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 enhancing cognition in a patient, treating psychosis in a patient, treating a patient suffering from inflammation due to an allergic or inflammatory disease, or treating a patient is 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 alkyl having 1 to 6 carbon atoms which is unsubstituted or substituted one or more times by halogen, hydroxy, or combinations thereof, and wherein one or more —CH 2 —CH 2 — groups can each be replaced by —CH═CH— or —C≡C—, 
 cycloalkyl having 3 to 6 carbon atoms, 
 cycloalkylalkyl having 4 to 7 C atoms, 
 methoxy, or 
 pyrrolidinyl; 
 
         R 2  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—,
 alkoxyalkyl 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 4-, carboxy, cyano, —C(O)—NHOH, —C(O)—NH 2 , C 2-4 -acyl, 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, 
 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 -acyl, 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, 
 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, 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, 
 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, 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, 
 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, 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 nonaromatic and is unsubstituted or is 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, 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 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 -acyl, 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; 
 
 
         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 16 carbon atoms, which is unsubstituted or substituted in the cycloalkyl portion and/or the alkyl portion one or more times by halogen, oxo, cyano, hydroxy, C 1-4 -alkyl, C 1-4 -alkoxy, halogenated C 1-4  alkyl, halogenated C 1-4  alkoxy 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 -acyl, 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, 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 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 16 carbon atoms, which is unsubstituted or substituted in the cycloalkyl portion and/or the alkyl portion one or more times by halogen, oxo, cyano, hydroxy, C 1-4 -alkyl, C 1-4 -alkoxy, halogenated C 1-4  alkyl, halogenated C 1-4  alkoxy 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 -acyl, 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, 
 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 -acyl, 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, 
 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, 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 nonaromatic and is unsubstituted or is 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, 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, 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 
 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, 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; 
 
         or 
         a pharmaceutically acceptable salt thereof, 
         with the provisos that: 
         (a) when R 1  is methoxy, R 2  is cycloalkyl or pyrimidinyl substituted by dialkylamino; and 
         (b) when R 1  is pyrrolidinyl, R 2  is cycloalkyl or arylalkyl. 
       
     
     
         2 . A method according to  claim 1 , wherein R 2  is not 4-methoxy-3-cyclopentyloxy-benzyl. 
     
