Methods for treatment of fibrotic diseases

Abstract

Methods for treatment of fibrotic diseases using compounds of formula Iwherein RA is hydrogen,R7 and R8 are independently selected from H and SO2NR3R4,one of R7 and R8 is hydrogen, andR1, R2, R3, and R4 are each independently selected from H, alkyl, heteroalkyl, cycloalkyl, arylcycloalkyl, aryl, heteroaryl, heterocycloalkyl, and each of NR1R2 and NR3R4 can independently combine to form a heterocycloalkyl, and wherein said alkyl, heteroalkyl, cycloalkyl, arylcycloalkyl, aryl, heteroaryl, or heterocycloalkyl may be optionally substituted,or a pharmaceutically acceptable salt, ester, amide, stereoisomer, geometric isomer or prodrug thereof.

What is claimed is: 
     
         1 . A method of treating and/or preventing a fibrotic disease, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I 
       
         
           
           
               
               
           
         
         wherein R A  is hydrogen, 
         R 7  and R 8  are independently selected from H and SO 2 NR 3 R 4 , 
         one of R 7  and R 8  is hydrogen, and 
         R 1 , R 2 , R 3 , and R 4  are each independently selected from H, alkyl, heteroalkyl, cycloalkyl, arylcycloalkyl, aryl, heteroaryl, heterocycloalkyl, and each of NR 1 R 2  and NR 3 R 4  can independently combine to form a heterocycloalkyl, and wherein said alkyl, heteroalkyl, cycloalkyl, arylcycloalkyl, aryl, heteroaryl, or heterocycloalkyl may be optionally substituted, 
         or a pharmaceutically acceptable salt, ester, amide, stereoisomer, geometric isomer or prodrug thereof. 
       
     
     
         2 . The method of  claim 1 , wherein NR 1 R 2  and NR 3 R 4  are independently 6- to 15-membered heterocycloalkyl containing one nitrogen in the ring. 
     
     
         3 . The method of  claim 1 , wherein the compound of formula I has the following structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, ester, amide, stereoisomer, geometric isomer or prodrug thereof. 
       
     
     
         4 . The method of  claim 1 , wherein the fibrotic disease is selected from the group consisting of pulmonary fibrosis, Dupuytren's contracture, scleroderma, systemic sclerosis, scleroderma-like disorders, sine scleroderma, liver cirrhosis, interstitial pulmonary fibrosis, keloids, chronic kidney disease, chronic graft rejection, and other scarring/wound healing abnormalities, post-operative adhesions, reactive fibrosis. 
     
     
         5 . The method of  claim 4 , wherein said disorder is pulmonary fibrosis. 
     
     
         6 . The method of  claim 4 , wherein said disorder is Dupuytren's contracture. 
     
     
         7 . The method of  claim 4 , wherein said disorder is keloids. 
     
     
         8 . A method of treating pulmonary fibrosis comprising intranasally administering the compound of formula I 
       
         
           
           
               
               
           
         
         wherein R A  is hydrogen, R 7  and R 8  are independently selected from H and SO 2 NR 3 R 4 , wherein one of R 7  and R 8  is hydrogen and wherein NR 1 R 2  and NR 3 R 4  are independently 6- to 15-membered heterocycloalkyl containing one nitrogen in the ring, 
         or a pharmaceutically acceptable salt, ester, amide, stereoisomer or geometric isomer thereof, 
         to a patient in need thereof. 
       
     
     
         9 . The method of  claim 8 , wherein the compound of formula I has the following structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, ester, amide, stereoisomer, geometric isomer or prodrug thereof. 
       
     
     
         10 . The method of  claim 1 , wherein said administering is done through one or more of intravenous, parenteral, oral, inhalation (including aerosolized delivery), buccal, intranasal, rectal, intra-lesional intraperitoneal, intradermal, transdermal, subcutaneous, intra-arterial, intracardiac, intraventricular, intracranial, intratracheal, intrathecal administration, intramuscular injection, intravitreous injection, and topical application methods.