Aminothiazole Derivatives Useful As Antiviral Agents

Abstract

to a process for their preparation and to their use as medicaments, in particular as antiviral medicaments.

1 . A compound represented by Formula (I) 
       
         
           
           
               
               
           
         
         or an enantiomer, diastereomer, tautomer, N-oxide, formulation and pharmaceutically acceptable salt thereof, wherein: 
         X is selected from 
       
       
         
           
           
               
               
           
         
         R 1  is selected from H, halogen, C 1-6 -alkyl, halo-C 1-6 -alkyl, C 3-6 -cycloalkyl, halo-C 3-6 -cycloalkyl, —O—C 1-6 -alkyl, —O-halo-C 1-6 -alkyl and —NH—C 1-6 -alkyl, with the proviso that in the case that X is one of 
       
       
         
           
           
               
               
           
         
       
       then R 1  is not hydrogen (H);
 R 2  is selected from H, —CN, —NO 2 , C 1-10 -alkyl, C 2-10 -alkenyl, C 2-10 -alkynyl, C 0-10 -alkylene-C 3-10 -cycloalkyl, C 0-10 alkylene-C 3-10 -heterocycloalkyl, C 0-10 -alkylene-(5- to 10-membered heteroaryl), C 0-10 -alkylene-(6- to 10-membered aryl), C 0-10 -alkylene-(6- to 10-membered heteroaryl), C 0-10 -alkylene-OR 11 , C 0-10 -alkylene-CO 2 R 11 , C 0-10 -alkylene-C(═O)NR 11 R 12 , C 0-10 -alkylene-C(═S)NR 11 R 12 , C 0-10 -alkylene-C(═O)NR 11 SO 2 R 13 , C 0-10 -alkylene-C(═S)NR 11 SO 2 R 11 , C 0-10 alkylene-C(═O)R 11 , C 0-10 -alkylene-C(═S)R 11 , C 0-10 -alkylene-SR 11 , C 0-10 alkylene-SO x R 13 , C 0-10 -alkylene-SO 3 R 11 , C 0-10 -alkylene-SO 2 NR 11 R 12 , C 0-10 -alkylene-NR 11 C(═O)R 11 , C 0-10 alkylene-NR 11 C(═S)R 11 , C 0-10 -alkylene-NR 11 SO 2 R 13 , C 0-10 -alkylene-NR 11 C(═O)NR 11 R 12 , C 0-10 -alkylene-NR 11 C(═S)NR 11 R 12 , C 0-10 -alkylene-NR 11 SO 2 NR 11 R 12 , C 0-10 -alkylene-NR 11 R 12 , wherein alkyl, alkenyl, alkynyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is unsubstituted or substituted with 1 to 7 substituents independently selected from the group consisting of oxo, —CN, —NO 2 , OR 11 , O—C 2-6 -alkylene-OR 11 , C 1-6 -alkyl, halo-C 1-6 -alkyl, halogen, CO 2 R 11 , C(═O)NR 11 R 12 , C(═O)NR 11 SO 2 R 11 , C(═O)R 11 , SR 11 , SO x R 11 , SO 3 R 11 , P(═O)(OR 11 ) 2 , SO 2 NR 11 R 12 , NR 11 C(═O)R 11 , NR 11 SO 2 R 13 , NR 11 C(═O)NR 11 R 12 NR 11 SO 2 NR 11 R 12 , C 3-10 -cycloalkyl, O—C 3-10 -cycloalkyl, C 3-10 -heterocycloalkyl, O—C 3-10 -heterocycloalkyl and NR 11 R 12 ; 
