Compositions and methods for the treatment of glioblastoma

Abstract

Provided are compositions that include a platelet-activating factor antagonist, pharmaceutical compositions including the platelet-activating factor antagonist, methods of treating a modulating the proliferation of a glioma or a pathological condition resulting from patient having a glioma.

1 . A composition comprising at least one compound having the formula I, or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 m is 1-4, 
 X is O or S, 
 R 1  and R 3  are independently H or Cl, 
 R 2  is H, butoxy, or Cl, 
 
       and wherein, when:
 R 2  is butoxy, m is 1 or 4, and 
 when R 1  and R 2  are both Cl, and X is O, m is 3 or 4. 
 
     
     
         2 . The composition of  claim 1 , wherein the at least one compound having the formula I is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt of any thereof. 
     
     
         3 . The composition of  claim 1 , wherein the compound is an R-enantiomer, an S-enantiomer, or a combination thereof. 
     
     
         4 . The composition of  claim 1 , wherein the compound or the pharmaceutically acceptable salt thereof is in an amount effective to inhibit the growth of a brain tumor or modulate a neurological activity induced by a brain tumor by antagonizing platelet-activating factor, and the composition further comprises a pharmaceutically acceptable carrier. 
     
     
         5 . The composition of  claim 4 , wherein the brain tumor is a selected from the group consisting of: a glioblastoma, an astrocytoma, an oligodendroglioma, an ependymal tumor, a neuronal tumor and a combination of glial tumors. 
     
     
         6 . The composition of  claim 1 , wherein the pharmaceutically acceptable salt is an acid addition salt. 
     
     
         7 . A method for treating or inhibiting a brain tumor or a pathological effect thereof, in a subject, the method comprising the steps:
 (a) selecting a subject in need of treatment, wherein the subject has been diagnosed with a brain tumor or a pathological effect of a brain tumor; and   (b) administering a therapeutic composition comprising a therapeutically effective amount of a platelet-activating factor (PAF) receptor antagonist and a pharmaceutically acceptable carrier,   
       wherein the PAF receptor antagonist is according to formula I, or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 m is 1-4, 
 X is O or S, 
 R 1  and R 3  are independently H or Cl, 
 R 2  is H, butoxy, or Cl, 
 
       and wherein, when:
 R 2  is butoxy, m is 1 or 4. 
 
     
     
         8 . The method of  claim 7 , wherein the compound having the formula I is 
       
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 7 , wherein the brain tumor is a selected from the group consisting of: a glioblastoma, an astrocytoma, an oligodendroglioma, an ependymal tumor, a neuronal tumor and a combination of glial tumors. 
     
     
         10 . The method of  claim 7 , wherein the pharmaceutically acceptable salt is an acid addition salt. 
     
     
         11 . The method of  claim 7 , wherein the compound having the formula I is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 10 , wherein the compound having the formula I is a pharmaceutically acceptable salt of 2,4,6-trimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 5-[2-(3,4-dichlorophenyl) sulfanethyl ester 3-[1,3-di-(4-morpholinyl)-2-propyl-1-ester (LAU-0901) and having the formula: 
       
         
           
           
               
               
           
         
       
     
     
         13 . The method of  claim 7 , wherein the therapeutic composition is formulated with an amount of the PAF receptor antagonist effective in reducing or inhibiting a pathological neurological condition associated with a brain tumor in a subject. 
     
     
         14 . The method of  claim 13 , wherein the therapeutic composition is formulated with an amount of the PAF receptor antagonist effective in reducing or inhibiting a seizure associated with glioblastoma in a subject. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . (canceled)