Method of use of (imidazol-5-yl)methyl-2-quinolinone derivatives to inhibit smooth muscle cell proliferation

An apparatus for reducing smooth muscle cell proliferation in a lumen of a warm-blooded animal comprising a transluminal device and a therapeutically effective amount of a composition of formula (I)

• a stereoisomeric form thereof, a pharmaceutically acceptable acid or base addition salt thereof, 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, wherein Alk1 is C1-6alkanediyl, and R9 is hydroxy, C1-6alkyl, C1-6alkyloxy, amino, C1-8alkylamino or C1-8alkylamino substituted with C1-6alkyloxycarbonyl;
• 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, or 4,4-dimethyloxazolyl, or when on adjacent positions R2 and R3 taken together may form a bivalent radical of formula
• —O—CH2—O— (a-1),
• —O—CH2—CH2—O— (a-2),
• —O—CH═CH— (a-3),
• —O—CH2—CH2— (a-4),
• —O—CH2—CH2—CH2— (a-5), or
• —CH═CH—CH═CH— (a-6);
• R4 and R5 each independently are hydrogen, halo, Ar1, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, hydroxycarbonyl, C1-6alkyloxycarbonyl, C1-6alkylS(O)C1-6alkyl, or C1-6alkylS(O)2C1-6alkyl;
• R6 and R7 each independently are hydrogen, halo, cyano, C1-6alkyl, C1-6alkyloxy, Ar2oxy, trihalomethyl, C1-6alkylthio, di(C1-6alkyl)amino, or when on adjacent positions R6 and R7 taken together may form a bivalent radical of formula
• —O—CH2—O— (c-1), or
• —CH═CH—CH═CH— (c-2);
• 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 (b-1),
• —S—R10 (b-2),
• —N—R11R12 (b-3), wherein
• R10 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, Ar1, Ar2C1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, a radical or formula -Alk2-OR13, or —Alk2—NR14R15;
• R11 is hydrogen, C1-12alkyl, Ar1, or Ar2C1-6alkyl;
• R12 is hydrogen, C1-6alkyl, C1-16alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylaminocarbonyl, Ar1, Ar2C1-6alkyl, C1-6alkylcarbonylC1-6alkyl, a natural amino acid, Ar1carbonyl, Ar2C1-6alkylcarbonyl, aminocarbonylcarbonyl, C1-6alkyloxyC1-6alkylcarbonyl, hydroxy, C1-6alkyloxy, aminocarbonyl, di(C1-6alkyl)aminoC1-6alkylcarbonyl, amino, C1-6alkylamino, C1-6alkylcarbonylamino, or a radical of formula —Alk2—OR13 or -Alk2-NR14R15;
• wherein Alk2 is C1-6alkanediyl;
• R13 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, hydroxyC1-6alkyl, Ar1 or Ar2C1-6alkyl;
• R14 is hydrogen, C1-6alkyl, Ar1 or Ar2C1-6alkyl;
• and R15 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, Ar1 or Ar2C1-6alkyl;
• R17 is hydrogen, halo, cyano, C1-6alkyl, C1-6alkyloxycarbonyl, or Ar1;
• R18 is hydrogen, C1-6alkyl, C1-6alkyloxy or halo;
• R19 is hydrogen or C1-6alkyl;
• Ar1 is phenyl or phenyl substituted with C1-6alkyl, hydroxy, amino, C1-6alkyloxy or halo;
• and
• Ar2 is phenyl or phenyl substituted with C1-6alkyl, hydroxy, amino, C1-6alkyloxy or halo.