(imidazol-5-yl)methyl-2-quinolinone derivatives as...

A - Human Necessities – 61 – K

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A61K 31/4709 (2006.01) A61P 9/10 (2006.01)

Patent

CA 2290992

The invention comprises the use of compounds of formula (I) wherein the dotted line represents an optional bond; X is oxygen or sulfur; R1 is hydrogen, C1-12alkyl, Ar1, Ar2C1-6alkyl, quinolinylC1-6alkyl, pyridylC1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, aminoC1-6alkyl, or a radical of formula -Alk1-C(=O)-R9, -Alk1-S(O)-R9 or -Alk1-S(O)2-R9; R2, R3 and R16 each independently are hydrogen, hydroxy, halo, cyano, C1-6alkyl, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkyloxyC1-6alkyloxy, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)aminoC1-6alkyloxy, Ar1, Ar2C1-6alkyl, Ar2oxy, Ar2C1-6alkyloxy, hydroxycarbonyl, C1-6alkyloxycarbonyl, trihalomethyl, trihalomethoxy, C2-6alkenyl; R4 and R5 each independently are hydrogen, halo, Ar1, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkyoloxy, C1-6alkylthio, amino, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylS(O)C1-4alkyl or C1-6alkylS(O)2C1-6alkyl; R6 and R7 each independently are hydrogen, halo, cyano, C1-6alkyl, 4,4-dimethyl-oxazolyl, C1-6alkyloxy or Ar2oxy; R8 is hydrogen, C1- 6alkyl, cyano, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonylC1-6alkyl, cyanoC1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, carboxyC1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, mono-- or di(C1-6alkyl)aminoC1-6alkyl, imidazolyl, haloC1-6alkyl, C1- 6alkyloxyC1-6alkyl, aminocarbonylC1-6alkyl, or a radical of formula -O-R10, -S-R10, -N-R11O12; R17 is hydrogen, halo, cyano, C1-6alkyl, C1- 6alkyloxycarbonyl, Ar1; R18 is hydrogen, C1-6alkyl, C1-6alkyloxy or halo; R19 is hydrogen or C1-6alkyl; for the manufacture of a medicament to inhibit smooth muscle cell proliferation.

L'invention concerne des composés selon la formule (I) dans laquelle la ligne en pointillés représente une liaison éventuelle. X est de l'oxygène ou du soufre. R<1> est de l'hydrogène, alkyle C1-12, Ar<1>, Ar<2> C1-6alkyle, quinolinylC1-6alkyle, pyridylC1-6alkyle, hydroxyC1-6alkyle, C1-6alkyloxyC1-6alkyl, mono- ou di(C1-6alkyl)aminoC1-6alkyle, aminoC1-6alkyle, ou un radical de la formule -Alk<1>-C(=O)-R<9>, -Alk<1>-S(O)-R<9> ou -Alk<1>-S(O)2-R<9>; R<2>, R<3> et R<16> sont chacun, indépendamment, hydrogène, hydroxy, halo, cyano, C1-6alkyle, C1-6alkyloxy, hydroxy C1-6alkyloxy, C1-6alkyloxy C1-6alkyloxy, amino C1-6alkyloxy, mono- ou di(C1-6alkyl)amino C1-6alkyloxy, Ar<1>, Ar<2>C1-6alkyle, Ar<2>oxy, Ar<2>C1-6alkyloxy, hydroxycarbonyl, C1-6alkyloxycarbonyl, trihalométhyle, trihalométhoxy, C2-6alkényl, R<4> et R<5> sont chacun, indépendamment, hydrogène, halo Ar<1>, C1-6alkyle, hydroxy C1-6alkyle, C1-6alkyloxy C1-6alkyle, C1-6alkyloxy, C1-6alkylthio, amino, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylS(O) C1-6alkyle ou C1-6alkylS(O)2 C1-6alkyle; R<6> et R<7> sont chacun, indépendamment, hydrogène, halo, cyano, C1-6alkyle, 4,4-diméthyl-oxazolyl, C1-6alkyloxy ou Ar<2>oxy; R<8> est hydrogène, C1-6alkyle, cyano, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonylC1-6alkyle, cyanoC1-6alkyle, C1-6alkyloxycarbonylC1-6alkyle, carboxyC1-6alkyle, hydroxyC1-6alkyle, aminoC1-6alkyle, mono- ou di(C1-6alkyl)aminoC1-6alkyle, imidazolyl, haloC1-6alkyle, C1-6alkyloxyC1-6alkyle, aminocarbonylC1-6alkyle, ou un radical de la formule -O-R<10>, -S-R<10>, -N-R<11>R<12>; R<17> est hydrogène, halo, cyano, C1-6alkyle, C1-6alkyloxycarbonyl, Ar<1>; R<18> est hydrogène, C1-6alkyle, C1-6alkyloxy ou halo; R<19> est hydrogène ou C1-6alkyle. Ces composés sont utiles dans la fabrication d'un médicament permettant d'inhiber la prolifération des cellules des muscles lisses.

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