 R 3  is selected from H, C 1-6 -alkyl, halo-C 1-6 -alkyl, —O—C 1-6 -alkyl, —O-halo-C 1-6 -alkyl, C 3-6 -cycloalkyl and C 3-6 -heterocycloalkyl, wherein alkyl, cycloalkyl and heterocycloalkyl are optionally substituted with 1 to 5 substituents independently selected from halogen, —CN, OH, oxo, C 1-3 -alkyl, halo-C 1-3 -alkyl, O—C 1-3 -alkyl, O-halo-C 1-3 -alkyl, SO 2 —C 1-3 -alkyl, CO 2 H; 
 or R 2  and R 3  when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing 1 or 2 additional heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO 2 , OH, oxo, C 1-3 -alkyl, halo-C 1-3 -alkyl, O—C 1-3 -alkyl, O-halo-C 1-3 -alkyl, SO 2 —C 1-3 -alkyl, CO 2 H; 
 R 4  is selected from H, C 1-6 -alkyl, C 1-6 -acyl, C 2-6 -alkenyl, C 3-8 -cycloalkyl and C 3-8 -heterocycloalkyl, wherein alkyl, acyl, alkenyl, cycloalkyl and heterocycloalkyl are optionally substituted with 1 to 5 substituents independently selected from halogen, —CN, OH, oxo, C 1-3 -alkyl, halo-C 1-3 -alkyl, O—C 1-3 -alkyl, O-halo-C 1-3 -alkyl; 
 R 5  and R 6  and R 5′  and R 6′  are independently selected from H, halogen, C 1-6 -alkyl, NH 2 , NHC 1-6 -alkyl, N(C 1-6 -alkyl) 2 , C 0-6 -alkylene-C(═O)NH 2 ; 
 or R 5  and R 6  and R 5′  and R 6′  independently when taken together with the carbon to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO 2 , OH, oxo, C 1-3 -alkyl, halo-C 1-3 -alkyl, O—C 1-3 -alkyl, O-halo-C 1-3 -alkyl, SO 2 —C 1-3 -alkyl, CO 2 H; 
 or R 5  and R 5′  and R 6  and R 6′  independently when taken together with the two adjacent carbon to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO 2 , OH, oxo, C 1-3 -alkyl, halo-C 1-3 -alkyl, O—C 1-3 -alkyl, O-halo-C 1-3 -alkyl, SO 2 —C 1-3 -alkyl, CO 2 H; 
 R 7  is selected from a 6-membered aryl and 5- or 6-membered heteroaryl, wherein aryl and heteroaryl are optionally substituted with 1 to 4 substituents independently selected from halogen, —CN, —NO 2 , OH, C 1-6 -alkyl, O—C 1-6 -alkyl, C 3-6 -cycloalkyl, O—C 3-6 -cycloalkyl, C 3-6 -heterocycloalkyl, O—C 3-6 -heterocycloalkyl, SO y —C 1-6 -alkyl, CO 2 H, C(═O)O—C 1-6 -alkyl, 6- to 10-membered aryl, 5- or 10-membered heteroaryl, O-(6- to 10-membered aryl) and O-(5- or 10-membered heteroaryl), wherein alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl are optionally substituted with 1 to 5 substituents independently selected from halogen, —CN, —NO 2 , OH, R 13 , OR 13 , CO 2 R 11 , NR 11 R 12 , C(═O)R 11 , C(═S)R 11 , C(═O)NR 11 R 12 , NR 11 C(═O)NR 11 R 12 , NR 11 C(═O)OR 13 , OC(═O)NR 11 R 12 C(═S)NR 11 R 12 , NR 11 C(═S)NR 11 R 12 , NR 11 C(═S)OR 13 , OC(═S)NR 11 R 12 ; SO—C 1-6 -alkyl, SO y -halo-C 1-6 -alkyl, SR 11 , SO x R 13 , SO 3 R 11 , SO 2 NR 11 R 12 , NR 11 SO 2 R 13 , NR 11 SO 2 NR 11 R 12 ; 
