Fatty acid niacin conjugates and their uses
Inventors
MILNE, JILL C. • Jirousek, Michael R. • Bemis, Jean E. • Vu, Chi B.
Assignees
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Publication Number
US-8304552-B2
Publication Date
2012-11-06
Expiration Date
Abstract
The invention relates to fatty acid niacin conjugates; compositions comprising an effective amount of a fatty acid niacin conjugate; and methods for treating or preventing an metabolic disease comprising the administration of an effective amount of a fatty acid niacin conjugate.
Core Innovation
The invention relates to compounds of Formula I, including a pharmaceutically acceptable salt, enantiomer or stereoisomer, under multiple constraints on allowed groups and index variables. The structure is defined by substituents R1, R2, and R3, W1 and W2, ring or heterocycle-forming groups, indexed variables n, o, p, q, r, s, t, and v, and a linker L.
The core structural variability includes allowed selections for W1 and W2 as O, S, NH, or NR, or W1 and W2 taken together to form an imidazolidine or piperazine group, with the proviso that W1 and W2 cannot be O simultaneously. The linker L is selected from O, S, S(O), S(O)2, or S-S-S, and additional substituent rules define R4, R5, R6, and R7 with allowances for deuterium, alkyl, halogen, hydroxyl, aryl, benzyl, alkene/alkyne, and heterocycle-forming group possibilities.
The disclosed subject matter also relates to niacin-fatty acid molecular conjugates in which niacin is linked to a fatty acid selected from specified polyunsaturated fatty acids, and the conjugate comprises at least two amides. Representative embodiments include nicotinamide-linked docosa and eicosa conjugates and related selections of compounds, with drawn chemical structures for target conjugates.
Claims Coverage
Two independent claims are present across the provided items. The claims cover niacin-fatty acid molecular conjugates containing at least two amides, and compounds of Formula I with extensive substituent and linker variability together with explicit structural constraints.
Niacin-fatty acid molecular conjugate with at least two amides
A molecular conjugate comprising niacin and a fatty acid selected from α-linolenic acid, stearidonic acid, eicosatrienoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, tetracosapentaenoic acid, and tetracosahexaenoic acid, wherein the conjugate comprises at least two amides.
Compound of Formula I and pharmaceutically acceptable forms
A compound of Formula I, or a pharmaceutically acceptable salt, enantiomer or stereoisomer thereof, defined by substituent variables R1-R3, W1-W2, n-q, r, s, t, v, L, R4-R7, e, Z, g, h, m, and related provisos and constraints, including limitations on W1 and W2 and conditions tying m, n, o, p, q, W1/W2, and Z.
Overall, the claims cover niacin-polyunsaturated-fatty-acid conjugates containing at least two amide linkages, and a broader family of compounds defined by Formula I with extensive substituent variability and explicit structural constraints.
Stated Advantages
Synergistic effect versus niacin or fatty acids alone.
Documented Applications
Treatment or prevention of metabolic diseases including dyslipidemia, atherosclerosis, coronary heart disease, Type 2 diabetes, metabolic syndrome, and cardiovascular disease.
Therapeutic use for metabolic diseases, including dyslipidemia, atherosclerosis, and Type 2 diabetes, via administration of fatty acid niacin derivatives.
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