Phosphodiesterase 4 inhibitors

Abstract

PDE4 inhibition is achieved by novel compounds of the Formula I: wherein R 1 and R 2 are as defined herein.

1 . (Cancelled)  
     
     
         2 . A method according to  claim 45 , wherein when R 1  is methyl, R 2  is not arylalkyl, heteroarylalkyl, 2-(1,2,3,4-tetrahydro)quinolinyl-methyl or C 1-5 -alkyl.  
     
     
         3 . A method compound according to  claim 45 , wherein R 1  is alkyl.  
     
     
         4 . A method to  claim 45 , wherein R 1  is cycloalkyl.  
     
     
         5 . A method according to  claim 45 , wherein R 1  is cycloalkylalkyl.  
     
     
         6 . A method according to  claim 45 , wherein R 2  is alkyl.  
     
     
         7 . A method according to  claim 45 , wherein R 2  is alkyl ether.  
     
     
         8 . A method according to  claim 45 , wherein R 2  is cycloalkyl.  
     
     
         9 . A method according to  claim 45 , wherein R 2  is aryl.  
     
     
         10 . A method according to  claim 45 , wherein R 2  is arylalkyl.  
     
     
         11 . A method according to  claim 45 , wherein R 2  is heteroaryl.  
     
     
         12 . A method according to  claim 45 , wherein R 2  is heteroarylalkyl.  
     
     
         13 . A method according to  claim 45 , wherein R 2  heterocycle.  
     
     
         14 . A method according to  claim 45 , wherein R 2  heterocycle-alkyl.  
     
     
         15 . A method according to  claim 45 , wherein R 2 carbocycle.  
     
     
         16 . A method according to  claim 45 , wherein R 1  is alkyl, substituted alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         17 . A method to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         18 . A method according to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         19 . A method according to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         20 . A method according to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         21 . A method according to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         22 . A method according to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         23 . A method according to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         24 . A method according to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         25 . A method according to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         26 . A method according to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         27 . A method according to  claim 45 , wherein R 1  is methyl, ethyl, isopropyl, 2-hydroxyethyl, cyclopropyl, cyclopentyl, or cyclopropylmethyl.  
     
     
         28 . A method according to  claim 45 , wherein R 1  is methyl, ethyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.  
     
     
         29 . A method according to  claim 45 , wherein R 1  is methyl, ethyl or cyclopropyl.  
     
     
         30 . A method according to  claim 45 , wherein R 2  is alkyl, arylalkyl, cycloalkyl, aryl, heteroaryl, heteroarylalkyl, or alkyl ether.  
     
     
         31 . A method according to  claim 45 , wherein R 2  is ethyl, isopropyl, butyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl, or arylalkyl which is unsubstituted or substituted one or more times by F, Cl, CN, CF 3 , CH 3 , C 2 H 5 , isopropyl, OCH 3 , methylenedioxy, ethylenedioxy or combinations thereof.  
     
     
         32 . A method according to  claim 45 , wherein R 2  is substituted or unsubstituted benzyl, phenethyl or phenpropyl.  
     
     
         33 . A method of treating a patient suffering from cognition impairment or decline comprising administering to said patient an effective amount of a compound of formula II  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1′  is methyl, ethyl, or cyclopropyl; and  
 R 2′  is cycloalkyl having 3 to 12 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, C 1-4  alkoxy, cyano or combinations thereof, 
 aryl having 6 to 14 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof,  
 heteroaryl having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, which is unsubstituted or substituted one or more times by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, hydroxamic acid, carboxamide, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl,or combinations thereof,  
 heterocycle having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, which is unsubstituted or is substituted one or more times inthe by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, or combinations thereof (e.g., piperidinyl, imidazolinyl, imidazolidinyl, pyrrolinyl, pyrrolidinyl, morpholinyl, piperazinyl, and indolinyl), or  
 carbocycle which is nonaromatic, monocyclic or bicyclic, group having 5 to 14 carbon atoms, which is unsubstituted or is substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof; and  
 
 pharmaceutically acceptable salts thereof.  
 
