Use of rapamycin derivatives in vasculop atheis and xenotransplantation

Abstract

Use of a rapamycin derivative of formula I as defined in the claims for preventing or treating vasculopathies and manifestations of xenotransplantation.

1 . Use of a compound of formula I  
       
         
           
           
               
               
           
         
       
       wherein 
 X is (H,H) or O;  
 Y is (H,OH) or O;  
 R 1  and R 2  are independently selected from H, alkyl, arylalkyl, hydroxyalkyl, dihydroxyalkyl, hydroxyalkoxycarbonylalkyl, hydroxyalkylarylalkyl, dihydroxyalkylarylalkyl, acyloxyalkyl, aminoalkyl, alkylaminoalkyl, alkoxycarbonylaminoalkyl, acylaminoalkyl, arylsulfonamidoalkyl, allyl, dihydroxyalkylalkyl, dioxolanylallyl, dialkyl-dioxolanylalkyl, di(alkoxycarbonyl)-triazolyl-alkyl and hydroxyalkoxyalkyl; wherein “alk-” or “alkyl” is C 1-6 alkyl, branched or linear; “aryl” is phenyl or tolyl; and acyl is a radical derived from a carboxylic acid; and  
 R 4  is methyl or  
 R 4  is methyl or  
 R 4  and R 1  together form C 2-6 alkyl;  
 provided that R 1  and R 2  are not both H; and hydroxyalkoxyalkyl is other than hydroxyalkoxymethyl in the preparation of a pharmaceutical composition for preventing or treating neointimal proliferation and thickening.  
 
     
     
         2 . Use of a compound of formula I as defined in  claim 1 , for use in the preparation of a pharmaceutical composition for preventing or combating manifestations of chronic rejection in a recipient of organ or tissue transplant.  
     
     
         3 . Use of a compound of formula I as defined in  claim 1 , for use in the preparation of a pharmaceutical composition, for preventing or treating restenosis and/or vascular occlusion following vascular injury.  
     
     
         4 . Use of a compound of formula I as defined in  claim 1 , for use in the preparation of a pharmaceutical composition, for preventing or combating acute or chronic rejection in a recipient of organ or tissue xenograft transplant.  
     
     
         5 . Use of a compound of formula I as defined in  claim 1 , for preventing or treating neointimal proliferation and thickening, restenosis and/or vascular occlusion following vascular injury, or for preventing or combating manifestations of chronic rejection in a recipient of organ or tissue transplant, or acute or chronic rejection in a recipient of organ or tissue xenograft transplant.  
     
     
         6 . A pharmaceutical composition for preventing or treating neointimal proliferation and thickening, restenosis and/or vascular occlusion following vascular injury, or for preventing or combating manifestations of chronic rejection in a recipient of organ or tissue transplant, or acute or chronic rejection in a recipient of organ or tissue xenograft transplant, comprising a compound of formula I as defined in  claim 1  together with one or more pharmaceutically acceptable diluents or carriers therefor.  
     
     
         7 . A method for preventing or treating neointimal proliferation and thickening, restenosis, and/or vascular occlusion following vascular injury, comprising the step of administering to said recipient a therapeutically effective amount of a compound of formula I as defined in  claim 1 .  
     
     
         8 . A method for preventing or combating manifestations of chronic rejection in a recipient of organ or tissue transplant, or acute or chronic rejection in a recipient of organ or tissue xenograft transplant, comprising the step of administering to said recipient a therapeutically effective amount of a compound of formula I as defined in  claim 1 .  
     
     
         9 . Use according to any one of  claims 1  to  5 , wherein the compound of formula I is 40-O-(2-hydroxy)ethylrapamycin.  
     
     
         10 . A pharmaceutical composition according to  claim 6 , wherein the compound of formula I is 40-O-(2-hydroxy)ethylrapamycin.