     
         3 . A method for enhancing cognition in a patient, treating psychosis in a patient, treating a patient suffering from inflammation due to an allergic or inflammatory disease, or treating a patient is suffering from drug addiction or morphine dependence, comprising administering to said patient an effective amount of a compound selected from: 
       6-Chloro-9-(2-fluorobenzyl)-2-trifluoromethylpurine, 
       6-Chloro-9-cyclopentyl-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-methoxy-2-trifluoromethylpurine, 
       9-(4-(2-N,N-Dimethylamino)pyrimidinyl)-6-methoxy-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-(1-pyrrolidinyl)-2-trifluoromethylpurine, 
       9-(2-Fluorobenzyl)-6-(1-pyrrolidinyl)-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-methyl-2-trifluoromethylpurine, 
       9-(2-Fluorobenzyl)-6-methyl-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-ethyl-2-trifluoromethylpurine, 
       6-Ethyl-9-(2-fluorobenzyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-Phenyl-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methoxyphenyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(2-methoxyphenyl)-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-(2-propyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methylsulfonylphenyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methylsulfinylphenyl)-2-trifluoromethylpurine, 
       6-(1-Butyl)-9-cyclopentyl-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-(1-propyl)-2-trifluoromethylpurine, 
       9-(2,3-Difluorobenzyl)-6-ethyl-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methylbenzyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methoxybenzyl)-2-trifluoromethylpurine, 
       9-(2,4-Difluorobenzyl)-6-ethyl-2-trifluoromethylpurine, 
       9-(3-Cyanophenyl)-6-ethyl-2-trifluoromethylpurine, 
       9-(2,3-Dichlorophenyl)-6-ethyl-2-trifluoromethylpurine, 
       9-(4-Chlorophenyl)-6-ethyl-2-trifluoromethylpurine, 
       6-Ethyl-9-(2-fluorophenyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-fluorophenyl)-2-trifluoromethylpurine, 
       9-(4-Benzyloxyphenyl)-6-ethyl-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methylthiophenyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methylphenyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(4-methylphenyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(4-fluorophenyl)-2-trifluoromethylpurine, 
       9-(2-Chlorophenyl)-6-ethyl-2-trifluoromethylpurine, 
       6-Ethyl-9-(4-pyridyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(4-methoxyphenyl)-2-trifluoromethylpurine, 
       9-(3-Chlorophenyl)-6-ethyl-2-trifluoromethylpurine, 
       9-(3-Chloro-4-pyridyl)-6-ethyl-2-trifluoromethylpurine, 
       6-Ethyl-9-(2-methyl-4-pyridyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methyl-4-pyridyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methoxy-4-pyridyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-ethylsulfonylphenyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-trifluoromethoxyphenyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methoxycarbonylphenyl)-2-trifluoromethylpurine. 
       6-Ethyl-9-(4-methoxycarbonylphenyl)-2-trifluoromethylpurine. 
       6-Ethyl-9-(4-hydroxyphenyl)-2-trifluoromethylpurine, 
       9-(3-Aminomethylphenyl)-6-ethyl-2-trifluoromethylpurine, 
       9-(3-Carboxyphenyl)-6-ethyl-2-trifluoromethylpurine, 
       9-(4-Carboxyphenyl)-6-ethyl-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methylsulfonylaminocarbonylphenyl)-2-trifluoromethylpurine; and
 pharmaceutically acceptable salts thereof. 
 
     
     
         4 . A method according to  claim 1 , wherein R 2  is aryl substituted by —CO—NH—SO 2 —R 5 . 
     
     
         5 . A method according to  claim 1 , wherein R 2  is phenyl substituted by —CO—NH—SO 2 —R 5 . 
     
     
         6 . A method according to  claim 4 , wherein R 5  is alkyl. 
     
     
         7 . A method according to  claim 5 , wherein R 5  is alkyl. 
     
     
         8 . A method according to  claim 1 , wherein R 2  is aryl substituted by —SO 2 —NH—CO—R 5 . 
     
     
         9 . A method according to  claim 1 , wherein R 2  is phenyl substituted by —SO 2 —NH—CO—R 5 . 
     
     
         10 . A method according to  claim 8 , wherein R 5  is alkyl. 
     
     
         11 . A method according to  claim 9 , wherein R 5  is alkyl. 
     
     
         12 . A method for enhancing cognition in a patient, treating psychosis in a patient, treating a patient suffering from inflammation due to an allergic or inflammatory disease, or treating a patient is 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 alkyl having 1 to 6 carbon atoms which is unsubstituted or substituted one or more times by halogen, hydroxy, or combinations thereof, and wherein one or more —CH 2 —CH 2 — groups can each be replaced by —CH═CH— or —C≡C—, 
 cycloalkyl having 3 to 6 carbon atoms, 
 cycloalkylalkyl having 4 to 7 C atoms, 
 methoxy, or 
 pyrrolidinyl; 
 
         R 2  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, —C(O)—NHOH, —C(O)—NH 2 , C 2-4 -acyl, 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, 
 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 -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, 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, 
 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, 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, 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, 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 nonaromatic and is unsubstituted or is 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, 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 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 -acyl, C 2-4 -alkoxycarbonyl, C 1-4 -alkylthio, C 1-4 -alkylsulphinyl, C 1-4 -alkylsulphonyl, phenoxy, or combinations thereof; 
 
         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 -acyl, 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, 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; and 
 
         R 4  is H or alkyl having 1 to 4 carbon atoms which is straight chain or branched;
 or 
 
         a pharmaceutically acceptable salt thereof, 
         with the provisos that: 
         (a) when R 1  is methoxy, R 2  is cycloalkyl or pyrimidinyl substituted by dialkylamino; and 
         (b) when R 1  is pyrrolidinyl, R 2  is cycloalkyl or arylalkyl. 
       
