Aryl sulfonamides
Compounds are provided that act as potent antagonists of the CCR9 receptor, and which have been further confirmed in animal testing for inflammation, one of the hallmark disease states for CCR9. The compounds are generally aryl sulfonamide derivatives and are useful in pharmaceutical compositions, methods for the treatment of CCR9-mediated diseases, and as controls in assays for the identification of CCR9 antagonists.
1. A compound of the formula (Ic):
where X is OCF3, tert-butyl, ethyl, isopropyl, oxazole, C(O)CH3, CN, fluorine, CF3, isopropyoxy, isoamyl, or hydroxybutyl.
2. A pharmaceutically acceptable salt of a compound of the formula (Ic):
where X is OCF3, tert-butyl, ethyl, isopropyl, oxazole, C(O)CH3, CN, fluorine, CF3, isopropyoxy, isoamyl, or hydroxybutyl.
3. The pharmaceutically acceptable salt of claim 2 , which is a sodium salt.
4. A composition comprising a pharmaceutically acceptable carrier and a compound of the formula (Ic):
where X is OCF3, tert-butyl, ethyl, isopropyl, oxazole, C(O)CH3, CN, fluorine, CF3, isopropyoxy, isoamyl, or hydroxybutyl.
5. A composition comprising a pharmaceutically acceptable carrier and a pharmaceutically acceptable salt of a compound of the formula (Ic):
where X is OCF3, tert-butyl, ethyl, isopropyl, oxazole, C(O)CH3, CN, fluorine, CF3, isopropyoxy, isoamyl, or hydroxybutyl.
6. The composition of claim 5 , wherein the pharmaceutically acceptable salt is a sodium salt.
7. A method of treating an inflammatory bowel disease in a subject in need thereof, comprising administering to the subject an effective amount of a compound the formula (Ic) or a pharmaceutically acceptable salt of a compound of the formula (Ic):
where X is OCF3, tert-butyl, ethyl, isopropyl, oxazole, C(O)CH3, CN, fluorine, CF3, isopropyoxy, isoamyl, or hydroxybutyl.
8. The method of claim 7 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.
9. A compound of the formula (Ic):
where X is isopropoxy.
10. A pharmaceutically acceptable salt of a compound of the formula (Ic):
where X is isopropoxy.
11. A composition comprising a pharmaceutically acceptable carrier and a compound of the formula (Ic):
where X is isopropoxy.
12. A composition comprising a pharmaceutically acceptable carrier and a pharmaceutically acceptable salt of compound of the formula (Ic):
where X is isopropoxy.
13. A composition comprising a pharmaceutically acceptable carrier and a pharmaceutically acceptable salt of compound of the formula (Ic):
where X is isopropoxy.
14. A method of treating an inflammatory bowel disease in a subject in need thereof, comprising administering to the subject an effective amount of compound of the formula (Ic):
where X is isopropoxy.
15. The method of claim 14 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.
16. A method of treating an inflammatory bowel disease in a subject in need thereof, comprising administering to the subject an effective amount of a pharmaceutically acceptable salt of a compound of the formula (Ic):
where X is isopropoxy.
17. The method of claim 16 , wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.