Heteroaryl syk inhibitors

Abstract

The invention relates to new substituted heteroaryls of formula 1 wherein A is selected from the group consisting of N and CH D is selected from the group consisting of CH, N, NH, S and O, E is selected from the group consisting of C and N, T is selected from the group consisting of C and N, G is selected from the group consisting of C and N, and wherein each of the broken (dotted) double bonds in ring 1 are selected from either a single bond or a double bond under the proviso that all single and double bonds of ring 1 are arranged in such a way that they all form together with ring 2 an aromatic ring system, and wherein R 1 , M and R 3 are defined according to claim 1, and to the above compounds for the treatment of a disease selected from the group consisting of asthma, COPD, allergic rhinitis, allergic dermatitis, lupus erythematodes, lupus nephritis and rheumatoid arthritis.

1 . An intermediate compound selected from the group consisting of formula 6 
       
         
           
           
               
               
           
         
         of formula 7 
       
       
         
           
           
               
               
           
         
         of formula 8 
       
       
         
           
           
               
               
           
         
         and of formula 11 
       
       
         
           
           
               
               
           
         
         wherein 
         Hal is Cl or Br 
         D is CH, 
         E is selected from the group consisting of C and N, 
         T is C, 
         G is selected from the group consisting of C and N, 
         and wherein each of the broken (dotted) double bonds in ring 1 are either a single bond or a double bond under the proviso that all single and double bonds of ring 1 are arranged in such a way that they all form together with ring 2 an aromatic ring system, 
         and wherein 
         Het is selected from the group consisting of 
         a five- to six-membered monocyclic heterocycle with 1, 2, 3 or 4 heteroatoms each independently from one another selected from the group consisting of N, S and O, 
         and a nine- to eleven-membered bicyclic heterocycle with 1, 2, 3 or 4 heteroatoms each independently from one another selected from the group consisting of N, S and O; 
         Hetaryl is selected from the group consisting of 
         a five- to six-membered monocyclic heteroaromate with 1, 2, 3 or 4 heteroatoms each independently from one another selected from the group consisting of N, S and O; 
         and a nine- to eleven-membered bicyclic heteroaromate with 1, 2, 3 or 4 heteroatoms each independently from one another selected from the group consisting of N, S and O; 
         and wherein 
         R 1  is selected from the group consisting of 
         C 6-10 -aryl, Het and Hetaryl; 
         which is optionally further substituted by one, two or three substituents Z, 
         whereby each Z is a substituent selected from the group consisting of 
         —OH, oxo, —CN, halogen, —C 1-6 -alkyl, —O—C 1-6 -alkyl, —C 1-6 -haloalkyl, three- to seven-membered cycloalkyl, Het, Hetaryl, —CO—N(CH 3 ) 2 , —CO—NHCH 3 , —CO—NH 2 , —(C 1-3 -alkylene)-O—(C 1-3 -alkyl), and —O-Het, 
         which is optionally further substituted by one, two or three substituents X, 
         whereby each X is selected from the group consisting of halogen, —OH, oxo, —C 1-4 -alkyl, —O—C 1-4 -alkyl, —C 1-4 -haloalkyl, —O—(C 1-4 -alkylene)-Het, Het, Hetaryl, —NH 2 ,—NH(CH 3 ), and —N(CH 3 ) 2 , 
         whereby substituent X is optionally further substituted by one, two or three substituents selected from the group consisting of from oxo, —OH, halogen and C 1-3 -alkyl,
 and wherein PG is a protecting group selected from the group consisting of benzyl, 1-phenylethyl, 1-(4-methoxyphenyl)ethyl. 
 
       
     
     
         2 . An intermediate compound selected from the group consisting of formula 6 
       
         
           
           
               
               
           
         
         of formula 7 
       
       
         
           
           
               
               
           
         
         of formula 8 
       
       
         
           
           
               
               
           
         
         and of formula 11 
       
       
         
           
           
               
               
           
         
         wherein R 1  is 
       
       
         
           
           
               
               
           
         
         and wherein 
         Hal is Cl or Br, 
         X is selected from the group consisting of halogen, —OH, oxo, —C 1-4 -alkyl, —O—C 1-4 -alkyl, —C 1-4 -haloalkyl, —O—(C 1-4 -alkylene)-Het, Het, Hetaryl, —NH 2 ,—NH(CH 3 ), and —N(CH 3 ) 2 , 
         whereby substituent X is optionally further substituted by one, two or three substituents of a group selected from oxo, —OH, halogen and C 1-3 -alkyl, 
         wherein each Het is selected from the group consisting of: 
         a five- to six-membered monocyclic heterocycle with 1, 2, 3 or 4 heteroatoms each independently from one another selected from the group consisting of N, S and O, 
         and a nine- to eleven-membered bicyclic heterocycle with 1, 2, 3 or 4 heteroatoms each independently from one another selected from the group consisting of N, S and O; 
         and wherein each Hetaryl is selected from the group consisting of: 
         a five- to six-membered monocyclic heteroaromate with 1, 2, 3 or 4 heteroatoms each independently from one another selected from the group consisting of N, S and O; 
         and a nine- to eleven-membered bicyclic heteroaromate with 1, 2, 3 or 4 heteroatoms each independently from one another selected from the group consisting of N, S and O; 
         and wherein PG is a protecting group selected from the group consisting of benzyl, 1-phenylethyl, 1-(4-methoxyphenyl)ethyl.