 R 8  is selected from H, —CN, —NO 2 , C 1-10 -alkyl, C 2-10 -alkenyl, C 2-10 -alkynyl, C 0-10 -alkylene-C 3-10 -cycloalkyl, C 0-10 -alkylene-C 3-10 -heterocycloalkyl, C 0-10 -alkylene-(5 to 10-membered heteroaryl), C 0-10 -alkylene-(6 to 10-membered aryl), C 0-10 -alkylene-(6 to 10-membered heteroaryl), C 0-10 -alkylene-OR 11 , C 0-10 -alkylene-CO 2 R 11 , C 0-10 -alkylene-C(═O)NR 11 R 12 , C 0-10 -alkylene-C(═S)NR 11 R 12 , C 0-10 -alkylene-C(═O)NR 11 SO 2 R 13 , C 0-10 -alkylene-C(═S)NR 11 SO 2 R 11 , C 0-10 -alkylene-C(═O)R 11 , C 0-10 -alkylene-C(═S)R 11 , C 0-10 -alkylene-SR 11 , C 0-10 -alkylene-SO x —R 13 , C 0-10 -alkylene-SO 3 R 11 , C 0-10 -alkylene-SO 2 NR 11 R 12 , C 0-10 -alkylene-NR 11 C(═O)R 11 , C 0-10 -alkylene-NR 11 C(═S)R 11 , C 0-10 -alkylene-NR 11 SO 2 R 11 , C 0-10 -alkylene-NR 11 C(═O)NR 11 R 12 , C 0-10 -alkylene-NR 11 C(═S)NR 11 R 12 , C 0-10 -alkylene-NR 11 —SO 2 —NR 11 R 12 , C 0-10 -alkylene-NR 11 R 12 , wherein alkyl, alkenyl, alkynyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is unsubstituted or substituted with 1 to 7 substituents independently selected from the group consisting of oxo, —CN, —NO 2 , OR 11 , O—C 2-6 -alkylene-OR 11 , C 1-6 -alkyl, halo-C 1-6 -alkyl, halogen, CO 2 R 11 , CONR 11 R 12 , CONR 11 SO 2 R 11 , COR 11 , SO x R 11 , SO 3 H, PO(OH) 2 , SO 2 NR 11 R 12 , NR 11 COR 11 , NR 11 SO 2 R 11 , NR 11 —CO—NR 11 R 12 , NR 11 —SO 2 —NR 11 R 12 , C 3-10 -cycloalkyl, O—C 3-10 -cycloalkyl, C 3-10 -heterocycloalkyl, O—C 3-10 -heterocycloalkyl and NR 11 R 12 ; 
 R 9  is selected from C 1-10 -alkyl, C 2-10 -alkenyl, C 2-10 -alkynyl, C 0-10 -alkylene-C 3-10 -cycloalkyl, C 1-10 -alkylene-C 3-10 -heterocycloalkyl, C 0-10 -alkylene-(5- to 10-membered heteroaryl), C 0-10 -alkylene-(6- to 10-membered aryl), C 0-10 -alkylene-(6- to 10-membered heteroaryl), C 0-10 alkylene-OR 11 , C 0-10 -alkylene-CO 2 R 11 , C 0-10 -alkylene-C(═O)NR 11 R 12 , C 0-10 -alkylene-C(═S)NR 11 R 12 , C 0-10 -alkylene-C(═O)NR 11 SO 2 R 13 , C 0-10 -alkylene-C(═S)NR 11 SO 2 R 11 , C 0-10 -alkylene-C(═O)R 11 , C 0-10 -alkylene-C(═S)R 11 , C 0-10 -alkylene-SR 11 , C 0-10 -alkylene-SO x R 13 , C 0-10 -alkylene-SO 3 R 11 , C 0-10 -alkylene-SO 2 NR 11 R 12 , C 0-10 -alkylene-NR 11 C(═O)R 11 , C 0-10 -alkylene-NR 11 C(═S)R 11 , C 0-10 -alkylene-NR 11 SO 2 R 13 , C 0-10 -alkylene-NR 11 C(═O)NR 11 R 12 , C 0-10 -alkylene-NR 11 C(═S)NR 11 R 12 , C 0-10 -alkylene-NR 11 SO 2 NR 11 R 12 , C 0-10 -alkylene-NR 11 R 12 , wherein alkyl, alkenyl, alkynyl, alkylene, cycloalkyl, heterocycloalkyl, aryl and heteroaryl is unsubstituted or substituted with 1 to 7 substituents independently selected from the group consisting of oxo, —CN, —NO 2 , OR 11 , O—C 2-6 -alkylene-OR 11 , C 1-6 -alkyl, halo-C 1-6 -alkyl, halogen, CO 2 R 11 , C(═O)NR 11 R 12 , C(═O)NR 11 SO 2 R 11 , C(═O)R 11 , SR 11 , SO x R 11 , SO 3 R 11 , P(═O)(OR 11 ) 2 , SO 2 NR 11 R 12 , NR 11 C(═O)R 11 , NR 11 SO 2 R 13 , NR 11 C(═O)NR 11 R 12 , NR 11 SO 2 NR 11 R 12 , C 3-10 -cycloalkyl, O—C 3-10 -cycloalkyl, C 3-10 -heterocycloalkyl, O—C 3-10 -heterocycloalkyl and NR 11 R 12 ; 
