Compositions and methods for the treatment of metabolic disorders
The present invention relates to treatment and/or prevention of one or more metabolic disorders utilizing fatostatin A and/or a derivative and/or analog thereof. In other aspects, the compound for treatment and/or prevention of one or more metabolic disorders utilizes an A-B-C tripartite structure, wherein A, B, and C are identical or non-identical structures and are described in detail herein. In specific aspects, the metabolic disorder includes obesity or diabetes, for example.
1. A compound selected from the group consisting of:
4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl benzoate;
4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol;
methyl 2-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenoxy)acetate;
4-(4-chlorophenyl)-2-(3,4-dimethoxyphenyl)thiazole;
4-(4-(2,4-difluorophenyl)thiazol-2-yl)-2-propylpyridine;
4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine;
N-isopropyl-4(2-(2-propylpyridin-4yl)thiazol-4yl)benzenamine;
N-(4-(2-(2-propylpyridin-4yl)thiazol-4yl)phenyl)acetamide;
N-(4-(2-(2-propylpyridin-4yl)thiazol-4yl)phenyl)methanesulfonamide;
N-benzyl-4-(2-(2-propylpyridin-4yl)thiazol-4yl)benzenamine;
N-(cyclopropylmethyl)-4-(2-(2-propylpyridin-4yl)thiazol-4yl)benzenamine;
4-(4-(3-methoxyphenyl)thiazol-2-yl)-2-propylpyridine;
4-(4-(2-methoxyphenyl)thiazol-2-yl)-2-propylpyridine;
4-(4-bromophenyl)-2-(2-propylpyridin-4-yl)thiazole-5-carboxylic acid;
methyl 4-(4bromophenyl)-2-(2-propylpyridin-4-yl)thiazole-5-carboxylate;
4-(4-(3-methoxyphenyl)thiazol-2-yl)-2-propylpyridine;
4-(4-(2-methoxyphenyl)thiazol-2-yl)-2-propylpyridine;
3-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol;
2-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol;
4-(4-bromophenyl)-N-isopropyl-2-(2-propylpyridin-4-yl)thiazole-5-carboxamide;
a pharmaceutically acceptable salt thereof;
a stereoisomer thereof; and
any combination or mixture thereof.
2. The compound of claim 1 wherein said compound is selected from the group consisting of N-isopropyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine, and N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methane sulfonamide.
3. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable excipient.
4. A kit comprising the compound of claim 1 , wherein the compound is housed in a suitable container.
5. The kit of claim 4 , further comprising an additional therapy for a metabolic disorder.
6. A composition or pharmaceutically acceptable salt or stereoisomer thereof, having the general formula:
wherein
X is N;
R 1 is independently selected from H, Et, OMe or n-propyl;
Y 3 is CH or
wherein R 2 is independently selected from OH, OMe, or NH-i-Pr;
R 3 is independently selected from H, F, or Cl; and
R 4 is independently selected from Cl, Br, OBz, OH, OCH 2 COOMe, OCH 2 COOH, F, NH 2 , NH-i-Pr, NHCOMe, NHSO 2 Me, NHBn,
OMe, NHBoc,
NHTs,
7. The composition of claim 6 , wherein R 1 is n-propyl.
8. The composition of claim 7 , wherein Y 3 is CH.
9. The composition of claim 8 , wherein R 3 is Cl and R 4 is Cl.
10. The composition of claim 8 , wherein R 3 is H.
11. The composition of claim 10 , wherein R 4 is selected from the group consisting of Br, NH-i-Pr, NHSO 2 Me, NHBn,
NHBoc, NHTs,
12. The composition of claim 11 , having the following formula:
13. The composition of claim 6 , wherein said compound is selected from the group consisting of:
4-(4-(4-bromophenyl)thiazol-2-yl)-2-propylpyridine;
4-(4-phenylthiazol-2-yl)-2-propylpyridine;
4-(4-(4-chlorophenyl)thiazol-2-yl)-2-propylpyridine;
4-(4-(4-ethylphenyl)thiazol-2-yl)pyridine;
4-(4-p-tolylthiazol-2-yl)pyridine;
4-(4-(4-methoxyphenyl)thiazol-2-yl)pyridine;
4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl benzoate;
4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol;
methyl 2-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenoxy)acetate;
2-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenoxy)acetic acid;
4-(4-(3,4-dichlorophenyl)thiazol-2-yl)-2-propylpyridine;
4-(4-(4-fluorophenyl)thiazol-2-yl)-2-propylpyridine;
4-(4-(2,4-difluorophenyl)thiazol-2-yl)-2-propylpyridine;
4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine;
N-isopropyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine;
N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)acetamide;
N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide;
N-benzyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine;
N-(cyclopropylmethyl)-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine;
4-(4-bromophenyl)-2-(2-propylpyridin-4-yl)thiazole-5-carboxylic acid;
methyl 4-(4-bromophenyl)-2-(2-propylpyridin-4-yl)thiazole-5-carboxylate;
4-(4-(4-methoxyphenyl)thiazol-2-yl)-2-propylpyridine;
4-(4-(3-methoxyphenyl)thiazol-2-yl)-2-propylpyridine;
4-(4-(2-methoxyphenyl)thiazol-2-yl)-2-propylpyridine;
3-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol;
2-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenol;
4-(4-bromophenyl)-N-isopropyl-2-(2-propylpyridin-4-yl)thiazole-5-carboxamide;
4-(4-(4-chlorophenyl)thiazol-2-yl)pyridine;
4-(4-(4-chlorophenyl)thiazol-2-yl)-2-ethylpyridine;
2-propyl-4-(4-(thiophen-2-yl)thiazol-2-yl)pyridine;
2-(2-propylpyridin-4-yl)-4-p-tolylthiazole-5-carboxylic acid;
2-ethyl-4-(4-p-tolylthiazol-2-yl)pyridine;
4-phenyl-2-(2-propylpyridin-4-yl)thiazole-5-carboxylic acid;
methyl 2-(2-propylpyridin-4-yl)-4-p-tolylthiazole-5-carboxylate;
tert-butyl 4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenylcarbamate;
N-cyclohexyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine;
4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)-N-tosylbenzenamine;
N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)-8-quinolinesulfonamide;
N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)-2-thiophenesulfonamide;
and any combination thereof.
14. The composition of claim 13 , wherein said at least one compound is selected from the group consisting of:
4-(4-(4-bromophenyl)thiazol-2-yl)-2-propylpyridine;
N-isopropyl-4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)benzenamine; and
N-(4-(2-(2-propylpyridin-4-yl)thiazol-4-yl)phenyl)methanesulfonamide;
a pharmaceutically acceptable salt;
a stereoisomer thereof; and
any combination thereof.