| 主权项 |
1. A method for treating a metabolic disorder in a subject in need thereof, the method comprising: administering to the subject an effective amount of a composition comprising a mixture of a niacin-EPA conjugate and a niacin-DHA conjugate wherein either DHA or EPA is linked to a moiety of formula I: wherein, each a, b, c, and d is independently —H, -D, —CH3, —OCH3, —OCH2CH3, —C(O)OR, 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; m is 0, 1, 2, or 3; each n, o, p, and q is independently 0 or 1; R1, R2, and R3 are each H; 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; each R6 is independently H or C1-C6 alkyl, or both R6 groups, when taken together with the nitrogen to which they are attached, 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 a naturally occurring amino acid; each R is independently —H, —C(O)—C1-C3 alkyl, or straight or branched C1-C4 alkyl optionally substituted with halogen; R4 and R5 are each independently —H, -D, —C1-C4 alkyl, -halogen, —OH, —C(O)C1-C4 alkyl, —O-aryl, —O-benzyl, —OC(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 wherein the metabolic disorder is selected from the group consisting of atherosclerosis, dyslipidemia, hypertriglyceridemia, hypertension, heart failure, cardiac arrhythmias, coronary heart disease, acute myocardial infarction, secondary prevention of myocardial infarction, type 2 diabetes, insulin resistance, impaired glucose tolerance, hypercholesterolemia, stroke, hyperlipidemia, hyperlipoproteinemia, chronic kidney disease, intermittent claudication, hyperphosphatemia, carotid atherosclerosis, peripheral arterial disease, diabetic nephropathy, hypercholesterolemia in HIV infection, acute coronary syndrome (ACS), non-alcoholic fatty liver disease, cerebral arteriosclerosis, myocardial ischemia, and diabetic autonomic neuropathy. |
