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 . A method for effecting PDE4 enzyme inhibition in a patient, enhancing cognition in a patient, treating psychosis in a patient, treating a patient suffering from a disease involving decreased cAMP levels, treating a patient suffering from an allergic or inflammatory disease, treating a patient suffering from neurodegeneration resulting from a disease or injury, or treating a patient suffering from drug addiction or morphine dependence, comprising administering to said patient an effective amount of a compound of Formula I: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is H,
 alkyl having 1 to 5 carbon atoms, which is unsubstituted 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  is aryl having 6 to 14 carbon atoms, which 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, —C(O)—NHOH, —C(O)—NH 2 , C 2-4 -alkanoyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, benzyloxy, —NR 3 R 4 , —CO—NH—SO 2 —R 5 , —SO 2 —NH—CO—R 5  or combinations thereof, wherein said aryl is substituted by at least one of benzyloxy, —NR 3 R 4 , —CO—NH—SO 2 —R 5  or —SO 2 —NH—CO—R 5 ,
 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, —C(O)—NHOH, —C(O)—NH 2 , C 2-4 -alkanoyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, benzyloxy, —NR 3 R 4 , —CO—NH—SO 2 —R 5 , —SO 2 —NH—CO—R 5  or combinations thereof, wherein said arylalkyl is substituted by at least one of benzyloxy, —NR 3 R 4 , —CO—NH—SO 2 —R 5 , or —SO 2 —NH—CO—R 5 , 
 heteroaryl having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, which is substituted one or more times by halogen, aryl having 6 to 14 carbon atoms, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH 2 , C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, morpholinyl, piperazinyl, —NR 3 R 4 , —CO—NH—SO 2 —R 5 , —SO 2 —NH—CO—R 5  or combinations thereof, wherein said heteroaryl is substituted by at least one of morpholinyl, piperazinyl, —NR 3 R 4 , —CO—NH—SO 2 —R 5 , or —SO 2 —NH—CO—R 5 , or 
 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 by halogen, aryl having 6 to 14 carbon atoms, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH 2 , C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, morpholinyl, piperazinyl, —NR 3 R 4 , —CO—NH—SO 2 —R 5 , —SO 2 —NH—CO—R 5  or combinations thereof, wherein said heteroarylalkyl is substituted by at least one of morpholinyl, piperazinyl, —NR 3 R 4 , —CO—NH—SO 2 —R 5 , or —SO 2 —NH—CO—R 5 ; 
 
         R 3  is cycloalkyl having 3 to 8 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, —C(O)—NHOH, —C(O)—NH 2 , C 2-4 -alkanoyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, benzyloxy, 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 having 6 to 14 carbon atoms, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH 2 , C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, morpholinyl, piperazinyl, or combinations thereof, 
 C 1-4 -alkylsulphonyl, or 
 C 1-4 -alkyl-CO—O—C 1-4 -alkylene; 
 
         R 4  is H or alkyl having 1 to 4 carbon atoms which is straight chain or branched, and which is unsubstituted or substituted one or more times by halogen, hydroxy, cyano or combinations thereof; and 
         R 5  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—,
 cycloalkyl having 3 to 8 carbon atoms (e.g., cyclopropyl), 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, —C(O)—NHOH, —C(O)—NH 2 , C 2-4 -alkanoyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, benzyloxy, 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, —C(O)—NHOH, —C(O)—NH 2 , C 2-4 -alkanoyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, benzyloxy, —NR 3 R 4 , 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 having 6 to 14 carbon atoms, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, NHOH, —C(O)—NH 2 , C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, morpholinyl, piperazinyl, 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 by halogen, aryl having 6 to 14 carbon atoms, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH 2 , C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, morpholinyl, piperazinyl, —NR 3 R 4 , 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 by halogen, aryl having 6 to 14 carbon atoms, 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 
 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 nonaromatic and is unsubstituted or is substituted one or more times by halogen, aryl having 6 to 14 carbon atoms, 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 a pharmaceutically acceptable salt thereof. 
 
