Novel inhibitor compounds of phosphodiesterase type 10a

Abstract

The present invention relates to compounds which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders.

We claim: 
     
         1 . Compound of formula I 
       
         
           
           
               
               
           
         
         where in formula I 
         X 1  is CH or N, 
         X 2  is C—R 5  or N, 
         Y is O or S, 
         R 1  is selected from the group consisting of C 2 -C 8 -alkyl, C 2 -C 8 -alkenyl, C 1 -C 4 -fluoroalkyl, C 3 -C 8 -cycloalkyl, C 5 -C 8 -cycloalkyl carrying a fused benzene ring, fluorinated C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, fluorinated C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 4 -alkyl-N(R b )(R c ) and a moiety Z 1 —Ar 1 ; 
         R 2  is a radical of the formula CR 21 R 22 R 23  or phenyl or 5- or 6-membered hetaryl having 1, 2 or 3 heteroatoms as ring members which are selected from O, S and N, where phenyl and monocyclic hetaryl are unsubstituted or may carry 1, 2 or 3 identical or different substituents R a , where
 R 21  is selected from the group consisting of hydrogen, C 1 -C 8 -alkyl, trimethylsilyl, C 2 -C 8 -alkenyl, C 1 -C 4 -fluoroalkyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, fluorinated C 3 -C 8 -cyclo alkyl-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 4 -alkyl-N(R b )(R c ), (CH 2 ) m C(O)O—R d , (CH 2 ) m C(O)N(R e )(R f ) and Z 2 —Ar 2 , 
 R 22  is selected from the group consisting of hydrogen, fluorine, C 1 -C 8 -alkyl, C 2 -C 8 -alkenyl, C 1 -C 4 -fluoroalkyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, fluorinated C 3 -C 8 -cyclo alkyl-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl and C 1 -C 4 -alkyl-N(R b )(R c ), or 
 R 21  and R 22  together with the carbon atom, to which they are bound form a saturated 5- to 7-membered carbocyclic ring or a saturated 5- to 7-membered heterocyclic ring which has 1, 2 or 3 heteroatoms or heteroatom containing groups selected from the group of O, N, S, SO and SO 2  as ring members, where the carbocyclic ring and the heterocyclic ring may be unsubstituted or may be substituted by 1, 2 or 3 identical or different substituents R g , and where the carbocyclic ring and the heterocyclic ring may carry a fused benzene ring or a fused 5- or 6-membered heteroaromatic ring, where the fused rings themselves are unsubstituted or carry 1, 2 or 3 substituents R h , 
 R 23  is selected from the group consisting of hydrogen, fluorine, C 1 -C 8 -alkyl and C 1 -C 4 -fluoroalkyl; 
 
         R 3  is selected from the group consisting of hydrogen, C 1 -C 8 -alkyl, C 2 -C 8 -alkenyl, C 1 -C 4 -fluoroalkyl, C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 4 -alkyl-N(R b )(R c ), and trimethylsilyl, or 
         R 2  and R 3  together with the nitrogen atom, to which they are bound form a saturated 5- to 7-membered heterocyclic ring which, in addition to the nitrogen atom, may have 1 or 2 further heteroatoms or heteroatom containing groups selected from the group of O, N, S, SO and SO 2  as ring members, where the heterocyclic ring may be unsubstituted or may be substituted by 1, 2 or 3 identical or different substituents R 31 , and where the heterocyclic ring may carry a fused benzene ring or a fused 5- or 6-membered heteroaromatic ring, where the fused rings themselves are unsubstituted or carry 1, 2 or 3 substituents R 32 , where
 R 31  is selected from the group consisting of halogen, CN, OH, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkoxy, N(R b )(R c ), C(O)O—R d , C(O)N(R e )(R f ), where one radical R 31  may also be a moiety Z 3 —Ar 3 , 
 R 32  is selected from the group consisting of halogen, CN, OH, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkoxy, N(R b )(R c ), C(O)O—R d  and C(O)N(R e )(R f ); 
 
