Compounds which interact with the thyroid hormone receptor for the treatment of fibrotic disease

Abstract

A method of alleviating psoriasis in a warm blooded animal, which comprises administering an effective amount of at least one compound having the formula (I) in which X stands for the oxygen or sulphur atom or for the imino (—NH—) or sulphonyl (—SO 2 —) radical, Y stands for a direct linkage, or for the oxygen or sulphur atom or for the sulphonyl (—SO 2 —) radical or for the radical of the formula —CR 1 R 2 —, wherein R 1 and R 2 which may be the same or different are hydrogen, alkyl or aryl radicals or R 1 and R 2 may be joined together to form a cycloalkyl ring, n is an integer having the value 0 or 1, provided that when n is 0, Y stands for the oxygen or sulphur atom or for the sulphonyl (—SO 2 —) radical, or an ester, amide or salt thereof.

1 . A method of alleviating fibrotic disease by regulating tissue destructive proteolytic enzyme production in the presence of thyroid receptor binding but in the substantial absence of substantive corticosteroid and androgen receptor binding:  
     
     
         2 . A method as claimed in  claim 1  in which the fibrotic disease is regulated by administration of an effective amount of at least one compound having the formula (I)  
       
         
           
           
               
               
           
         
       
       in which X stands for the oxygen or sulphur atom or for the imino (—NH—) or sulphonyl (—SO 2 —) radical, Y stands for a direct linkage, or for the oxygen or sulphur atom or for the sulphonyl (—SO 2 —) radical or for the radical of the formula —CR 1 R 2 —, wherein R 1  and R 2  which may be the same or different are hydrogen, alkyl or aryl radicals as hereinafter described, ring B may be optionally substituted by one or more substituents selected from halogen atoms and alkyl and aryl radicals, n is an integer having the value 0 or 1, and esters, amides and salts thereof.  
     
     
         3 . A method as claimed in  claim 1  in which the fibrotic disease is regulated by administration of an effective amount of at least one compound having the formula (II)  
       
         
           
           
               
               
           
         
       
     
     
         4 . A method as claimed in  claim 1  in which the fibrotic disease is regulated by administration of an effective amount of at least one compound having the formula (III)  
       
         
           
           
               
               
           
         
       
     
     
         5  A method of regulating MMP gene activation in the substantial absence of occupation of either corticosteroid receptor or androgen receptor.  
     
     
         6  A method of regulating MMP gene activation in by the occupation of thyroid receptor  
     
     
         7 . A method of regulating MMP gene activation by the occupation of thyroid receptor but in the substantial absence of occupation of either corticosteroid receptor or androgen receptor  
     
     
         8 . A method of regulating MMP gene activation by the occupation of thyroid receptor but in the substantial absence of occupation of either corticosteroid receptor or androgen receptor by administration of an effective amount of at least one compound having the formula (I)  
     
     
         9 . The use of a compound having the structure (I) in the preparation of a medicament for the structural modification of fibrotic tissue in a warm blooded animal by regulating tissue destructive proteolytic enzyme production in the presence of thyroid receptor binding but in the substantial absence of substantive corticosteroid and androgen receptor binding  
       
         
           
           
               
               
           
         
       
       in which X stands for the oxygen or sulphur atom or for the imino (—NH—) or sulphonyl (—SO 2 —) radical, Y stands for a direct linkage, or for the oxygen or sulphur atom or for the sulphonyl (—SO 2 —) radical or for the radical of the formula —CR 1 R 2 —, wherein R 1  and R 2  which may be the same or different are hydrogen, alkyl or aryl radicals as hereinafter described, ring B may be optionally substituted by one or more substituents selected from halogen atoms and alkyl and aryl radicals, n is an integer having the value 0 or 1, and esters, amides and salts thereof.  
     
     
         10 . The use as claimed in  claim 4  in which the compound has the formula (II)  
       
         
           
           
               
               
           
         
       
     
     
         11 . The use as claimed in  claim 4  in which the compound has the formula (III)  
       
         
           
           
               
               
           
         
       
     
     
         12 . The use of a compound having the formula (I) in the preparation of a medicament for the regulation of MMP gene activation in the substantial absence of occupation of either corticosteroid receptor or androgen receptor.  
     
     
         13 . The use of a compound having the formula (I) in the preparation of a medicament for the regulation of MMP gene activation in by the occupation of thyroid receptor.  
     
     
         14  The use of a compound having the formula (I) in the preparation of a medicament for the regulation of MMP gene activation by the occupation of thyroid receptor but in the substantial absence of occupation of either corticosteroid receptor or androgen receptor.