DERIVES FUSIONNES D'IMIDAZOLE EN TANT QUE MODULATEURS DE LA RESISTANCE A DES MEDICAMENTS MULTIPLES

N° de brevet: WO9734897 (A1)
Date de publication: 1997-09-25
Inventeur(s): JANSSENS FRANS EDUARD [BE];LEENAERTS JOSEPH ELISABETH [BE];SOMMEN FRANCOIS MARIA [BE];SURLERAUX DOMINIQUE LOUIS NEST [BE];
Demandeur(s): JANSSEN PHARMACEUTICA NV [BE];JANSSENS FRANS EDUARD [BE];LEENAERTS JOSEPH ELISABETH [BE];SOMMEN FRANCOIS MARIA [BE];SURLERAUX DOMINIQUE LOUIS NEST [BE];
Classification: A61K31/00;A61K31/47;A61K31/4738;A61K31/4745;A61K31/5365;A61K31/55;A61K31/553;A61K45/00;A61P31/00;A61P31/06;A61P33/00;A61P33/02;A61P33/04;A61P33/06;A61P35/00;A61P35/02;A61P43/00;C07D471/04;C07D487/04;C07D487/14;C07D491/147;C07D495/14;C07D498/04;
N° de demande: WO1997EP01264 19970311 
Numéro(s) de priorité: EP19960200755 19960319 
This invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein the dotted line is an optional bond; n is 1 or 2; R<1> is hydrogen; halo; formyl; C1-4alkyl optionally substituted with hydroxy, C1-4alkyloxy, C1-4alkylcarbonyloxy, imidazolyl, thiazolyl or oxazolyl; or a radical of formula -X-COOR<5>, -X-CONR<6>R<7> or -X-COR<10> wherein -X- is a direct bond, C1-4alkanediyl or C2-6alkenediyl; R<5> is hydrogen, C1-12alkyl, Ar, Het, C1-6alkyl substituted with C1-4alkyloxy, aryl or heteroaryl; R<6> and R<7> each independently are hydrogen or C1-4alkyl; R<2> is hydrogen, halo, C1-4alkyl, hydroxyC1-4alkyl, C1-4alkyloxycarbonyl, carboxyl, formyl or phenyl; R<3> is hydrogen, C1-4alkyl or C1-4alkyloxy; R<4> is hydrogen, halo, C1-4alkyl, C1-4alkyloxy or haloC1-4alkyl; Z is -CH2-, -CH2-CH2-, -CH="CH"-, -CHOH-CH2-, -O-CH2-, -C(="O")-CH2- or -C(="NOH")-CH2-; -A-B- is a bivalent radical; A<1> is a direct bond, optionally substituted C1-6alkanediyl, C1-6alkanediyl-oxy-C1-6alkanediyl, carbonyl, C1-6alkanediylcarbonyl, optionally substituted C1-6alkanediyloxy; A<2> is a direct bond or C1-6alkanediyl; and Q is aryl. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for inhibiting or reversing the effects of multidrug resistance.

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