Method of treating focal segmental glomerulosclerosis
A method of treating focal segmental glomerulosclerosis with a compound of Formula I is provided. FSGS may be primary (no known cause) or secondary. The secondary FSGS may be associated with infections or viruses such as HIV, diseases such as sickle cell disease or lupus, toxins or drugs such as anabolic steroids, heroin or pamidronate, nephron loss and hyperfiltration, such as with chronic pyelonephritis and reflux, morbid obesity, or diabetes mellitus.
1. A method of treating focal segmental glomerulosclerosis (FSGS) in a patient with primary FSGS, comprising administering to the patient an effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt thereof,
wherein
R 1 is halogen or C 1-6 alkyl;
R 2 is hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, or —CN;
R 3 is hydrogen, halogen, or C 1-6 alkyl;
R 4 is hydrogen, halogen, or C 1-6 alkyl;
each R 5 is independently C 1-6 alkyl, —OH, or —NH 2 ;
n is 0, 1, 2, or 3; and
each of A 1 , A 2 , and A 3 is —CH— or —N—, where at least one of A 1 , A 2 , or A 3 is —N—.
2. The method of claim 1 wherein
R 1 is halogen or methyl;
R 2 is halogen or C 1-3 haloalkyl;
R 3 is halogen or C 1-3 alkyl;
R 4 is hydrogen;
n is 0;
A 2 is —CH—; and A 3 is —N—.
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 1 , wherein the compound or a pharmaceutically acceptable salt thereof is administered orally.
7. The method of claim 1 , wherein the compound or a pharmaceutically acceptable salt thereof is administered twice per day.
8. The method of claim 1 , wherein the compound or a pharmaceutically acceptable salt thereof is administered once per day.
9. The method of claim 1 , further comprising administering to the patient one or more additional therapeutic compound.
10. The method of claim 9 wherein the one or more additional therapeutic compound is selected from one or more of an antihypertensive, a statin, a vasodilator, a steroid, a cytotoxic drug, a diuretic, a non-steriodal anti-inflammatory drug (NSAID), a cholesterol or triglycerides reducing agent, and an immunosuppressive drug.
11. The method of claim 9 wherein the one or more additional therapeutic compound is selected from the group consisting of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin receptor II blocker (ARB).
12. The method of claim 11 wherein the one or more additional therapeutic compound is selected from the group consisting of ramipril, perindopril, lisinopril, perindopril arginine, captopril, spirapril, quinapril, enalapril, imridapril, fosinopril, zofenopril, benazepril, trandolapril, verapamil, benazepril, arnlodipine, trandolapril, P-003, cilazapril, delapril, moexipril, quinapril, fosinopril, temocapril, losartan, candesartan, irbesartan, telmisartan, olmesartan, valsartan, azilsartan, telmisartan, fimasartan, EMA-401, azilsartan medoxomil potassium, sparsentan, candesartan cilexetil, olmesartan medoxomil, TRV-027, losartan potassium, YH-22189, azilsartan trimethylethanolamine, allisartan isoproxil, and eprosartan.
13. The method of claim 1 , wherein the patient is also subjected to extracorporeal blood purification, allogenic transplantation, and/or stem cell therapy.
14. The method of claim 9 , wherein the one or more additional therapeutic compound is administered concurrently or sequentially.
15. The method of claim 9 , wherein the one or more additional therapeutic compound is administered as a single pharmaceutical composition together with the compound of formula I or as a separate pharmaceutical composition.