PPAR activity regulators
The object of the present invention is to provide PPAR (peroxisome proliferator-activated receptor) activity regulators, which can be widely used for improving insulin resistance and preventing/treating various diseases such as diabetes, metabolic syndromes, hyperlipemia, high-blood pressure, vascular disorders, inflammation, hepatitis, fatty liver, liver fibrosis, NASH (non-alcoholic steatohepatitis) and obesity. The present invention provides PPAR activity regulators which comprise an acylamide compound having the specific structure, prodrugs thereof, or pharmaceutically acceptable salts thereof.
1. A peroxisome proliferator-activated receptor activity regulator, which comprises an acylamide compound of the formula (1), or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, diluent, excipient, disintegrating agent, lubricant, and/or flow improver:
wherein R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms;
R2 is an alkyl group having 1 to 10 carbon atoms, aryl group having 6 to 10 carbon atoms, arylalkyl group having 7 to 20 carbon atoms, or alkylthioalkyl group having 2 to 6 carbon atoms;
R3 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 may bond each other to form a ring;
R4 is a hydrogen atom or an alkyl group having 1 to 16 carbon atoms;
R5 is a straight-chain hydrocarbon group having 5 to 21 carbon atoms which may have 1 to 3 double bond(s); and
X is NH.
2. A peroxisome proliferator-activated receptor activity regulator according to claim 1 , wherein, in the formula (1), R1 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms; R2 is a straight- or branched-chain alkyl group having 1 to 4 carbon atoms; R3 is a hydrogen atom; R4 is a hydrogen atom, a straight-chain alkyl group having 1 to 16 carbon atoms, a branched-chain alkyl group having 1 to 16 carbon atoms, or a cyclic alkyl group having 3 to 16 carbon atoms; R5 is a straight-chain alkyl group having 5 to 21 carbon atoms which may have one double bond; and X is NH.
3. A method of regulating peroxisome proliferator-activated receptor-α activity, comprising administering an effective amount of a peroxisome proliferator-activated receptor activity regulator according to claim 1 to a subject in need thereof.
4. A method of regulating peroxisome proliferator-activated receptor-γ activity, comprising administering an effective amount of a peroxisome proliferator-activated receptor activity regulator according to claim 1 to a subject in need thereof.
5. A method of regulating peroxisome proliferator-activated receptor-α and -γ activity, comprising administering an effective amount of a peroxisome proliferator-activated receptor activity regulator according to claim 1 to a subject in need thereof.
6. A method of treating a disease selected from the group consisting of diabetes, metabolic syndromes, hyperlipemia, high-blood pressure, vascular disorders, inflammation, hepatitis, fatty liver, liver fibrosis, non-alcoholic steatohepatitis, and obesity, comprising administering an effective amount of a peroxisome proliferator-activated receptor activity regulator according to claim 1 to a subject in need thereof.
7. The method of claim 6 , wherein said peroxisome proliferator-activated receptor activity regulator is administered intravenously, intra-arterially, subcutaneously, intramuscularly, or by infusion.
8. The method of claim 6 , wherein said peroxisome proliferator-activated receptor activity regulator is administered orally.
9. The method of claim 6 , wherein said peroxisome proliferator-activated receptor activity regulator is administered in an amount of 0.1 to 1000 mg per kg by weight of said subject per day.
10. The method of claim 6 , wherein said subject is a human.
11. A method of regulating peroxisome proliferator-activated receptor-α activity, comprising administering an effective amount of a peroxisome proliferator-activated receptor activity regulator according to claim 2 to a subject in need thereof.
12. A method of regulating peroxisome proliferator-activated receptor-γ activity, comprising administering an effective amount of a peroxisome proliferator-activated receptor activity regulator according to claim 2 to a subject in need thereof.
13. A method of regulating peroxisome proliferator-activated receptor-α and -γ activity, comprising administering an effective amount of a peroxisome proliferator-activated receptor activity regulator according to claim 2 to a subject in need thereof.
14. A method of treating a disease selected from the group consisting of diabetes, metabolic syndromes, hyperlipemia, high-blood pressure, vascular disorders, inflammation, hepatitis, fatty liver, liver fibrosis, non-alcoholic steatohepatitis, and obesity, comprising administering an effective amount of a peroxisome proliferator-activated receptor activity regulator according to claim 2 to a subject in need thereof.
15. The method of claim 14 , wherein said peroxisome proliferator-activated receptor activity regulator is administered intravenously, intra-arterially, subcutaneously, intramuscularly, or by infusion.
16. The method of claim 14 , wherein said peroxisome proliferator-activated receptor activity regulator is administered orally.
17. The method of claim 14 , wherein said peroxisome proliferator-activated receptor activity regulator is administered in an amount of 0.1 to 1000 mg per kg by weight of said subject per day.
18. The method of claim 14 , wherein said subject is a human.
19. The method of claim 3 , wherein said peroxisome proliferator-activated receptor activity regulator is administered intravenously, intra-arterially, subcutaneously, intramuscularly, or by infusion.
20. The method of claim 3 , wherein said peroxisome proliferator-activated receptor activity regulator is administered orally.
21. The method of claim 3 , wherein said peroxisome proliferator-activated receptor activity regulator is administered in an amount of 0.1 to 1000 mg per kg by weight of said subject per day.
22. The method of claim 3 , wherein said subject is a human.
23. The method of claim 11 , wherein said peroxisome proliferator-activated receptor activity regulator is administered intravenously, intra-arterially, subcutaneously, intramuscularly, or by infusion.
24. The method of claim 11 , wherein said peroxisome proliferator-activated receptor activity regulator is administered orally.
25. The method of claim 11 , wherein said peroxisome proliferator-activated receptor activity regulator is administered in an amount of 0.1 to 1000 mg per kg by weight of said subject per day.
26. The method of claim 11 , wherein said subject is a human.