Anti-Inflammatory Pyrazolopyrimndines

Abstract

The present invention provides anti-inflammatory compounds useful in the treatment of diseases and conditions in which inflammation is involved in disease progression or the manifestation of symptoms of the disease or condition.

1 . A compound having the formula: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is substituted or unsubstituted heteroaryl; 
         R 2 , R 3 , and R 4  are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and 
         L 1  is a bond, substituted or unsubstituted alkylene, substituted or unsubstituted cycloalkylene or substituted or unsubstituted heteroalkylene. 
       
     
     
         2 . A compound according to  claim 1 , wherein
 R 2  is R 10 -substituted C 1 -C 20  alkyl, 2 to 20 membered substituted or unsubstituted heteroalkyl, R 11 -substituted C 3 -C 8  cycloalkyl, R 11 -substituted C 3 -C 8  heterocycloalkyl, R 12 -substituted heteroaryl, or R 13 -substituted aryl,   wherein   R 10  is oxo, —OH, halogen, —CF 3 , —NH 2 , 2 to 20 membered substituted or unsubstituted heteroalkyl, 3 to 7 membered substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, or R 13 -substituted aryl,   R 11  is oxo, —OH, halogen, —CF 3 , —NH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl,   R 12  is —OH, halogen, —CF 3 , —NH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and   R 13  is —OH; —NH 2 , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted aryl.   
     
     
         3 . A compound according to  claim 1 , wherein
 R 1  is R 15 -substituted heteroaryl, and further wherein   R 15  is —OH, halogen, —CF 3 , —NH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.   
     
     
         4 . A compound according to  claim 1 , wherein
 R 1  is substituted or unsubstituted fused-ring heteroaryl.   
     
     
         5 . A compound according to  claim 1 ,
 R 3  and R 4  are hydrogen   
     
     
         6 . A method for treating a disorder, said method comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         7 . The method of  claim 6 , wherein
 R 1  is R 15 -substituted heteroaryl, and further wherein   R 15  is —OH, halogen, —CF 3 , —NH 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl.   
     
     
         8 . The method of  claim 6 , wherein
 R 1  is substituted or unsubstituted fused-ring heteroaryl.   
     
     
         9 . The method of  claim 6 , wherein
 R 3  and R 4  are hydrogen.   
     
     
         10 . The method of  claim 6 , wherein said disorder is an inflammatory process that occurs in response to infection, trauma, autoimmune disease, cardiovascular disease, neoplasia, hyperplasia, addiction, infection, obesity, cellular degeneration, apoptosis, or senescence, or differentiation. 
     
     
         11 . The method of  claim 6 , wherein said disorder is selected from the group consisting of vasculitis, multiple sclerosis, diabetes, inflammatory bowel disease, psoriasis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, asthma, stroke, atherosclerosis, and lupus. 
     
     
         12 . The method of  claim 6 , wherein said disorder is selected from the group consisting of headaches, bronchitis, menstrual cramps, tendonitis, gastritis, vascular diseases, uveitis, Sjogren's disease, sclerodoma, nephrotic syndrome, swelling occurring after injury, myocardial ischemia, fever, common cold, dysmenorrhea, emphysema, acute respiratory distress syndrome, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant toxicity, cachexia, allergic reactions, allergic contact hypersensitivity, cancer, tissue ulceration, peptic ulcers, regional enteritis, ulcerative colitis, diverticulitis, recurrent gastrointestinal lesion, gastrointestinal bleeding, coagulation, synovitis, gout, ankylosing spondylitis, restenosis, periodontal disease, epidermolysis bullosa, osteoporosis, loosening of artificial joint implants, aortic aneurysm, periarteritis nodosa, congestive heart failure, myocardial infarction, cerebral ischemia, head trauma, spinal cord injury, neuralgia, neuro-degenerative disorders, autoimmune disorders, Huntington's disease, Parkinson's disease, migraine, depression, peripheral neuropathy, pain, gingivitis, cerebral amyloid angiopathy, nootropic or cognition enhancement, amyotrophic lateral sclerosis, multiple sclerosis, ocular angiogenesis, corneal injury, macular degeneration, conjunctivitis, abnormal wound healing, muscle or joint sprains or strains, tendonitis, skin disorders, myasthenia gravis, polymyositis, myositis, bursitis, burns, diabetes, tumor invasion, tumor growth, tumor metastasis, corneal scarring, scleritis, immunodeficiency diseases, sepsis, premature labor, hypoprothrombinemia, hemophilia, thyroiditis, sarcoidosis, Behcet's syndrome, hypersensitivity, kidney disease, Rickettsial infections, Protozoan diseases, reproductive disorders, and septic shock.