USRE46605EActiveUtility
Fatty acid niacin conjugates and their uses
Assignee: CATABASIS PHARMACEUTICALS INCPriority: Sep 1, 2009Filed: Jun 25, 2015Granted: Nov 14, 2017
Est. expirySep 1, 2029(~3.1 yrs left)· nominal 20-yr term from priority
A61P 43/00A61P 9/00A61P 3/10A61P 9/10A61P 3/06A61P 7/00A61P 3/08A61P 3/04A61P 25/00A61P 3/00A61P 27/02C07D 213/82A61K 31/44C07D 213/80A61K 31/455A61K 47/50A61K 41/0038A61K 47/542A61K 47/55A61K 31/20A61K 31/202A61P 1/16A61P 13/12A61K 31/4406A61K 47/481A61K 47/48038
77
PatentIndex Score
1
Cited by
109
References
52
Claims
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.
Claims
exact text as granted — not AI-modifiedThe invention claimed is:
1. 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
R 1 , R 2 , and R 3 are each independently selected from the group consisting of —H, -D, —Cl, —F, —CN, —NH 2 , —NH(C, -C 3 alkyl), —N(C 1 -C 3 alkyl) 2 , —NH(C(O)C 1 -C 3 alkyl), —N(C(O)C 1 -C 3 alkyl) 2 , —C(O)H, —C(O)C 1 -C 3 alkyl, —C(O)OC 1 -C 3 alkyl, —C(O)NH 2 , —C(O)NH(C 1 -C 3 alkyl), —C(O)N(C 1 -C 3 alkyl) 2 , —C 1 -C 3 alkyl, —O—C 1 -C 3 alkyl, —S(O)C 1 -C 3 alkyl, and —S(O) 2 C 1 -C 3 alkyl;
W 1 and W 2 are each NR;
each a, b, c, and d is independently —H, -D, Halogen, —CH 3 , —OCH 3 , —OCF 3 , —OCH 2 CH 3 , 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 R 6 is independently H —H or C 1 -C 6 alkyl —C 1 -C 6 alkyl, or both R 6 groups, when taken together with the nitrogen to which they are attached, can form a heterocycle;
each R 7 is independently e, H —H, or straight or branched C 1 -C 10 alkyl —C 1 -C 10 alkyl which can be optionally substituted with OH, NH 2 , CO 2 R, CONH 2 —OH, —NH 2 , —CO 2 R, —C(O)NH 2 , phenyl, C 6 H 4 OH —C 6 H 4 OH, 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 R 9 is independently —H, -D, C 1 -C 4 alkyl, halogen, cyano, oxo, thiooxo, —OH, C(O)C 1 -C 4 alkyl, O-aryl, O-benzyl, OC(O)C 1 -C 4 alkyl, C 1 -C 3 alkene, C 1 -C 3 alkyne, C(O)C 1 -C 4 alkyl, NH 2 , NH(C 1 -C 3 alkyl), N(C 1 -C 3 alkyl) 2 , NH(C(O)C 1 -C 3 alkyl), N(C(O)C 1 -C 3 alkyl) 2 , SH, S(C 1 -C 3 alkyl), S(O)C 1 -C 3 alkyl, S(O) 2 C 1 -C 3 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;
R 4 and R 5 are each independently hydrogen, deuterium, —C 1 -C 4 alkyl, -halogen, —OH, —C(O)C 1 -C 4 alkyl, —O-aryl, —O-benzyl, —OC(O)C 1 -C 4 alkyl, —C 1 -C 3 alkene, —C 1 -C 3 alkyne, —C(O)C 1 -C 4 alkyl, —C 2 -C 3 alkene, —C 2 -C 3 alkyne, —NH 2 , —NH(C 1 -C 3 alkyl), —N(C 1 -C 3 alkyl) 2 , —NH(C(O)C 1 -C 3 alkyl), —N(C(O)C 1 -C 3 alkyl) 2 , —SH, —S(C 1 -C 3 alkyl), —S(O)C 1 -C 3 alkyl, or —S(O) 2 C 1 -C 3 alkyl; and
each R is independently —H, or straight or branched C 1 -C 4 alkyl optionally substituted with OR, NR 2 , or halogen.