     
     
         34 . A method of treating a patient suffering from cognition impairment or decline comprising administering to said patient an effective amount of a compound of Formula III:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1″  is methyl, ethyl, or cyclopropyl; and  
 R 2″  is phenyl, 
 phenyl which is substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof, or  
 heteroaryl having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, substituted heteroaryl having 5 to 10 ring atoms, in which at least 1 ring atom is a heteroatom, which is unsubstituted or substituted one or more times by halogen, aryl, C 1-4 -alkyl, C 1-4 -alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino or combinations thereof,  
 or when R 1  is methyl or cyclopropyl R 2  can also be cycloalkyl having 3 to 12 carbon atoms; and  
 
 pharmaceutically acceptable salts thereof.  
 
     
     
         35 . A method according to  claim 45 , wherein said compound is selected from: 
 6-Cyclopropylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine    6-Ethylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-fluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,6-difluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,3-difluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-propyl 2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclopentyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-dimethoxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-methylenedioxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-thiophenemethyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-methylphenethyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-cycloheptyl-2-trifluoromethylpurine    6-Methylamino-9-cyclopentyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclohexyl-2-trifluoromethylpurine    6-Methylamino-9-cycloheptyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclopentylmethyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-phenyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-fluorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclobutyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-norboranane)-2-trifluoromethylpurine    6-Cyclopropylamino-9-( 1-indanyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-fluorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-chlorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-thienyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-cyclopentyloxy-4-methoxybenzyl)-2-trifluoromethylpufine    6-Cyclopropylamino-9-(3,4-dimethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,6-dichloro-4-pyridylmethyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-methoxybenzyl)-2-trifluoromethylpufine    6-Cyclopropylamino-9-(3-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-nitrophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-cyanophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,4-dimethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-nitrobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(6-methoxy-3-pyridyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-pyridyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-pyridyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-dimethylaminophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-aminophenyl)-2-trifluoromethylpurine    6-Methylamino-9-(2,4-dimethoxy-5-pyrimidyl)-2-trifluoromethylpurine    6-Methylamino-9-(2-methoxyphenyl)-2-trifluoromethylpurine    6-Methyl amino-9-(4-methoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3-acetylphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3-methoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3-nitrophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-furanyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-ethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-ethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-methylenedioxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-ethoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3,4-dimethoxyphenyl)-2-trifluoromethylpurine; and pharmaceutically acceptable salts thereof    
     
     
         36 . A method according to  claim 34 , wherein said compound is selected from: 
 6-Cyclopropylamino-9-(2,3-difluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclopentyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-dimethoxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-cycloheptyl-2-trifluoromethylpurine    6-Methylamino-9-cyclopentyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclohexyl-2-trifluoromethylpurine    6-Methylamino-9-cycloheptyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-phenyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-fluorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclobutyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-norboranane)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-fluorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-chlorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-thienyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-dimethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,6-dichloro-4-pyridylmethyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-methoxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-nitrophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-cyanophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-nitrobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-pyridyl)-2-trifluoromethylpurine    6-Methylamino-9-(2,4-dimethoxy-5-pyrimidyl)-2-trifluoromethylpurine    6-Methylamino-9-(4-methoxyphenyl)-2-trifluoromethylpurine    6-Methyl amino-9-(3-acetylphenyl)-2-trifluoromethylpurine    6-Methyl amino-9-(3-methoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3-nitrophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-ethoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3,4-dimethoxyphenyl)-2-trifluoromethylpurine; and pharmaceutically acceptable salts thereof.    
     
