1,4,5,6-tetrahydro-pyrimidin-2-ylamine compounds

Abstract

This invention relates to compounds of the formula wherein R 1 to R 9 are as described below, or to pharmaceutically acceptable salts thereof. These compounds are BACE2 inhibitors and can be used as medicaments for the therapeutic and/or prophylactic treatment of diseases such as diabetes, particularly type 2 diabetes, and other metabolic disorders.

1 . A compound according to formula I 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is selected from the group consisting of hydrogen, C 1-7 -alkyl, C 3-7 -cycloalkyl, C 3-7 -cycloalkyl-C 1-7 -alkyl and benzyl; 
         R 2  is selected from the group consisting of hydrogen, C 1-7 -alkyl and C 3-7 -cycloalkyl; 
         R 3  is selected from the group consisting of hydrogen, C 1-7 -alkyl and C 3-7 -cycloalkyl; 
         or R 2  and R 3  together with the C atom they are attached to form a C 3-7 -cycloalkyl ring; 
         R 4  is C 1-7 -alkyl or C 3-7 -cycloalkyl; 
         R 5  is selected from the group consisting of hydrogen, C 1-7 -alkyl, halogen, cyano and C 1-7 -alkoxy; 
         or R 4  and R 5  together are —(CH 2 ) m — with m being 2 or 3 and thus form a ring; 
         R 6 , R 7  and R 8  independently from each other are selected from hydrogen and halogen; and 
         R 9  is —(CO)—R 10  or —R 11 , wherein 
         R 10  is selected from the group consisting of 
         C 1-7 -alkyl, 
         —(CHR 12 ) m —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, cyano, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 12  is hydrogen or C 1-7 -alkyl, and m is 0, 1 or 2, 
         halogen-C 1-7 -alkyl, 
         hydroxy-halogen-C 1-7 -alkyl, 
         C 1-7 -alkoxy-halogen-C 1-7 -alkyl, 
         —(CHR 13 ) n -heterocyclyl, wherein heterocyclyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, hydroxy, cyano, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 13  is hydrogen or C 1-7 -alkyl, and n is 0, 1 or 2, and 
         —CH(OH)-phenyl, wherein phenyl is unsubstituted or substituted by halogen; and 
         R 11  is selected from the group consisting of 
         —(CHR 14 ) p —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, cyano, carboxyl, C 1-7 -alkoxycarbonyl, carboxyl-C 1-7 -alkyl, C 1-7 -alkoxycarbonyl-C 1-7 -alkyl, C 1-7 -alkylcarbonyloxy, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen, 
         R 14  is hydrogen or C 1-7 -alkyl, and p is 0, 1 or 2, 
         halogen-C 1-7 -alkyl, 
         indanyl, being unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, carboxyl, carboxyl-C 1-7 -alkyl and halogen, 
         tetrahydronaphtalenyl, being unsubstituted or substituted by one, two or three groups selected from C 1-7 -alkyl and halogen, 
         6,7-dihydro-5H-cyclopenta[b]pyridinyl, being unsubstituted or substituted by one, two or three groups selected from C 1-7 -alkyl and halogen, 
         hydroxy-halogen-C 1-7 -alkyl, 
         C 1-7 -alkoxy-halogen-C 1-7 -alkyl, 
         —(CHR 15 ) q -heterocyclyl, wherein heterocyclyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, carboxyl-C 1-7 -alkyl, C 1-7 -alkoxycarbonyl-C 1-7 -alkyl, C 1-7 -alkylcarbonyl, C 1-7 -alkylcarbonyloxy, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 15  is hydrogen or C 1-7 -alkyl, and q is 0, 1 or 2; 
         —(CHR 16 ) s -aryl, wherein aryl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, —SO 2 —C 1-7 -alkyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 16  is hydrogen or C 1-7 -alkyl, and s is 0, 1 or 2; and 
