Methods of treating aquaporin-mediated conditions
View Patent ↗The present invention relates to the use of selective aquaporin inhibitors, e.g., of aquaporin-4 or aquaporin-2, e.g., certain phenylbenzamide compounds, for the prophylaxis, treatment and control of aquaporin-mediated conditions, e.g., glioblastoma and ovarian hyperstimulation syndrome. The invention provides, inter alia, methods of treating or controlling a disease condition mediated by an aquaporin, e.g., diseases or conditions of water imbalance and other diseases.
1. A method of treating or controlling a disease or condition selected from glioblastoma, ovarian hyperstimulation syndrome, pulmonary edema, fibromyalgia, and multiple sclerosis comprising administering to a patient in need thereof an effective amount of a compound of formula 1a:
wherein:
R 1 is selected from trifluoromethyl, chloro, fluoro, and bromo;
R 3 and R 5 are the same or different and selected from trifluoromethyl, chloro, fluoro, and bromo; and
R 2 and R 4 are both H; and
R 6 is selected from H and physiologically hydrolysable and acceptable acyl;
in free or pharmaceutically acceptable salt form.
2. The method of claim 1 , wherein:
R 1 is selected from chloro and bromo;
R 3 and R 5 are both trifluoromethyl; and
R 2 , R 4 , and R 6 are all H.
3. The method of claim 1 , wherein R 6 is a phosphono group, which may be substituted or unsubstituted.
4. The method of claim 1 , wherein the compound of formula 1a is selected from:
5. The method of claim 1 , wherein the compound of formula 1a is:
in free or pharmaceutically acceptable salt form.
6. The method of claim 1 , wherein the compound of formula 1a is:
in free form.
7. The method of claim 1 , wherein the compound of formula 1a is:
in free or pharmaceutically acceptable salt form.
8. The method of claim 6 , wherein the disease or condition is glioblastoma.
9. The method of claim 6 , wherein the disease or condition is ovarian hyperstimulation syndrome.
10. The method of claim 6 , wherein the disease or condition is pulmonary edema.
11. The method of claim 6 , wherein the disease or condition is fibromyalgia.
12. The method of claim 6 , wherein the disease or condition is multiple sclerosis.
13. The method of claim 7 , wherein the disease or condition is glioblastoma.
14. The method of claim 7 , wherein the disease or condition is ovarian hyperstimulation syndrome.
15. The method of claim 7 , wherein the disease or condition is pulmonary edema.
16. The method of claim 7 , wherein the disease or condition is fibromyalgia.
17. The method of claim 7 , wherein the disease or condition is multiple sclerosis.