Prodrugs of kallikrein inhibitors
Disclosed are compounds of formula I, II, and III, and pharmaceutically acceptable salts thereof, which are inhibitors of kallikrein. Also provided are pharmaceutical compositions comprising such a compound, and methods involving use of the compounds and compositions in the treatment and prevention of acquired or hereditary angioedema, or other diseases and conditions characterized by aberrant kallikrein activity.
1. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having the following structure:
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having the following structure:
4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having the following structure:
5. A pharmaceutical composition, comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
6. A method of treating acquired angioedema or hereditary angioedema, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein the subject has acquired angioedema.
8. The method of claim 6 , wherein the subject has hereditary angioedema.
9. The method of claim 6 , wherein the subject has hereditary angioedema, and the hereditary angioedema is Type I hereditary angioedema.
10. The method of claim 6 , wherein the subject has hereditary angioedema, and the hereditary angioedema is Type II hereditary angioedema.
11. The method of claim 6 , wherein the subject has hereditary angioedema, and the hereditary angioedema is Type III hereditary angioedema.
12. A method of treating a disease or condition associated with aberrant activity of kallikrein, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
13. A method of inhibiting blood coagulation, comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.