         R 4  is selected from the group consisting of C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl and Z 4 —Ar 4 ., 
         R 5  is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -fluoroalkoxy, —Z 5 —Ar 5 , —O—Z 5 —Ar 5 , C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, C 3 -C 6 -cycloalkoxy and C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkoxy, where the cyclic radical in the last four mentioned groups may be unsubstituted, partially or completely fluorinated or carries 1, 2, 3 or 4 methyl groups;
 Ar 1  is selected from the group consisting of phenyl, monocyclic 5- or 6-membered hetaryl or bicyclic 9- or 10-membered hetaryl, where hetaryl has 1, 2 or 3 heteroatoms as ring members which are selected from O, S and N, where phenyl and hetaryl are unsubstituted or may carry 1, 2 or 3 identical or different substituents R h ; 
 Ar 2  is phenyl or monocyclic 5- or 6-membered hetaryl having 1, 2 or 3 heteroatoms as ring members which are selected from O, S and N, where phenyl and monocyclic hetaryl are unsubstituted or may carry 1, 2 or 3 identical or different substituents R h ; 
 Ar 3  is phenyl or monocyclic 5- or 6-membered hetaryl having 1, 2 or 3 heteroatoms as ring members which are selected from O, S and N, where phenyl and monocyclic hetaryl are unsubstituted or may carry 1, 2 or 3 identical or different substituents R h ; 
 Ar 4  and Ar 5  are independently of each other selected from the group consisting of phenyl and monocyclic 5- or 6-membered hetaryl having 1, 2 or 3 heteroatoms as ring members which are selected from O, S and N, where phenyl and monocyclic hetaryl are unsubstituted or may carry 1, 2 or 3 identical or different substituents R k ; 
 Z 1 , Z 4 , Z 5  are independently of each other C 1 -C 4 -alkylene; 
 Z 2  is a single bond or C 1 -C 4 -alkylene; 
 Z 3  is a single bond, C 1 -C 4 -alkylene, O, N, S, SO or SO 2 ; 
 R a  is selected from the group consisting of halogen, CN, OH, NO 2 , C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkoxy, (CH 2 ) m N(R b )(R c ), C(O)O—R d , C(O)N(R e )(R f ), N(R ee )S(O) 2 (R ff ) and S(O) 2 N(R e )(R f ); 
 R b , R c , independently of each other are selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkylmethyl and benzyl or R b  and R c  form together with the N atom to which they are attached a 3- to 7-membered, nitrogen heterocycle which may have 1, 2 or 3 further different or identical heteroatoms or heteroatom containing groups selected from the group of O, N, S, SO and SO 2  as ring members and which may carry 1, 2, 3, 4, 5 or 6 substituents selected from C 1 -C 4 -alkyl; 
 R d  is selected from the group consisting of C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkylmethyl and benzyl; 
 R e , R f , independently of each other are selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkylmethyl and benzyl or R e  and R f  form together with the N atom to which they are attached a 3- to 7-membered, nitrogen heterocycle which may have 1, 2 or 3 further different or identical heteroatoms or heteroatom containing groups selected from the group of O, N, S, SO and SO 2  as ring members and which may carry 1, 2, 3, 4, 5 or 6 substituents selected from C 1 -C 4 -alkyl; 
 R g  is selected from the group consisting of halogen, CN, OH, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 1 -C 4 -fluoroalkyl, C 3 -C 6 -cycloalkyl, fluorinated C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, fluorinated C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, hydroxy-C 1 -C 4 -alkyl, C 1 -C 4 -alkyl-N(R b )(R c ), C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkoxy, one R g  together with a carbon atom to which R g  is attached may also form a carbonyl group, one R g  may also be phenyl or benzyl, where the phenyl ring in the last 2 mentioned radicals is unsubstituted or carries 1, 2 or 3 radicals R h ; 
 R h  is selected from the group consisting of halogen, CN, OH, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 6 -alkoxy, fluorinated C 1 -C 4 -alkoxy, C 1 -C 4 -alkylsulfanyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkoxy, C 3 -C 6 -cycloalkyl, fluorinated C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkoxy, C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkoxy, phenoxy, N(R b )(R c ), C 1 -C 4 -alkyl-N(R b )(R c ), C(O)O—R d , C(O)N(R e )(R f ), N(R ee )S(O) 2 (R ff ), S(O) 2 N(R e )(R f ), 3- to 7-membered heterocyclyloxy, 3- to 7-membered heterocyclyl-C 1 -C 4 -alkoxy, where heterocyclyl in the two last mentioned radicals has 1, 2 or 3 heteroatoms as ring members which are selected from O, S and N, and 5- to 6-membered hetaryl-C 1 -C 4 -alkoxy, where hetaryl has 1, 2 or 3 heteroatoms as ring members which are selected from O, S and N; 
 R k  is selected from the group consisting of halogen, CN, OH, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkoxy, N(R b )(R c ), C(O)O—R d , C(O)N(R e )(R f ), N(R ee )S(O) 2 (R ff ) and S(O) 2 N(R e )(R f ) or two radicals R k  that are bound to adjacent carbon atoms together with said carbon atoms may form fused benzene ring or a fused 5- or 6-membered heteroaromatic ring having 1 or 2 ring members selected from O, N and S, where the fused benzene ring and the fused heteroaromatic ring are unsubstituted or may carry 1, 2 or 3 radicals R h ; 
 R ee  is selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -cycloalkylmethyl and benzyl; 
 R ff  is selected from the group consisting of C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl and phenyl, which is unsubstituted or carries 1, 2 or 3 radicals R h ; 
 m is 0, 1, 2, 3 or 4, 
 
         the N-oxides, hydrates, tautomers, the prodrugs thereof and the pharmaceutically acceptable salts thereof. 
       
     
     
         2 . The compound of  claim 1 , where R h  is selected from the group consisting of halogen, CN, OH, C 1 -C 4 -alkyl, fluorinated C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, fluorinated C 1 -C 4 -alkoxy, C 3 -C 6 -cycloalkyl, fluorinated C 3 -C 6 -cycloalkyl, N(R b )(R c ), C 1 -C 4 -alkyl-N(R b )(R c ), C(O)O—R d , C(O)N(R e )(R f ), N(R ee )S(O) 2 (R ff ) and S(O) 2 N(R e )(R f ). 
     