 R 10  is selected from —CN, OH, and —NO 2 ; 
 R 11  is independently selected from H, C 1-6 -alkyl, C 0-6 -alkylene-C 3-10 -cycloalkyl and C 0-6 -alkylene-C 3-10 -heterocycloalkyl, wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl is unsubstituted or substituted with 1 to 6 substituents independently selected from the group consisting of halogen, —CN, OH, oxo, C 1-3 -alkyl, halo-C 1-3 -alkyl, O—C 1-3 -alkyl, O-halo-C 1-3 -alkyl, NH 2 , NH(C 1-3 -alkyl), N(C 1-3 -alkyl) 2 , C 3-6 -heterocycloalkyl, C 3-6 -cycloalkyl, SO 2 —NHC 1-3 -alkyl, SO 2 —N(C 1-3 -alkyl) 2  and SO 2 —C 1-3 -alkyl, wherein cycloalkyl and heterocycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from the group consisting of F, OH, oxo, CH 3 , CHF 2  and CF 3 ; 
 R 12  is independently selected from H, C 1-6 -alkyl, halo-C 1-6 -alkyl and C 3-6 -cycloalkyl; 
 or R 11  and R 12  when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO 2 , OH, oxo, C 1-3 -alkyl, halo-C 1-3 -alkyl, O—C 1-3 -alkyl, O-halo-C 1-3 -alkyl, SO 2 —C 1-3 -alkyl, CO 2 H; 
 R 13  is independently selected from C 1-6 -alkyl, C 0-6 -alkylene-C 3-10 -cycloalkyl and C 0-6 -alkylene-C 3-10 -heterocycloalkyl, wherein alkyl, alkylene, cycloalkyl and heterocycloalkyl is unsubstituted or substituted with 1 to 6 substituents independently selected from the group consisting of halogen, —CN, OH, oxo, C 1-3 -alkyl, halo-C 1-3 -alkyl, O—C 1-3 -alkyl, O-halo-C 1-3 -alkyl, NH 2 , NH(C 1-3 -alkyl), N(C 1-3 -alkyl) 2 , C 3-6 -heterocycloalkyl, C 3-6 -cycloalkyl, SO 2 —NHC 1-3 -alkyl, SO 2 —N(C 1-3 -alkyl) 2  and SO 2 —C 1-3 -alkyl, wherein cycloalkyl and heterocycloalkyl is unsubstituted or substituted with 1 to 3 substituents independently selected from the group consisting of F, OH, oxo, CH 3 , CHF 2  and CF 3 ; 
 n is selected from 0 and 1; 
 x is independently selected from 1 and 2; 
 y is independently selected from 0, 1 and 2; 
 and wherein optionally R 1  is connected to one residue selected from R 2 , R 3 , R 8 , R 9 , R 10  or R 12  to form a 5 to 8-membered heterocycle, which is optionally substituted with 1 to 4 substituents independently selected from the group consisting of halogen, —CN, —NO 2 , OH, oxo, C 1-3 -alkyl, halo-C 1-3 -alkyl, O—C 1-3 -alkyl, O-halo-C 1-3 -alkyl, SO 2 —C 1-3 -alkyl, CO 2 H. 
 