     
         37 . A method for enhancing cognition in a patient in whom such enhancement is desired comprising administering to said patient an effective amount of a compound according to formula I c :  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1c  is H, 
 alkyl having 1 to 5 carbon atoms, which is unsustituted or substituted one or more times by halogen, hydroxy, or combinations thereof, and wherein a —CH 2 — group can be optionally replaced by —O—, —S—, or —NH—,  
 cycloalkyl having 3 to 6 carbon atoms, or  
 cycloalkylalkyl having 4 to 7 C atoms;  
 R 2c  is alkyl having 1 to 12 carbon atoms, which is unsubstituted or substituted one or more times by halogen, hydroxy, cyano or combinations thereof, wherein one or more —CH 2 — groups is each independently optionally replaced by —O—, —S—, or —NH—, and wherein optionally one or more —CH 2 CH 2 — groups is replaced in each case by —CH═CH— or —C≡C— 
 alkyl ether having 3 to 12 carbon atoms,  
 cycloalkyl having 3 to 12 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, C 1-4  alkoxy, cyano or combinations thereof,  
 cycloalkylalkyl having 4 to 12 C atoms, which is unsubstituted or substituted one or more times by C 1-4  alkyl, halogenated C 1-4  alkyl, C 1-4  alkoxy, cyano, halogen, or combinations thereof,  
 aryl having 6 to 14 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof,  
 arylalkyl having 7 to 16 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof,  
 heteroaryl having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, which is unsubstituted or substituted one or more times by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, hydroxamic acid, carboxamide, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl,or combinations thereof,  
 beteroarylalkyl wherein the heteroaryl portion has 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom and the alkyl portion has 1 to 3 carbon atoms, the heteroaryl portion is unsubstituted or is substituted one or more times in by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, hydroxamic acid, carboxamide, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl,or combinations thereof,  
 heterocycle having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, which is unsubstituted or is substituted one or more times in the by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, or combinations thereof,  
 heterocycle-alkyl wherein the heterocycle portion has 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom and the alkyl portion has 1 to 3 carbon atoms, the heterocycle portion is nonarmoatic and is unsubstituted or is substituted one or more times in the by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, or combinations thereof, or  
 carbocycle which is nonaromatic, monocyclic or bicyclic, group having 5 to 14 carbon atoms, which is unsubstituted or is substituted one or more times in the by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof;  
 and  
 pharmaceutically acceptable salts thereof, with the proviso that said compound is not 6-methylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine.  
 
 
     
     
         38 . A method according to  claim 37 , wherein said compound is administered in an amount of 0.01-100 mg/kg of body weight/day.  
     
     
         39 . A method according to  claim 37 , wherein said patient is a human.  
     
     
         40 . A method according to  claim 37 , wherein said compound is selected from: 
 6-Cyclopropylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine;    6-Ethylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-fluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,6-difluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,3-difluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-propyl 2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclopentyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-dimethoxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-methylenedioxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-thiophenemethyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-methylphenethyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclopropylmethyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-cycloheptyl-2-trifluoromethylpurine    6-Methylamino-9-cyclopentyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclohexyl-2-trifluoromethylpurine    6-Methylamino-9-cycloheptyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclopentylmethyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-phenyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-fluorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclobutyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-norboranane)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(1-indanyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-fluorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-chlorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-tolyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-thienyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-cyclopentyloxy-4-methoxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-dimethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,6-dichloro-4-pyridylmethyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-methoxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-nitrophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-cyanophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,4-dimethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-nitrobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(6-methoxy-3-pyridyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-pyridyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-pyridyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-dimethylaminophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-aminophenyl)-2-trifluoromethylpurine    6-Methylamino-9-(2,4-dimethoxy-5-pyrimidyl)-2-trifluoromethylpurine    6-Methylamino-9-(2-methoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(4-methoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3-acetylphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3-methoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3-nitrophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-furanyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-ethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-ethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-methylenedioxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-ethoxyphenyl)-2-trifluoromethylpurine    6-Methyl amino-9-(3 4-dimethoxyphenvl)-2-trifluoromethylpurine; and pharmaceutically acceptable salts thereof.    
     
     
         41 . A method according to  claim 40 , wherein said patient is a human.  
     
     
         42 . A method according to  claim 41 , wherein said compound is administered in an amount of 0.01-100 mg/kg of body weight/day.  
     
     
         43 . A method according to  claim 37 , wherein when R 1c  is methyl, then R 2c  is not arylalkyl, methyl or 2-butyl, and when R 1c  is H, then R 2c  is not benzyl  
     
     
         44 . A method according to  claim 37 , wherein: 
 (a) when R 1c  is methyl, then R 2c  is not arylalkyl, heteroarylalkyl, 2-(1,2,3,4-tetrahydro)quinolinyl-methyl, methyl or 2-butyl;    (b) when R 1c  is cyclopropyl, R 2c  is not 4-methylbenzyl;    (c) when R 1c  is ethyl, then R 2c  is not ethyl, 3-aminobenzyl, 2-thienylmethyl, 3-thienylmethyl, or 2-pyridylmethyl;    (d) when R 1c  is cyclopropyl, then R 2c  is not cyclopropylmethyl;    (e) when R 1c  is H, then R 2c  is not methyl, ethyl, benzyl, 4-methylbenzyl, or substituted tetrahydrofuranyl;    (f) when R 1c  is methoxyethyl, then R 2c  is not benzyl, 3-dimethylaminobenzyl, or 3-thienylmethyl;    (g) when R 1c  is iso-butyl, then R 2c  is not benzyl; and    (h) when R 1c  is n-butyl, then R 2c  is not n-butyl.    
     
