5-(arylsulfonyl)-,5-(arylsulfinyl), and 5-(arylsulfanyl)-thiazolidine-2,4-diones useful for inhibition of farnesyl-protein transferase

A process for the preparation 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;
• 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, —NHCO2R10, —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
• then n is other than 2;
• further provided that when n is 1, m is 0 or 2, R6 is H and W is
• then:
• Ar is not phenyl, 2-naphthyl, alkyl substituted phenyl, alkoxy substituted phenyl, halogen substituted phenyl, 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-thienyl, 2-benzo-[b]-thienyl;
• and
• Ar′ is not phenyl, alkyl substituted phenyl, perfluoroalkyl (mono or di)substituted phenyl, halogen substituted phenyl, alkoxy substituted phenyl, perfluoroalkoxy substituted phenyl and alkylthio substituted phenyl;
• or pharmaceutically acceptable salts thereof,
• which comprises:
• reacting a compound of the formula:
• with an alkyne of the formula:
• Ar′W—(CH2)m—LG
• wherein LG is a leaving group,
• in the presence of a base to give a compound of Formula (I) or a pharmaceutically acceptable salt thereof.