     
     
         2 . The compound according to  claim 1 , wherein X is selected:
 from the group consisting of   
       
         
           
           
               
               
           
         
       
       and/or
 from the group consisting of 
 
       
         
           
           
               
               
           
         
       
       with the proviso that then R 1  is not hydrogen (H); and/or
 from the group consisting of 
 
       
         
           
           
               
               
           
         
         and wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 5′ , R 6′ , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , n, X and y have the meaning as defined in  claim 1 . 
       
     
     
         3 . The compound according to  claim 1 , wherein:
 R 4  is selected from C 1-6 -alkyl, C 1-6 -acyl, C 3-8 -cycloalkyl and C 3-8 -heterocycloalkyl, wherein alkyl, acyl, alkenyl, cycloalkyl and heterocycloalkyl are optionally substituted with 1 to 5 substituents independently selected from halogen, —CN, OH, oxo, C 1-3 -alkyl, halo-C 1-3 -alkyl, O—C 1-3 -alkyl, O-halo-C 1-3 -alkyl;   R 5  and R 6  and R 5′  and R 6′  are independently selected from H and C 1-3 -alkyl;   or R 5  and R 6  and R 5′  and R 6′  independently when taken together with the carbon to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, OH, oxo, Me (—CH 3 ), OMe (—O—CH 3 ), CHF 2 , CF 3 , OCHF 2 , OCF 3 ;   or R 5  and R 5′  and R 6  and R 6′  independently when taken together with the two adjacent carbon to which they are attached complete a 3- to 8-membered ring containing carbon atoms and optionally containing 1 or 2 heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of halogen, OH, oxo, Me (—CH 3 ), OMe (—O—CH 3 ), CHF 2 , CF 3 , OCHF 2 , OCF 3 ;   R 7  is selected from a 6-membered aryl and 5- or 6-membered heteroaryl, wherein aryl and heteroaryl are optionally substituted with 1 to 3 substituents independently selected from halogen, OH, Me (—CH 3 ), OMe (—O—CH 3 ), CHF 2 , CF 3 , OCHF 2 , OCF 3  and substituted with 6-membered aryl and 5- or 6-membered heteroaryl, wherein aryl and heteroaryl are optionally substituted with 1 to 5 substituents independently selected from halogen, —CN, —NO 2 , OH, R 13 , OR 13 , CO 2 R 11 , NR 11 R 12 , C(═O)R 11 , C(═S)R 11 , C(═O)NR 11 R 12 , NR 11 C(═O)NR 11 R 12 , NR 11 C(═O)OR 13 , OC(═O)NR 11 R 12 , C(═S)NR 11 R 12 , NR 11 C(═S)NR 11 R 12 , NR 11 C(═S)OR 13 , OC(═S)NR 11 R 12 ; SO y —C 1-6 -alkyl, SO y -halo-C 1-6 -alkyl, SR 11 , SO x R 13 , SO 3 R 11 , SO 2 NR 11 R 12 , NR 11 SO 2 R 13 , NR 11 SO 2 NR 11 R 12 ; and   the remaining substituents have the meaning as defined in  claim 1 .   
     
     
         4 . The compound according to any  claim 1 , wherein R 7  is phenyl, optionally substituted with 1 to 4 substituents (R x ), wherein the 1 to 4 substituents R x  independently have the meaning of the possible substituents of R 7  as defined in any  claim 1  and which is represented by Formula (II) 
       
         
           
           
               
               
           
         
       
     
     
         5 . The compound according to any one of the preceding  claim 1 , wherein R 7  is selected from 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound according to  claim 1 , wherein:
 X is selected from   
       
         
           
           
               
               
           
         
       
       and
 R 1  is selected from H, halogen, C 1-6 -alkyl, halo-C 1-6 -alkyl, C 3-6 -cycloalkyl, halo-C 3-6 -cycloalkyl, —O—C 1-6 -alkyl, —O-halo-C 1-6 -alkyl and —NH—C 1-6 -alkyl. 
 
     
     
         7 . The compound according to  claim 1 , wherein:
 R 2  and R 3  are independently selected from H, C 1-3 -alkyl, halo-C 1-3 -alkyl, —O—C 1-3 -alkyl, —O-fluoro-C 1-3 -alkyl, C 3-6 -cycloalkyl and C 3-6 -heterocycloalkyl, wherein alkyl, cycloalkyl and heterocycloalkyl are optionally substituted with 1 to 5 substituents independently selected from F, Cl, OH, oxo, Me (—CH 3 ), CHF 2  and CF 3 ;   or R 2  and R 3  when taken together with the nitrogen to which they are attached complete a 5- to 6-membered ring containing carbon atoms and optionally containing one heteroatoms selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of F, Cl, OH, oxo, Me (—CH 3 ), CHF 2  and CF 3 ;   R 8  is selected from H, —CN, —NO 2 , OH, C 1-3 -alkyl, O—C 1-3 -alkyl, fluoro-C 1-3 -alkyl and O-fluoro-C 1-3 -alkyl,   R 9  is selected from C 1-3 -alkyl, t-butyl, fluoro-C 1-3 -alkyl, and -cyclopropyl;   R 10  is selected from —CN, OH, and —NO 2 ; and   R 12  is independently selected from H, Me (—CH 3 ) and Et (—CH 2 —CH 3 ).   
     
