Method of using 5-(arysulfonyl)-, 5-(arylsulfanyl)-and 5-(arylsulfanyl)thiazolidine-2,4-diones for inhibition of farnesyl-protein transferase

A method of treating, inhibiting or controlling a ras-associated disease by inhibiting farnesyl-protein transferase(FPTase) enzyme in a mammal in need thereof which comprises administering to said mammal an effective amount of a compound of Formula (I):

• wherein:
• Ar is 1-naphthyl, 2-naphthyl, 8-quinolinyl, 2-thienyl, 5-chloro-2-thienyl, 5-(2-pyridyl)-2-thienyl, 2-pyridinyl, substituted 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-quinolinyl, 2-pyrimidinyl, 2-benzoxazolyl, 2-benzthiazolyl, 2-benzimidazolyl, 2-furanyl, 2-benzo-[b]-furanyl, 2-benzo-[b]-thienyl or a moiety of the formula:
• R1 is hydrogen, fluoro, bromo, chloro, iodo, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, 4-pyridyloxy, azido, nitro, acetamido, trifluoromethoxy, phenoxy, or benzyloxy;
• R2 is hydrogen, fluoro, bromo, chloro, iodo, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, trifluoromethoxy, phenoxy, or benzyloxy;
• m is 0, 1 or 2;
• R6 is hydrogen, alkyl of 1 to 6 carbon atoms, benzyl, substituted benzyl, imidazolylpropyl, or —CO2Y;
• Y is 2-methoxyethyl, alkyl is 1 to 6 carbon atoms, benzyl, or substituted benzyl;
• W is
• E- and Z —CH═CH—, —CONH—, —CONHCH2—, —CONHCH2CH2— or —CH2—CH2—;
• n is an integer of 1 to 9;
• Ar′ is thienyl, pyridinyl or a moiety of the formula
• R3, R4, R5, are independently selected from hydrogen, alkoxy of 1 to 6 carbon atoms, alkyl of 1 to 6 carbon atoms, fluoro, bromo, chloro, iodo, nitro, amino, hydroxy, azido, cyano, phenyl, phenoxy, trifluoromethyl, trifluoromethoxy, methanesulphonyl, 1-pyrrolyl, —CO2R7, —CONHR8, —CH2CONHR9, —NHCO2R1c, —NHCOR11, and —NHCONHR12;
• R7 is selected from H, and alkyl of 1 to 6 carbon atoms,
• R8 is selected from H, and alkyl of 1 to 6 carbon atoms;
• R9 is selected from H, and alkyl of 1 to 6 carbon atoms;
• R10 is selected from alkyl of 1 to 6 carbon atoms, benzyl, nitrobenzyl, and chlorophenyl;
• R11 is selected from alkyl of 1 to 6 carbon atoms, benzyl, phenyl, halophenyl, alkyl(1 to 6 carbon atoms)phenyl, alkoxy(1 to 6 carbon atoms)phenyl, and biphenyl;
• R12 is benzyl, alkyl of 1 to 6 carbon atoms, alkoxy(1 to 6 carbon atoms)phenyl, halophenyl, and alkyl(1 to 6 carbon atoms)phenyl;
• provided that when W is
• n is other than 2
• or pharmaceutically acceptable salts thereof.