         —(CHR 17 ) t -heteroaryl, wherein heteroaryl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, hydroxy, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, C 1-7 -alkyl-carbonyl, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 17  is hydrogen or C 1-7 -alkyl and t is 0, 1 or 2; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . A compound according to  claim 1  wherein
 R 1  is selected from the group consisting of hydrogen, C 1-7 -alkyl, C 3-7 -cycloalkyl, C 3-7 -cycloalkyl-C 1-7 -alkyl and benzyl; 
 R 2  is selected from the group consisting of hydrogen, C 1-7 -alkyl and C 3-7 -cycloalkyl; 
 R 3  is selected from the group consisting of hydrogen, C 1-7 -alkyl and C 3-7 -cycloalkyl; 
 or R 2  and R 3  together with the C atom they are attached to form a C 3-7 -cycloalkyl ring; 
 R 4  is C 1-7 -alkyl or C 3-7 -cycloalkyl; 
 R 5  is selected from the group consisting of hydrogen, C 1-7 -alkyl, halogen, cyano and C 1-7 -alkoxy; 
 or R 4  and R 5  together are —(CH 2 ) m — with m being 2 or 3 and thus form a ring; 
 R 6 , R 7  and R 8  independently from each other are selected from hydrogen and halogen; and 
 R 9  is —(CO)—R 10  or —R 11 , wherein 
 R 10  is selected from the group consisting of 
 —(CHR 12 ) m —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, cyano, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 12  is hydrogen or C 1-7 -alkyl, and m is 0, 1 or 2, 
 halogen-C 1-7 -alkyl, 
 hydroxy-halogen-C 1-7 -alkyl, 
 C 1-7 -alkoxy-halogen-C 1-7 -alkyl, 
 —(CHR 13 ) n -heterocyclyl, wherein heterocyclyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, hydroxy, cyano, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 13  is hydrogen or C 1-7 -alkyl, R 13  is hydrogen or C 1-7 -alkyl, and n is 0, 1 or 2, and 
 —CH(OH)-phenyl, wherein phenyl is unsubstituted or substituted by halogen; and 
 R 11  is selected from the group consisting of 
 C 1-7 -alkyl, 
 —(CHR 14 ) p —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, cyano, carboxyl, C 1-7 -alkoxycarbonyl, carboxyl-C 1-7 -alkyl, C 1-7 -alkoxycarbonyl-C 1-7 -alkyl, C 1-7 -alkylcarbonyloxy, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen, 
 R 14  is hydrogen or C 1-7 -alkyl, and p is 0, 1 or 2, 
 halogen-C 1-7 -alkyl, 
 indanyl, being unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, carboxyl, carboxyl-C 1-7 -alkyl and halogen, 
 tetrahydronaphtalenyl, being unsubstituted or substituted by one, two or three groups selected from C 1-7 -alkyl and halogen, 
 6,7-dihydro-5H-cyclopenta[b]pyridinyl, being unsubstituted or substituted by one, two or three groups selected from C 1-7 -alkyl and halogen, 
 hydroxy-halogen-C 1-7 -alkyl, 
 C 1-7 -alkoxy-halogen-C 1-7 -alkyl, 
 —(CHR 15 ) q -heterocyclyl, wherein heterocyclyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, carboxyl-C 1-7 -alkyl, C 1-7 -alkoxycarbonyl-C 1-7 -alkyl, C 1-7 -alkylcarbonyl, C 1-7 -alkylcarbonyloxy, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 15  is hydrogen or C 1-7 -alkyl, and q is 0, 1 or 2; 
 —(CHR 16 ) s -aryl, wherein aryl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 16  is hydrogen or C 1-7 -alkyl, and s is 0, 1 or 2; and 
 —(CHR 17 ) t -heteroaryl, wherein heteroaryl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, hydroxy, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, and t is 0, 1 or 2; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         3 . A compound according to  claim 1 , wherein R 1  is C 1-7 -alkyl or C 3-7 -cycloalkyl-C 1-7 -alkyl. 
     
