Arginine Derivatives with NP-I Antagonistic Activity

Abstract

The present invention is a compound of formula (I) or formula (II) which are suitable as NP-1 antagonists.

1 . A compound of formula I or formula II 
       
         
           
           
               
               
           
         
       
       wherein
 X is CH 2 , C(O), NH, O or SO 2 ; 
 Y is a direct bond or furanylene; 
 Z 1  is an arylene or heteroaromatic group; 
 Z 2  is a direct bond, a SO 2 NH, CONH or NHCONH group; 
 Z 3  is an aryl or heteroaromatic group; 
 Z 4  is CH 2  or NR 1 ; 
 Z 5  is H, OH, C(O)OR 1  or P(O)(OR 1 ) 2 ; 
 Z 6  is, OR 1  or NHR 2 ; 
 each R 1  is independently H or an alkyl group; 
 each R 2  is independently H or a CN, OH or SO 2 CH 3  group; and 
 n is 0, 1 or 2, 
 or a pharmaceutically acceptable salt, solvate or polymorph thereof. 
 
     
     
         2 . A compound according to  claim 1 , wherein Z 2  is an SO 2 NH group. 
     
     
         3 . A compound according to  claim 1  or  claim 2 , wherein Z 1  is phenylene, biphenylene, thiophenylene, -thiophenylene(phenyl), -thiophenylene(alkyl), furanylene, thiazolylene or pyridylene. 
     
     
         4 . A compound according to any preceding claim, wherein Z 3  is an aryl group. 
     
     
         5 . A compound according to  claim 4 , wherein Z 3  is an -aryl(nitro) or aryl(amino) group. 
     
     
         6 . A compound according to any of  claims 1  to  3 , wherein Z 3  is a benzofused 5-membered ring containing one or more heteroatoms selected from N, O or S. 
     
     
         7 . A compound according to  claim 6 , wherein Z 3  is benzo[1,2,5]thiadiazole. 
     
     
         8 . A compound according to any preceding claim for use in therapy. 
     
     
         9 . A compound according to any preceding claim, for use in stimulating nerve repair. 
     
     
         10 . A compound according to any of  claims 1  to  8 , for use in the treatment of neurodegeneration. 
     
     
         11 . A compound according to any of  claims 1  to  8 , for use in the treatment of cancer. 
     
     
         12 . A compound according to any of  claims 1  to  8 , for use in immune system modulation. 
     
     
         13 . A method of stimulating nerve repair, using a compound according to any of  claims 1  to  7 . 
     
     
         14 . A method of treating neurodegeneration, using a compound according to any of  claims 1  to  7 . 
     
     
         15 . A method of treating cancer, using a compound according to any of  claims 1  to  7 . 
     
     
         16 . A method of immune system modulation, using a compound according to any of  claims 1  to  7 .