Fatty acid niacin conjugates and their uses

A method for treating a metabolic disease selected from dyslipidemia, hypertriglyceridemia, hypercholesterolemia, fatty liver disease, atherosclerosis, Type 2 diabetes, diabetic nephropathy, metabolic syndrome, and cardiovascular disease associated with dyslipidemia, hypertriglyceridemia, hypercholesterolemia, or Type 2 diabetes, the method comprising administering to a patient in need thereof an effective amount of a compound of Formula I:

• or a pharmaceutically acceptable salt, enantiomer, or stereoisomer thereof;
• wherein
• R1, R2, and R3 are each independently selected from the group consisting of —H, -D, —Cl, —F, —CN, —NH2, —NH(C1-C3 alkyl), —N(C1-C3 alkyl)2, —NH(C(O)C1-C3 alkyl), —N(C(O)C1-C3 alkyl)2, —C(O)H, —C(O)C1-C3 alkyl, —C(O)OC1-C3 alkyl, —C(O)NH2, —C(O)NH(C1-C3 alkyl), —C(O)N(C1-C3 alkyl)2, —C1-C3 alkyl, —O—C1-C3 alkyl, —S(O)C1-C3 alkyl, and —S(O)2C1-C3 alkyl;
• W1 and W2 are each independently null, O, S, NH, NR, or W1 and W2 can be taken together can to form an imidazolidine or piperazine group, with the proviso that W1 and W2 can not be O simultaneously;
• each a, b, c, and d is independently —H, -D, —CH3, —OCH3, —OCH2CH3, or —C(O)OR, —O—Z, or benzyl, or two of a, b, c, and d can be taken together along with the single carbon to which they are bound to form a cycloalkyl or heterocycle;
• each n, o, p, and q is independently 0 or 1;
• each L is independently-O—, —S—, —S(O)—, —S(O)2—, —S—S—,
• each g is independently 2, 3 or 4;
• each h is independently 1, 2, 3 or 4;
• m is 0, 1, 2, or 3;
• each R6 is independently H or C1-C6 alkyl, or both R6 groups, when taken together with the nitrogen to which they are attached, can form a heterocycle;
• each R7 is independently e, H or straight or branched C1-C10 alkyl which can be optionally substituted with OH, NH2, CO2R, CONH2, phenyl, C6H4OH, imidazole or arginine;
• each e is independently H or any one of the side chains of the naturally occurring amino acids;
• each Z is independently —H, or
• with the proviso that there is at least one
• in the compound;
• each r is independently 2, 3, or 7;
• each s is independently 3, 5, or 6;
• each t is independently 0 or 1;
• each v is independently 1, 2, or 6;
• R4 and R5 are each independently hydrogen, deuterium, —C1-C4 alkyl, -halogen, —OH, —C(O)C1-C4 alkyl, —O-aryl, —O-benzyl, —OC(O)C1-C4 alkyl, —C1-C3 alkene, —C1-C3 alkyne —C2-C3 alkene, —C2-C3 alkyne, —C(O)C1-C4 alkyl, —NH2, —NH(C1-C3 alkyl), —N(C1-C3 alkyl)2, —NH(C(O)C1-C3 alkyl), —N(C(O)C1-C3 alkyl)2, —SH, —S(C1-C3 alkyl), —S(O)C1-C3 alkyl, —S(O)2C1-C3 alkyl;
• and
• each R is independently —H or —C1-C3 alkyl;
• provided that
• when m, n, o, p, and q are each 0, W1 and W2 are each null, and Z is
• then t must be 0;
• and
• when each of m, n, o, p, and q is 0, and W1 and W2 are each null, then Z must not be
• .