     
         4 . A compound according to  claim 1 , wherein R 1  is C 1-7 -alkyl. 
     
     
         5 . A compound according to  claim 1 , wherein R 1  is methyl. 
     
     
         6 . A compound according to  claim 1 , wherein R 2  and R 3  are independently from each other selected from hydrogen and C 1-7 -alkyl. 
     
     
         7 . A compound according to  claim 1 , wherein R 2  and R 3  are C 1-7 -alkyl. 
     
     
         8 . A compound according to  claim 1 , wherein R 2  and R 3  are methyl. 
     
     
         9 . A compound according to  claim 1 , wherein R 4  is C 1-7 -alkyl. 
     
     
         10 . A compound according to  claim 1 , wherein R 4  is methyl. 
     
     
         11 . A compound according to  claim 1 , wherein R 5  is hydrogen or halogen. 
     
     
         12 . A compound according to  claim 1 , wherein R 5  is halogen. 
     
     
         13 . A compound according to  claim 1 , wherein R 5  is fluoro. 
     
     
         14 . A compound according to  claim 1 , wherein R 6 , R 7  and R 8  are hydrogen. 
     
     
         15 . A compound according to  claim 1 , wherein R 9  is —(CO)—R 10  and R 10  is selected from the group consisting of
 —(CHR 12 ) m —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, cyano, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 12  is hydrogen or C 1-7 -alkyl, and m is 0, 1 or 2, 
 halogen-C 1-7 -alkyl, 
 hydroxy-halogen-C 1-7 -alkyl, 
 C 1-7 -alkoxy-halogen-C 1-7 -alkyl, 
 —(CHR 13 ) n -heterocyclyl, wherein heterocyclyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, cyano, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 13  is hydrogen or C 1-7 -alkyl, R 13  is hydrogen or C 1-7 -alkyl, and n is 0, 1 or 2, and 
 —CH(OH)-phenyl, wherein phenyl is unsubstituted or substituted by halogen. 
 
     
     
         16 . A compound according to  claim 15 , wherein R 10  is
 —(CHR 12 ) m —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, cyano, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 12  is hydrogen or C 1-7 -alkyl, and m is 0, 1 or 2.   
     
     
         17 . A compound according to  claim 15 , wherein R 10  is selected from the group consisting of halogen-C 1-7 -alkyl, hydroxy-halogen-C 1-7 -alkyl, and C 1-7 -alkoxy-halogen-C 1-7 -alkyl. 
     
     
         18 . A compound according to  claim 15 , wherein R 10  is selected from the group consisting of
 —(CHR 12 ) m —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one or two halogen-C 1-7 -alkyl groups, and m is 0, and   hydroxy-halogen-C 1-7 -alkyl.   
     
     
         19 . A compound according to  claim 18 , wherein R 10  is 1-trifluoromethyl-cyclopropanyl, 2,2,2-trifluoro-1-hydroxy-ethyl or 1,1,1-trifluoro-2-hydroxy-2-methyl-ethyl. 
     
     
         20 . A compound according to  claim 1 , wherein R 9  is R 11  and
 R 11  is selected from the group consisting of   C 1-7 -alkyl,   —(CHR 14 ) p —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, cyano, carboxyl, C 1-7 -alkoxycarbonyl, carboxyl-C 1-7 -alkyl, C 1-7 -alkoxycarbonyl-C 1-7 -alkyl, C 1-7 -alkylcarbonyloxy, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen,   R 14  is hydrogen or C 1-7 -alkyl, and p is 0, 1 or 2,   halogen-C 1-7 -alkyl,   indanyl, being unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, carboxyl, carboxyl-C 1-7 -alkyl and halogen,   tetrahydronaphtalenyl, being unsubstituted or substituted by one, two or three groups selected from C 1-7 -alkyl or halogen,   6,7-dihydro-5H-cyclopenta[b]pyridinyl, being unsubstituted or substituted by one, two or three groups selected from C 1-7 -alkyl or halogen, hydroxy-halogen-C 1-7 -alkyl,   C 1-7 -alkoxy-halogen-C 1-7 -alkyl,   —(CHR 15 ) q -heterocyclyl, wherein heterocyclyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, carboxyl-C 1-7 -alkyl, C 1-7 -alkoxycarbonyl-C 1-7 -alkyl, C 1-7 -alkylcarbonyl, C 1-7 -alkylcarbonyloxy, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 15  is hydrogen or C 1-7 -alkyl, and q is 0, 1 or 2;   —(CHR 16 ) s -aryl, wherein aryl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 16  is hydrogen or C 1-7 -alkyl, and s is 0, 1 or 2; and   —(CHR 17 ) t -heteroaryl, wherein heteroaryl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, hydroxy, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, and t is 0, 1 or 2.   
     
