Compositions and methods for the treatment of metabolic and related disorders
The present invention relates to 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, for example, but not limited to, heterocyclic, phenyl or benzyl ring structures with or without substitutions and are described in detail herein. Also provided are methods for the treatment and/or prevention of one or more metabolic disorders, for example, obesity or diabetes, utilizing fatostatin A and/or a derivative and/or analog thereof and/or the A-B-C tripartite compounds.
1. A compound with a chemical structure:
wherein R 1 is H, halogen, —OH, —O—C 1-3 alkoxy, —OC(O)R 3 or —NHR 5 ;
R 3 is C 1 -C 3 alkyl or aryl, —OCH 2 —C(O)OR 4 ;
R 4 is H or C 1 -C 3 alkyl;
R 5 is H, C 1 -C 4 alkyl, alkylcyclopropane, benzyl, —NHC(O)C 1 -C 3 amide, —NHC(O)O—R 6 carbamate;
R 6 is tert-butyl or fluorenylmethyl or —NH—SO 2 —R 7 sulfonamide;
R 7 is alkyl or aryl,
R 2 is alkyl or R 8 OC(O)— and
R 8 is C 3 -C 5 alkyl or aryl.
2. The compound of claim 1 , wherein said halogen is bromine.
3. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
4. A method for treating a metabolic disorder in an individual, comprising the step of:
administering to the individual a therapeutically effective amount of at least one compound of claim 1 , or a pharmaceutically acceptable salt or a stereoisomer thereof or a combination thereof.
5. The method of claim 4 , wherein said metabolic disorder comprises obesity, hyperlipemia, diabetes or complications thereof, fatty liver, hypertension prostate, cancer or cardiovascular disease.
6. The method of claim 4 , further comprising the step of:
providing an additional therapy to said individual.
7. The method of claim 6 , wherein the additional therapy comprises dietary therapy, physical therapy, behavior therapy, surgery, drug therapy or a combination thereof.
8. A kit comprising:
the compound of claim 1 ; and
a container housing the compound.
9. A compound that is:
tert-butyl 2-(4-(4-bromophenyl)thiazol-2-yl)pyrrolidine-1-carboxylate,
benzyl-2-(4-(4-bromophenyl)thiazol-2-yl)pyrrolidine-1-carboxylate,
4-(4-bromophenyl)-2-(pyrrolidin-2-yl)thiazole,
4-(4-bromophenyl)-2-(1-propylpyrrolidin-2-yl)thiazole,
benzyl-(R)-2-(4-(4-(methylsulfonamido)phenyl)thiazol-2-yl)pyrrolidine-1-carboxylate.