     
     
         13 . A method according to  claim 12 , wherein R 2  is not 4-methoxy-3-cyclopentyloxy-benzyl. 
     
     
         14 . A method according to  claim 3 , wherein said compound is selected from: 
       6-Chloro-9-(2-fluorobenzyl)-2-trifluoromethylpurine, 
       6-Chloro-9-cyclopentyl-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-methoxy-2-trifluoromethylpurine, 
       9-(4-(2-N,N-Dimethylamino)pyrimidinyl)-6-methoxy-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-(1-pyrrolidinyl)-2-trifluoromethylpurine, 
       9-(2-Fluorobenzyl)-6-(1-pyrrolidinyl)-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-methyl-2-trifluoromethylpurine, 
       9-(2-Fluorobenzyl)-6-methyl-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-ethyl-2-trifluoromethylpurine, 
       9-(2-Fluorobenzyl)-6-ethyl-2-trifluoromethylpurine, 
       9-Phenyl-6-ethyl-2-trifluoromethylpurine, 
       6-Ethyl-9-(3-methoxyphenyl)-2-trifluoromethylpurine, 
       6-Ethyl-9-(2-methoxyphenyl)-2-trifluoromethylpurine, 
       9-Cyclopentyl-6-(2-propyl)-2-trifluoromethylpurine, and
 pharmaceutically acceptable salts thereof. 
 
     
     
         15 . A method according to  claim 12 , wherein R 1  is an alkyl having up to 5 carbon atoms. 
     
     
         16 . A method according to  claim 12 , wherein R 1  is an alkyl having 1 to 4 carbon atoms. 
     
     
         17 . A method according to  claim 12 , wherein R 1  is an alkyl having 1 to 3 carbon atoms. 
     
     
         18 . A method according to  claim 12 , wherein R 1  is methyl, ethyl, propyl, isopropyl, butyl, isopropyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl or 1-ethylpropyl. 
     
     
         19 . A method according to  claim 12 , wherein R 2  is methyl, ethyl, propyl, isopropyl, butyl, isopropyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, 1-, 2-, 3- or 4-methylpentyl, tert-butyl, 1,1-, 1,2-, 1,3-, 2,2-, 2,3- or 3,3-dimethylbutyl, 1- or 2-ethylbutyl, ethylmethylpropyl, trimethylpropyl, methylhexyl, dimethylpentyl, ethylpentyl, ethylmethylbutyl, or dimethylbutyl. 
     
     
         20 . A method according to  claim 12 , wherein R 2  is an alkyl having 3 to 8 carbon atoms. 
     
     
         21 . A method according to  claim 12 , wherein R 2  is an alkyl having 3 to 6 carbon atoms. 
     
     
         22 . A method according to  claim 12 , wherein heteroaryl is an aromatic heterocyclic group having one or two rings containing 1 to 3 hetero-ring atoms selected from N, O and S, which is unsubstituted or substituted in one or more places by halogen, hydroxyl, aryl, alkyl, alkoxy, carboxy, methylene, cyano, trifluoromethyl, nitro, amino, alkylamino, dialkylamino, or combinations thereof. 
     
     
         23 . A method according to  claim 12 , wherein heteroaryl is an aromatic heterocyclic group selected from furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, benzofuranyl, isobenzofuranyl, thionaphthenyl, isothionaphthenyl, indolyl, isoindolyl, indazolyl, benzisoxazolyl, benzoxazolyl, benzthiazolyl, benzisothiazolyl, purinyl, benzopyranyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, naphthyridinyl, and benzoxazinyl, which in each case is unsubstituted or substituted in one or more places by halogen, hydroxyl, aryl, alkyl, alkoxy, carboxy, cyano, trifluoromethyl, nitro, amino, alkylamino, dialkylamino, or combinations thereof. 
     