     
         21 . A compound according to  claim 20 , wherein R 11  is selected from the group consisting of
 —(CHR 14 ) p —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, cyano, carboxyl, C 1-7 -alkoxycarbonyl, carboxyl-C 1-7 -alkyl, C 1-7 -alkoxycarbonyl-C 1-7 -alkyl, C 1-7 -alkylcarbonyloxy, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen,   R 14  is hydrogen or C 1-7 -alkyl, and p is 0, 1 or 2,   indanyl, being unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, carboxyl, carboxyl-C 1-7 -alkyl and halogen,   tetrahydronaphtalenyl, being unsubstituted or substituted by one, two or three groups selected from C 1-7 -alkyl or halogen,   6,7-dihydro-5H-cyclopenta[b]pyridinyl, being unsubstituted or substituted by one, two or three groups selected from C 1-7 -alkyl or halogen,   —(CHR 15 ) q -heterocyclyl, wherein heterocyclyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, carboxyl-C 1-7 -alkyl, C 1-7 -alkoxycarbonyl-C t-7 -alkyl, C 1-7 -alkylcarbonyl, C 1-7 -alkylcarbonyloxy, oxo, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 15  is hydrogen or C 1-7 -alkyl, and q is 0, 1 or 2;   —(CHR 16 ) s -aryl, wherein aryl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 16  is hydrogen or C 1-7 -alkyl, and s is 0, 1 or 2; and   —(CHR 17 ) 1 -heteroaryl, wherein heteroaryl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, hydroxy, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 17  is hydrogen or C 1-7 -alkyl, and t is 0, 1 or 2.   
     
     
         22 . A compound according to  claim 20 , wherein R 11  is —(CHR 14 ) p —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, cyano, carboxyl, C 1-7 -alkoxycarbonyl, carboxyl-C 1-7 -alkyl, C 1-7 -alkoxycarbonyl-C 1-7 -alkyl, C 1-7 -alkylcarbonyloxy, benzyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 14  is hydrogen or C 1-7 -alkyl, and p is 0, 1 or 2. 
     
     
         23 . A compound according to  claim 20 , wherein R 11  is selected from the group consisting of
 indanyl, being unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, C 1-7 -alkoxy, carboxyl, carboxyl-C 1-7 -alkyl and halogen,   tetrahydronaphtalenyl, being unsubstituted or substituted by one, two or three groups selected from C 1-7 -alkyl and halogen,   6,7-dihydro-5H-cyclopenta[b]pyridinyl, being unsubstituted or substituted by one, two or three groups selected from C 1-7 -alkyl and halogen, and   —(CHR 15 ) q -heterocyclyl, wherein heterocyclyl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, carboxyl-C 1-7 -alkyl, C 1-7 -alkoxycarbonyl-C 1-7 -alkyl, C 1-7 -alkylcarbonyl, C 1-7 -alkylcarbonyloxy, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 15  is hydrogen or C 1-7 -alkyl, and q is 0, 1 or 2.   
     
     
         24 . A compound according to  claim 20 , wherein R 11  is —(CHR 16 ) s -aryl, wherein aryl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, hydroxy, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 16  is hydrogen or C 1-7 -alkyl, and s is 0, 1 or 2. 
     
     
         25 . A compound according to  claim 20 , wherein R 11  is —(CHR 17 ) e -heteroaryl, wherein heteroaryl is unsubstituted or substituted by one, two or three groups selected from the group consisting of C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, hydroxy, halogen-C 1-7 -alkoxy, cyano, hydroxy-C 1-7 -alkyl, carboxyl, C 1-7 -alkoxycarbonyl, oxo, C 3-7 -cycloalkyl, imidazolyl, benzyl, phenylsulfanyl and phenyl, said phenyl being unsubstituted or substituted by halogen, R 17  is hydrogen or C 1-7 -alkyl and t is 0, 1 or 2. 
     
     
         26 . A compound according to  claim 20 , wherein R 11  is selected from the group consisting of C 1-7 -alkyl, halogen-C 1-7 -alkyl, hydroxy-halogen-C 1-7 -alkyl and C 1-7 -alkoxy-halogen-C 1-7 -alkyl. 
     
     
         27 . A compound according to  claim 20 , wherein R 11  is selected from the group consisting of
 —(CHR 14 ) p —C 3-7 -cycloalkyl, wherein cycloalkyl is unsubstituted or substituted by one or two groups selected from the group consisting of hydroxy, halogen and cyano, R 14  is hydrogen, and p is 0 or 1,   —(CHR 15 ) q -heterocyclyl, wherein heterocyclyl is unsubstituted, R 15  is hydrogen, and q is 0 or 1;   —(CHR 16 ) s -aryl, wherein aryl is unsubstituted or substituted by one or two groups selected from the group consisting of halogen-C 1-7 -alkyl, and C 1-7 -alkoxy, and s is 0; and   —(CHR 17 ) t -heteroaryl, wherein heteroaryl is unsubstituted or substituted by one or two groups selected from the group consisting of C 1-7 -alkyl, halogen, halogen-C 1-7 -alkyl, C 1-7 -alkoxy, and oxo, R 17  is hydrogen or C 1-7 -alkyl, and t is 0 or 1.   
     