     
         3 . The compound of  claim 1 , where X 1  is C—H. 
     
     
         4 . The compound of  claim 1 , where X 1  is N. 
     
     
         5 . The compound of  claim 1 , where X 2  is C—R 5 . 
     
     
         6 . The compound of  claim 1 , where X 2  is N. 
     
     
         7 . The compound of  claim 1 , where Y is O. 
     
     
         8 . The compound of  claim 1 , where R 1  is C 2 -C 8 -alkyl, C 3 -C 8 -cycloalkyl or C 3 -C 8 -cycloalkylmethyl. 
     
     
         9 . The compound of  claim 8 , where R 1  is a radical of the formula CHR 1a R 1b , where R 1a  is selected from the group consisting of hydrogen and C 1 -C 3 -alkyl and where R 1b  is selected from the group consisting of C 1 -C 4 -alkyl. 
     
     
         10 . The compound of  claim 1 , where R 1  is a moiety Z 1 —Ar 1 . 
     
     
         11 . The compound of  claim 1 , where R 2  is a radical of the formula CR 21 R 22 R 23 . 
     
     
         12 . The compound of  claim 11 , where
 R 21  and R 22  together with the carbon atom, to which they are bound form a saturated 5- to 7-membered carbocyclic ring or a saturated 5- to 7-membered heterocyclic ring which has 1, 2 or 3 heteroatoms or heteroatom containing groups selected from the group of O, N, S, SO and SO 2  as ring members, where the carbocyclic ring and the heterocyclic ring may be unsubstituted or may be substituted by 1, 2 or 3 identical or different substituents R g , and where the carbocyclic ring and the heterocyclic ring may carry a fused benzene ring or a fused 5- or 6-membered heteroaromatic ring, where the fused rings themselves are unsubstituted or carry 1, 2 or 3 substituents R h , where R h  and R g  are as defined in  claim 1 , and where   R 23  is hydrogen.   
     
     
         13 . The compound of  claim 11 , where
 R 21  and R 22  together with the carbon atom, to which they are bound form a saturated 5- to 7-membered carbocyclic ring or a 3-tetrahydrofuryl or 3-tetrahydrothienyl, where the 5- to 7-membered carbocyclic ring and the 3-tetrahydrofuryl or 3-tetrahydrothienyl ring carry a fused benzene ring or a fused 5- or 6-membered heteroaromatic ring, where the fused rings themselves are unsubstituted or carry 1, 2 or 3 substituents R h , where R h  are as defined in  claim 1 , and where   R 23  is hydrogen.   
     
     
         14 . The compound of  claim 11 , where
 R 21  is selected from the group consisting of C 1 -C 8 -alkyl, trimethylsilyl, C 2 -C 8 -alkenyl, C 1 -C 4 -fluoroalkyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, fluorinated C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl and Z 2 —Ar 2 , where Z 2  and Ar 2  are as defined in  claim 1 ;   R 22  is selected from the group consisting of hydrogen, fluorine, C 1 -C 8 -alkyl; and   R 23  is hydrogen.   
     
     
         15 . The compound of  claim 14 , where R 21  is a moiety Z 2 —Ar 2 , where Z 2  and Ar 2  are as defined in  claim 1 . 
     
     
         16 . The compound of  claim 1 , where R 3  is hydrogen or C 1 -C 4 -alkyl. 
     
     
         17 . The compound of  claim 1 , where R 2  and R 3  together with the nitrogen atom, to which they are bound form a saturated 5- to 7-membered heterocyclic ring which, in addition to the nitrogen atom, may have 1 or 2 further heteroatoms or heteroatom containing groups selected from the group of O, N, S, SO and SO 2  as ring members, where the heterocyclic ring may be unsubstituted or may be substituted by 1, 2 or 3 identical or different substituents R 31 , and where the heterocyclic ring may carry a fused benzene ring or a fused 5- or 6-membered heteroaromatic ring, where the fused rings themselves are unsubstituted or carry 1, 2 or 3 substituents R 32 , where R 31  and R 32  are as defined in  claim 1 . 
     
     
         18 . The compound of  claim 1 , where R 4  is C 1 -C 4 -alkyl. 
     
     
         19 . The compound of  claim 1 , where X 2  is C—R 5  and R 5  is hydrogen, fluorine, C 1 -C 4 -alkoxy or a radical O—Z 5 —Ar 5 . 
     
     
         20 . The compound of  claim 19 , where R 4  is methyl and R 5  is hydrogen, fluorine or methoxy. 
     
     
         21 . The compound of  claim 19 , where R 4  is methyl and R 5  is O—Z 5 —Ar 5 . 
     
     
         22 . The compound of  claim 1  which is a compound of the formula Ia 
       
         
           
           
               
               
           
         
         where R 1 , R 2 , R 3 , R 4  and R 5  are as defined in  claim 1 . 
       