     
         24 . A method according to  claim 12 , wherein heteroaryl is an aromatic heterocyclic group selected from 2-thienyl, 3-thienyl, 2-, 3- or 4-pyridyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolinyl, and 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolinyl, which in each case is unsubstituted or substituted in one or more places by halogen, hydroxyl, aryl, alkyl, alkoxy, carboxy, cyano, trifluoromethyl, nitro, amino, alkylamino, dialkylamino, or combinations thereof. 
     
     
         25 . A method according to  claim 12 , wherein heteroarylalkyl is pyridylmethyl, thienylmethyl, pyrimidinylmethyl, pyrazinylmethyl, or isoquinolinylmethyl, wherein the heteroaryl portion is unsubstituted or is 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, 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, or combinations thereof. 
     
     
         26 . A method according to  claim 12 , wherein heteroarylalkyl is pyridylmethyl, thienylmethyl, pyrimidinylmethyl, pyrazinylmethyl, or isoquinolinylmethyl. 
     
     
         27 . A method according to  claim 12 , wherein heterocycle is a non-aromatic cyclic group containing at least one hetero-ring atom selected from N, S and O. 
     
     
         28 . A method according to  claim 12 , wherein heterocycle is 3-tetrahydrofuranyl, piperidinyl, imidazolinyl, imidazolidinyl, pyrrolinyl, pyrrolidinyl, morpholinyl, piperazinyl, or indolinyl. 
     
     
         29 . A method according to  claim 12 , wherein heterocycle-alkyl is piperidinyl-ethyl and pyrrolinyl-methyl. 
     
     
         30 . A method according to  claim 12 , wherein carbocycle is a non-aromatic monocyclic or bicyclic structure structures containing 6 to 10 carbon atoms. 
     
     
         31 . A method according to  claim 12 , wherein carbocycle is cyclopentenyl, cyclohexenyl, cyclohexadienyl, tetrahydronaphthenyl or indan-2-yl. 
     
     
         32 . A method according to  claim 12 , wherein R 1  is methoxy, pyrrolidinyl, methyl, ethyl or isopropyl. 
     
     
         33 . A method according to  claim 12 , wherein R 2  is cycloalkyl, aryl, arylalkyl, or heteroaryl. 
     
     
         34 . A method according to  claim 12 , wherein R 2  is cyclopentyl, phenyl, benzyl, or pyrimidinyl. 
     
     
         35 . A method according to  claim 12 , wherein R 2  is cyclopentyl, phenyl which is unsubstituted or substituted, benzyl which is unsubstituted or substituted, or pyrimidinyl which is unsubstituted or substituted. 
     
     
         36 . A method according to  claim 12 , wherein R 2  is cyclopentyl, phenyl which is unsubstituted or substituted one or more times by, alkoxy, benzyl which is unsubstituted or substituted by F, or pyrimidinyl which is unsubstituted or substituted by alkylsulfonyl or dialkylamino. 
     
     
         37 . A method according to  claim 12 , wherein:
 R 1  is methyl, ethyl, isopropyl, propyl, methoxy, or pyrrolidinyl; and   R 2  is cycloalkyl, aryl, arylalkyl, or heteroaryl, which in each case is unsubstituted or substituted,   with the provisos that:   (a) when R 1  is methoxy, R 2  is cycloalkyl or pyrimidinyl substituted by dialkylamino; and   (b) when R 1  is pyrrolidinyl, R 2  is cycloalkyl or arylalkyl.   
     
     
         38 . A method according to  claim 12 , wherein:
 R 1  is methyl, ethyl, isopropyl, propyl, methoxy, or pyrrolidinyl; and   R 2  is cycloalkyl, aryl, arylalkyl, or heteroaryl, which in each case is unsubstituted or substituted,   with the provisos that:   (a) when R 1  is methoxy, R 2  is cyclopentyl or pyrimidinyl substituted by dimethylamino; and   (b) when R 1  is pyrrolidinyl, R 2  is cyclopentyl or fluorine substituted benzyl.   
     
