Fatty acid niacin conjugates and their uses

A method for treating a metabolic disease selected from the group consisting of dyslipidemia, hypertriglyceridemia, hypercholesterolemia, fatty liver disease, atherosclerosis, Type 2 diabetes, diabetic nephropathy, and 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(C, -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 NR;
• each a, b, c, and d is independently —H, -D, Halogen, —CH3, —OCH3, —OCF3, —OCH2CH3, or —C(O)OR, or benzyl;
• up to two of a, b, c, and d can be —O—Z;, 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— 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;
• each m is independently 0, or 1, 2, or 3;
• if m is more than 1, then L can be the same or different;
• wherein when m is 2 or 3 up to one of the heteroatoms —O—, —S—, —S(O)—, —S(O)2—, —S—S— can be L;
• each m1 is independently 0, 1, 2, or 3;
• k is 0, 1, 2, or 3;
• each R6 is independently H —H or C1-C6 alkyl —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 —H, or straight or branched C1-C10 alkyl —C1-C10 alkyl which can be optionally substituted with OH, NH2, CO2R, CONH2 —OH, —NH2, —CO2R, —C(O)NH2, phenyl, C6H4OH —C6H4OH, imidazole, or arginine;
• each e is independently H —H or any one of the side chains of the a naturally occurring amino acids acid;
• each R9 is independently —H, -D, C1-C4 alkyl, halogen, cyano, oxo, thiooxo, —OH, C(O)C1-C4 alkyl, O-aryl, O-benzyl, OC(O)C1-C4 alkyl, C1-C3alkene, C1-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;
• each Z is independently —H,
• 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, —C(O)C1-C4 alkyl, —C2-C3 alkene, —C2-C3 alkyne, —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, or —S(O)2C1-C3 alkyl;
• and
• each R is independently —H, or straight or branched C1-C4 alkyl optionally substituted with OR, NR2, or halogen.