Composition of 5-nitrobenzoate derivatives as anti-metastatic agent that inhibits tumor cell-induced platelet aggregation

Abstract

Disclosed are 5-nitrobenzoate derivatives of Formula I, and the preparation method therefor, wherein R is referred to hydrogen (H), unsubstituted, mono-substituted, di-substituted or tri-substituted benzoyl moiety. 5-Nitrobenzoate derivatives of Formula I do not affect the platelet aggregation, possesses the inhibitory activity related to the tumor cell-induced platelet aggregation (TCIPA), and further specifically inhibits podoplanin-induced platelet aggregation. Therefore, 5-nitrobenzoates of the invention are applicable in its therapeutic use as the novel therapeutic agent in preventing tumor metastasis.

What is claimed is: 
     
         1 . A method of inhibiting metastasis of a tumor, the method comprising a step of administrating to a subject in need thereof an effective amount of a 5-nitrobenzoate derivative as represented by formula I, 
       
         
           
           
               
               
           
         
       
       wherein R one is selected from a group consisting of a hydrogen, an unsubstituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       a mono-substituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       a di-substituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       and a tri-substituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       and each of R 1 , R 2 , R 3 , R 4 , R 5  and R 6  is one selected from a group consisting of a fluoride, a chloride, a bromide, an iodide and a methyl group. 
     
     
         2 . The method according to  claim 1 , wherein the subject is one of a human and a mammal excluding the human. 
     
     
         3 . A method for blocking an interaction between a C-type lectin-like receptor 2 and a podoplanin or blocking an effect caused by the interaction therebetween, by comprising step of using a 5-nitrobenzoate derivative as represented by formula I, 
       
         
           
           
               
               
           
         
       
       wherein R is one selected from a group consisting of a hydrogen, an unsubstituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       a mono-substituted benzoyl moiety ( 
       
         
           
           
               
               
           
         
       
       a di-substituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       and a tri-substituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       and each of R 1 , R 2 , R 3 , R 4 , R 5  and R 6  is one selected from a group consisting of a fluoride, a chloride, a bromide, an iodide and a methyl group. 
     
     
         4 . A method for blocking a pathway of a tumor cell-induced platelet aggregation, comprising a step of using a 5-nitrobenzoate derivative as represented by formula I, 
       
         
           
           
               
               
           
         
       
       wherein R is one selected from a group consisting of a hydrogen, an unsubstituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       a mono-substituted benzoyl moiety ( 
       
         
           
           
               
               
           
         
       
       a di-substituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       and a tri-substituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       and each of R 1 , R 2 , R 3 , R 4 , R 5  and R 6  is one selected from a group consisting of a fluoride, a chloride, a bromide, an iodide and a methyl group. 
     
     
         5 . A 5-nitrobenzoate derivative represented by formula I, 
       
         
           
           
               
               
           
         
       
       wherein R is one selected from a group consisting of a hydrogen, an unsubstituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       a mono-substituted benzoyl moiety ( 
       
         
           
           
               
               
           
         
       
       a di-substituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       and a tri-substituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       each of R 1 , R 2 , R 3 , R 4 , R 5  and R 6  is one selected from a group consisting of a fluoride, a chloride, a bromide, an iodide and a methyl group. 
     
     
         6 . The 5-nitrobenzoate derivative according to  claim 5  being prepared as a pharmaceutical composition. 
     
     
         7 . The 5-nitrobenzoate derivative according to  claim 5  being prepared as a pharmacologically acceptable salt. 
     
     
         8 . A method for preparing a 5-nitrobenzoate derivative as represented by formula I, 
       
         
           
           
               
               
           
         
       
       the method comprising a step of using an N-(2-aminoethyl)-2-hydroxy-5-nitrobenzamide as one of a starting material and an intermediate, wherein R is one selected from a group consisting of a hydrogen, an unsubstituted benzoyl moiety ( 
       
         
           
           
               
               
           
         
       
       a mono-substituted benzoyl moiety 
                         
a di-substituted benzoyl moiety                  
 
       and a tri-substituted benzoyl moiety 
       
         
           
           
               
               
           
         
       
       and each of R 1 , R 2 , R 3 , R 4 , R 5  and R 6  is one selected from a group consisting of a fluoride, a chloride, a bromide, an iodide and a methyl group.