S1p receptor modulators for treating multiple sclerosis

Abstract

The present invention relates uses of an S1P receptor modulator such as 2-substituted 2-amino-propane-1,3-diol or 2-amino-propanol derivatives, e.g. a compound comprising a group of formula X for the treatment or prevention of neo-angiogenesis associated with a demyelinating disease, e.g. multiple sclerosis.

1 - 3 . (canceled) 
   
   
       4 . A method according to  claim 7 , wherein the medicament is co-administered, e.g. concomitantly or in sequence, with a VEGF-receptor antagonist. 
   
   
       5 . A pharmaceutical composition for use in the method according to  claim 7 , comprising an S1P receptor modulator together with one or more pharmaceutically acceptable diluents or carriers therefor. 
   
   
       6 . A pharmaceutical combination, e.g. a kit, comprising a) a first agent which is a S1P receptor modulator, in free form or in pharmaceutically acceptable salt form, and b) a VEGF-receptor antagonist. 
   
   
       7 . A method for preventing, inhibiting or treating neo-angiogenesis associated with a demyelinating disease in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of an S1P receptor modulator. 
   
   
       8 . A method according to  claim 7 , wherein the demyelinating disease is multiple sclerosis. 
   
   
       9 . A method according to  claim 8 , wherein the S1P receptor modulator is administered intermittently. 
   
   
       10 . A method according to  claim 14 , wherein the S1P receptor modulator or agonist is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol, 2-amino-2-[4-(3-benzyloxyphenoxy)-2-chlorophenyl]ethyl-1,3-propane-diol, or 1-{4-[1-(4-cyclohexyl-3-trifluoromethyl-benzyloxyimino)-ethyl]-2-ethyl-benzyl}-azetidine-3-carboxylic acid, in free form or in a pharmaceutically acceptable salt form. 
   
   
       11 . A method according to  claim 10 , wherein the S1P receptor modulator is 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in free form or in a pharmaceutically acceptable salt form. 
   
   
       12 . A method according to  claim 7 , wherein the demyelinating disease is primary progressive multiple sclerosis (PP-MS). 
   
   
       13 . A method according to  claim 7 , wherein the S1P receptor modulator comprises a group of formulae I to IXb. 
   
   
       14 . A method according to  claim 7 , wherein the S1P receptor modulator comprises a group of formula X: 
     
       
         
         
             
             
         
       
     
     wherein Z is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, phenyl, phenyl substituted by OH, C 1-6 alkyl substituted by 1 to 3 substituents selected from the group consisting of halogen, C 3-8 cycloalkyl, phenyl and phenyl substituted by OH, or CH 2 —R 4z  wherein R 4z  is OH, acyloxy or a residue of formula (a) 
     
       
         
         
             
             
         
       
     
     wherein Z 1  is a direct bond or O, preferably O;
 each of R 5z  and R 6z , independently, is H, or C 1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms; 
 R 1z  is OH, acyloxy or a residue of formula (a); and each of R 2z  and R 3z  independently, is H, C 1-4 alkyl or acyl.