Aminopyrimidinyl compounds

Abstract

Methods of treatment as Janus Kinase inhibitors containing the compound of the invention having the structure:or a pharmaceutically acceptable salt thereof, wherein X is N; A is selected from the group consisting of a bond and C═O; R1 is C3-C6 cycloalkyl, wherein said cycloalkyl is further optionally substituted with one or more halo; R2 is hydrogen; R3 is hydrogen; R4 is monocyclic heteroaryl wherein said heteroaryl is optionally substituted with one or more C1-C6 alkyl; and, R5 is hydrogen; and, j is 0 or 1.

1 - 54 . (canceled) 
     
     
         55 . A method of treating or preventing a disease or condition selected from [inflammation, autoimmune disease, neuroinflammation, arthritis, rheumatoid arthritis, spondyloarthropathies, systemic lupus erythematous, lupus nephritis, osteoarthritis, gouty arthritis, pain, fever, pulmonary sarcoidosis, silicosis, cardiovascular disease, atherosclerosis, myocardial infarction, thrombosis, congestive heart failure and cardiac reperfusion injury, cardiomyopathy, stroke, ischemia, reperfusion injury, brain edema, brain trauma, neurodegeneration, liver disease, inflammatory bowel disease, Crohn's disease, ulcerative colitis, nephritis, retinitis, retinopathy, macular degeneration, glaucoma, diabetes (type 1 and type 2), diabetic neuropathy, viral and bacterial infection, myalgia, endotoxic shock, toxic shock syndrome, osteoporosis, multiple sclerosis, endometriosis, menstrual cramps, vaginitis, candidiasis, cancer, fibrosis, obesity, muscular dystrophy, polymyositis, dermatomyositis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis,] vitiligo, [Alzheimer's disease, skin flushing,] eczema, hand eczema, pruritis, psoriasis, atopic dermatitis, [sunburn, keloid, hypertrophic scar, rheumatic diseases, urticaria, discoid lupus,] cutaneous lupus, [central nervous system lupus, psoriatic arthritis, asthma, allergic asthma, type I interferonopathies including Aicardi-Goutières syndrome and other mendelian diseases of overexpression of type I interferon, primary progressive multiple sclerosis, relapsing remitting multiple sclerosis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, scleroderma,] alopecia areata, scarring alopecia, [prurigo, prurigo nodularis, CPUO, lichen diseases, lichen planus, Steven's Johnson's syndrome, spondylopathy, myositis, vasculitis, pemphigus, lupus, major depression disorder, allergy, dry eye syndrome, transplant rejection, cancer, septic shock, cardiopulmonary dysfunction, acute respiratory disease, ankylosing spondylitis, cachexia, chronic graft-versus-host disease, acute graft-versus-host disease, Celiac Sprue, idiopathic thrombocytopenic thrombotic purpura, thrombotic thrombocytopenic purpura, myasthenia gravis, Sjogren's syndrome, epidermal hyperplasia, cartilage inflammation, bone degradation, juvenile arthritis, juvenile rheumatoid arthritis, pauciarticular juvenile rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, systemic onset juvenile rheumatoid arthritis, juvenile ankylosing spondylitis, juvenile enteropathic arthritis, juvenile Reter's Syndrome, SEA Syndrome, juvenile dermatomyositis, juvenile psoriatic arthritis, juvenile scleroderma, juvenile systemic lupus erythematosus, juvenile vasculitis, pauciarticular rheumatoid arthritis, polyarticular rheumatoid arthritis, systemic onset rheumatoid arthritis, enteropathic arthritis, reactive arthritis, Reter's Syndrome, myolitis, polymyolitis, dermatomyolitis, polyarteritis nodosa, Wegener's granulomatosis, arteritis, polymyalgia rheumatica, sarcoidosis, sclerosis, primary biliary sclerosis, sclerosing cholangitis, dermatitis, Still's disease, chronic obstructive pulmonary disease, Guillain-Barre disease, Graves' disease, Addison's disease, Raynaud's phenomenon, psoriatic epidermal hyperplasia,] plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, [an immune disorder associated with or arising from activity of pathogenic lymphocytes, noninfectious uveitis, Behcet's disease and Vogt-Koyanagi-Harada syndrome,] comprising administering to a subject in need thereof a therapeutically effective amount of a compound [of claim  44  to  51 ] having the structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein
 is N; 
 A is selected from the group consisting of a bond and C═O; 
 R 1  is C 3 -C 6  cycloalkyl, wherein said cycloalkyl is further optionally substituted with one or more halo; 
 R 2  is hydrogen; 
 R 3  is hydrogen; 
 R 4  is monocyclic heteroaryl wherein said heteroaryl is optionally substituted with one or more C 1 -C 6  alkyl; and, 
 R 5  is hydrogen; and, j is 0 or 1, 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
         56 . The method of  claim 55  wherein the compound has the structure: 
       
         
           
           
               
               
           
         
       
       wherein R′ is C 1 -C 6  alkyl. 
     
     
         57 . The method of  claim 55  or  56 , wherein the disease or condition is psoriasis. 
     
     
         58 . The method of  claim 55  or  56 , wherein the disease or condition is atopic dermatitis. 
     
     
         59 . The method of  claim 55  or  56 , wherein the disease or condition is hand eczema. 
     
     
         60 . The method of  claim 55  or  56 , wherein the disease or condition is pruritis. 
     
     
         61 . The method of  claim 55  or  56 , wherein the disease or condition is cutaneous lupus. 
     
     
         62 . The method of  claim 55  or  56 , wherein the compound is administered topically. 
     
     
         63 - 64 . (canceled)