     
     
         23 . The compound of  claim 1  which is a compound of the formula Ib 
       
         
           
           
               
               
           
         
         where R 1 , R 2 , R 3 , R 4  and R 5  are as defined in  claim 1 . 
       
     
     
         24 . The compound of  claim 22 , where
 R 1  is a radical of the formula CHR 1a R 1b , where R 1a  is selected from the group consisting of hydrogen and C 1 -C 3 -alkyl and where R 1b  is selected from the group consisting of C 1 -C 4 -alkyl;   R 2  is a radical of the formula CR 21 R 22 R 23 ;   R 3  is hydrogen or C 1 -C 4 -alkyl;   R 4  is C 1 -C 4 -alkyl, and   R 5  is hydrogen, fluorine, C 1 -C 4 -alkoxy or a radical O—Z 5 —Ar 5 .   
     
     
         25 . The compound of  claim 22 , where
 R 1  is a moiety Z 1 —Ar 1 ;   R 2  is a radical of the formula CR 21 R 22 R 23 ;   R 3  is hydrogen or C 1 -C 4 -alkyl;   R 4  is C 1 -C 4 -alkyl, and   R 5  is hydrogen, fluorine or C 1 -C 4 -alkoxy.   
     
     
         26 . The compound of  claim 24 , where
 R 21  and R 22  together with the carbon atom, to which they are bound form a saturated 5- to 7-membered carbocyclic ring, which carries a fused benzene ring or a fused 5- or 6-membered heteroaromatic ring, where the fused rings themselves are unsubstituted or carry 1, 2 or 3 substituents R h , where R h  are as defined in  claim 1 , and where   R 23  is hydrogen.   
     
     
         27 . The compound of  claim 24 , where
 R 21  is selected from the group consisting of C 1 -C 8 -alkyl, trimethylsilyl, C 2 -C 8 -alkenyl, C 1 -C 4 -fluoroalkyl, C 3 -C 8 -cycloalkyl, fluorinated C 3 -C 8 -cycloalkyl, C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl, fluorinated C 3 -C 8 -cycloalkyl-C 1 -C 4 -alkyl and Z 2 —Ar 2 , where Z 2  and Ar 2  are as defined in  claim 1 ;   R 22  is selected from the group consisting of hydrogen, fluorine, C 1 -C 8 -alkyl; and   R 23  is hydrogen.   
     
     
         28 . The compound of  claim 22 , where R 4  is methyl and R 5  is hydrogen, fluorine or methoxy. 
     
     
         29 . The compound of  claim 22 , where R 4  is methyl and R 5  is O—Z 5 —Ar 5 . 
     
     
         30 . The compound of  claim 1 , which is selected from the group consisting of
 2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid methylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid cyclopropylmethyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid methyl-phenethyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2-methoxy-benzyl)-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (4-methoxy-benzyl)-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (3-methoxy-benzyl)-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid methyl-(3-trifluoromethyl-benzyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid benzyl-(2-dimethylamino-ethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (1-benzyl-piperidin-4-yl)-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid tert-butylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid sec-butylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid isobutyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid cyclopentylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (1-methyl-butyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (1,1-dimethyl-propyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (1,2-dimethyl-propyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2,2-dimethyl-propyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (1-ethyl-propyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ethylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2-methyl-butyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid pentylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid cyclohexylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (1,3-dimethyl-butyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (3,3-dimethyl-butyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2-ethyl-butyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid dicyclopropylmethyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2-fluoro-ethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid cyclohexylmethyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (1-phenyl-ethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2-fluoro-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 3-fluoro-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 4-fluoro-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2,3-difluoro-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2,4-difluoro-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2,6-difluoro-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 3,4-difluoro-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2,2,2-trifluoro-ethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 3,5-difluoro-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid phenethyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid [1-(4-fluoro-phenyl)-ethyl]-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid indan-1-ylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid indan-2-ylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid [1-(4-fluoro-phenyl)-1-methyl-ethyl]-amide,   4-(Azetidine-1-carbonyl)-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid cyclopropylamide,   2-Ethyl-6,7-dimethoxy-4-(2-methyl-pyrrolidine-1-carbonyl)-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-4-(morpholine-4-carbonyl)-2H-isoquinolin-1-one,   2-Ethyl-4-(3-fluoro-pyrrolidine-1-carbonyl)-6,7-dimethoxy-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-4-(4-methyl-piperazine-1-carbonyl)-2H-isoquinolin-1-one,   4-(3,3-Difluoro-pyrrolidine-1-carbonyl)-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   4-(3-Dimethylamino-pyrrolidine-1-carbonyl)-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-4-((R)-2-methoxymethyl-pyrrolidine-1-carbonyl)-2H-isoquinolin-1-one,   4-(1,3-Dihydro-isoindole-2-carbonyl)-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   4-(4,4-Difluoro-piperidine-1-carbonyl)-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid isopropylamide,   2-Ethyl-4-(4-isopropyl-piperazine-1-carbonyl)-6,7-dimethoxy-2H-isoquinolin-1-one,   4-(4-Dimethylamino-piperidine-1-carbonyl)-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-4-(2-trifluoromethyl-pyrrolidine-1-carbonyl)-2H-isoquinolin-1-one,   4-(4-Cyclopropylmethyl-piperazine-1-carbonyl)-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-4-((S)-2-pyrrolidin-1-ylmethyl-pyrrolidine-1-carbonyl)-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-4-(4-pyrrolidin-1-yl-piperidine-1-carbonyl)-2H-isoquinolin-1-one,   4-[4-(2-Dimethylamino-ethyl)-piperazine-1-carbonyl]-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   4-([1,4′]Bipiperidinyl-1′-carbonyl)-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   4-[4-(3-Dimethylamino-propyl)-piperazine-1-carbonyl]-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid propylamide,   2-Ethyl-6,7-dimethoxy-4-[4-(2-pyrrolidin-1-yl-ethyl)-piperazine-1-carbonyl]-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid dimethylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ethyl-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid isopropyl-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid diethylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid methyl-propyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ethyl-isopropyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid tert-butyl-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid isobutyl-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butyl-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ethyl-propyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2-dimethylamino-ethyl)-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ethyl-(2-methoxy-ethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid cyclopentyl-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butyl-ethyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid methyl-pentyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid diisopropylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid isopropyl-propyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid cyclobutylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid dipropylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (3-dimethylamino-propyl)-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid cyclohexyl-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid cyclopropylmethyl-propyl-amide   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid diisobutylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid benzyl-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2-fluoro-benzyl)-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (4-fluoro-benzyl)-methyl-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (3-fluoro-benzyl)-methyl-amide,   2-tert-Butyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-sec-Butyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Isobutyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Butyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Cyclopropylmethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-(2-Dimethylamino-ethyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Cyclopentyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   6,7-Dimethoxy-1-oxo-2-(2,2,2-trifluoro-ethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide   6,7-Dimethoxy-1-oxo-2-(2-pyrrolidin-1-yl-ethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-(2-Fluoro-ethyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Benzyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-(2,4-Difluoro-benzyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Cyclopropyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   6,7-Dimethoxy-1-oxo-2-(2-piperidin-1-yl-ethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   6,7-Dimethoxy-1-oxo-2-phenethyl-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   6,7-Dimethoxy-2-(2-methoxy-benzyl)-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Indan-1-yl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Isopropyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   6,7-Dimethoxy-1-oxo-2-propyl-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   6,7-Dimethoxy-1-oxo-2-(3,3,3-trifluoro-propyl)-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   6,7-Dimethoxy-2-(2-methoxy-ethyl)-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Cyclobutyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid butylamide,   2-Ethyl-7-methoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid indan-1-ylamide,   2-Ethyl-7-methoxy-1-oxo-6-(2-quinolin-2-yl-ethoxy)-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   2-Ethyl-7-methoxy-1-oxo-6-(3-quinolin-2-yl-propoxy)-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-amide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (R)-indan-1-ylamide,   2-Ethyl-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid indan-1-ylamide,   2-Ethyl-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid butylamide,   2-(1-Ethyl-propyl)-7-methoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid indan-1-ylamide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl)-amide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (1,2,3,4-tetrahydro-naphthalen-2-yl)-amide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (4-bromo-indan-1-yl)-amide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (5-bromo-indan-1-yl)-amide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid 2-dimethylaminomethyl-benzylamide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (6,7-dihydro-5H-[1]pyrindin-5-yl)-amide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (6,7-dihydro-5H-[1]pyrindin-7-yl)-amide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid 3-dimethylaminomethyl-benzylamide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid 4-dimethylaminomethyl-benzylamide,   7-Methoxy-1-oxo-2-(2-quinolin-2-yl-ethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid butylamide,   7-Methoxy-1-oxo-2-(2-quinolin-2-yl-ethyl)-1,2-dihydro-isoquinoline-4-carboxylic acid indan-1-ylamide,   3-Ethyl-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (S)-indan-1-ylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (6,7-dihydro-5H-[1]pyrindin-5-yl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2-dimethylaminomethyl-benzylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 3,5-difluoro-benzylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 3,4-difluoro-benzylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid cyclohexylmethyl-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (R)-indan-1-ylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (S)-indan-1-ylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (1,2,3,4-tetrahydro-naphthalen-1-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid pyridin-3-ylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (pyrimidin-4-ylmethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2-methoxy-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (4-morpholin-4-yl-phenyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 3-chloro-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (pyridin-4-ylmethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid o-tolylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid m-tolylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2-methoxy-phenyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (3-methoxy-phenyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (pyridin-3-ylmethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (pyridin-2-ylmethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (3-dimethylamino-propyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid phenylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 4-methoxy-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 3-methyl-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2-methyl-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2-methoxy-ethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (4-fluoro-phenyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (4-methoxy-phenyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid p-tolylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (3-fluoro-phenyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2-fluoro-phenyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 4-methyl-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2-chloro-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid [(R)-1-(4-fluoro-phenyl)-ethyl]-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid pyridin-4-ylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-1-(4-fluoro-phenyl)-ethyl]-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (6-methyl-indan-1-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2-morpholin-4-ylmethyl-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (5-chloro-indan-1-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (6-chloro-indan-1-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (6-fluoro-indan-1-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (5,6-dihydro-4H-cyclopenta[b]thiophen-4-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (4-fluoro-indan-1-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (4-methyl-indan-1-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (5-methyl-indan-1-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (6-methoxy-indan-1-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (5-fluoro-indan-1-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2-diethylaminomethyl-benzylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2-pyrrolidin-1-ylmethyl-benzylamide,   2-Ethyl-6,7-dimethoxy-4-(4-methyl-piperidine-1-carbonyl)-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (tetrahydro-furan-2-ylmethyl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (3-methoxy-propyl)-amide,   4-(3,5-Dimethyl-piperidine-1-carbonyl)-2-ethyl-6,7-dimethoxy-2H-isoquinolin-1-one,   2-Ethyl-4-(4-ethyl-piperazine-1-carbonyl)-6,7-dimethoxy-2H-isoquinolin-1-one,   2-Isobutyl-6,7-dimethoxy-4-(4-methyl-piperazine-1-carbonyl)-2H-isoquinolin-1-one,   2-Isobutyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2-dimethylamino-ethyl)-amide,   2-Isobutyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid butyl-methyl-amide,   [(2-Isobutyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carbonyl)-amino]-acetic acid methyl ester,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (3-isopropoxy-propyl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (5,6-dihydro-4H-cyclopenta[b]thiophen-4-yl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2,3-dihydro-benzofuran-3-yl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophen-4-yl)-amide,   2-Cyclopropyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid indan-1-ylamide,   2-sec-Butyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid indan-1-ylamide,   2-Isopropyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid indan-1-ylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-4-(3-phenyl-piperidine-1-carbonyl)-2H-isoquinolin-1-one,   2-(1-Ethyl-propyl)-6,7-dimethoxy-4-(3-phenoxy-piperidine-1-carbonyl)-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (S)indan-1-ylamide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (R)indan-1-ylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-4-[3-(3-methoxy-phenyl)-piperazine-1-carbonyl]-2H-isoquinolin-1-one,   2-(1-Ethyl-propyl)-6,7-dimethoxy-4-[8-(4-methyl-piperazine-1-sulfonyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2H-isoquinolin-1-one,   2-(1-Ethyl-propyl)-6,7-dimethoxy-4-[8-(morpholine-4-sulfonyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-2H-isoquinolin-1-one,   2-(1-Ethyl-propyl)-6,7-dimethoxy-4-[3-(3-methoxy-phenyl)-4-methyl-piperazine-1-carbonyl]-2H-isoquinolin-1-one,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid ([1,3,4]thiadiazol-2-ylmethyl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2-(morpholine-4-sulfonyl)-benzylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (thiazol-4-ylmethyl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-4-[(R)-3-(quinoxalin-2-yloxy)-pyrrolidine-1-carbonyl]-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (S)(5,6-dihydro-4H-cyclopenta[b]thiophen-4-yl)-amide,   2-Ethyl-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (R)(5,6-dihydro-4H-cyclopenta[b]thiophen-4-yl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (thiophen-3-ylmethyl)-amide,   4-(7-Amino-3,4-dihydro-1H-isoquinoline-2-carbonyl)-2-(1-ethyl-propyl)-6,7-dimethoxy-2H-isoquinolin-1-one,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 3-(4-chloro-benzenesulfonylamino)-benzylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (2,3-dihydro-benzo[b]thiophen-3-yl)-amide,   2-(1-Ethyl-propyl)-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid (5,6-dihydro-4H-cyclopenta[b]thiophen-4-yl)-amide,   2-(1-Ethyl-propyl)-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid (S)-indan-1-ylamide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 2-(4-methyl-piperazine-1-sulfonyl)-benzylamide,   2-(1-Ethyl-propyl)-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid 2-(morpholine-4-sulfonyl)-benzylamide,   2-(1-Ethyl-propyl)-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid (6,7-dihydro-5H-[1]pyrindin-5-yl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid 3-(4-methoxy-benzenesulfonylamino)-benzylamide,   2-(1-Ethyl-propyl)-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid 3,5-difluoro-benzylamide,   2-(1-Ethyl-propyl)-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid 4-methyl-benzylamide,   2-(1-Ethyl-propyl)-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid cyclohexylmethyl-amide,   2-(1-Ethyl-propyl)-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid butylamide,   2-(1-Ethyl-propyl)-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid (2,3-dihydro-benzofuran-3-yl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (thiazol-2-ylmethyl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid (thiophen-2-ylmethyl)-amide,   2-Ethyl-7-methoxy-1-oxo-1,2-dihydro-[2,6]naphthyridine-4-carboxylic acid (5,6-dihydro-4H-cyclopenta[b]thiophen-4-yl)-amide,   3-(1-Ethyl-propyl)-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (5,6-dihydro-4H-cyclopenta[b]thiophen-4-yl)-amide,   3-(1-Ethyl-propyl)-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (2,3-dihydro-benzofuran-3-yl)-amide,   3-(1-Ethyl-propyl)-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid indan-1-ylamide,   3-(1-Ethyl-propyl)-6,7-dimethoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid (6,7-dihydro-5H-[1]pyrindin-5-yl)-amide,   2-(1-Ethyl-propyl)-6,7-dimethoxy-4-(3-phenyl-propionyl)-2H-isoquinolin-1-one,   2-Ethyl-6,7-dimethoxy-N-(4-nitrophenyl)-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   and the N-oxides, the tautomers, the hydrates, the prodrugs and the pharmaceutically acceptable salts thereof.   
     
     
         31 . The compound of  claim 1 , which is selected from the group consisting of
 6,7-Dimethoxy-1-oxo-2-(pentan-3-yl)-N-(pyridin-3-ylmethyl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((5-methylthiophen-2-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   N-((3,5-Dimethylisoxazol-4-yl)methyl)-6,7-dimethoxy-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-dimethoxy-N-((5-methylthiazol-2-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-1-oxo-2-(pentan-3-yl)-N-(pyrimidin-4-ylmethyl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((3-methylisoxazol-5-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   N-((2,5-Dimethylthiophen-3-yl)methyl)-6,7-dimethoxy-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((2-methylthiazol-5-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((5-methylisoxazol-3-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   (R)—N-(1-(4-Fluorophenyl)ethyl)-6,7-dimethoxy-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   (S)—N-(1-(4-Fluorophenyl)ethyl)-6,7-dimethoxy-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((4-methylthiazol-2-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((2-methylthiazol-4-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((4-methylthiazol-5-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-1-oxo-2-(pentan-3-yl)-N-((5-(trifluoromethyl)furan-2-yl)methyl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((5-methylfuran-2-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   N-(5-Fluoro-2,3-dihydro-1H-inden-1-yl)-6,7-dimethoxy-1-oxo-2-(pentan-3-yl)-1,2-dihydroiso-quinoline-4-carboxamide,   6,7-Dimethoxy-N-(5-methyl-2,3-dihydro-1H-inden-1-yl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-(4-methyl-2,3-dihydro-1H-inden-1-yl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   N-((2-Ethylthiazol-4-yl)methyl)-6,7-dimethoxy-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-(6-methoxy-2,3-dihydro-1H-inden-1-yl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((4-methylthiophen-2-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((3-methylthiophen-2-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((5-methyloxazol-2-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-(6-methyl-2,3-dihydro-1H-inden-1-yl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-1-oxo-2-(pentan-3-yl)-N-(pyridin-4-ylmethyl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-(4-methylbenzyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-1-oxo-2-(pentan-3-yl)-N-(pyridin-2-ylmethyl)-1,2-dihydroisoquinoline-4-carboxamide,   N-((5-Cyanofuran-2-yl)methyl)-6,7-dimethoxy-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   N-(4-Chloro-2,3-dihydro-1H-inden-1-yl)-6,7-dimethoxy-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   N-((5-Ethylthiophen-2-yl)methyl)-6,7-dimethoxy-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((3-methylfuran-2-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((2-methylfuran-3-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   6,7-Dimethoxy-N-((1-methyl-1H-pyrazol-3-yl)methyl)-1-oxo-2-(pentan-3-yl)-1,2-dihydroisoquinoline-4-carboxamide,   N-[(3,4-Dimethylphenyl)methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   N-[(2-Chloro-4-methyl-phenyl)methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   N-[[2-(Dimethylamino)-4-methyl-phenyl]methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-N-[(2-fluoro-4-methyl-phenyl)methyl]-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[(3-methoxy-4-methyl-phenyl)methyl]-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[(4-methyl-2-morpholino-phenyl)methyl]-1-oxo-isoquinoline-4-carboxamide,   N-[(2-tert-Butoxy-4-methyl-phenyl)methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   N-[[2-(1,1-Dimethylpropoxy)-4-methyl-phenyl]methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   N-[(2,3-Difluoro-4-methyl-phenyl)methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-N-[(3-fluoro-4-methyl-phenyl)methyl]-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   N-[(3-Chloro-4-methyl-phenyl)methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-1-oxo-N-[(2,4,6-trimethylphenyl)methyl]isoquinoline-4-carboxamide,   N-[(2,4-Dimethylphenyl)methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[[2-(3-methoxypropoxy)-4-methyl-phenyl]methyl]-1-oxo-isoquinoline-4-carboxamide,   N-[[2-(2-Ethoxyethoxy)-4-methyl-phenyl]methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   N-[[2-(Cyclopentoxy)-4-methyl-phenyl]methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[(4-methyl-2-phenoxy-phenyl)methyl]-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[[2-(2-methoxy-1-methyl-ethoxy)-4-methyl-phenyl]methyl]-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[[4-methyl-2-(2,2,2-trifluoroethoxy)phenyl]methyl]-1-oxo-isoquinoline-4-carboxamide,   N-[[2-(Cyclohexoxy)-4-methyl-phenyl]methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   N-[[2-(Cyclopropylmethoxy)-4-methyl-phenyl]methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-N-[(2-hexoxy-4-methyl-phenyl)methyl]-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[[4-methyl-2-(tetrahydrofuran-3-ylmethoxy)phenyl]methyl]-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[[2-(2-methoxyethoxy)-4-methyl-phenyl]methyl]-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-N-(2-isobutoxy-4-methylbenzyl)-6,7-dimethoxy-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-N-(2-(furan-2-ylmethoxy)-4-methylbenzyl)-6,7-dimethoxy-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-(4-methyl-2-(pentyloxy)benzyl)-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   N-(2-Ethoxy-4-methylbenzyl)-2-ethyl-6,7-dimethoxy-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   N-(2-sec-Butoxy-4-methylbenzyl)-2-ethyl-6,7-dimethoxy-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-N-(2-(isopentyloxy)-4-methylbenzyl)-6,7-dimethoxy-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-(4-methyl-2-propoxybenzyl)-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-(4-methyl-2-(methylthio)benzyl)-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-N-(2-isopropoxy-4-methylbenzyl)-6,7-dimethoxy-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-(4-methyl-2-(tetrahydrofuran-3-yloxy)benzyl)-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-1-oxo-N-(2,4,5-trimethylbenzyl)-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-(4-methyl-2-((tetrahydrofuran-2-yl)methoxy)benzyl)-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-(4-methyl-2-(4-methylpentan-2-yloxy)benzyl)-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-(4-methyl-2-(4-methylpentyloxy)benzyl)-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-(2-methoxy-4-methylbenzyl)-1-oxo-1,2-dihydroisoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-1-oxo-N-(thiazol-4-ylmethyl)isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-1-oxo-N-[[4-(trifluoromethyl)phenyl]methyl]isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-1-oxo-N-[(1S)-1-(p-tolyl)ethyl]isoquinoline-4-carboxamide,   2-Ethyl-N-[(4-isopropylphenyl)methyl]-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-N-[(4-ethylphenyl)methyl]-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-1-oxo-N-[(1R)-1-(p-tolyl)ethyl]isoquinoline-4-carboxamide,   N-[[4-(Difluoromethyl)phenyl]methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[(2-methylthiazol-4-yl)methyl]-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[(4-methyl-2-thienyl)methyl]-1-oxo-isoquinoline-4-carboxamide,   N-[(4-Cyclopropylphenyl)methyl]-2-ethyl-6,7-dimethoxy-1-oxo-isoquinoline-4-carboxamide,   N-Indan-1-yl-6,7-dimethoxy-2-[2-(5-methyl-2-pyridyl)-ethyl]-1-oxo-isoquinoline-4-carboxamide,   N-Butyl-6,7-dimethoxy-2-[2-(5-methyl-2-pyridyl)-ethyl]-1-oxo-isoquinoline-4-carboxamide,   2-Ethyl-6,7-dimethoxy-N-[2-(6-methoxy-2-pyridyl)-ethyl]-1-oxo-isoquinoline-4-carboxamide,   N-Butyl-6,7-dimethoxy-1-oxo-2-[2-(2-quino lyl)ethyl]isoquinoline-4-carboxamide,   N-Indan-1-yl-6,7-dimethoxy-1-oxo-2-[2-(2-quino lyl)ethyl]iso quinoline-4-carboxamide;   and the N-oxides, the tautomers, the hydrates, the prodrugs and the pharmaceutically acceptable salts thereof.   
     