     
         45 . A method of treating a patient suffering from cognition impairment or decline comprising administering to said patient an effective amount of a compound according to formula I c :  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1c  is H, 
 alkyl having 1 to 5 carbon atoms, which is unsustituted or substituted one or more times by halogen, hydroxy, or combinations thereof, and wherein a —CH 2 — group can be optionally replaced by —O—, —S—, or —NH—,  
 cycloalkyl having 3 to 6 carbon atoms, or  
 cycloalkylalkyl having 4 to 7 C atoms;  
 
 R 2c  is alkyl having 1 to 12 carbon atoms, which is unsubstituted or substituted one or more times by halogen, hydroxy, cyano or combinations thereof, wherein one or more —CH 2 — groups is each independently optionally replaced by —O—, —S—, or —NH—, and wherein optionally one or more —CH 2 CH 2 — groups is replaced in each case by —CH═CH— or —C≡C—
 alkyl ether having 3 to 12 carbon atoms,  
 cycloalkyl having 3 to 12 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, C 1-4  alkoxy, cyano or combinations thereof,  
 cycloalkylalkyl having 4 to 12 C atoms, which is unsubstituted or substituted one or more times by C 1-4  alkyl, halogenated C 1-4  alkyl, C 1-4  alkoxy, cyano, halogen, or combinations thereof,  
 aryl having 6 to 14 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof,  
 arylalkyl having 7 to 16 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof,  
 heteroaryl having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom,  
 which is unsubstituted or substituted one or more times by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, hydroxamic acid, carboxamide, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl,or combinations thereof,  
 heteroarylalkyl wherein the heteroaryl portion has 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom and the alkyl portion has 1 to 3 carbon atoms, the heteroaryl portion is unsubstituted or is substituted one or more times in by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, hydroxamic acid, carboxamide, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, or combinations thereof,  
 heterocycle having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, which is unsubstituted or is substituted one or more times in the by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, or combinations thereof,  
 heterocycle-alkyl wherein the heterocycle portion has 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom and the alkyl portion has 1 to 3 carbon atoms, the heterocycle portion is nonarmoatic and is unsubstituted or is substituted one or more times in the by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, or combinations thereof, or  
 carbocycle which is nonaromatic, monocyclic or bicyclic, group having 5 to 14 carbon atoms, which is unsubstituted or is substituted one or more times in the by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof;  
 and  
 pharmaceutically acceptable salts thereof,  
 
 with the proviso that said compound is not 6-methylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine.  
 
     
     
         46 . A method according to  claim 45 , wherein said patient is a human.  
     
     
         47 . A method according to  claim 46 , wherein said patient is suffering from memory impairment.  
     
     
         48 . A method according to  claim 45 , wherein said compound is administered in an amount of 0.01-100 mg/kg of body weight/day.  
     
     
         49 . A method according to  claim 45 , wherein said patient is suffering from memory impairment due to Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeld-Jakob disease, depression, aging, head trauma, stroke, CNS hypoxia, cerebral senility, multiinfarct dementia, HIV or cardiovascular disease.  
     
