Human plasma kallikrein inhibitors
Disclosed are compounds of formula I: as described herein, and pharmaceutically acceptable salts thereof. The compounds are inhibitors of plasma kallikrein. Also provided are pharmaceutical compositions comprising at least one such compound, and methods involving use of the compounds and compositions in the treatment and prevention of diseases and conditions characterized by unwanted plasma kallikrein activity.
1. A method of treating or preventing angioedema, comprising orally administering to a subject in need thereof an oral dosage form comprising a therapeutically effective amount of a compound having the structure:
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the oral dosage form is administered once per day.
3. The method of claim 1 , wherein the oral dosage form is a capsule and the oral dosage form is administered once per day.
4. The method of claim 1 , wherein the angioedema is hereditary angioedema.
5. The method of claim 4 , wherein the oral dosage form is administered once per day.
6. The method of claim 4 , wherein the oral dosage form is a capsule and the oral dosage form is administered once per day.
7. The method of claim 1 , wherein the compound is the (+)-enantiomer.
8. The method of claim 7 , wherein the angioedema is hereditary angioedema.
9. The method of claim 7 , wherein the oral dosage form is administered once per day.
10. The method of claim 7 , wherein the oral dosage form is a capsule and the oral dosage form is administered once per day.
11. The method of claim 1 , wherein the compound is the (−)-enantiomer.
12. The method of claim 11 , wherein the angioedema is hereditary angioedema.
13. The method of claim 11 , wherein the oral dosage form is administered once per day.
14. The method of claim 11 , wherein the oral dosage form is a capsule and the oral dosage form is administered once per day.
15. The method of claim 1 , wherein the oral dosage form comprises a hydrochloride salt of the compound.
16. The method of claim 15 , wherein the angioedema is hereditary angioedema.
17. The method of claim 15 , wherein the oral dosage form is administered once per day.
18. The method of claim 15 , wherein the oral dosage form is a capsule and the oral dosage form is administered once per day.
19. The method of claim 1 , wherein the oral dosage form comprises a bis(hydrochloride) salt of the compound.
20. The method of claim 19 , wherein the angioedema is hereditary angioedema.
21. The method of claim 19 , wherein the oral dosage form is administered once per day.
22. The method of claim 19 , wherein the oral dosage form is a capsule and the oral dosage form is administered once per day.