     
         39 . A method according to  claim 12 , wherein:
 R 1  is methyl, ethyl, isopropyl, propyl, methoxy, or pyrrolidinyl; and   R 2  is cyclopentyl, phenyl, benzyl or pyrimidinyl, which in each case is unsubstituted or substituted,   with the provisos that:   (a) when R 1  is methoxy, R 2  is cyclopentyl or pyrimidinyl substituted by dialkylamino; and   (b) when R 1  is pyrrolidinyl, R 2  is cyclopentyl or benzyl which is substituted or unsubstituted.   
     
     
         40 . A method according to  claim 12 , wherein:
 R 1  is methyl, ethyl, isopropyl, propyl, methoxy, or pyrrolidinyl; and   R 2  is cyclopentyl, phenyl, benzyl or pyrimidinyl, which in each case is unsubstituted or substituted,   with the provisos that:   (a) when R 1  is methoxy, R 2  is cyclopentyl or pyrimidinyl substituted by dimethylamino; and   (b) when R 1  is pyrrolidinyl, R 2  is cyclopentyl or fluorine substituted benzyl.   
     
     
         41 . A method according to  claim 12 , wherein:
 R 1  is methyl, ethyl, isopropyl, propyl, methoxy, or pyrrolidinyl; and   R 2  is cyclopentyl, phenyl which is unsubstituted or substituted one or more times by alkoxy, benzyl which is unsubstituted or substituted by F, or pyrimidinyl which is unsubstituted or substituted by alkylsulfonyl, or dialkylamino,   with the provisos that:   (a) when R 1  is methoxy, R 2  is cyclopentyl or pyrimidinyl substituted by dialkylamino; and   (b) when R 1  is pyrrolidinyl, R 2  is cyclopentyl or a benzyl which is unsubstituted or substituted by F.   
     
     
         42 . A method according to  claim 12 , wherein:
 R 1  is methyl, ethyl, isopropyl, propyl, methoxy, or pyrrolidinyl; and   R 2  is cyclopentyl, phenyl which is unsubstituted or substituted one or more times by alkoxy, benzyl which is unsubstituted or substituted by F, or pyrimidinyl which is unsubstituted or substituted by alkylsulfonyl, or dialkylamino, with the provisos that:   (a) when R 1  is methoxy, R 2  is cyclopentyl or pyrimidinyl substituted by dimethylamino; and   (b) when R 1  is pyrrolidinyl, R 2  is cyclopentyl or fluorine substituted benzyl.   
     
     
         43 . A method according to  claim 12 , wherein:
 R 1  is methyl, ethyl, isopropyl, propyl, methoxy, or pyrrolidinyl; and   R 2  is cyclopentyl, phenyl which is unsubstituted or substituted one or more times by methoxy, benzyl which is unsubstituted or substituted by F, or pyrimidinyl which is unsubstituted or substituted by methylsulfonyl, or dimethylamino, with the provisos that:   (a) when R 1  is methoxy, R 2  is cyclopentyl or pyrimidinyl substituted by dialkylamino; and   (b) when R 1  is pyrrolidinyl, R 2  is cyclopentyl or a benzyl which is unsubstituted or substituted by F.   
     
     
         44 . A method according to  claim 12 , wherein:
 R 1  is methyl, ethyl, isopropyl, propyl, methoxy, or pyrrolidinyl; and   R 2  is cyclopentyl, phenyl which is unsubstituted or substituted one or more times by methoxy, benzyl which is unsubstituted or substituted by F, or pyrimidinyl which is unsubstituted or substituted by methylsulfonyl, or dimethylamino, with the provisos that:   (a) when R 1  is methoxy, R 2  is cyclopentyl or pyrimidinyl substituted by dimethylamino; and   (b) when R 1  is pyrrolidinyl, R 2  is cyclopentyl or fluorine substituted benzyl.   
     