     
         50 . A method according to  claim 45 , wherein said compound is selected from: 
 6-Cyclopropylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine    6-Methylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine    6-Ethylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-fluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,6-difluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,3-difluorobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-propyl 2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclopentyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-dimethoxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-methylenedioxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-thiophenemethyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-methylphenethyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclopropylmethyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-cycloheptyl-2-trifluoromethylpurine    6-Methylamino-9-cyclopentyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclohexyl-2-trifluoromethylp urine    6-Methylamino-9-cycloheptyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclopentylmethyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-phenyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-fluorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-cyclobutyl-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-norboranane)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(1-indanyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-fluorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-chlorophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-tolyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-thienyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-cyclopentyloxy-4-methoxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-dimethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,6-dichloro-4-pyridylmethyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-methoxybenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-nitrophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-methoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-cyanophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2,4-dimethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-nitrobenzyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(6-methoxy-3-pyridyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-pyridyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-pyridyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-dimethylaminophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-aminophenyl)-2-trifluoromethylpurine    6-Methylamino-9-(2,4-dimethoxy-5-pyrimidyl)-2-trifluoromethylpurine    6-Methylamino-9-(2-methoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(4-methoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3-acetylphenyl)-2-trifluoromethylpurine    6-Methyl amino-9-(3-methoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3-nitrophenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-furanyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(4-ethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(2-ethoxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3,4-methylenedioxyphenyl)-2-trifluoromethylpurine    6-Cyclopropylamino-9-(3-ethoxyphenyl)-2-trifluoromethylpurine    6-Methylamino-9-(3,4-dimethoxyphenyl)-2-trifluoromethylpurine; and pharmaceutically acceptable salts thereof.    
     
     
         51 . A method according to  claim 50 , wherein said patient is a human.  
     
     
         52 . A method according to  claim 45 , wherein when R 1c  is methyl, then R 2c  is not arylalkyl, methyl or 2-butyl, and when R 1c  is H, then R 2c  is not benzyl.  
     
     
         53 . A method according to  claim 45 , wherein: 
 (a) when R 1c  is methyl, then R 2c  is not arylalkyl, heteroarylalkyl, 2-(1,2,3,4-tetrahydro)quinolinyl-methyl, methyl or 2-butyl;    (b) when R 1c  is cyclopropyl, R 2c  is not 4-methylbenzyl;    (c) when R 1c  is ethyl, then R 2c  is not ethyl, 3-aminobenzyl, 2-thienylmethyl, 3-thienylmethyl, or 2-pyridylmethyl;    (d) when R 1c  is cyclopropyl, then R 2c  is not cyclopropylmethyl;    (e) when R 1c  is H, then R 2c  is not methyl, ethyl, benzyl, 4-methylbenzyl, or substituted tetrahydrofuranyl;    (f) when R 1c  is methoxyethyl, then R 2c  is not benzyl, 3-dimethylaminobenzyl, or 3-thienylmethyl;    (g) when R 1c  is iso-butyl, then R 2c  is not benzyl; and    (h) when R 1c  is n-butyl, then R 2c  is not n-butyl.    
     
     
         54 . (Cancelled):  
     
     
         55 . (Cancelled):  
     
     
         56 . (Cancelled):  
     
     
         57 . (Canceled):  
     
     
         58 . (Canceled):  
     
     
         59 . (Canceled):  
     
     
         60 . (Canceled):  
     
     
         61 . (Canceled):  
     
     
         62 . A method of treating a patient suffering from memory impairment due to a neurodegenerative disease comprising administering to said patient an effective amount of a compound according to formula I c :  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1c  is H, 
 alkyl having 1 to 5 carbon atoms, which is unsustituted or substituted one or more times by halogen, hydroxy, or combinations thereof, and wherein a —CH 2 — group can be optionally replaced by —O—, —S—, or —NH—,  
 cycloalkyl having 3 to 6 carbon atoms, or  
 cycloalkylalkyl having 4 to 7 C atoms;  
 