2. The method of claim 1 , wherein Z is
3. The method of claim 2 , wherein t is 1.
4. The method of claim 3 , wherein r is 2 and s is 6.
5. The method of claim 3 , wherein r is 3 and s is 5.
6. The method of claim 3 , wherein r is 7 and s is 3.
7. The method of claim 5 , wherein L is —S—S—.
8. The method of claim 5 , wherein L is —O—.
9. The method of claim 5 , wherein L is
10. The method of claim 5 , wherein L is
11. The method of claim 5 , wherein L is
12. The method of claim 5 , wherein L is
13. The method of claim 5 , wherein one of n, o, p, and q are each 1.
14. The method of claim 5 , wherein two of n, o, p, and q are each 1.
15. The method of claim 5 , wherein m is 1, n, o, p, and q are each 1, and L is O —O—.
16. The method of claim 5 , wherein m is 1, n, o, p, and q are each 1, and L is —S—S—.
17. The method of claim 5 , wherein m, n, and o are each 0, and p and q are each 1.
18. The method of claim 5 , wherein m is 1, n, and o are each 0, p, and q are each 0 1, and L is
19. The method of claim 5 , wherein m is 1, n and o are each 1, p and q are each 0, and L is
20. The method of claim 5 , wherein m is 1, n, o, p, and q are each 1, and L is
21. The method of claim 5 , wherein m is 1, n, o, p, and q are each 1, and L is NR 6 .
22. The method of claim 5 , wherein m, n, and o are each 0, and p and q are each 1, and one c is —CH 3 and the other c is —CH 3 .
23. The method of claim 5 , wherein m is 1, n and o are each 1, p and q are each 0, and L is
24. The method of claim 5, wherein W 1 and W 2 are each NH.
25. The method of claim 4, wherein L is —S—S—.
26. The method of claim 4, wherein L is —O—.
27. The method of claim 4, wherein L is
28. The method of claim 4, wherein L is
29. The method of claim 4, wherein L is
30. The method of claim 4, wherein L is
31. The method of claim 4, wherein n, o, p, and q are each 1.
32. The method of claim 4, wherein two of n, o, p, and q are each 1.
33. The method of claim 4, wherein m is 1, n, o, p, and q are each 1, and L is —O—.
34. The method of claim 4, wherein m is 1, n, o, p, and q are each 1, and L is —S—S—.
35. The method of claim 4, wherein m, n, and o are each 0, and p and q are each 1.
36. The method of claim 4, wherein m is 1, n and o are each 0, p and q are each 1, and L is
37. The method of claim 4, wherein m is 1, n and o are each 1, p and q are each 0, and L is
38. The method of claim 4, wherein m is 1, n, o, p, and q are each 1, and L is
39. The method of claim 4, wherein m is 1, n, o, p, and q are each 1, and L is NR 6 .
40. The method of claim 4, wherein m is 1, n and o are each 1, p and q are each 0, and L is
41. The method of claim 4, wherein W 1 and W 2 are each NH, m, n, and o are each 0, and p and q are each 1.
42. The method of claim 1, wherein m is 0.
43. The method of claim 1, wherein the metabolic disease is hypertriglyceridemia.
44. The method of claim 4, wherein the metabolic disease is hypertriglyceridemia.
45. The method of claim 5, wherein the metabolic disease is hypertriglyceridemia.
46. The method of claim 35, wherein the metabolic disease is hypertriglyceridemia.
47. The method of claim 41, wherein the metabolic disease is hypertriglyceridemia.
48. The method of claim 1, wherein the metabolic disease is hypercholesterolemia.
49. The method of claim 4, wherein the metabolic disease is hypercholesterolemia.
50. The method of claim 5, wherein the metabolic disease is hypercholesterolemia.
51. The method of claim 35, wherein the metabolic disease is hypercholesterolemia.
52. The method of claim 41, wherein the metabolic disease is hypercholesterolemia.Cited by (0)
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