     
         45 . A method according to  claim 12 , wherein R 1  is methyl, ethyl, propyl, or cyclopropylmethyl. 
     
     
         46 . A method according to  claim 12 , wherein R 1  is methyl, ethyl, propyl, or cyclopropylmethyl, and R 2  is cycloalkyl, aryl, or heteroaryl, which in each case is unsubstituted or substituted. 
     
     
         47 . A method according to  claim 1 , wherein said compound is administered as a pharmaceutical composition containing said compound and a pharmaceutically acceptable carrier. 
     
     
         48 . A method according to  claim 47 , wherein said compound is administered in a unit dosage of 0.1-50 mg. 
     
     
         49 . A method according to  claim 1  for enhancing cognition and/or treating psychosis in a patient. 
     
     
         50 . A method according to  claim 49 , wherein said compound is administered in an amount of 0.01-100 mg/kg of body weight/day. 
     
     
         51 . A method according to  claim 49 , wherein said patient is a human. 
     
     
         52 . A method for enhancing cognition in a patient according to  claim 49 , wherein said patient is suffering from cognition impairment or decline. 
     
     
         53 . A method according to  claim 49 , wherein said patient is suffering from memory impairment. 
     
     
         54 . A method according to  claim 53 , 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. 
     
     
         55 . A method according to  claim 53 , wherein said patient is suffering from memory impairment due to dementia. 
     
     
         56 . A method according to  claim 49 , wherein said patient is suffering from a psychosis. 
     
     
         57 . A method according to  claim 56 , wherein said patient is suffering from schizophrenia, bipolar or manic depression, or major depression. 
     
     
         58 . (canceled) 
     
     
         59 . (canceled) 
     
     
         60 . A method according to  claim 1  for treating a patient suffering from inflammation due to an allergic or inflammatory disease. 
     
     
         61 . A method according to  claim 60 , wherein the patient is suffering from inflammation due to chronic obstructive pulmonary disease. 
     
     
         62 . A method according to  claim 49  for enhancing cognition in a patient, wherein said patient is suffering from neurodegeneration resulting from a disease or injury. 
     
     
         63 . A method according to  claim 62 , wherein the disease or injury is stroke, spinal cord injury, Alzheimer's disease, multiple sclerosis, amylolaterosclerosis (ALS), or multiple systems atrophy (MSA). 
     
     
         64 . A method according to  claim 53 , 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, an acute neuronal disease, HIV or a cardiovascular disease. 
     
     
         65 . A method according to  claim 12 , wherein said compound is administered as a pharmaceutical composition containing said compound and a pharmaceutically acceptable carrier. 
     
     
         66 . A method according to  claim 65 , wherein said compound is administered in a unit dosage of 0.1-50 mg. 
     
     
         67 . A method according to  claim 12  for enhancing cognition and/or treating psychosis in a patient. 
     
     
         68 . A method according to  claim 67 , wherein said compound is administered in an amount of 0.01-100 mg/kg of body weight/day. 
     
     
         69 . A method according to  claim 67 , wherein said patient is a human. 
     
     
         70 . A method according to  claim 67 , wherein the patient is suffering from cognition impairment or decline. 
     
     
         71 . A method according to  claim 67 , wherein said patient is suffering from memory impairment. 
     
     
         72 . A method according to  claim 71 , 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. 
     
     
         73 . A method according to  claim 71 , wherein said patient is suffering from memory impairment due to dementia. 
     
     
         74 . A method according to  claim 67 , wherein said patient is suffering from a psychosis. 
     
     
         75 . A according to  claim 74 , wherein said patient is suffering from schizophrenia, bipolar or manic depression, or major depression. 
     
     
         76 . (canceled) 
     
     
         77 . (canceled) 
     
     
         78 . A method according to  claim 12  for treating a patient suffering from inflammation due to an allergic or inflammatory disease. 
     