 R 2c  is alkyl having 1 to 12 carbon atoms, which is unsubstituted or substituted one or more times by halogen, hydroxy, cyano or combinations thereof, wherein one or more —CH 2 — groups is each independently optionally replaced by —O—, —S—, or —NH—, and wherein optionally one or more —CH 2 CH 2 — groups is replaced in each case by —CH═CH— or —C≡C—
 alkyl ether having 3 to 12 carbon atoms,  
 cycloalkyl having 3 to 12 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, C 1-4  alkoxy, cyano or combinations thereof,  
 cycloalkylalkyl having 4 to 12 C atoms, which is unsubstituted or substituted one or more times by C 1-4  alkyl, halogenated C 1-4  alkyl, C 1-4  alkoxy, cyano, halogen, or combinations thereof,  
 aryl having 6 to 14 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof,  
 arylalkyl having 7 to 16 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof,  
 heteroaryl having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom,  
 which is unsubstituted or substituted one or more times by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, hydroxamic acid, carboxamide, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl,or combinations thereof,  
 heteroarylalkyl wherein the heteroaryl portion has 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom and the alkyl portion has 1 to 3 carbon atoms, the heteroaryl portion is unsubstituted or is substituted one or more times in by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, hydroxamic acid, carboxamide, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, or combinations thereof,  
 heterocycle having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, which is unsubstituted or is substituted one or more times in the by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, or combinations thereof,  
 heterocycle-alkyl wherein the heterocycle portion has 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom and the alkyl portion has 1 to 3 carbon atoms, the heterocycle portion is nonarmoatic and is unsubstituted or is substituted one or more times in the by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, or combinations thereof,or  
 carbocycle which is nonaromatic, monocyclic or bicyclic, group having 5 to 14 carbon atoms, which is unsubstituted or is substituted one or more times in the by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof; and  
 pharmaceutically acceptable salts thereof,  
 with the proviso that said compound is not 6-methylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine.  
 
 
     
     
         63 . A method according to  claim 62 , wherein when R 1c  is methyl, then R 2c  is not arylalkyl, methyl or 2-butyl, and when R 1c  is H, then R 2c  is not benzyl.  
     
     
         64 . A method according to  claim 62 , wherein: 
 (a) when R 1c  is methyl, then R 2c  is not arylalkyl, heteroarylalkyl, 2-(1,2,3,4-tetrahydro)quinolinyl-methyl, methyl or 2-butyl;    (b) when R 1c  is cyclopropyl, R 2c  is not 4-methylbenzyl;    (c) when R 1c  is ethyl, then R 2c  is not ethyl, 3-aminobenzyl, 2-thienylmethyl, 3-thienylmethyl, or 2-pyridylmethyl;    (d) when R 1c  is cyclopropyl, then R 2c  is not cyclopropylmethyl;    (e) when R 1c  is H, then R 2c  is not methyl, ethyl, benzyl, 4-methylbenzyl, or substituted tetrahydrofuranyl;    (f) when R 1c  is methoxyethyl, then R 2c  is not benzyl, 3-dimethylaminobenzyl, or 3-thienylmethyl;    (g) when R 1c  is iso-butyl, then R 2c  is not benzyl; and    (h) when R 1c  is n-butyl, then R 2c  is not n-butyl.    
     
     
         65 . A method of treating a patient suffering from memory impairment due to an acute neurodegenerative disorder comprising administering to said patient an effective amount of a compound according to formula I c :  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1c  is H, 
 alkyl having 1 to 5 carbon atoms, which is unsustituted or substituted one or more times by halogen, hydroxy, or combinations thereof, and wherein a —CH 2 — group can be optionally replaced by —O—, —S—, or —NH—,  
 cycloalkyl having 3 to 6 carbon atoms, or  
 cycloalkylalkyl having 4 to 7 C atoms;  
 R 2 C is alkyl having 1 to 12 carbon atoms, which is unsubstituted or substituted one or more times by halogen, hydroxy, cyano or combinations thereof, wherein one or more —CH 2 — groups is each independently optionally replaced by —O—, —S—, or —NH—, and wherein optionally one or more —CH 2 CH 2 — groups is replaced in each case by —CH═CH— or —C≡C— 
 alkyl ether having 3 to 12 carbon atoms,  
 cycloalkyl having 3 to 12 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, C 1-4  alkoxy, cyano or combinations thereof,  
 cycloalkylalkyl having 4 to 12 C atoms, which is unsubstituted or substituted one or more times by C 1-4  alkyl, halogenated C 1-4  alkyl, C 1-4  alkoxy, cyano, halogen, or combinations thereof,  
 aryl having 6 to 14 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof,  
 arylalkyl having 7 to 16 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof,  
 heteroaryl having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, which is unsubstituted or substituted one or more times by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, hydroxamic acid, carboxamide, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl,or combinations thereof,  
 heteroarylalkyl wherein the heteroaryl portion has 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom and the alkyl portion has 1 to 3 carbon atoms, the heteroaryl portion is unsubstituted or is substituted one or more times in by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, hydroxamic acid, carboxamide, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, or combinations thereof,  
 heterocycle having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, which is unsubstituted or is substituted one or more times in the by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, or combinations thereof,  
 heterocycle-alkyl wherein the heterocycle portion has 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom and the alkyl portion has 1 to 3 carbon atoms, the heterocycle portion is nonarmoatic and is unsubstituted or is substituted one or more times in the by halogen, aryl, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, or combinations thereof, or  
 carbocycle which is nonaromatic, monocyclic or bicyclic, group having 5 to 14 carbon atoms, which is unsubstituted or is substituted one or more times in the by halogen, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C 1-4  alkylamino, di-C 1-4 -alkylamino, C 1-4 -hydroxyalkyl, C 1-4 -hydroxyalkoxy, carboxy, cyano, hydroxamic acid, carboxamide, C 2-4 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof;  
 and  
 pharmaceutically acceptable salts thereof,  
 with the proviso that said compound is not 6-methylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine.  
 