       
     
     
         2 . A method according to  claim 1 , wherein R 2  is aryl which is substituted by benzyloxy, —NR 3 R 4 , —CO—NH—SO 2 —R 5  and/or —SO 2 —NH—CO—R 5 . 
     
     
         3 . A method according to  claim 1 , wherein R 2  is heteroaryl which is substituted by morpholinyl, piperazinyl, —NR 3 R 4 , —CO—NH—SO 2 —R 5  and/or —SO 2 —NH—CO—R 5 . 
     
     
         4 . A method according to  claim 2 , wherein R 2  is phenyl which is substituted by benzyloxy, —NR 3 R 4 , —CO—NH—SO 2 —R 5  and/or —SO 2 —NH—CO—R 5 . 
     
     
         5 . A method according to  claim 4 , wherein R 2  is phenyl which is substituted by —CO—NH—SO 2 —R 5  and R 5  is methyl, ethyl, phenyl, fluorophenyl, difluorophenyl, chlorophenyl thienyl, chlorothienyl, benzothienyl, chloromethylbenzothienyl, benzothiazolyl, ethoxybenzothiazolyl, pyridyl, methylpyridyl, or chloropyridyl. 
     
     
         6 . A method according to  claim 4 , wherein R 2  is phenyl which is substituted by —SO 2 —NH—CO—R 5  and R 5  is methyl, ethyl, phenyl, fluorophenyl, difluorophenyl, chlorophenyl thienyl, chlorothienyl, benzothienyl, chloromethylbenzothienyl, benzothiazolyl, ethoxybenzothiazolyl, pyridyl, methylpyridyl, or chloropyridyl. 
     
     
         7 . A method according to  claim 1 , wherein R 2  is heteroarylalkyl which is substituted by morpholinyl, piperazinyl, —NR 3 R 4 , —CO—NH—SO 2 —R 5  and/or —SO 2 —NH—CO—R 5 . 
     
     
         8 . A method according to  claim 1 , wherein R 2  is carbocycle which is substituted by —CO—NH—SO 2 —R 5  and/or —SO 2 —NH—CO—R 5 . 
     
     
         9 . A method according to  claim 1 , wherein R 1  is H, methyl, ethyl, isopropyl, HOCH 2 CH 2 —, cyclopropyl, cyclobutyl, cyclopentyl, or cyclopropylmethyl. 
     
     
         10 . A method according to  claim 1 , wherein R 1  methyl, ethyl, cyclopropyl, cyclobutyl, or cyclopentyl. 
     
     
         11 . A method according to  claim 1 , wherein R 1  is methyl, ethyl or cyclopropyl. 
     
     
         12 . A method according to  claim 1 , wherein R 2  is phenyl substituted by —CO—NH—SO 2 —R 5 . 
     
     
         13 . A method according to  claim 12 , wherein R 5  is alkyl, phenyl, thienyl, benzothienyl, benzothiazolyl, or pyridyl, which in each case is substituted or unsubstituted. 
     
     
         14 . A method for effecting PDE4 enzyme inhibition in a patient, enhancing cognition in a patient, treating psychosis in a patient, treating a patient suffering from a disease involving decreased cAMP levels, treating a patient suffering from an allergic or inflammatory disease, treating a patient suffering from neurodegeneration resulting from a disease or injury, or treating a patient suffering from drug addiction or morphine dependence, comprising administering to said patient an effective amount of a compound of Formula I′: 
       
         
           
           
               
               
           
         
         wherein, 
         R 1  is H,
 alkyl having 1 to 5 carbon atoms, which is unsubstituted 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  is aryl having 6 to 14 carbon atoms, which 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, —C(O)—NHOH, —C(O)—NH 2 , C 2-4 -alkanoyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, benzyloxy, —NR 3 R 4 , —CO—NH—SO 2 —R 5  or combinations thereof, wherein said aryl is substituted by at least one of benzyloxy, or —NR 3 R 4 , or
 heteroaryl having 5 to 10 ring atoms in which at least 1 ring atom is a heteroatom, which is substituted one or more times by halogen, aryl having 6 to 14 carbon atoms, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH 2 , C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, morpholinyl, piperazinyl, —NR 3 R 4  or combinations thereof, wherein said heteroaryl is substituted by at least one of morpholinyl, piperazinyl, and —NR 3 R 4 ; 
 
