Methods for treating inflammatory conditions
View Patent ↗The present invention relates to compounds and pharmaceutically acceptable salts thereof and formulations comprising tenilsetam or pharmaceutically acceptable salts thereof that are useful in modulating inflammation. In particular, the compounds or pharmaceutically acceptable salts thereof are useful for treating or preventing a disease or disorder involving inflammation, including, but not limited to, delayed type hypersensitivity and contact hypersensitivity.
1. A method of treating delayed-type hypersensitivity, contact dermatitis, atopic dermatitis, or septic shock in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of a compound of formula I
wherein:
X is 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, or phenyl, each unsubstituted, mono-substituted, di-substituted, or tri-substituted with, independently, OH, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or (C 1 -C 4 ) alkoxy-(C 1 -C 4 ) alkyl;
R 1 and R 4 are, independently, H or C 1 -C 4 alkyl;
R 2a and R 2b are, independently, H, OH, or C 1 -C 4 alkyl, or, together, R 2a and R 2b are C═O;
R 3a and R 3b are, independently, H, OH, or C 1 -C 4 alkyl, or, together, R 3a and R 3b are C═O; and
R X is H, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or (C 1 -C 4 ) alkoxy-(C 1 -C 4 ) alkyl;
or a pharmaceutically acceptable salt thereof, wherein the compound of formula I is administered in the absence of another therapeutic agent.
2. A method of claim 1 wherein X is 2-thienyl, 3-thienyl, 2-furyl, or 3-furyl, each unsubstituted, mono-substituted, di-substituted, or tri-substituted with, independently, OH, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or (C 1 -C 4 ) alkoxy-(C 1 -C 4 ) alkyl.
3. A method of claim 1 wherein X is 2-thienyl, 3-thienyl, 2-furyl, or 3-furyl, each unsubstituted, mono-substituted, or di-substituted with, independently, OH, halogen, C 1 -C 4 alkyl, or C 1 -C 4 alkoxy.
4. A method of claim 1 wherein X is 2-thienyl or 2-furyl, each unsubstituted, mono-substituted, or di-substituted with, independently, OH, halogen, or C 1 -C 4 alkyl.
5. A method of claim 1 wherein X is unsubstituted 2-thienyl or 2-thienyl mono-substituted with OH, halogen, or C 1 -C 4 alkyl.
6. A method of claim 1 wherein X is unsubstituted 2-thienyl.
7. A method of claim 1 wherein R 1 and R 4 are H.
8. A method of claim 1 wherein R 1 and R 4 are C 1 -C 4 alkyl.
9. A method of claim 1 wherein R 2a and R 2b are, independently, H or C 1 -C 4 alkyl, or, together, R 2a and R 2b are C═O.
10. A method of claim 1 wherein R 2a and R 2b are, independently, H or OH.
11. A method of claim 1 wherein R 2a and R 2b are both H.
12. A method of claim 1 wherein R 3a and R 3b are, independently, H or C 1 -C 4 alkyl, or, together, R 3a and R 3b are C═O.
13. A method of claim 1 wherein R 3a and R 3b are, independently, H or OH.
14. A method of claim 1 wherein R 3a and R 3b are both H.
15. A method of claim 1 wherein R X is H, C 1 -C 4 alkyl, or C 1 -C 4 alkoxy.
16. A method of claim 1 wherein R X is H or C 1 -C 4 alkyl.
17. A method of claim 1 wherein R X is H.
18. A method of claim 1 wherein:
X is 2-thienyl or 2-furyl, each unsubstituted, mono-substituted, or di-substituted with, independently, OH, halogen, or C 1 -C 4 alkyl;
R 2a and R 2b are, independently, H or OH;
R 3a and R 3b are, independently, H or OH; and
R X is H.
19. A method of claim 1 wherein:
X is unsubstituted 2-thienyl or 2-thienyl mono-substituted with OH, halogen, or C 1 -C 4 alkyl;
R 1 and R 4 are, independently, H or C 1 -C 4 alkyl;
R 2a and R 2b are, independently, H or OH;
R 3a and R 3b are, independently, H or OH; and
R X is H.
20. A method of claim 1 wherein:
X is unsubstituted 2-thienyl or 2-thienyl mono-substituted with OH, halogen, or C 1 -C 4 alkyl;
R 1 and R 4 are H;
R 2a and R 2b are, independently, H or OH;
R 3a and R 3b are, independently, H or OH; and
R X is H or halogen.
21. A method of claim 1 wherein:
X is unsubstituted 2-thienyl or 2-thienyl mono-substituted with OH, halogen, or C 1 -C 4 alkyl; and
R 1 , R 4 , R 2a , R 3a , R 3b , and R X are H.
22. A method of claim 1 wherein:
X is unsubstituted 2-thienyl;
R 1 and R 4 are, independently, H or C 1 -C 4 alkyl;
R 2a and R 2b are, independently, H or OH;
R 3a and R 3b are, independently, H or OH; and
R X is H.
23. A method of claim 1 wherein:
X is unsubstituted 2-thienyl; and
R 1 , R 4 , R 2a , R 3a , R 3b , and R X are H.
24. A method of claim 1 wherein the compound of formula I, or pharmaceutically acceptable salt thereof, is present within a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
25. A method of treating delayed-type hypersensitivity, contact dermatitis, or septic shock in a mammal comprising administering to the mammal in need thereof a therapeutically effective amount of a compound of formula I
wherein:
X is 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, or phenyl, each unsubstituted, mono-substituted, di-substituted, or tri-substituted with, independently, OH, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or (C 1 -C 4 ) alkoxy-(C 1 -C 4 ) alkyl;
R 1 and R 4 are, independently, H or C 1 -C 4 alkyl;
R 2a and R 2b are, independently, H, OH, or C 1 -C 4 alkyl, or, together, R 2a and R 2b are C═O;
R 3a and R 3b are, independently, H, OH, or C 1 -C 4 alkyl, or, together, R 3a and R 3b are C═O; and
R X is H, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or (C 1 -C 4 ) alkoxy-(C 1 -C 4 ) alkyl;
or a pharmaceutically acceptable salt thereof, wherein the compound of formula I is administered in the absence of another therapeutic agent.