     
         8 . The compound according to  claim 1 , wherein n is 0. 
     
     
         9 . The compound according to  claim 1 , wherein the compound is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         10 . A medicament for the treatment or prophylaxis of a disease or disorder associated with viral infections of a patient, the medicament including the compound according to  claim 1  and one or more selected from a pharmaceutically acceptable carrier and excipients. 
     
     
         11 . A method of treatment or prophylaxis of a disease or disorder associated with viral infections, the method including a step of administering to a patient in need thereof, an effective amount of the compound according to  claim 1 . 
     
     
         12 . The method according to  claim 11 , wherein the disease or disorder is associated with viral infections caused by herpes viruses. 
     
     
         13 . A method of treatment or prophylaxis of neurodegenerative diseases caused by viruses, the method including a step of administering to a patient in need thereof, an effective amount of the compound according to  claim 1 . 
     
     
         14 . The method according to  claim 11 , wherein:
 the disease or disorder associated with viral infections includes Alzheimers disease, encephalitis, pneumonia, hepatitis, and a suppressed immune system,   the effective amount of the compound according to  claim 1  is administered to AIDS patients, cancer patients, patients having a genetic immunodeficiency, transplant patients, new-born children, infants, Herpes-positive patients, and   the effective amount of the compound suppresses recurrence of the disease or disorder in patients who are resistant to nucleosidic antiviral therapy.   
     
     
         15 . A pharmaceutical composition comprising one or more of the compounds according to  claim 1  and at least one pharmaceutically acceptable carrier and/or excipient and/or at least one further active substance being effective in treating a disease or disorder associated with viral infections. 
     
     
         16 . The compound according to  claim 5 , wherein R 7  is 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound according to  claim 3 , wherein R 7  is phenyl, optionally substituted with 1 to 4 substituents (R x ), wherein the 1 to 4 substituents R x  independently have the meaning of the possible substituents of R 7  as defined in  claim 3  and which is represented by Formula (II) 
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound according to  claim 3 , wherein R 7  is selected from 
       
         
           
           
               
               
           
         
       
     
     
         19 . The compound according to  claim 3 , wherein:
 X is selected from   
       
         
           
           
               
               
           
         
       
       and
 R 1  is selected from H, halogen, C 1-6 -alkyl, halo-C 1-6 -alkyl, C 3-6 -cycloalkyl, halo-C 3-6 -cycloalkyl, —O—C 1-6 -alkyl, —O-halo-C 1-6 -alkyl and —NH—C 1-6 -alkyl. 
 
     
     
         20 . The compound according to  claim 3 , wherein:
 R 2  and R 3  are independently selected from H, C 1-3 -alkyl, halo-C 1-3 -alkyl, —O—C 1-3 -alkyl, —O-fluoro-C 1-3 -alkyl, C 3-6 -cycloalkyl and C 3-6 -heterocycloalkyl, wherein alkyl, cycloalkyl and heterocycloalkyl are optionally substituted with 1 to 5 substituents independently selected from F, Cl, OH, oxo, Me (—CH 3 ), CHF 2  and CF 3 ;   or R 2  and R 3  when taken together with the nitrogen to which they are attached complete a 5- to 6-membered ring containing carbon atoms and optionally containing one additional heteroatom selected from O, S or N, wherein the ring is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of F, Cl, OH, oxo, Me (—CH 3 ), CHF 2  and CF 3 ;   R 8  is selected from H, —CN, —NO 2 , OH, C 1-3 -alkyl, O—C 1-3 -alkyl, fluoro-C 1-3 -alkyl and O-fluoro-C 1-3 -alkyl;   R 9  is selected from C 1-3 -alkyl, t-butyl, fluoro-C 1-3 -alkyl, and -cyclopropyl;   R 10  is selected from —CN, OH, and —NO 2 ; and   R 12  is independently selected from H, Me (—CH 3 ) and Et (—CH 2 —CH 3 ).