         R 3  is cycloalkyl having 3 to 8 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, —C(O)—NHOH, —C(O)—NH 2 , C 2-4 -alkanoyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, benzyloxy, 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 having 6 to 14 carbon atoms, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH 2 , C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, morpholinyl, piperazinyl, or combinations thereof, 
 C 1-4 -alkylsulphonyl, or 
 C 1-4 -alkyl-CO—O—C 1-4 -alkylene; 
 
         R 4  is H or alkyl having 1 to 4 carbon atoms which is straight chain or branched; and 
         R 5  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—,
 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, —C(O)—NHOH, —C(O)—NH 2 , C 2-4 -alkanoyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, benzyloxy, 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 having 6 to 14 carbon atoms, C 1-4  alkyl, halogenated C 1-4  alkyl, hydroxy, C 1-4 -alkoxy, halogenated C 1-4  alkoxy, cyano, trifluoromethyl, nitro, amino, C 1-4 -alkylamino, di-C 1-4 -alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH 2 , C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, morpholinyl, piperazinyl, or combinations thereof; 
 or a pharmaceutically acceptable salt thereof. 
 
       
     
     
         15 . A method according to  claim 14 , wherein R 2  is aryl which is substituted by benzyloxy and/or —NR 3 R 4 . 
     
     
         16 . A method according to  claim 14 , wherein R 2  is heteroaryl which is substituted by morpholinyl, piperazinyl, and/or —NR 3 R 4 . 
     
     
         17 . A method according to  claim 15 , wherein R 2  is phenyl which is substituted by benzyloxy, and/or —NR 3 R 4 . 
     
     
         18 . A method according to  claim 14 , wherein R 2  is phenyl which is substituted by morpholinyl, piperazinyl, and/or —NR 3 R 4 . 
     
     
         19 . A method according to  claim 14 , wherein R 1  is H, methyl, ethyl, isopropyl, HOCH 2 CH 2 —, cyclopropyl, cyclobutyl, cyclopentyl, or cyclopropylmethyl. 
     
     
         20 . A method according to  claim 14 , wherein R 1  is methyl, ethyl, cyclopropyl, cyclobutyl, or cyclopentyl. 
     
     
         21 . A method according to  claim 14 , wherein R 1  is methyl, ethyl or cyclopropyl. 
     
