IMIDAZOLES FOR THE TREATMENT OF ATHEROSCLEROSIS

摘要

This invention relates to imidazoles as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT), processes for their preparation, and their use as antihypercholesterolemic agents or antiatherosclerotic. The compounds for use in the described method are compounds of Formula (I): (I) wherein R1 and R2 are selected independently from H, C1-C8 alkyl, C3-C8 branched alkyl, C3-C7 cycloalkyl, C4-C10 cycloalkylalkyl, C7-C14 araalkyl, phenyl optionally substituted with 1 to 3 groups selected from F, Cl, Br, OH, C1-C4 alkoxy, C1-C4 alkyl, C3-C8 branched alkyl, CH3S(O)r, NO2, CF3, or NR7R8; R3 is H, C1-C6 alkyl, allyl, benzyl, or phenyl optionally substituted with F, Cl, CH3, CH3O, or CF3; R4 is straight chain C1-C8 alkyl optionally substituted with F; C3-C8 branched alkyl, C3-C7 cycloalkyl, C4-C10 cycloalkylalkyl, C7-C14 aralkyl where the aryl group is optionally substituted with 1 to 3 groups selected from C1-C4 alkyl or alkoxy, F, Br, Cl, NH2, OH, CN, CO2H, CF3, NO2, C1-C4 carboalkoxy, NR7R8, or NCOR7; C3-C6 alkenyl or alkynyl, C1-C3 perfluoroalkyl, phenyl optionally substituted with 1 to 3 groups selected from C1-C4 alkyl, C3-C8 branched alkyl, C1-C4, alkoxy, F, Br, Cl, NH2, OH, CN, CO2H, CF3, NO2, C1-C4 carboalkoxy, NR7R8 or NCOR7; pentafluorophenyl, benzyl optionally substituted with 1 to 3 groups selected from C1-C4 alkyl or alkoxy, F, Br, Cl, NH2, OH, CN, CO2H, CF3, NO2, C1-C4 carboalkoxy, NR7R8, or NCOR7; 2-, 3-, or 4- or pyrindinyl, pyrimidinyl, or biphenyl; R5 is H, C1-C6 alkyl, or benzyl; R6 is C1-C8 alkyl, C3-C8 branched alkyl, C3-C7 cycloalkyl, C3-C8 alkenyl of alkynyl, phenyl optionally substituted with 1 to 3 groups selected from C1-C4 alkyl or alkoxy, F, Br, Cl, NH2, OH, CN, CO2H, CF3, NO2, C1-C4 carboalkoxy, NR7R8, or NCOR7; pentafluorophenyl, benzyl optionally substituted with 1 to 3 groups selected from C1-C4 alkyl or alkoxy, F, Br, Cl, NH2, OH, CN, CO2H, CF3, NO2, C1-C4 carboalkoxy, NR7R8, or NCOR7; R7 and R8 are selected independently from H or C1-C4 alkyl; A is C2-C10 alkyl, C3-C10 branched alkyl, C3-C10 alkenyl, or C3-C10 alkynyl; Y is O; Z is NHR4, OR4, or R4; r is 0-2, or a pharmaceutically acceptable salt thereof.