Methods to treat autoimmune and inflammatory conditions

Abstract

This invention provides methods for treating inflammatory or autoimmune diseases by contacting the affected cell or tissue with a therapeutic compound as described herein. Such pathologies include, but are not limited to rheumatoid arthritis, systemic lupus erythmatosus, psoriatic arthritis, reactive arthritis, Crohn's disease, ulcerative colitis and scleroderma. Therapeutic compounds useful in the methods of this invention are selected from the group consisting of a 1,5-substituted pyrimidine derivative or analog and substituted furano-pyrimidone analog.

1 . A method for treating a subject having an autoimmune disorder or inflammatory condition comprising delivering to the subject an effective amount of a compound selected from the group consisting of a 1,5-substituted pyrimidine derivative or analog and a substituted furano-pyrimidone derivative or analog.  
   
   
       2 . The method of  claim 1 , wherein the compound is a 1,5-substituted deoxyuridine derivative or analog.  
   
   
       3 . The method of  claim 1 , wherein the compound is a substituted furanopyrimidone derivative or analog.  
   
   
       4 . The method of  claim 2 , wherein the 1,5-substituted deoxylsridine derivative or analog is a compound selected from the group consisting of a 5′-phosphoramidatyl deoxyuridine, a substituted 5′-phosphoramidyl deoxyuridine, a 5′-phosphoryl deoxyuridine, and a substituted, 5′-phosphoryl deoxyuridine.  
   
   
       5 . The method of  claim 2 , wherein the 1,5-substituted deoxyuridine is substituted at the 5 position with a substituent selected from the group consisting of alkyl, alkenyl, alkynyl, vinyl, propargyl and substituted derivatives thereof.  
   
   
       6 . The method of  claim 5 , wherein the substituted derivatives are halogen-substituted derivatives.  
   
   
       7 . The method of  claim 6 , wherein the halogen-substituted derivative is a 5-haloalkyl substituted deoxyuridine.  
   
   
       8 . The method of  claim 7 , wherein the compound is 5-bromovinyl substituted deoxyuridine.  
   
   
       9 . The method of  claim 4 , wherein the 1,5-substituted deoxyuridine is a 5′-phosphoryl derivative of pyrimidine.  
   
   
       10 . The method of  claim 4 , wherein the 1,5-substituted deoxyuridine is a 5′-phosphoramidatyl derivative of pyrimidine.  
   
   
       11 . The method of  claim 10 , wherein the a 5′-phosphoramidatyl derivative is (E)-5-(2-bromovinyl)-2′-deoxy-5′-uridyl phenyl L-alaninylphosphoramidate.  
   
   
       12 . The method of  claim 1 , wherein the subject has an autoimmune disease.  
   
   
       13 . The method of  claim 12 , wherein the autoimmune disease is selected from the group consisting of multiple sclerosis, Type 1 diabetes, glomerulonephotis systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, reactive arthritis, Sjogren's syndrome, graft-versus-host disease (GVHD), muscular dystrophy, myasthenia gravis, atherosclerosis and osteoarthritis.  
   
   
       14 . The method of  claim 1 , wherein the subject has an inflammatory condition.  
   
   
       15 . The method of  claim 14 , wherein the inflammatory condition is selected from the group consisting of psoriasis, ulcerative colitis, scleroderma, inflammatory bowel disease, asthma, and Crohn's disease.  
   
   
       16 . The method of  claim 1 , further comprising administering an effective amount of an agent that treats an autoimmune and/or inflammatory condition.  
   
   
       17 . The method of  claim 16 , wherein the agent is selected from the group consisting of a corticosteroid, a N-SAID, an anti-rheumatic drug and an anti-TNF agent.  
   
   
       18 . A method for treating cells or tissue involved in a pathology selected from the group consisting of an autoimmune disease and an inflammatory condition, comprising contacting the cells or tissue with an effective amount of a compound selected from the group consisting of a 13-substituted pyrimidine derivative or analog and a substituted furano-pyrimidone derivative or analog thereof.  
   
   
       19 . The method of  claim 18 , wherein the compound is (E)-5-(2-bromovinyl)-2′-deoxy-5′-uridyl phenyl L-alaninylphosphoramidate.  
   
   
       20 . An assay for selecting agents that treat cells or tissue involved in a pathology selected from the group consisting of an autoimmune disease and an inflammatory condition, comprising contacting a first sample comprising suitable cells or tissue with an effective amount of a compound selected from the group consisting of a deoxyuridine, a substituted deoxyuridine, a substituted deoxyuridine derivative and analogs thereof and contacting a second sample of the suitable cells or tissue with the agent to be assayed and comparing the treatment of the first and second samples.  
   
   
       21 - 22 . (canceled)