Aryl, heteroaryl, and heterocyclic compounds for treatment of medical disorders
Compounds, methods of use, and processes for making inhibitors of complement Factor D comprising Formula I, or a pharmaceutically acceptable salt or composition thereof wherein R12 or R13 on the A group is an aryl, heteroaryl or heterocycle (R32) are provided. The inhibitors of Factor D described herein reduce the excessive activation of complement.
1. A method for the treatment of a disorder mediated by complement factor D, comprising administering an effective amount to a patient in need thereof a compound of structure:
or a pharmaceutically acceptable salt thereof; wherein the disorder is selected from the group consisting of paroxysmal nocturnal hemoglobinuria (PNH), atypical or typical hemolytic uremic syndrome, rheumatoid arthritis, age-related macular degeneration (AMD), retinal degeneration, ischemia/reperfusion injury, a cardiovascular disease, and asthma.
2. The method of claim 1 , wherein the patient is a human.
3. The method of claim 2 , wherein the disorder is paroxysmal nocturnal hemoglobinuria (PNH).
4. The method of claim 2 , wherein the disorder is a cardiovascular disease.
5. The method of claim 2 , wherein the disorder is atypical or typical hemolytic uremic syndrome.
6. The method of claim 2 , wherein the disorder is rheumatoid arthritis.
7. The method of claim 2 , wherein the disorder is age-related macular degeneration (AMD) or retinal degeneration the compound is administered via topical, intravitreal, subchoroidal, or suprachoroidal delivery.
8. The method of claim 2 , wherein the disorder is age-related macular degeneration (AMD) or retinal degeneration.
9. The method of claim 7 , wherein the disorder is age-related macular degeneration (AMD).
10. The method of claim 2 , wherein the compound is administered orally or parenterally.
11. The method of claim 10 , wherein the disorder is paroxysmal nocturnal hemoglobinuria (PNH).
12. The method of claim 10 , wherein the disorder is atypical or typical hemolytic uremic syndrome.
13. The method of claim 2 , wherein the compound is administered intravenously.
14. The method of claim 13 , wherein the disorder is paroxysmal nocturnal hemoglobinuria (PNH).
15. The method of claim 13 , wherein the disorder is atypical or typical hemolytic uremic syndrome.
16. The method of claim 2 , wherein the disorder is ischemia/reperfusion injury.
17. The method of claim 2 , wherein the disorder is asthma.