Compounds and Dosage Regimen for Use in the Prevention or Treatment of Chronic Inflammatory and/or Autoimmune Diseases

Abstract

and a novel dosage regimen as well as their uses in the treatment of chronic inflammatory and/or autoimmune diseases. The said compound of formula (I) inhibits dihydroorotate dehydrogenase (DHODH), and is known for the treatment and prevention of diseases, in particular their use in diseases where there is an advantage in inhibiting dihydroorotate dehydrogenase (DHODH).

1 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) according to formula (I) 
       
         
           
           
               
               
           
         
       
       or salts thereof or solvates of the said compound (I) or the salts thereof for use as a medicament in a patient in need thereof, wherein the compound (I) or salts thereof or solvates of the compound (I) and the salts thereof is initially administered to said patient in an initial daily dose of 14-130 μmol of the active moiety of the compound (I) for a period of minimum 5 and maximum 10 days and is thereafter administered in a subsequent dose that is 1.5 to 8.0-fold higher than the said initial daily dose. 
     
     
         2 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or salts thereof or solvates of the said compound or the salts thereof for use as a medicament in a patient in need thereof according to  claim 1 , wherein said subsequent dose is 28-200 μmol of the active moiety of the compound daily. 
     
     
         3 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or salts thereof or solvates of the said compound or the salts thereof for use as a medicament in a patient in need thereof according to  claim 1 , wherein said patient suffers from a chronic inflammatory and/or autoimmune disease. 
     
     
         4 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or salts thereof or solvates of the said compound or the salts thereof for use as a medicament in a patient in need thereof according to  claim 1 , wherein said patient suffers from a chronic inflammatory and/or autoimmune disease selected from the group consisting of rheumatism, acute immunological disorders, autoimmune diseases, diseases caused by malignant cell proliferation, inflammatory diseases, diseases that are caused by protozoal infestations in humans and animals, diseases that are caused by viral infections and neumocystis  carinii , fibrosis, uveitis, rhinitis, asthma or athropathy. 
     
     
         5 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or salts thereof or solvates of the said compound or the salts thereof for use as a medicament in a patient in need thereof according to  claim 1 , wherein said patient suffers from a chronic inflammatory and/or autoimmune disease selected from the group comprising graft versus host and host versus graft reactions, rheumatoid arthritis, multiple sclerosis, lupus erythematosus, inflammatory bowel disease, type 1 diabetes and psoriasis. 
     
     
         6 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or salts thereof or solvates of the said compound or the salts thereof for use as a medicament in a patient in need thereof according to  claim 1 , wherein said patient suffers from inflammatory bowel disease, in particular ulcerative colitis and Crohn's disease. 
     
     
         7 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or salts thereof or solvates of the said compound or the salts thereof for use as a medicament in a patient in need thereof according to  claim 1 , wherein the compound 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or a solvate thereof is administered. 
     
     
         8 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or salts thereof or solvates of the said compound or the salts thereof for use as a medicament in a patient in need thereof according to  claim 1 , wherein the calcium salt of the said compound or a solvate thereof is administered. 
     
     
         9 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or salts thereof or solvates of the said compound or the salts thereof for use as a medicament in a patient in need thereof according to  claim 1 , wherein the first daily dose is 60-70 μmol and the subsequent dose is 120-140 μmol. 
     
     
         10 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or salts thereof or solvates of the said compound or the salts thereof for use as a medicament in a patient in need thereof according to  claim 1 , wherein the first daily dose is 6-8 days. 
     
     
         11 . A compound that is 2-({3-fluoro-3′-methoxy-[1,1′-biphenyl]-4-yl}carbamoyl)cyclopent-1-ene-1-carboxylic acid) or salts thereof or solvates of the said compound or the salts thereof for use as a medicament in a patient in need thereof according to  claim 1 , wherein the solvate is an ethanol solvate or a dehydrate.