     
         22 . A compound selected from: 
       6-Cyclopropylamino-9-(2,6-dimethoxypyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(4,6-dimethoxypyrimidin-2-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-methylsulfonylpyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-methoxypyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methoxycarbonylphenyl)-2-trifluoromethylpurine [or 9-(3-Methoxycarbonylphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Cyclopropylamino-9-(3-carboxyphenyl)-2-trifluoromethylpurine [or 9-(3-Carboxyphenyl)-6-cyclopropylamino-2-trifluoromethylpurine], 
       6-Cyclopropylamino-9-(3-methoxycarbonylphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methylthiopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methoxypyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Ethylamino-9-(2-chloropyrimidin-4-yl)-2-trifluoromethylpurine [or 9-(2-Chloropyrimidin-4-yl)-6-ethylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-N,N-dimethylaminopyrimidin-4-yl)-2-trifluoromethylpurine [or -9-(2-N,N-Dimethylaminopyrimidin-4-yl)-6-methylamino 2-trifluoromethylpurine, 
       6-Methylamino-9-(2-aminopyrimidin-4-yl)-2-trifluoromethylpurine [or 9-(2-Aminopyrimidin-4-yl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-N-methylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-N-ethylaminopyrimidin-4-yl)-2-trifluoromethylpurine [or 9-(2-N-Ethylaminopyrimidin-4-yl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-N-phenylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N-(4-pyridylamino)pyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N,N-dimethylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-methylpyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N-methylaminopyrimidin-4-yl)-2-trifluoromethylpurine, Methane sulfonic acid salt, 
       6-Cyclopropylamino-9-(2-N-ethylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N-cyclopropylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-N-methylaminopyrimidin-4-yl)-2-trifluoromethylpurine, Methane sulfonic acid salt, 
       6-Methylamino-9-(2-N-cyclopropylaminopyrimidin-4-yl)-2-trifluoromethylpurine [or 9-(2-N-Cyclopropylaminopyrimidin-4-yl)-6-methylamino-2-trifluoromethylpurine], 
       6-Cyclopropylamino-9-(2-N-methoxycarbonylmethylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N-methoxycarbonylethylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-(4-morpholinyl)pyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N-hydroxyethylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-(1-piperazinyl)pyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-benzyloxyphenyl)-2-trifluoromethylpurine [or 9-(2-Benzyloxyphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(3-benzyloxyphenyl)-2-trifluoromethylpurine [or 9-(3-Benzyloxyphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(3-iodophenyl)-2-trifluoromethylpurine [or 9-(3-Iodophenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-methylsulfinylpyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-hydroxyphenyl)-2-trifluoromethylpurine [or 9-(3-Hydroxyphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-hydroxyphenyl)-2-trifluoromethylpurine [or 9-(2-Hydroxyphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-methylsulfonylpyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(3-benzyloxyphenyl)-2-trifluoromethylpurine [or 9-(3-Benzyloxyphenyl)-6-cyclopropylamino-2-trifluoromethylpurine], 
       6-Cyclopropylamino-9-(4-benzyloxyphenyl)-2-trifluoromethylpurine [or 9-(4-Benzyloxyphenyl)-6-cyclopropylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-fluoro-3-methoxyphenyl)-2-trifluoromethylpurine [or 9-(2-Fluoro-3-methoxyphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(3-nitrophenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-trifluoromethoxyphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methylsulfonylaminophenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-hydroxyphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-nitrophenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methylthiophenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methoxycarbonylphenyl)-2-trifluoromethylpurine [or 9-(2-Methoxycarbonylphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(8-quinolinyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-aminophenyl)-2-trifluoromethylpurine [or 9-(3-Aminophenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(3-N,N-dimethylaminophenyl)-2-trifluoromethylpurine [or 9-(3-N,N-Dimethylaminophenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Cyclopropylamino-9-(3-hydroxyphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(4-hydroxyphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methylaminophenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-trifluoromethoxyphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methylsulfinylphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methylsulfonylphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methylsulfonylaminophenyl)-2-trifluoromethylpurine, 
       9-(3-Chloro-4-pyridyl)-6-cyclopropylamino-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-methyl-4-pyridyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(3-methyl-4-pyridyl)-2-trifluoromethylpurine, 
       9-(3-Ethylsulfonylphenyl)-6-methylamino-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(3-ethylsulfonylphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(3-trifluoromethoxylphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-trifluoromethyl-5-pyridyl)-2-trifluoromethyl-purine, 
       9-(2-Chloro-4-pyridyl)-6-cyclopropylamino-2-trifluoromethylpurine, 
       9-(5-Chloro-3-pyridyl)-6-cyclopropylamino-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-methoxycarbonylphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(4-methoxycarbonylphenyl)-2-trifluoromethylpurine, 
       9-(3-Methoxycarbonylphenyl)-6-methylamino-2-trifluoromethylpurine, 
       9-(4-Methoxycarbonylphenyl)-6-methylamino-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(3-methylsulfonylphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methylsulfinylpyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methylsulfonylpyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methylsulfinylphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methylsulfonylphenyl)-2-trifluoromethylpurine, 
       9-(4-Carboxyphenyl)-6-cyclopropylamino-2-trifluoromethylpurine, 
       9-(2-Carboxyphenyl)-6-cyclopropylamino-2-trifluoromethylpurine, 
       9-(3-Carboxyphenyl)-6-methylamino-2-trifluoromethylpurine, 
       9-(4-Carboxyphenyl)-6-methylamino-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(3-methylsulfonylaminocarbonylphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(3-methylsulfonylaminocarbonylphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methylsulfonylaminocarbonylphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(4-methylsulfonylaminocarbonylphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(4-methylsulfonylaminocarbonylphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(3-ethylsulfonylaminocarbonylphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-[3-(4-fluorophenyl)sulfonylaminocarbonylphenyl]-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(4-ethylsulfonylaminocarbonylphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(3-phenylsulfonylaminocarbonylphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-[4-(4-fluorophenyl)sulfonylaminocarbonylphenyl]-2-trifluoromethylpurine trifluoromethylacetic acid salt, 
       6-Cyclopropylamino-9-(4-phenylsulfonylaminocarbonylphenyl)-2-trifluoromethylpurine, 
       9-[3-(3-Chlorophenyl)sulfonylaminocarbonylphenyl]-6-cyclopropylamino-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-[3-(2,6-difluorophenyl)sulfonylamino-carbonylphenyl]-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-[3-(2,4-difluorophenyl)sulfonylamino-carbonylphenyl]-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-[3-(2-thienyl)sulfonylaminocarbonylphenyl]-2-trifluoromethylpurine, 
       9-[3-(5-Chloro-2-thienyl)sulfonylaminocarbonylphenyl]-6-cyclopropylamino-2-trifluoromethylpurine, 
       9-[3-(5-Chloro-3-methylbenzothien-2-yl)sulfonylaminocarbonylphenyl]-6-cyclopropylamino-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-[3-(6-ethoxy-2-benzothiazolyl)sulfonylaminocarbonylphenyl]-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-[3-(5-methyl-2-pyridyl)sulfonylamino-carbonylphenyl]-2-trifluoromethylpurine, 
       9-[3-(4-Chloro-3-pyridyl)sulfonylaminocarbonylphenyl]-2-trifluoromethylpurine, and, 
       6-Methylamino-9-(2-methylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       and pharmaceutically acceptable salts thereof. 
     
     
         23 . A compound according to  claim 22 , wherein said compound is selected from: 
       6-Cyclopropylamino-9-(2,6-dimethoxypyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(4,6-dimethoxypyrimidin-2-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-methylsulfonylpyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-methoxypyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methoxycarbonylphenyl)-2-trifluoromethylpurine [or 9-(3-Methoxycarbonylphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Cyclopropylamino-9-(3-carboxyphenyl)-2-trifluoromethylpurine [or 9-(3-Carboxyphenyl)-6-cyclopropylamino-2-trifluoromethylpurine], 
       6-Cyclopropylamino-9-(3-methoxycarbonylphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methylthiopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methoxypyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Ethylamino-9-(2-chloropyrimidin-4-yl)-2-trifluoromethylpurine [or 9-(2-Chloropyrimidin-4-yl)-6-ethylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-N,N-dimethylaminopyrimidin-4-yl)-2-trifluoromethylpurine [or -9-(2-N,N-Dimethylaminopyrimidin-4-yl)-6-methylamino 2-trifluoromethylpurine, 
       6-Methylamino-9-(2-aminopyrimidin-4-yl)-2-trifluoromethylpurine [or 9-(2-Aminopyrimidin-4-yl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-N-methylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-N-ethylaminopyrimidin-4-yl)-2-trifluoromethylpurine [or 9-(2-N-Ethylaminopyrimidin-4-yl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-N-phenylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N-(4-pyridylamino)pyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N,N-dimethylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-methylpyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N-methylaminopyrimidin-4-yl)-2-trifluoromethylpurine, Methane sulfonic acid salt, 
       6-Cyclopropylamino-9-(2-N-ethylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N-cyclopropylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-N-methylaminopyrimidin-4-yl)-2-trifluoromethylpurine, Methane sulfonic acid salt, 
       6-Methylamino-9-(2-N-cyclopropylaminopyrimidin-4-yl)-2-trifluoromethylpurine [or 9-(2-N-Cyclopropylaminopyrimidin-4-yl)-6-methylamino-2-trifluoromethylpurine], 
       6-Cyclopropylamino-9-(2-N-methoxycarbonylmethylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N-methoxycarbonylethylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-(4-morpholinyl)pyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-N-hydroxyethylaminopyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-(1-piperazinyl)pyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-benzyloxyphenyl)-2-trifluoromethylpurine [or 9-(2-Benzyloxyphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(3-benzyloxyphenyl)-2-trifluoromethylpurine [or 9-(3-Benzyloxyphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(3-iodophenyl)-2-trifluoromethylpurine [or 9-(3-Iodophenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-methylsulfinylpyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-hydroxyphenyl)-2-trifluoromethylpurine [or 9-(3-Hydroxyphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-hydroxyphenyl)-2-trifluoromethylpurine [or 9-(2-Hydroxyphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-methylsulfonylpyrimidin-4-yl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(3-benzyloxyphenyl)-2-trifluoromethylpurine [or 9-(3-Benzyloxyphenyl)-6-cyclopropylamino-2-trifluoromethylpurine], 
       6-Cyclopropylamino-9-(4-benzyloxyphenyl)-2-trifluoromethylpurine [or 9-(4-Benzyloxyphenyl)-6-cyclopropylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(2-fluoro-3-methoxyphenyl)-2-trifluoromethylpurine [or 9-(2-Fluoro-3-methoxyphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(3-nitrophenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-trifluoromethoxyphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methylsulfonylaminophenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(2-hydroxyphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-nitrophenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methylthiophenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methoxycarbonylphenyl)-2-trifluoromethylpurine [or 9-(2-Methoxycarbonylphenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(8-quinolinyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-aminophenyl)-2-trifluoromethylpurine [or 9-(3-Aminophenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Methylamino-9-(3-N,N-dimethylaminophenyl)-2-trifluoromethylpurine [or 9-(3-N,N-Dimethylaminophenyl)-6-methylamino-2-trifluoromethylpurine], 
       6-Cyclopropylamino-9-(3-hydroxyphenyl)-2-trifluoromethylpurine, 
       6-Cyclopropylamino-9-(4-hydroxyphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methylaminophenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-trifluoromethoxyphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methylsulfinylphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(3-methylsulfonylphenyl)-2-trifluoromethylpurine, 
       6-Methylamino-9-(2-methylsulfonylaminophenyl)-2-trifluoromethylpurine, and 
       pharmaceutically acceptable salts thereof. 
     
     
         24 . A method according to  claim 1 , wherein said method is for treating a patient suffering from drug addiction or morphine dependence. 
     
     
         25 . (canceled) 
     
     
         26 . A method according to  claim 1 , wherein said method is for effecting PDE4 enzyme inhibition, enhancing cognition and/or treating psychosis in a patient. 
     
     
         27 . A method according to  claim 26 , wherein said compound is administered in an amount of 0.01-100 mg/kg of body weight/day. 
     
     
         28 . A method according to  claim 26 , wherein said patient is a human. 
     
     
         29 . A method of  claim 26 , wherein the patient is suffering from cognition impairment or decline. 
     
     
         30 . A method according to  claim 26 , wherein said patient is suffering from memory impairment. 
     
     
         31 . A method according to  claim 30 , wherein said patient is suffering from memory impairment due to Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, HIV, cardiovascular disease, head trauma or age-related cognitive decline. 
     
     
         32 . A method according to  claim 30 , wherein said patient is suffering from memory impairment due to dementia. 
     
     
         33 . A method according to  claim 26 , wherein said patient is suffering from a psychosis. 
     
     
         34 . A method according to  claim 33 , wherein the psychosis is schizophrenia, bipolar or manic depression, or major depression. 
     
     
         35 . A method according to  claim 1 , wherein said method is for treating a patient having a disease involving decreased cAMP levels. 
     
     
         36 . A method of  claim 26 , wherein the patient is treated to effect PDE4 enzyme inhibition. 
     
     
         37 . A method according to  claim 1 , wherein said method is for treating a patient suffering from an allergic or inflammatory disease. 
     
     
         38 . A method according to  claim 37 , wherein the patient is suffering from chronic obstructive pulmonary disease. 
     
     
         39 . A method according to  claim 1 , wherein said method is for treating a patient suffering from neurodegeneration resulting from a disease or injury. 
     
     
         40 . A method according to  claim 39 , wherein the disease or injury is stroke, spinal cord injury, neurogenesis, Alzheimer's disease, multiple sclerosis, amylolaterosclerosis (ALS), or multiple systems atrophy (MSA). 
     
     
         41 . A method according to  claim 28 , wherein said patient is suffering from memory impairment Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, depression, aging, head trauma, stroke, CNS hypoxia, cerebral senility, multiinfarct dementia, an acute neuronal disease, HIV or a cardiovascular disease. 
     
     
         42 . A method according to  claim 14 , wherein said method is for treating a patient suffering from drug addiction or morphine dependence. 
     
     
         43 . (canceled) 
     
     
         44 . A method according to  claim 14 , wherein said method is for effecting PDE4 enzyme inhibition, enhancing cognition and/or treating psychosis in a patient. 
     
     
         45 . A method according to  claim 44 , wherein said compound is administered in an amount of 0.01-100 mg/kg of body weight/day. 
     
     
         46 . A method according to  claim 44 , wherein said patient is a human. 
     
     
         47 . A method according to  claim 44 , wherein the patient is suffering from cognition impairment or decline. 
     
     
         48 . A method according to  claim 44 , wherein said patient is suffering from memory impairment. 
     
     
         49 . A method according to  claim 48 , wherein said patient is suffering from memory impairment due to Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, HIV, cardiovascular disease, head trauma or age-related cognitive decline. 
     
     
         50 . A method according to  claim 48 , wherein said patient is suffering from memory impairment due to dementia. 
     
     
         51 . A method according to  claim 44 , wherein said patient is suffering from a psychosis. 
     
     
         52 . A method according to  claim 51 , wherein the psychosis is schizophrenia, bipolar or manic depression, or major depression. 
     
     
         53 . A method according to  claim 14 , wherein said method is for treating a patient having a disease involving decreased cAMP levels. 
     
     
         54 . A method according to  claim 53 , wherein the patient is treated to effect PDE4 enzyme inhibition. 
     
     
         55 . A method according to  claim 14 , wherein said method is for treating a patient suffering from an allergic or inflammatory disease. 
     
     
         56 . A method according to  claim 55 , wherein the patient is suffering from chronic obstructive pulmonary disease. 
     
     
         57 . A method according to  claim 14 , wherein said method is for treating a patient suffering from neurodegeneration resulting from a disease or injury. 
     
     
         58 . A method according to  claim 57 , wherein the disease or injury is stroke, spinal cord injury, neurogenesis, Alzheimer's disease, multiple sclerosis, amylolaterosclerosis (ALS), or multiple systems atrophy (MSA). 
     
     
         59 . A method according to  claim 53 , wherein said patient is suffering from memory impairment Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, depression, aging, head trauma, stroke, CNS hypoxia, cerebral senility, multiinfarct dementia, an acute neuronal disease, HIV or a cardiovascular disease. 
     
     
         60 . A method according to  claim 22 , wherein said method is for treating a patient suffering from drug addiction or morphine dependence. 
     
     
         61 . (canceled) 
     
     
         62 . A method according to  claim 22 , wherein said method is for effecting PDE4 enzyme inhibition, enhancing cognition and/or treating psychosis in a patient. 
     
     
         63 . A method according to  claim 62 , wherein said compound is administered in an amount of 0.01-100 mg/kg of body weight/day. 
     
     
         64 . A method according to  claim 62 , wherein said patient is a human. 
     
     
         65 . A method according to  claim 62 , wherein the patient is suffering from cognition impairment or decline. 
     
     
         66 . A method according to  claim 62 , wherein said patient is suffering from memory impairment. 
     
     
         67 . A method according to  claim 66 , wherein said patient is suffering from memory impairment due to Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, HIV, cardiovascular disease, head trauma or age-related cognitive decline. 
     
     
         68 . A method according to  claim 66 , wherein said patient is suffering from memory impairment due to dementia. 
     
     
         69 . A method according to  claim 62 , wherein said patient is suffering from a psychosis. 
     
     
         70 . A method according to  claim 69 , wherein the psychosis is schizophrenia, bipolar or manic depression, or major depression. 
     
