Substituted benzofuran, benzopyrrole, benzothiophene, and structurally related complement inhibitors
Disclosed are compounds of formulae I and II, and pharmaceutically acceptable salts and prodrugs thereof, which are inhibitors of the complement system. Also provided are pharmaceutical compositions comprising such a compound, and methods of using the compounds and compositions in the treatment or prevention of a disease or condition characterized by aberrant complement system activity.
1. A method of treating or a disease or condition characterized by aberrant complement system activity, comprising administering to a subject in need thereof a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
wherein the disease or condition characterized by aberrant complement system activity is selected from the group consisting of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, organ transplant rejection, myasthenia gravis, neuromyelitis optica, membranoproliferative glomerulonephritis, dense-deposit disease, cold agglutinin disease, catastrophic antiphospholipid syndrome, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), IgA nephropathy, age-related macular degeneration (AMD), erythematosus, warm autoimmune hemolytic anemia, and focal segmental glomerulosclerosis.
2. The method of claim 1 , wherein the disease or condition characterized by aberrant complement system activity is selected from the group consisting of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, organ transplant rejection, myasthenia gravis, neuromyelitis optica, membranoproliferative glomerulonephritis, dense-deposit disease, cold agglutinin disease, and catastrophic antiphospholipid syndrome.
3. The method of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
5. The method of claim 1 , wherein the compound is
or a pharmaceutically acceptable salt thereof.
6. The method of claim 2 , wherein the disease or condition characterized by aberrant complement system activity is selected from the group consisting of paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, dense-deposit disease, and age-related macular degeneration (AMD).
7. The method of claim 3 , wherein the disease or condition characterized by aberrant complement system activity is paroxysmal nocturnal hemoglobinuria.
8. The method of claim 4 , wherein the disease or condition characterized by aberrant complement system activity is paroxysmal nocturnal hemoglobinuria.
9. The method of claim 5 , wherein the disease or condition characterized by aberrant complement system activity is paroxysmal nocturnal hemoglobinuria.