     
         79 . A method according to  claim 78 , wherein the patient is suffering from inflammation due to chronic obstructive pulmonary disease. 
     
     
         80 . A method according to  claim 67  for enhancing cognition in a patient suffering from neurodegeneration resulting from a disease or injury. 
     
     
         81 . A method according to  claim 80 , wherein the disease or injury is stroke, spinal cord injury, Alzheimer's disease, multiple sclerosis, amylolaterosclerosis (ALS), or multiple systems atrophy (MSA). 
     
     
         82 . (canceled) 
     
     
         83 . A method according to  claim 3  for treating a patient suffering from memory impairment. 
     
     
         84 . A method according to  claim 14  for treating a patient suffering from memory impairment. 
     
     
         85 . A method according to  claim 3  for treating a patient suffering from inflammation due to an allergic or inflammatory disease. 
     
     
         86 . A method of  claim 85 , wherein the patient is suffering from inflammation due to chronic obstructive pulmonary disease. 
     
     
         87 . A method according to  claim 14  for treating a patient suffering from inflammation due to an allergic or inflammatory disease. 
     
     
         88 . A method of  claim 87 , wherein the patient is suffering from inflammation due to chronic obstructive pulmonary disease. 
     
     
         89 . A method according to  claim 60 , wherein the patient is suffering from inflammation due to asthma, chronic bronchitis, chronic obstructive pulmonary disease, atopic dermatitis, urticaria, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, esoniophilic granuloma, psoriasis, inflammatory arthritis, rheumatoid arthritis, septic shock, ulcerative colitis, Crohn's disease, reperfusion injury of the myocardium and brain, chronic glomerulonephritis, endotoxic shock, adult respiratory distress syndrome, cystic fibrosis, arterial restenosis, artherosclerosis, keratosis, rheumatoid spondylitis, osteoarthritis, pyresis, diabetes mellitus, pneumoconiosis, chronic obstructive airways disease, chronic obstructive pulmonary disease, toxic contact eczema, allergic contact eczema, atopic eczema, seborrheic eczema, lichen simplex, sunburn, pruritis in the anogenital area, alopecia greata, hypertrophic scars, discoid lupus erythematosus, systemic lupus erythematosus, follicular and wide-area pyodermias, endogenous acne, exogenous acne, acne rosacea, Behcet's disease, anaphylactoid purpura nephritis, an inflammatory bowel disease, leukemia, multiple sclerosis, a gastrointestinal disease, or an autoimmune disease. 
     
     
         90 . A method according to  claim 78 , wherein the patient is suffering from inflammation due to asthma, chronic bronchitis, chronic obstructive pulmonary disease, atopic dermatitis, urticaria, allergic rhinitis, allergic conjunctivitis, vernal conjunctivitis, esoniophilic granuloma, psoriasis, inflammatory arthritis, rheumatoid arthritis, septic shock, ulcerative colitis, Crohn's disease, reperfusion injury of the myocardium and brain, chronic glomerulonephritis, endotoxic shock, adult respiratory distress syndrome, cystic fibrosis, arterial restenosis, artherosclerosis, keratosis, rheumatoid spondylitis, osteoarthritis, pyresis, diabetes mellitus, pneumoconiosis, chronic obstructive airways disease, chronic obstructive pulmonary disease, toxic contact eczema, allergic contact eczema, atopic eczema, seborrheic eczema, lichen simplex, sunburn, pruritis in the anogenital area, alopecia greata, hypertrophic scars, discoid lupus erythematosus, systemic lupus erythematosus, follicular and wide-area pyodermias, endogenous acne, exogenous acne, acne rosacea, Behcet's disease, anaphylactoid purpura nephritis, an inflammatory bowel disease, leukemia, multiple sclerosis, a gastrointestinal disease, or an autoimmune disease. 
     
     
         91 . A method according to  claim 3 , wherein said compound is 9-(4-carboxyphenyl)-6-ethyl-2-trifluoromethylpurine, or a pharmaceutically acceptable salt thereof.