     
         28 . A compound according to  claim 27 , wherein R 11  is selected from the group consisting of: tetrahydro-furyl, tetrahydro-pyranyl, 2,2-difluoro-cyclopropyl-methyl, 3-chloro-6,7-dihydro-5H-cyclopenta[b]pyridinyl, tetrahydro-furyl-methyl, 4-chloro-1-methyl-1H-pyrazolyl-methyl, 1-methyl-1H-pyrazolyl, 5-hydroxybicyclo[2.2.1]heptanyl, 5-methyl-isoxazol-3-yl-methyl, pyridinyl, 1-(2H-pyrazolyl)-ethyl, 2-methoxy-5-(trifluoromethyl)phenyl, 1-(5-methyl-2H-pyrazolyl)-ethyl, 4-chloro-2H-pyrazolyl, cyano-cyclopentyl and 1,1-dioxo-2,3-dihydro-1H-1-benzo[b]thiophenyl. 
     
     
         29 . A compound according to  claim 1 , selected from the group consisting of
 salt of 1-Trifluoromethyl-cyclopropanecarboxylic acid [3-((S)-2-amino-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-4-yl)-4-fluoro-phenyl]-amide with trifluoro-acetic acid,   (6S)-2-Amino-6-(2-fluoro-5-(5-hydroxybicyclo[2.2.1]heptan-2-ylamino)phenyl)-3,5,5,6-tetramethyl-5,6-dihydropyrimidin-4(3H)-one,   (6S)-2-Amino-6-(5-(3-chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-ylamino)-2-fluorophenyl)-3,5,5,6-tetramethyl-5,6-dihydropyrimidin-4(3H)-one,   salt of (R)—N-(3-((S)-2-amino-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydropyrimidin-4-yl)-4-fluorophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide with trifluoro-acetic acid,   (S)-2-Amino-6-(2-fluoro-5-(2-methoxy-5-(trifluoromethyl)phenylamino)phenyl)-3,5,5,6-tetramethyl-5,6-dihydropyrimidin-4(3H)-one,   (S)-2-Amino-6-(2-fluoro-5-(pyridin-2-ylamino)phenyl)-3,5,5,6-tetramethyl-5,6-dihydropyrimidin-4(3H)-one,   (S)-2-Amino-6-[2-fluoro-5-(1-methyl-1H-pyrazol-3-ylamino)-phenyl]-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-[2-fluoro-5-(tetrahydro-furan-3-ylamino)-phenyl]-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-[2-fluoro-5-(tetrahydro-pyran-3-ylamino)-phenyl]-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-[2-fluoro-5-(tetrahydro-pyran-4-ylamino)-phenyl]-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-[5-(1,1-dioxo-2,3-dihydro-1H-1-benzo[b]thiophen-3-ylamino)-2-fluoro-phenyl]-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-{2-fluoro-5-[(5-methyl-isoxazol-3-ylmethyl)-amino]-phenyl}-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-{2-fluoro-5-[(tetrahydro-furan-3-ylmethyl)-amino]-phenyl}-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-{2-fluoro-5-[1-(2H-pyrazol-3-yl)-ethylamino]-phenyl}-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-{2-fluoro-5-[1-(5-methyl-2H-pyrazol-3-yl)-ethylamino]-phenyl}-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-{5-[(2,2-difluoro-cyclopropylmethyl)-amino]-2-fluoro-phenyl}-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-{5-[(4-chloro-1-methyl-1H-pyrazol-3-ylmethyl)-amino]-2-fluoro-phenyl}-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   (S)-2-Amino-6-{5-[(4-chloro-2H-pyrazol-3-ylmethyl)-amino]-2-fluoro-phenyl}-3,5,5,6-tetramethyl-5,6-dihydro-3H-pyrimidin-4-one,   2-[3-((S)-2-Amino-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-4-yl)-4-fluoro-phenylamino]-cyclopentanecarbonitrile, and   salt of N-[3-((S)-2-Amino-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-4-yl)-4-fluoro-phenyl]-3,3,3-trifluoro-2-hydroxy-propionamide with trifluoro-acetic acid.   
     
     
         30 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable carrier and/or adjuvant.