Method and pharmaceutical composition for inhibiting invasion and/or metastasis of ovarian carcinoma

Abstract

The invention discloses a compound of the general formula (I) wherein X is selected from the group consisting of —(CH 2 ) n OH, —(CH 2 ) n NH 2 , —(CH 2 ) n SH, —(CH 2 ) m COOH, —(CH 2 ) m COOR, —(CH 2 ) m CONH 2 , —(CH 2 ) m″ CONH—OH, (CH 2 ) m″ CONH—R, and —(CH 2 ) n′ O(PO 3 ) m″ (m″+1) , wherein n=2, 3, 4 or 5; n′=2 or 3; m=1, 2, 3 or 4; m′=1, 2, 3, 4, 5 or 6; m″=1, 2 or 3; and R=—C m′ H 2m′+1 , or an aryl group, especially 1-[3,4-dihydroxy-5-(2-hydroxyethyl)-tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione, methods for treating or preventing MMP-related disorders and TNFα-related disorders alone or simultaneously, methods for the inhibition of the invasion and/or metastasis of ovarian carcinoma, and pharmaceutical compositions containing said compound for said treatments.

What is claimed is:  
     
         1 . A method for inhibiting the invasion and/or metastasis of a carcinoma in a mammal in need thereof, comprising administering to said mammal an effective amount of a compound of formula I  
       
         
           
           
               
               
           
         
         wherein X is selected from the group consisting of —(CH 2 ) n OH, —(CH 2 ) n NH 2 , —(CH 2 ) n SH, —(CH 2 ) m COOH, —(CH 2 ) m COOR, —(CH 2 ) m CONH 2 , —(CH 2 ) m″ CONH—OH, —(CH 2 ) m″ CONH—R, and —(CH 2 ) n′ O(PO 3 ) m″   (m″+1) , wherein n=2, 3, 4 or 5; n′=2 or 3; m=1, 2, 3 or 4; m′=1, 2, 3, 4, 5 or 6; m″=1, 2 or 3; and R=—C m′ H 2m′+1  or an aryl group.  
       
     
     
         2 . The method of  claim 1 , wherein said carcinoma is an ovarian carcinoma.  
     
     
         3 . The method of  claim 2 , wherein said ovarian carcinoma is a human ovarian carcinoma.  
     
     
         4 . The method of  claim 1 , wherein said compound is 1-[3,4-dihydroxy-5-(2-hydroxyethyl)-tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione.  
     
     
         5 . The method of  claim 2 , wherein said compound is 1-[3,4-dihydroxy-5-(2-hydroxyethyl)-tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione.  
     
     
         6 . The method of  claim 3 , wherein said compound is 1-[3,4-dihydroxy-5-(2-hydroxyethyl)-tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione.  
     
     
         7 . The method of  claim 1 , wherein said mammal is a human.  
     
     
         8 . A pharmaceutical composition for inhibiting the invasion and/or metastasis of a carcinoma in a mammal in need thereof, which comprises an effective amount of the compound of formula I  
       
         
           
           
               
               
           
         
         wherein X is selected from the group consisting of —(CH 2 ) n OH, —(CH 2 ) n NH 2 , —(CH 2 ) n SH, —(CH 2 ) m COOH, —(CH 2 ) m COOR, —(CH 2 ) m CONH 2 , —(CH 2 ) m″ CONH—OH, —(CH 2 ) m″ CONH—R, and —(CH 2 ) n′ O(PO 3 ) m″   (m″+1) , wherein n=2, 3, 4 or 5; n′=2 or 3; m=1, 2, 3 or 4; m′=1, 2, 3, 4, 5 or 6; m″=1, 2 or 3; and R——C m′ H 2m′+1  or an aryl group in admixture with a pharmaceutically acceptable excipient or diluent.  
       
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein said carcinoma is an ovarian carcinoma.  
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein said ovarian carcinoma is a human ovarian carcinoma.  
     
     
         11 . The pharmaceutical composition of  claim 8 , wherein said compound is 1-[3,4-dihydroxy-5-(2-hydroxyethyl)-tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione.  
     
     
         12 . The pharmaceutical composition of  claim 9 , wherein said compound is 1-[3,4-dihydroxy-5-(2-hydroxyethyl)-tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione.  
     
     
         13 . The pharmaceutical composition of  claim 10 , wherein said compound is 1-[3,4-dihydroxy-5-(2-hydroxyethyl)-tetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione.  
     
     
         14 . The pharmaceutical composition of  claim 8 , wherein said mammal is human.