Patent ID: 6365600
Filing Date: 2002-04-02
Classification: A61K,A61P

Abstract:
A method for treating a condition associated with smooth muscle cell proliferation in a warm-blooded animal which comprises administering to said warm-blooded animal a prophylactically or therapeutically effective amount of a compound of formula (I), a stereoisomeric form thereof, a pharmaceutically acceptable acid or base addition salt thereof, whereinthe 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 â€”Alk1â€”C(&boxH;O)â€”R9, â€”Alk1â€”S(O)â€”R9 or â€”Alk1â€”S(O)2â€”R9, wherein Alk1 is C1-6alkanediyl, 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, 4,4-dimethyloxazolyl; or when on adjacent positions R2 and R3 taken together may form a bivalent radical of formula â€”Oâ€”CH2â€”Oâ€”â€ƒâ€ƒ(a-1), â€”Oâ€”CH2â€”CH2â€”Oâ€”â€ƒâ€ƒ(a-2), â€”Oâ€”CH&boxH;CHâ€”â€ƒâ€ƒ(a-3), â€”Oâ€”CH2â€”CH2â€”â€ƒâ€ƒ(a-4), â€”Oâ€”CH2â€”CH2â€”CH2â€”â€ƒâ€ƒ(a-5), or â€”CH&boxH;CHâ€”CH&boxH;CHâ€”â€ƒâ€ƒ(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 â€”Oâ€”CH2â€”Oâ€”â€ƒâ€ƒ(c-1), or â€”CH&boxH;CHâ€”CH&boxH;CHâ€”â€ƒâ€ƒ(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 â€”Oâ€”R10â€ƒâ€ƒ(b-1), â€”Sâ€”R10â€ƒâ€ƒ(b-2), â€”Nâ€”R11R12â€ƒâ€ƒ(b-3), wherein R10 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, Ar1, Ar2C1-6alkyl, C1-6alkyloxycarbonylC1-6alkyl, a radical or formula â€”Alk2â€”OR13 or â€”Alk2â€”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 â€”Alk2â€”OR13 or â€”Alk2â€”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; R15 is hydrogen, C1-6alkyl, C1-6alkylcarbonyl, Ar1 or Ar2C1-6alkyl; 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; 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.