     
         71 . A method according to  claim 22 , wherein said method is for treating a patient having a disease involving decreased cAMP levels. 
     
     
         72 . A method according to  claim 62 , wherein the patient is treated to effect PDE4 enzyme inhibition. 
     
     
         73 . A method according to  claim 1 , wherein said method is for treating a patient suffering from an allergic or inflammatory disease. 
     
     
         74 . A method according to  claim 73 , wherein the patient is suffering from chronic obstructive pulmonary disease. 
     
     
         75 . A method according to  claim 22 , wherein said method is for treating a patient suffering from neurodegeneration resulting from a disease or injury. 
     
     
         76 . A method according to  claim 67 , wherein the disease or injury is stroke, spinal cord injury, neurogenesis, Alzheimer's disease, multiple sclerosis, amylolaterosclerosis (ALS), or multiple systems atrophy (MSA). 
     
     
         77 . A method according to  claim 64 , wherein said patient is suffering from memory impairment Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, depression, aging, head trauma, stroke, CNS hypoxia, cerebral senility, multiinfarct dementia, an acute neuronal disease, HIV or a cardiovascular disease. 
     
     
         78 . A method according to  claim 23 , wherein said method is for treating a patient suffering from drug addiction or morphine dependence. 
     
     
         79 . (canceled) 
     
     
         80 . A method for effecting PDE4 enzyme inhibition, enhancing cognition and/or treating psychosis in a patient comprising administering to said patient an effective amount of a compound according to  claim 23 . 
     
     
         81 . A method according to  claim 80 , wherein said compound is administered in an amount of 0.01-100 mg/kg of body weight/day. 
     
     
         82 . A method according to  claim 80 , wherein said patient is a human. 
     
     
         83 . A method according to  claim 80 , wherein the patient is suffering from cognition impairment or decline. 
     
     
         84 . A method according to  claim 80 , wherein said patient is suffering from memory impairment. 
     
     
         85 . A method according to  claim 84 , wherein said patient is suffering from memory impairment due to Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, HIV, cardiovascular disease, head trauma or age-related cognitive decline. 
     
     
         86 . A method according to  claim 84 , wherein said patient is suffering from memory impairment due to dementia. 
     
     
         87 . A method according to  claim 80 , wherein said patient is suffering from a psychosis. 
     
     
         88 . A method according to  claim 87 , wherein the psychosis is schizophrenia, bipolar or manic depression, or major depression. 
     
     
         89 . A method according to  claim 22 , wherein said method is for treating a patient having a disease involving decreased cAMP levels. 
     
     
         90 . A method according to  claim 89 , wherein the patient is treated to effect PDE4 enzyme inhibition. 
     
     
         91 . A method according to  claim 23 , wherein said method is for treating a patient suffering from an allergic or inflammatory disease. 
     
     
         92 . A method according to  claim 91 , wherein the patient is suffering from chronic obstructive pulmonary disease. 
     
     
         93 . A method according to  claim 23 , wherein said method is for treating a patient suffering from neurodegeneration resulting from a disease or injury. 
     
     
         94 . A method according to  claim 92 , wherein the disease or injury is stroke, spinal cord injury, neurogenesis, Alzheimer's disease, multiple sclerosis, amylolaterosclerosis (ALS), or multiple systems atrophy (MSA). 
     
     
         95 . A method according to  claim 89 , wherein said patient is suffering from memory impairment Alzheimer's disease, schizophrenia, Parkinson's disease, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, depression, aging, head trauma, stroke, CNS hypoxia, cerebral senility, multiinfarct dementia, an acute neuronal disease, HIV or a cardiovascular disease. 
     
     
         96 . A compound according to  claim 22 , wherein said compound is 9-(4-carboxyphenyl)-6-cyclopropylamino-2-trifluoromethylpurine, or a pharmaceutically acceptable salt thereof. 
     
     
         97 . A compound according to  claim 22 , wherein said compound is 9-(4-carboxyphenyl)-6-methylamino-2-trifluoromethylpurine, or a pharmaceutically acceptable salt thereof.