 
     
     
         66 . A method according to  claim 67 , wherein when R 1c  is methyl, then R 2c  is not arylalkyl, methyl or 2-butyl, and when R 1c  is H, then R 2c  is not benzyl.  
     
     
         67 . A method according to  claim 67 , wherein: 
 (a) when R 1c  is methyl, then R 2c  is not arylalkyl, heteroarylalkyl, 2-(1,2,3,4-tetrahydro)quinolinyl-methyl, methyl or 2-butyl;    (b) when R 1c  is cyclopropyl, R 2c  is not 4-methylbenzyl;    (c) when R 1  is ethyl, then R 2c  is not ethyl, 3-aminobenzyl, 2-thienylmethyl, 3-thienylmethyl, or 2-pyridylmethyl;    (d) when R 1c  is cyclopropyl, then R 2c  is not cyclopropylmethyl;    (e) when R 1c  is H, then R 2c  is not methyl, ethyl, benzyl, 4-methylbenzyl, or substituted tetrahydrofuranyl;    (f) when R 1c  is methoxyethyl, then R 2c  is not benzyl, 3-dimethylaminobenzyl, or 3-thienylmethyl;    (g) when R 1c  is iso-butyl, then R 2c  is not benzyl; and    (h) when R 1c  is n-butyl, then R 2c  is not n-butyl.    
     
     
         68 . (Canceled):  
     
     
         69 . (Canceled):  
     
     
         70 . (Canceled):  
     
     
         71 . (Canceled):  
     
     
         72 . A method according to  claim 45 , wherein R 2  is cycloalkylalkyl.  
     
     
         73 . A method according to  claim 45 , wherein R 1  is alkyl, cycloalkyl or cycloalkylalkyl.  
     
     
         74 . A method according to  claim 37  wherein said compound is 6-cyclopropylamino-9-(2-methoxyphenyl)-2-trifluoromethylpurine, or a pharmaceutically acceptable salt thereof.  
     
     
         75 . A method according to  claim 45 , wherein said compound is 6-cyclopropylamino-9-(2-methoxyphenyl)-2-trifluoromethylpurine, or a pharmaceutically acceptable salt thereof.  
     
     
         76 . A method according to  claim 53 , wherein said compound 6-cyclopropylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine, or a pharmaceutically acceptable salt thereof.  
     
     
         77 . A method according to  claim 64 , wherein said compound 6-cyclopropylamino-9-(2-fluorobenzyl)-2-trifluoromethylpurine, or a pharmaceutically acceptable salt thereof.  
     
     
         78 . A method according to  claim 37 , wherein R 1  is alkyl or cycloalkyl and R 2  is phenyl or heteroaryl, in each case substituted or unsubstituted.  
     
     
         79 . A method according to  claim 45 , wherein R 1  is alkyl or cycloalkyl and R 2  is phenyl or heteroaryl, in each case substituted or unsubstituted.  
     
     
         80 . A method according to  claim 53 , wherein R 1  is alkyl or cycloalkyl and R 2  is phenyl or heteroaryl, in each case substituted or unsubstituted.  
     
     
         81 . A method according to  claim 64 , wherein R 1  is alkyl or cycloalkyl and R 2  is phenyl or heteroaryl, in each case substituted or unsubstituted.