R5, trans- CH=CHCO2R5, wherein R5 is C1-11 alkyl, or phenyl C1-11 alkyl; R2 and R3 are mono-, di, and tri-substituted phenyl wherein the substituents are independently selected from: (i) halo; (ii) C1-6 alkyl-amino, or di(C1-6 alkyl)amino, and R4 is hydrogen. These compounds are useful for restoring the sensitivity of multidrug resistant cells to cancer chemotherapeutic agents.

La présente invention concerne des dérivés de l'imidazole, de formule 1 (voir fig. 1) dans laquelle : R1 est choisi parmi le groupe constitué : de phényles ou de thiényles mono, di et trisubstitués, les substituants étant choisis parmi le groupe constitué : i) des alkyles substitutés C1 à C6, des alcoxy substitués C2 à C6, dans lesquels les substituants sont un hydrogène ou un alcoxy C1 à C6; ii) CO2R5, trans-CH=CHCO2R5 dans lesquels R5 est un alkyle C1 à C11 ou un phénylalkyle dans lequel l'alkyle est un C1 à C11; R2 et R3 sont des phényles mono, di ou trisubstitués dans lesquels les substituants sont choisis de manière indépendante parmi : i) un halogénure; ii) un alkylamino C1 à C6 ou un dialkylamino, chaque alkyle étant un C1 à C6; et R4 est un hydrogène. Ces composés sont utiles pour restaurer la sensibilité à des agents chimiothérapeutiques anticancéreux de cellules résistant à plusieurs médicaments.

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