Methods for treating inflammatory conditions or inhibiting JNK

Abstract

This invention generally relates to methods for treating or preventing an inflammatory disease or disorder comprising administering to a patient in need thereof an effective amount of a Pyrazoloanthrone Derivative having the following structure: or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are as defined herein.

What is claimed is:  
     
         1 . A method for the treating or preventing an inflammatory condition, comprising administering to a patient in need thereof an effective amount of a compound having the structure:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, 
 wherein 
 R 1  and R 2  are absent or present and independently represent alkyl halogen, nitro, trifluoromethyl, sulfonyl, carboxyl, alkoxycarbonyl, alkoxy, aryl, aryloxy, arylalkyloxy, arylalkyl, cycloalkylalkyloxy, cycloalkyloxy, alkoxyalkyl, alkoxyalkoxy, aminoalkoxy, mono- or di-alkylaminoalkoxy, or a group represented by formula (a), (b), (c) or (d):  
                     
 R 3  and R 4  taken together represent alkylidene or a heteroatom-containing alkylidene, or R 3  and R 4  are the same or different and independently represent hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, cycloalkylalkyl, aryloxyalkyl, alkoxyalkyl, alkoxyamono, or alkoxy(mono- or di-alkylamino): and  
 R 5  represents hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, cycloalkylalkyl, alkoxy, amino, mono- or di-alkylamino, arylamino, arylalkylamino, cycloalkylamino, or cycloalkylalkylamino.  
 
 
     
     
         2 . The method of  claim 1  wherein the treating or preventing comprises inhibiting JNK in vivo.  
     
     
         3 . The method of  claim 2  wherein inhibiting JNK in vivo comprises inhibiting TNF-α in vivo.  
     
     
         4 . The method of  claim 1  wherein the inflammatory condition is Type II diabetes or obesity.  
     
     
         5 . The method of  claim 1  wherein the inflammatory condition is rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gout, asthma, bronchitis, allergic rhinitis, inflammatory bowel disease, irritable bowel syndrome, mucous colitis, ulcerative colitis, Crohn's disease, gastritis, esophagitis, transplant rejection, endotoxin shock, psoriasis, eczema, dermatitis or multiple sclerosis.  
     
     
         6 . The method of  claim 1  wherein the inflammatory condition is hereditary obesity, dietary obesity, hormone related obesity or obesity related to the administration of medication.  
     
     
         7 . The method of  claim 1  wherein the inflammatory condition is Type I diabetes, diabetes insipidus, diabetes mellitus, maturity-onset diabetes, juvenile diabetes, insulin-dependant diabetes, non-insulin dependant diabetes, malnutrition-related diabetes, ketosis-prone diabetes or ketosis-resistant diabetes.  
     
     
         8 . The method of  claim 1  wherein the inflammatory condition is otitis externa, acute otitis media, hearing loss, systemic lupus erythematosus, pancreatitis, peritonitis, sepsis, alcohol or toxin-induced liver disease, sclerosis, steatosis, ischemia-reperfusion injury, allergic rhinitis, an allergy, nephropathy, acute respiratory distress syndrome, chronic obstructive pulmonary disease, pulmonary interstitial fibrosis, liver fibrosis, renal fibrosis, wound-healing or burn-healing.  
     
     
         9 . The method of  claim 1  wherein the compound has the following structure:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         10 . The method of  claim 1  wherein the compound has one of the following structures:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         11 . The method of  claim 1  wherein the compound has one of the following structures:  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof.  
     
     
         12 . The method of  claim 11  wherein in the compound or pharmaceutically acceptable salt thereof, R 1  and R 2  are:  
       
         
           
           
               
               
           
         
       
     
     
         13 . The method of  claim 11  wherein in the compound or pharmaceutically acceptable salt thereof, R 1  and R 2  are:  
       
         
           
           
               
               
           
         
       
     
     
         14 . The method of  claim 11  wherein in the compound or pharmaceutically acceptable salt thereof, R 1  and R 2  are:  
       
         
           
           
               
               
           
         
       
     
     
         15 . The method of  claim 11  wherein in the compound or pharmaceutically acceptable salt thereof, R 1  and R 2  are: