Triazolophthalazines

Abstract

The compounds of formula I in which R1 and R2 have the meanings as given in the description are novel effective PDE2 inhibitors.

1 - 14 . (canceled) 
     
     
         15 . A method for treating pneumonia or acute respiratory distress syndrome (ARDS) in septic shock in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound of formula I 
       
         
           
           
               
               
           
         
         in which 
         R1 is —U-A, in which 
         U is a direct bond, or methylene (—CH 2 —), 
         A is phenyl, pyridinyl, thiophenyl, or R11- and/or R111-substituted phenyl, in which 
         R11 is 1-4C-alkyl, halogen, trifluoromethyl, hydroxyl, 1-4C-alkoxy, phenoxy, 1-4C-alkoxycarbonyl, morpholino, di-1-4C-alkylamino, or completely or predominantly fluorine-substituted 1-4C-alkoxy, 
         R111 is 1-4C-alkoxy, halogen, hydroxyl, or 1-4C-alkyl, 
         R2 is amino, carboxyl, 1-4C-alkoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which 
         R3 is 1-4C-alkyl, 2-4C-alkenyl, 3-7C-cycloalkyl, trifluoromethyl, phenyl, R31- and/or R311-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-4C-alkyl, or 1N—(R33)-piperidinyl, in which 
         R31 is 1-4C-alkoxy, halogen, nitro, 1-4C-alkyl, trifluoromethyl, hydroxyl, 1-4C-alkoxycarbonyl, 3-7C-cyloalkylmethoxy, morpholino, or mono- or di-1-4C-alkylamino, 
         R311 is 1-4C-alkoxy, halogen, 1-4C-alkyl, hydroxyl, or 3-7C-cyloalkylmethoxy, 
         or R31 and R311 together are a 1-2C-alkylenedioxy group, 
         R32 is hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy, phenyl, R321- and/or R3211-substituted phenyl, mono- or di-1-4C-alkylamino, morpholino, or 4N—(R322)-piperazin-1-yl, in which 
         R321 is 1-4C-alkoxy, halogen, nitro, 1-4C-alkyl, trifluoromethyl, hydroxyl, 1-4C-alkoxycarbonyl, 3-7C-cyloalkylmethoxy, or mono- or di-1-4C-alkylamino, 
         R3211 is 1-4C-alkoxy, halogen, 1-4C-alkyl, hydroxyl, or 3-7C-cyloalkylmethoxy, 
         or R321 and R3211 together are a 1-2C-alkylenedioxy group, 
         R322 is 1-4C-alkyl, 
         R33 is hydrogen, 1-4C-alkyl, or 1-4C-alkylcarbonyl, 
         R4 is hydrogen, 1-4C-alkyl, R41-substituted 2-4C-alkyl, phenyl, R42- and/or R421-substituted phenyl, or pyridinyl, in which 
         R41 is hydroxyl, 1-4C-alkoxy, mono- or di-1-4C-alkylamino, or morpholino, 
         R42 is 1-4C-alkoxy, halogen, nitro, 1-4C-alkyl, trifluoromethyl, hydroxyl, 1-4C-alkoxycarbonyl, 3-7C-cyloalkylmethoxy, or mono- or di-1-4C-alkylamino, 
         R421 is 1-4C-alkoxy, halogen, 1-4C-alkyl, hydroxyl, or 3-7C-cyloalkylmethoxy, 
         or R42 and R421 together are a 1-2C-alkylenedioxy group, 
         R5 is hydrogen, or 1-4C-alkyl, 
         or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which 
         Het is morpholino, or 4N-(1-4C-alkyl)-piperazin-1-yl, 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         16 . The method according to  claim 15 , in which
 R1 is —U-A, in which   U is a direct bond, or methylene (—CH 2 —),   A is phenyl, pyridinyl, thiophenyl, di-(1-4C-alkoxy)-phenyl, or R11-substituted phenyl, in which   R11 is 1-4C-alkyl, halogen, trifluoromethyl, hydroxyl, 1-4C-alkoxy, phenoxy, 1-4C-alkoxycarbonyl, morpholino, di-1-4C-alkylamino, or completely or predominantly fluorine-substituted 1-4C-alkoxy,   R2 is amino, carboxyl, 1-4C-alkoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which   R3 is 1-4C-alkyl, 2-4C-alkenyl, 3-7C-cycloalkyl, trifluoromethyl, phenyl, R31-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-4C-alkyl, or 1N—(R33)-piperidinyl, in which   R31 is 1-4C-alkoxy, morpholino, or di-1-4C-alkylamino,   R32 is hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy, phenyl, R321-substituted phenyl, di-1-4C-alkylamino, morpholino, or 4N—(R322)-piperazin-1-yl, in which   R321 is 1-4C-alkoxy,   R322 is 1-4C-alkyl,   R33 is hydrogen, 1-4C-alkyl, or 1-4C-alkylcarbonyl,   R4 is hydrogen, 1-4C-alkyl, R41-substituted 2-4C-alkyl, phenyl, R42-substituted phenyl, or pyridinyl, in which   R41 is hydroxyl, 1-4C-alkoxy, di-1-4C-alkylamino, or morpholino,   R42 is 1-4C-alkoxy, or di-1-4C-alkylamino,   R5 is hydrogen, or 1-4C-alkyl,   or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which   Het is morpholino, or 4N-(1-4C-alkyl)-piperazin-1-yl,   or a pharmaceutically acceptable salt thereof.   
     
     
         17 . The method according to  claim 15 , in which
 R1 is —U-A, in which   U is a direct bond, or methylene (—CH 2 —),   A is phenyl, pyridinyl, thiophenyl, dimethoxyphenyl, or R11-substituted phenyl, in which   R11 is methyl, tertbutyl, chlorine, fluorine, bromine, trifluoromethyl, hydroxyl, methoxy, ethoxy, trifluoromethoxy, phenoxy, methoxycarbonyl, morpholino, or dimethylamino,   R2 is amino, carboxyl, 1-4C-alkoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which   R3 is 1-4C-alkyl, 2-4C-alkenyl, 3-7C-cycloalkyl, trifluoromethyl, phenyl, R31-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-4C-alkyl, or 1N—(R33)-piperidinyl, in which   R31 is 1-4C-alkoxy, morpholino, or di-1-4C-alkylamino,   R32 is hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy, phenyl, R321-substituted phenyl, di-1-4C-alkylamino, morpholino, or 4N—(R322)-piperazin-1-yl, in which   R321 is 1-4C-alkoxy,   R322 is 1-4C-alkyl,   R33 is hydrogen, 1-4C-alkyl, or 1-4C-alkylcarbonyl,   R4 is hydrogen, 1-4C-alkyl, R41-substituted 2-4C-alkyl, phenyl, R42-substituted phenyl, or pyridinyl, in which   R41 is hydroxyl, 1-4C-alkoxy, di-1-4C-alkylamino, or morpholino,   R42 is 1-4C-alkoxy, or di-1-4C-alkylamino,   R5 is hydrogen, or 1-4C-alkyl,   or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which   Het is morpholino, or 4N-(1-4C-alkyl)-piperazin-1-yl,   or a pharmaceutically acceptable salt thereof.   
     
     
         18 . The method according to  claim 15 , in which
 R1 is —U-A, in which   U is a direct bond, or methylene (—CH 2 —),   A is phenyl, or R11-substituted phenyl, in which   R11 is methyl, chlorine, fluorine, bromine, trifluoromethyl, hydroxyl, methoxy, phenoxy, methoxycarbonyl, or dimethylamino,   R2 is amino, carboxyl, methoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which   R3 is methyl, vinyl, cyclopropyl, cyclohexyl, trifluoromethyl, phenyl, R31-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-2C-alkyl, or 1N—(R33)-piperidinyl, in which   R31 is methoxy, morpholino, or dimethylamino,   R32 is hydroxyl, benzyloxy, methoxy, phenyl, R321-substituted phenyl, dimethylamino, morpholino, or 4N-methyl-piperazin-1-yl, in which   R321 is methoxy,   R33 is hydrogen, methyl, or acetyl,   R4 is hydrogen, methyl, 2-(R41)-ethyl, phenyl, R42-substituted phenyl, or pyridinyl, in which   R41 is hydroxyl, methoxy, dimethylamino, or morpholino,   R42 is methoxy, or dimethylamino,   R5 is hydrogen, or methyl,   or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which   Het is morpholino, or 4N-methyl-piperazin-1-yl,   or a pharmaceutically acceptable salt thereof.   
     
     
         19 . The method according to  claim 15 , in which
 R1 is —U-A, in which   U is a direct bond,   A is phenyl, or R11-substituted phenyl, in which   R11 is fluorine, bromine, trifluoromethyl, or methoxy,   R2 is attached in the meta or para position with respect to the binding position in which the phenyl ring is bonded to the amino group of the triazolophthalazine scaffold, and is amino, carboxyl, methoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which   R3 is methyl, vinyl, cyclopropyl, cyclohexyl, trifluoromethyl, phenyl, R31-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-2C-alkyl, or 1N—(R33)-piperidinyl, in which   R31 is methoxy, morpholino, or dimethylamino,   R32 is hydroxyl, benzyloxy, methoxy, phenyl, R321-substituted phenyl, dimethylamino, morpholino, or 4N-methyl-piperazin-1-yl, in which   R321 is methoxy,   R33 is hydrogen, methyl, or acetyl,   R4 is hydrogen, methyl, 2-(R41)-ethyl, phenyl, R42-substituted phenyl, or pyridinyl, in which   R41 is hydroxyl, methoxy, dimethylamino, or morpholino,   R42 is methoxy, or dimethylamino,   R5 is hydrogen, or methyl,   or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which   Het is morpholino, or 4N-methyl-piperazin-1-yl,   or a pharmaceutically acceptable salt thereof.   
     
     
         20 . The method according to  claim 15 , in which
 R1 is —U-A, in which   U is a direct bond,   A is phenyl, or R11-substituted phenyl, in which   R11 is fluorine, bromine, chlorine, trifluoromethyl, methyl or methoxy,   R2 is attached in the meta or para position with respect to the binding position in which the phenyl ring is bonded to the amino group of the triazolophthalazine scaffold, and is amino, carboxyl, methoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which   R3 is methyl, vinyl, cyclopropyl, cyclohexyl, trifluoromethyl, phenyl, R31-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-2C-alkyl, or 1N—(R33)-piperidinyl, in which   R31 is methoxy, morpholino, or dimethylamino,   R32 is hydroxyl, benzyloxy, methoxy, phenyl, R321-substituted phenyl, dimethylamino, morpholino, or 4N-methyl-piperazin-1-yl, in which   R321 is methoxy,   R33 is hydrogen, methyl, or acetyl,   R4 is hydrogen, methyl, 2-(R41)-ethyl, phenyl, R42-substituted phenyl, or pyridinyl, in which   R41 is hydroxyl, methoxy, dimethylamino or morpholino,   R42 is methoxy, or dimethylamino,   R5 is hydrogen, or methyl,   or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which   Het is morpholino, 4N-methyl-piperazin-1-yl, or 4N-ethyl-piperazin-1-yl,   or a pharmaceutically acceptable salt thereof.   
     
     
         21 . The method according to  claim 15 , in which
 R1 is 4-methoxy-phenyl, 2-methoxy-phenyl, 2-bromo-phenyl, 2-fluoro-phenyl, 2-(trifluoromethyl)-phenyl, 2-chloro-phenyl, 4-bromo-phenyl or 2-methyl-phenyl,   or a pharmaceutically acceptable salt thereof.   
     
     
         22 . The method according to  claim 15 , wherein the compound of formula I is selected from the group consisting of
 Cyclopropanecarboxylic acid {4-[3-(4-methoxy-phenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-ylamino]-phenyl}-amide,   Cyclopropanecarboxylic acid {3-[3-(4-methoxy-phenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-ylamino]-phenyl}-amide, and   1-{4-[3-(4-Methoxy-phenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-ylamino]-phenyl}-1-(4-methyl-piperazin-1-yl)-methanone.   
     
     
         23 . A method for treating acute or chronic airway disorders in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of a compound of formula I 
       
         
           
           
               
               
           
         
         in which 
         R1 is —U-A, in which 
         U is a direct bond, or methylene (—CH 2 —), 
         A is phenyl, pyridinyl, thiophenyl, or R11- and/or R111-substituted phenyl, in which 
         R11 is 1-4C-alkyl, halogen, trifluoromethyl, hydroxyl, 1-4C-alkoxy, phenoxy, 1-4C-alkoxycarbonyl, morpholino, di-1-4C-alkylamino, or completely or predominantly fluorine-substituted 1-4C-alkoxy, 
         R111 is 1-4C-alkoxy, halogen, hydroxyl, or 1-4C-alkyl, 
         R2 is amino, carboxyl, 1-4C-alkoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which 
         R3 is 1-4C-alkyl, 2-4C-alkenyl, 3-7C-cycloalkyl, trifluoromethyl, phenyl, R31- and/or R311-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-4C-alkyl, or 1 N—(R33)-piperidinyl, in which 
         R31 is 1-4C-alkoxy, halogen, nitro, 1-4C-alkyl, trifluoromethyl, hydroxyl, 1-4C-alkoxycarbonyl, 3-7C-cyloalkylmethoxy, morpholino, or mono- or di-1-4C-alkylamino, 
         R311 is 1-4C-alkoxy, halogen, 1-4C-alkyl, hydroxyl, or 3-7C-cyloalkylmethoxy, 
         or R31 and R311 together are a 1-2C-alkylenedioxy group, 
         R32 is hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy, phenyl, R321- and/or R3211-substituted phenyl, mono- or di-1-4C-alkylamino, morpholino, or 4N—(R322)-piperazin-1-yl, in which 
         R321 is 1-4C-alkoxy, halogen, nitro, 1-4C-alkyl, trifluoromethyl, hydroxyl, 1-4C-alkoxycarbonyl, 3-7C-cyloalkylmethoxy, or mono- or di-1-4C-alkylamino, 
         R3211 is 1-4C-alkoxy, halogen, 1-4C-alkyl, hydroxyl, or 3-7C-cyloalkylmethoxy, 
         or R321 and R3211 together are a 1-2C-alkylenedioxy group, 
         R322 is 1-4C-alkyl, 
         R33 is hydrogen, 1-4C-alkyl, or 1-4C-alkylcarbonyl, 
         R4 is hydrogen, 1-4C-alkyl, R41-substituted 2-4C-alkyl, phenyl, R42- and/or R421-substituted phenyl, or pyridinyl, in which 
         R41 is hydroxyl, 1-4C-alkoxy, mono- or di-1-4C-alkylamino, or morpholino, 
         R42 is 1-4C-alkoxy, halogen, nitro, 1-4C-alkyl, trifluoromethyl, hydroxyl, 1-4C-alkoxycarbonyl, 3-7C-cyloalkylmethoxy, or mono- or di-1-4C-alkylamino, 
         R421 is 1-4C-alkoxy, halogen, 1-4C-alkyl, hydroxyl, or 3-7C-cyloalkylmethoxy, 
         or R42 and R421 together are a 1-2C-alkylenedioxy group, 
         R5 is hydrogen, or 1-4C-alkyl, 
         or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which 
         Het is morpholino, or 4N-(1-4C-alkyl)-piperazin-1-yl, 
         or a pharmaceutically acceptable salt thereof, 
         wherein the acute or chronic airway disorder is selected from the group consisting of rhinitis, bronchitis, bronchial asthma, emphysema and COPD. 
       
     
     
         24 . The method according to  claim 23 , in which
 R1 is —U-A, in which   U is a direct bond, or methylene (—CH 2 —),   A is phenyl, pyridinyl, thiophenyl, di-(1-4C-alkoxy)-phenyl, or R11-substituted phenyl, in which   R11 is 1-4C-alkyl, halogen, trifluoromethyl, hydroxyl, 1-4C-alkoxy, phenoxy, 1-4C-alkoxycarbonyl, morpholino, di-1-4C-alkylamino, or completely or predominantly fluorine-substituted 1-4C-alkoxy,   R2 is amino, carboxyl, 1-4C-alkoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which   R3 is 1-4C-alkyl, 2-4C-alkenyl, 3-7C-cycloalkyl, trifluoromethyl, phenyl, R31-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-4C-alkyl, or 1N—(R33)-piperidinyl, in which   R31 is 1-4C-alkoxy, morpholino, or di-1-4C-alkylamino,   R32 is hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy, phenyl, R321-substituted phenyl, di-1-4C-alkylamino, morpholino, or 4N—(R322)-piperazin-1-yl, in which   R321 is 1-4C-alkoxy,   R322 is 1-4C-alkyl,   R33 is hydrogen, 1-4C-alkyl, or 1-4C-alkylcarbonyl,   R4 is hydrogen, 1-4C-alkyl, R41-substituted 2-4C-alkyl, phenyl, R42-substituted phenyl, or pyridinyl, in which   R41 is hydroxyl, 1-4C-alkoxy, di-1-4C-alkylamino, or morpholino,   R42 is 1-4C-alkoxy, or di-1-4C-alkylamino,   R5 is hydrogen, or 1-4C-alkyl,   or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which   Het is morpholino, or 4N-(1-4C-alkyl)-piperazin-1-yl,   or a pharmaceutically acceptable salt thereof.   
     
     
         25 . The method according to  claim 23 , in which
 R1 is —U-A, in which   U is a direct bond, or methylene (—CH 2 —),   A is phenyl, pyridinyl, thiophenyl, dimethoxyphenyl, or R11-substituted phenyl, in which   R11 is methyl, tertbutyl, chlorine, fluorine, bromine, trifluoromethyl, hydroxyl, methoxy, ethoxy, trifluoromethoxy, phenoxy, methoxycarbonyl, morpholino, or dimethylamino,   R2 is amino, carboxyl, 1-4C-alkoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which   R3 is 1-4C-alkyl, 2-4C-alkenyl, 3-7C-cycloalkyl, trifluoromethyl, phenyl, R31-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-4C-alkyl, or 1N—(R33)-piperidinyl, in which   R31 is 1-4C-alkoxy, morpholino, or di-1-4C-alkylamino,   R32 is hydroxyl, phenyl-1-4C-alkoxy, 1-4C-alkoxy, phenyl, R321-substituted phenyl, di-1-4C-alkylamino, morpholino, or 4N—(R322)-piperazin-1-yl, in which   R321 is 1-4C-alkoxy,   R322 is 1-4C-alkyl,   R33 is hydrogen, 1-4C-alkyl, or 1-4C-alkylcarbonyl,   R4 is hydrogen, 1-4C-alkyl, R41-substituted 2-4C-alkyl, phenyl, R42-substituted phenyl, or pyridinyl, in which   R41 is hydroxyl, 1-4C-alkoxy, di-1-4C-alkylamino, or morpholino,   R42 is 1-4C-alkoxy, or di-1-4C-alkylamino,   R5 is hydrogen, or 1-4C-alkyl,   or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which   Het is morpholino, or 4N-(1-4C-alkyl)-piperazin-1-yl,   or a pharmaceutically acceptable salt thereof.   
     
     
         26 . The method according to  claim 23 , in which
 R1 is —U-A, in which   U is a direct bond, or methylene (—CH 2 —),   A is phenyl, or R11-substituted phenyl, in which   R11 is methyl, chlorine, fluorine, bromine, trifluoromethyl, hydroxyl, methoxy, phenoxy, methoxycarbonyl, or dimethylamino,   R2 is amino, carboxyl, methoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which   R3 is methyl, vinyl, cyclopropyl, cyclohexyl, trifluoromethyl, phenyl, R31-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-2C-alkyl, or 1N—(R33)-piperidinyl, in which   R31 is methoxy, morpholino, or dimethylamino,   R32 is hydroxyl, benzyloxy, methoxy, phenyl, R321-substituted phenyl, dimethylamino, morpholino, or 4N-methyl-piperazin-1-yl, in which   R321 is methoxy,   R33 is hydrogen, methyl, or acetyl,   R4 is hydrogen, methyl, 2-(R41)-ethyl, phenyl, R42-substituted phenyl, or pyridinyl, in which   R41 is hydroxyl, methoxy, dimethylamino, or morpholino,   R42 is methoxy, or dimethylamino,   R5 is hydrogen, or methyl,   or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which   Het is morpholino, or 4N-methyl-piperazin-1-yl,   or a pharmaceutically acceptable salt thereof.   
     
     
         27 . The method according to  claim 23 , in which
 R1 is —U-A, in which   U is a direct bond,   A is phenyl, or R11-substituted phenyl, in which   R11 is fluorine, bromine, trifluoromethyl, or methoxy,   R2 is attached in the meta or para position with respect to the binding position in which the phenyl ring is bonded to the amino group of the triazolophthalazine scaffold, and is amino, carboxyl, methoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which   R3 is methyl, vinyl, cyclopropyl, cyclohexyl, trifluoromethyl, phenyl, R31-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-2C-alkyl, or 1N—(R33)-piperidinyl, in which   R31 is methoxy, morpholino, or dimethylamino,   R32 is hydroxyl, benzyloxy, methoxy, phenyl, R321-substituted phenyl, dimethylamino, morpholino, or 4N-methyl-piperazin-1-yl, in which   R321 is methoxy,   R33 is hydrogen, methyl, or acetyl,   R4 is hydrogen, methyl, 2-(R41)-ethyl, phenyl, R42-substituted phenyl, or pyridinyl, in which   R41 is hydroxyl, methoxy, dimethylamino, or morpholino,   R42 is methoxy, or dimethylamino,   R5 is hydrogen, or methyl,   or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which   Het is morpholino, or 4N-methyl-piperazin-1-yl,   or a pharmaceutically acceptable salt thereof.   
     
     
         28 . The method according to  claim 23 , in which
 R1 is —U-A, in which   U is a direct bond,   A is phenyl, or R11-substituted phenyl, in which   R11 is fluorine, bromine, chlorine, trifluoromethyl, methyl or methoxy,   R2 is attached in the meta or para position with respect to the binding position in which the phenyl ring is bonded to the amino group of the triazolophthalazine scaffold, and is amino, carboxyl, methoxycarbonyl, —N(H)—C(O)R3, or —C(O)—N(R4)R5, in which   R3 is methyl, vinyl, cyclopropyl, cyclohexyl, trifluoromethyl, phenyl, R31-substituted phenyl, furanyl, imidazol-4-yl, pyridinyl, R32-substituted 1-2C-alkyl, or 1N—(R33)-piperidinyl, in which   R31 is methoxy, morpholino, or dimethylamino,   R32 is hydroxyl, benzyloxy, methoxy, phenyl, R321-substituted phenyl, dimethylamino, morpholino, or 4N-methyl-piperazin-1-yl, in which   R321 is methoxy,   R33 is hydrogen, methyl, or acetyl,   R4 is hydrogen, methyl, 2-(R41)-ethyl, phenyl, R42-substituted phenyl, or pyridinyl, in which   R41 is hydroxyl, methoxy, dimethylamino or morpholino,   R42 is methoxy, or dimethylamino,   R5 is hydrogen, or methyl,   or R4 and R5 together and with inclusion of the nitrogen atom, to which they are bonded, form a heterocyclic ring radical Het, in which   Het is morpholino, 4N-methyl-piperazin-1-yl, or 4N-ethyl-piperazin-1-yl,   or a pharmaceutically acceptable salt thereof.   
     
     
         29 . The method according to  claim 23 , in which
 R1 is 4-methoxy-phenyl, 2-methoxy-phenyl, 2-bromo-phenyl, 2-fluoro-phenyl, 2-(trifluoromethyl)-phenyl, 2-chloro-phenyl, 4-bromo-phenyl or 2-methyl-phenyl,   or a pharmaceutically acceptable salt thereof.   
     
     
         30 . The method according to  claim 23 , wherein the compound of formula I is selected from the group consisting of
 Cyclopropanecarboxylic acid {4-[3-(4-methoxy-phenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-ylamino]-phenyl}-amide,   Cyclopropanecarboxylic acid {3-[3-(4-methoxy-phenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-ylamino]-phenyl}-amide, and   1-{4-[3-(4-Methoxy-phenyl)-[1,2,4]triazolo[3,4-a]phthalazin-6-ylamino]-phenyl}-1-(4-methyl-piperazin-1-yl)-methanone.