     
         32 . The compound of  claim 1  for the use in the treatment of a medical disorder, selected from neurological and psychiatric disorders which can be treated by modulation of phosphodiesterase type 10 in a mammalian. 
     
     
         33 . The compound of  claim 1  for treating, controlling, ameliorating or reducing the risk of CNS disorders in a mammalian. 
     
     
         34 . The compound of  claim 1  for treating, controlling, ameliorating or reducing the risk of schizophrenia in a mammalian. 
     
     
         35 . The compound of  claim 1  for treating, controlling, ameliorating or reducing cognitive dysfunction associated with schizophrenia in a mammalian. 
     
     
         36 . The compound of  claim 1  for treating, controlling, ameliorating or reducing the risk of bipolar disorders in a mammalian. 
     
     
         37 . The compound of  claim 1  for treating, controlling, ameliorating or reducing the risk of depression in a mammalian. 
     
     
         38 . The compound of  claim 1  for treating, controlling, ameliorating or reducing cognitive dysfunction associated with Alzheimer's disease in a mammalian. 
     
     
         39 . The compound of  claim 1  for treating, controlling, ameliorating or reducing the risk of diet-induced obesity in a mammalian. 
     
     
         40 . A method for treating a medical disorder, selected from neurological and psychiatric disorders which can be treated by modulation of phosphodiesterase type 10, said method comprising administering an effective amount of at least one compound of  claim 1  to a subject in need thereof. 
     
     
         41 . Pharmaceutical composition which comprises a carrier and a compound as claimed in  claim 1 .