Monocyclic Heteroaryl Cycloalkyldiamine Derivatives

Abstract

The present invention relates to monocyclic heteroaryl cycloalkyldiamine derivatives, to processes for their production, to their use as pharmaceuticals and to pharmaceutical compositions comprising them.

What is claimed is: 
     
         1 . A compound of the formula (I) or a pharmaceutically acceptable salt thereof, 
       
         
           
           
               
               
           
         
         wherein 
         X1 is CH or N; 
         Y1, Y2 and Y3 are depending on the position of the double bond independently of each other CH, NH or N, and the bent bond indicates aromaticity of the ring system; 
         R1 is H, alkyl, CN, or Hal; and 
         R2 is H, alkyl, or Hal; and 
       
       
         
           
           
               
               
           
         
         wherein the above structural part (L) in a compound of formula (I) is a fully aromatic bicyclic system containing at least 1 nitrogen atom represented by anyone of the members Y1, Y2 and Y3. 
       
     
     
         2 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein
 X1 is N; 
 Y1 is NH, Y2 is N and Y3 is CH; or 
 Y1 is CH, Y2 is N and Y3 is NH; 
 R1 is H, C 1-4 alkyl, CN, or Hal; and 
 R2 is H, C 1-4 alkyl or Hal. 
 
     
     
         3 . A compound of  claim 1  or a pharmaceutically acceptable salt thereof, wherein
 X1 is N; 
 Y1 is NH; Y2 and Y3 are CH; 
 R1 is H, C 1-4 alkyl, CN, or Hal; and 
 R2 is H, C 1-4 alkyl or Hal. 
 
     
     
         4 . A compound according to  claim 1  which is a compound of formula (II) or a pharmaceutically acceptable salt thereof, wherein 
       
         
           
           
               
               
           
         
         X1 is CH or N; 
         R1 is H, C 1-4 alkyl, CN, or Hal; and 
         R2 is H, C 1-4 alkyl or Hal. 
       
     
     
         5 . A compound in accordance to  claim 4  or a pharmaceutically acceptable salt thereof, wherein
 X1 is CH; 
 R1 is H, C 1-4 alkyl, CN, or Hal; and 
 R2 is H, C 1-4 alkyl or Hal. 
 
     
     
         6 . A compound in accordance to  claim 4  or a pharmaceutically acceptable salt thereof, wherein
 X1 is CH; 
 R1 is H or methyl; and 
 R2 is H or fluoro. 
 
     
     
         7 . A compound of  claim 4  or a pharmaceutically acceptable salt thereof, wherein
 X1 is N; 
 R1 is H, C 1-4 alkyl, CN, or Hal; and 
 R2 is H, C 1-4 alkyl or Hal. 
 
     
     
         8 . A compound of  claim 4  or a pharmaceutically acceptable salt thereof, wherein
 X1 is N; 
 R1 is H or methyl; and 
 R2 is H or fluoro. 
 
     
     
         9 . A compound of  claim 4  or a pharmaceutically acceptable salt thereof, wherein X1 is N, and wherein R1 and R2 are both hydrogen. 
     
     
         10 . A compound according to  claim 1 , which is a compound of formula (III) or a pharmaceutically acceptable salt thereof, wherein 
       
         
           
           
               
               
           
         
         R is H or C 1-4 alkyl; 
         R1 is H, C 1-4 alkyl, CN, or Hal; and 
         R2 is H, C 1-4 alkyl or Hal. 
       
     
     
         11 . A compound of  claim 10  or a pharmaceutically acceptable salt thereof, wherein
 R is methyl; 
 R1 is H or methyl; and 
 R2 is H, methyl or fluoro. 
 
     
     
         12 . A compound in accordance to  claim 1 , which is a compound of formula (IV) or a pharmaceutically acceptable salt thereof, wherein 
       
         
           
           
               
               
           
         
         R1 is H, C 1-4 alkyl, CN, or Hal; and 
         R2 is H, C 1-4 alkyl or Hal. 
       
     
     
         13 . A compound of  claim 12  or a pharmaceutically acceptable salt thereof, wherein
 R1 is H or methyl; and 
 R2 is H, methyl or fluoro. 
 
     
     
         14 . A compound of  claim 12  or a pharmaceutically acceptable salt thereof, wherein
 R1 is H or methyl; and R2 is H. 
 
     
     
         15 . A compound in accordance to  claim 1  or a pharmaceutically acceptable salt thereof, wherein said compound is selected from:
 3-((1R,2S)-2-Amino-cyclohexylamino)-5-(1H-indol-7-ylamino)-[1,2,4]triazine-6-carboxylic acid amide; 
 3-((1R,2S)-2-Amino-cyclohexylamino)-5-(5-fluoro-3-methyl-1H-indol-7-ylamino)-[1,2,4]triazine-6-carboxylic acid amide; 
 3-((1R,2S)-2-Amino-cyclohexylamino)-5-(3-methyl-1H-indol-7-ylamino)-[1,2,4]triazine-6-carboxylic acid amide; 
 3-((1R,2S)-2-Amino-cyclohexylamino)-5-(1H-indol-4-ylamino)-[1,2,4]triazine-6-carboxylic acid amide; 
 3-((1R,2S)-2-Amino-cyclohexylamino)-5-(1-methyl-1H-indazol-4-ylamino)-[1,2,4]triazine-6-carboxylic acid amide; 
 3-((1R,2S)-2-Amino-cyclohexylamino)-5-(2-methyl-2H-indazol-4-ylamino)-[1,2,4]triazine-6-carboxylic acid amide; 
 3-((1R,2S)-2-Amino-cyclohexylamino)-5-(3-chloro-1H-indol-7-ylamino)-[1,2,4]triazine-6-carboxylic acid amide; 
 3-((1R,2S)-2-Amino-cyclohexylamino)-5-(3-cyano-1H-indol-7-ylamino)-[1,2,4]triazine-6-carboxylic acid amide; 
 3-((1R,2S)-2-Amino-cyclohexylamino)-5-(1H-indazol-4-ylamino)-[1,2,4]triazine-6-carboxylic acid amide; 
 3-((1R,2S)-2-Amino-cyclohexylamino)-5-(5-fluoro-1H-indol-7-ylamino)-[1,2,4]triazine-6-carboxylic acid amide; 
 5-((1R,2S)-2-Amino-cyclohexylamino)-3-(1-methyl-1H-indol-4-ylamino)-pyrazine-2-carboxylic acid amide; 
 5-((1R,2S)-2-Amino-cyclohexylamino)-3-(1H-indol-7-ylamino)-pyrazine-2-carboxylic acid amide; and 
 5-((1R,2S)-2-Amino-cyclohexylamino)-3-(3-methyl-1H-indol-7-ylamino)-pyrazine-2-carboxylic acid amide. 
 
     
     
         16 . A pharmaceutical composition comprising a therapeutically effective amount of a compound according to  claim 1  and one or more pharmaceutically acceptable carriers. 
     
     
         17 . A combination comprising a therapeutically effective amount of a compound according to  claim 1  and one or more therapeutically active co-agents. 
     
     
         18 . A method of modulating SYK activity in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of the compound according to  claim 1 . 
     
     
         19 - 20 . (canceled)