Substituted aromatic compounds and related method for the treatment of fibrosis

1. A method for preventing and/or slowing progression of and/or treating a fibrotic disease in a subject in need thereof, comprising the administration to the subject of a therapeutically effective amount of a compound represented by the formula:

or a pharmaceutically acceptable salt thereof, wherein

A is straight C 5 alkyl, straight C 6 alkyl, C 5 alkenyl, C 6 alkenyl, C(O)—(CH 2 ) n —CH 3 or CH(OH)—(CH 2 ) n —CH 3 wherein n is 3 or 4;

R 1 is H, F or OH;

R 2 is straight C 5 alkyl, straight C 6 alkyl, C 5 alkenyl, C 6 alkenyl, C(O)—(CH 2 ) n —CH 3 or CH(OH)—(CH 2 ) n —CH 3 wherein n is 3 or 4;

R 3 is H, F, OH or CH 2 Ph;

R 4 is H, F or OH;

Q is

1) (CH 2 ) m C(O)OH wherein m is 1 or 2,

2) CH(CH 3 )C(O)OH,

3) C(CH 3 ) 2 C(O)OH,

4) CH(F)—C(O)OH,

5) CF 2 —C(O)OH, or

6) C(O)—C(O)OH.

2. The method of claim 1 , wherein the salt is the sodium salt.

3. The method of claim 1 , wherein the fibrotic disease is pulmonary fibrosis, liver fibrosis, skin fibrosis, renal fibrosis, pancreas fibrosis, systemic sclerosis, cardiac fibrosis or macular degeneration.

4. The method of claim 1 , wherein the therapeutically effective amount is between about 1 to about 50 mg/kg, the compound is administered orally, and the subject is human.

5. The method of claim 4 , wherein the therapeutically effective amount is between about 1 to about 20 mg/kg.

6. The method according to claim 3 , wherein the pulmonary fibrosis is idiopathic pulmonary fibrosis; sarcoidosis; cystic fibrosis; familial pulmonary fibrosis; silicosis; asbestosis; coal worker's pneumoconiosis; carbon pneumoconiosis; hypersensitivity pneumonitides; pulmonary fibrosis caused by inhalation of inorganic dust; pulmonary fibrosis caused by an infectious agent; pulmonary fibrosis caused by inhalation of noxious gases, aerosols, chemical dusts, fumes or vapors; drug-induced interstitial lung disease; pulmonary hypertension or chronic obstructive pulmonary disease.

7. The method according to claim 3 , wherein the liver fibrosis is resulting from a chronic liver disease, hepatitis B virus infection, hepatitis C virus infection, hepatitis D virus infection, schistosomiasis, alcoholic liver disease or non-alcoholic steatohepatitis, obesity, diabetes, protein malnutrition, coronary artery disease, auto-immune hepatitis, cystic fibrosis, alpha-1-antitrypsin deficiency, primary biliary cirrhosis, drug reaction or exposure to toxins.

8. The method according to claim 3 , wherein the skin fibrosis is scarring, hypertrophic scarring, keloid scarring, dermal fibrotic disorder, wound healing, delayed wound healing, psoriasis or scleroderma.

9. The method of claim 8 , wherein said scarring derives from a burn, a trauma, a surgical injury, a radiation or an ulcer.

10. The method of claim 9 , wherein said ulcer is diabetic foot ulcer, venous leg ulcer or pressure ulcer.

11. A method according to claim 3 , wherein the kidney fibrosis is resulting from dialysis following kidney failure, catheter placement, a nephropathy, glomerulosclerosis, glomerulonephritis, chronic renal insufficiency, acute kidney injury, chronic kidney diseases, end stage renal disease or renal failure.

12. The method according to claims 1 , wherein said compound is one of the following compounds:

Com- pound 1

Com- pound 2

Com- pound 3

Com- pound 4

Com- pound 5

Com- pound 6

Com- pound 7

Com- pound 8

or a pharmaceutically acceptable salt of said compound, or a free acid form of said compound.