Inhibitors of aldose reductase

A compound of Formula (I)

• wherein,
• X1 is N or CR1;
• X2 is N, CR2, or S;
• X3 is N, CR3, or a bond;
• X4 is N or CR4;
• with the proviso that when X2 is S, X1 is CR1, X4 is CR4, and X3 is a single bond;
• or that two or three of X1, X2, X3, or X4 are N;
• Y is a bond, C═O, C═S, C═NH, or C═N(C1-C4)-alkyl;
• Z is
• A1 is NR9, O, S or CH2;
• A2 is N or CH;
• A3 is NR9, O, or S;
• R1 through R8 are independently hydrogen, halogen, cyano, acyl, haloalkyl, haloalkoxy, haloalkylthio, trifluoroacetyl, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, or (C1-C4)-alkylsulfonyl;
• or two of R1 through R4 or two of R5 through R8 taken together are (C1-C4)-alkylenedioxy;
• R9 is hydrogen, C1-C4 alkyl, or C(O)O—(C1-C4)-alkyl;
• X5 is Q-R10;
• Q is O, NH, O—(C1-C6)-alkyl, O—(C1-C6)-hydroxyalkyl, O—(C1-C6)-aminoalkyl, O-aryl, O-heteroaryl, O-biaryl, O-benzyl, NH—(C1-C6)-alkyl, NH—(C1-C6)-hydroxyalkyl, NH—(C1-C6)-aminoalkyl, NH-aryl, NH-heteroaryl, NH-biaryl, NH-benzyl, or a bond;
• R10 is
• aryl, heteroaryl, biaryl, benzyl, heterocycle, C(O)OR11 or OH, with the proviso that when Q is NH, R10 can also be H;
• and
• R11 and R12 are independently H or (C1-C6)-alkyl optionally substituted with one or more substituents selected from the group consisting of OR13, NHR13, SR13, CO2R13, CONHR13, aryl, hydroxyaryl, indolyl, imidazolyl, and NH(CNH)NH2;
• or R11 and R12, taken together with the atoms to which they are attached, form a 3-7 membered heterocyclic ring;
• R13 is H or (C1-C6)-alkyl;
• and
• n is 0, 1, or 2;
• or a pharmaceutically acceptable salt thereof.