Pyridinone derivatives for treatment of atherosclerosis

A compound of formula (I):

• 304
• in which:
• R1 is an aryl group, optionally substituted by 1, 2, 3 or 4 substituents which may be the same or different selected from C(1-6)alkyl, C(1-6)alkoxy, C(1-6)alkylthio, hydroxy, halogen, CN, mono to perfluoro-C(1-4)alkyl, mono to perfluoro-C(1-4)alkoxyaryl, and arylC(1-4)alkyl;
• R2 is halogen, C(1-3)alkyl, C(1-3)alkoxy, hydroxyC(1-3)alkyl, C(1-3)alkylthio, C(1-3)alkylsulphinyl, aminoC(1-3)alkyl, mono- or di-C(1-3)alkylaminoC(1-3)allyl, C(1-3)alkylcarbonylaminoC(1-3)alkyl, C(1-3)alkoxyC(1-3)alkylcarbonylaminoC(1-3)alkyl, C(1-3)alkylsulphonylaminoC(1-3)alkyl, C(1-3)alkylcarboxy, C(1-3)alkylcarboxyC(1-3)alkyl, and
• R3 is hydrogen, halogen, C(1-3)alkyl, or hydroxyC(1-3)alkyl;
• or
• R2 and R3 together with the pyridone ring carbon atoms to which they are attached form a fused 5-or 6-membered carbocyclic ring;
• or
• R2 and R3 together with the pyridone ring carbon atoms to which they are attached form a fused benzo or heteroaryl ring optionally substituted by 1, 2, 3 or 4 substituents which may be the same or different selected from halogen, C(1-4)alkyl, cyano, C(1-3)alkoxyC(1-3)alkyl, C(1-4)alkoxy or C(1-4)alkylthio, or mono to perfluoro-C(1-4)alkyl;
• R4 is hydrogen, C(1-6)alkyl which may be unsubstituted or substituted by 1, 2 or 3 substituents selected from hydroxy, halogen, OR7, COR7, carboxy, COOR7, CONR9R10, NR9R10, NR7COR8, mono- or di-(hydroxyC(1-6)allyl)amino and N-hydroxyC(1-6)alkyl-N—C(1-6)alkylamino;
• or
• R4 is Het-C(0-4)alkyl in which Het is a 5- to 7-membered heterocyclyl ring comprising N and optionally O or S, and in which N may be substituted by COR7, COOR7, CONR9R10, or C(1-6)alkyl optionally substituted by 1, 2 or 3 substituents selected from hydroxy, halogen, OR7, COR7, carboxy, COOR7, CONR9R10 or NR9R10, for instance, piperidin4-yl, pyrrolidin-3-yl;
• R5 is an aryl or a heteroaryl ring optionally substituted by 1, 2, 3 or 4 substituents which may be the same or different selected from C(1-6)alkyl, C(1-6)alkoxy, C(1-6)alkylthio, arylC(1-6)alkoxy, hydroxy, halogen, CN, COR7, carboxy, COOR7, NR7COR8, CONR9R10, SO2NR9R10, NR7SO2R8, NR9R10, mono to perfluoro-C(1-4)alkyl and mono to perfluoro-C(1-4)alkoxy;
• R6 is an aryl or a heteroaryl ring which is further optionally substituted by 1, 2, 3 or 4 substituents which may be the same or different selected from C(1-6)alkyl, C(1-6)alkoxy, C(1-6)alkylthio, C(1-6)alkylsulfonyl, arylC(1-6)alkoxy, hydroxy, halogen, CN, COR7, carboxy, COOR7, CONR9R10, NR7COR8, SO2NR9R10, NR7SO2R8, NR9R10, mono to perfluoro-C1-4)alkyl and mono to perfluoro-C(1-4)alkoxy, or C(5-10)alkyl;
• R7 and R8 are independently hydrogen or C(1-12)alkyl, for instance C(1-4)alkyl (e.g. methyl or ethyl);
• R9 and R10 which may be the same or different is each selected from hydrogen, or C(1-12)alkyl, or R9 and R10 together with the nitrogen to which they are attached form a 5- to 7 membered ring optionally containing one or more further heteroatoms selected from oxygen, nitrogen and sulphur, and optionally substituted by one or two substituents selected from hydroxy, oxo, C(1-4)alkyl, C(1-4)alkylcarboxy, aryl, e.g. phenyl, or aralkyl, e.g benzyl, for instance morpholine or piperazine;
• and
• X is a C(2-4)alkylene group (optionally substituted by 1, 2 or 3 substituents selected from methyl and ethyl), CH═CH, (CH2)nS or (CH2)nO where n is 1, 2 or 3.