Compounds and method for treating autoimmune diseases
Compounds and embodiments of a method for treating and/or preventing autoimmune diseases are disclosed. The method includes administering to a subject having an autoimmune disease, such as an inflammatory bowel disease, a therapeutically effective amount of a compound according to formula I wherein X and Y independently are O or NR 1 ; each R 1 is independently H or C 1 -C 6 alkyl; ring A is aryl; each R 2 independently is H, alkyl, alkoxy, amide, cyano, halo, haloalkyl, hydroxyalkyl, heteroalkyl, heterocyclyl, sulfonyl, sulfonamide, or two R 2 groups, taken together with the atom or atoms to which they are attached, combine to form a 4-10 membered ring system; p is 0, 1, 2, 3, or 4; R 3 and R 4 independently are H or C 1 -C 6 alkyl; and R 5 is halo, cyano, or C 1 -C 6 alkyl.
1. A method, comprising administering to a subject identified as having alopecia, or at risk of developing alopecia, a therapeutically effective amount of
or a salt thereof, or administering therapeutically effective amounts of both compounds, or a salt or salts thereof, to the subject.
2. The method of claim 1 wherein the compound
or a salt thereof, is administered topically.
3. The method of claim 1 wherein the compound
or a salt thereof, is administered orally.
4. The method according to claim 3 wherein the compound is
5. The method of claim 1 , further comprising determining a therapeutic blood level of the compound or a metabolite thereof in the subject.
6. The method of claim 5 , further comprising, after determining the therapeutic blood level:
comparing the therapeutic blood level to a control; and
adjusting a second dose of the compound or compounds, based at least in part on the comparison, to optimize therapeutic effect, where adjusting the second dose comprises decreasing the second dose relative to the first dose if the therapeutic blood level is greater than the control or increasing the second dose relative to the first dose if the therapeutic blood level is less than the control.
7. The method of claim 6 where the therapeutically effective amount is from about 0.0001 mg/kg body weight/day to about 100 mg/kg/day.
8. The method of claim 1 , further comprising administering the compound or compounds serially in plural administrations to the subject.
9. The method of claim 1 where the compound is, or the compounds are, administered as a pharmaceutical composition.
10. The method of claim 1 where the compound is, or the compounds are, administered prophylactically.
11. The method of claim 1 , further comprising administering another therapeutic to the subject.
12. The method of claim 1 where a single compound is administered serially in plural administrations to the subject.
13. The method of claim 1 where both compounds are administered either serially, or in combination, in plural administrations to the subject.
14. The method of claim 13 where the therapeutically effective amount is a daily dose of from about 1 mg/day up to about 2 grams/day.
15. The method of claim 13 where the compounds are administered together as a pharmaceutical composition.
16. The method of claim 13 where the compound is, or the compounds are, administered prophylactically.
17. The method of claim 1 comprising evaluating the subject by determining a level of a biomarker associated with alopecia.
18. The method of claim 1 , wherein the compound
or a salt thereof, is administered orally.
19. The method of claim 1 , wherein the compound
or a salt thereof, is administered topically.
20. The method of claim 1 , wherein the compound is
or a salt thereof.
21. The method of claim 1 , wherein the compound is
or a salt thereof.
22. The method of claim 21 , wherein the salt is a hydrochloride.
23. The method of claim 21 , wherein the salt is a trifluoroactate.
24. The method of claim 1 , wherein the compound is administered orally.
25. The method of claim 1 , wherein the compound is administered topically.