Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs

Abstract

PDE4 inhibition is achieved by novel compounds, e.g., aminoindazole and aminobenzofuran analogs. The compounds of the present invention are of Formulas I and II: wherein R 1 , R 2 , R 3 , R 4 , R 7 and R 8 are as defined herein.

1 . A method for enhancing cognition, treating psychosis in a patient, treating a patient suffering from an allergic or inflammatory disease, treating a patient suffering from drug addiction or morphine dependence, or treating a patient suffering from neurodegeneration resulting from a disease or injury comprising administering to said patient an effective amount of a compound of formula I or formula II: 
     
       
         
         
             
             
         
       
       wherein 
       R 1  is H,
 alkyl having 1 to 8 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen, 
 cycloalkyl having 3 to 10 carbon atoms, which is unsubstituted or substituted one or more times by halogen, hydroxy, oxo, cyano, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, or combinations thereof, or 
 a heterocyclic group, which is saturated, partially saturated or unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, which is unsubstituted or substituted one or more times by halogen, alkyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, amino, aminomethyl, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, or combinations thereof, 
 
       R 2  is H, or
 alkyl having 1 to 4 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen, cyano, and/or C 1-4 -alkoxy, and where one or more —CH 2 CH 2 — groups are optionally replaced in each case by —CH═CH— or C≡C—, 
 
       R 3  is H,
 alkyl having 1 to 8 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times with halogen, cyano, C 1-4 -alkoxy, or combinations thereof, 
 a partially unsaturated carbocycle-alkyl group wherein the carbocyclic portion has 5 to 14 carbon atoms and the alkyl portion which is branched or unbranched has 1 to 5 carbon atoms, and which is unsubstituted or substituted in the carbocyclic portion one or more times by halogen, alkyl, alkoxy, nitro, cyano, oxo, or combinations thereof, and the alkyl portion is optionally substituted by halogen, C 1-4 -alkoxy, cyano or combinations thereof, 
 arylalkyl having 7 to 19 carbon atoms, wherein the aryl portion has 6 to 14 carbon atoms and the alkyl portion, which is branched or unbranched, has 1 to 5 carbon atoms, arylalkyl radical is unsubstituted or substituted, in the aryl portion, one or more times by halogen, trifluoromethyl, CF 3 O, nitro, amino, alkyl, alkoxy, alkylamino, dialkylamino and/or substituted in the alkyl portion by halogen, cyano, or methyl, or 
 heterocyclic-alkyl group, wherein the heterocyclic portion may be partially or fully saturated and has 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, the alkyl portion, which is branched or unbranched, has 1 to 5 carbon atoms, the heterocyclic-alkyl group is unsubstituted or substituted one or more times in the heterocyclic portion by halogen, alkyl, alkoxy, cyano, trifluoromethyl, CF 3 O, nitro, amino, alkylamino, dialkylamino, or combinations thereof and/or substituted in the alkyl portion by halogen, cyano, or methyl or combinations thereof; 
 
       R 4  is H,
 aryl having 6 to 14 carbon atoms and which is unsubstituted or substituted one or more times by halogen, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, OCF 3 , amino, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, 2(-heterocycle)tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, trialkylsilyloxy, R 5 -L-, or combinations thereof, or 
 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, alkyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, amino, aminomethyl, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, trialkylsilyloxy, R 5 -L-, or combinations thereof; 
 
       R 5  is H,
 alkyl having 1 to 8 carbon atoms, which is unsubstituted or substituted one or more times with halogen, C 1-4 -alkyl, C 1-4 -alkoxy, oxo, or combinations thereof, alkylamino or dialkylamino wherein each alkyl portion has independently 1 to 8 carbon atoms, 
 a partially unsaturated carbocycle-alkyl group wherein the carbocyclic portion has 5 to 14 carbon atoms and the alkyl portion has 1 to 5 carbon atoms, which is unsubstituted or substituted one or more times by halogen, alkyl, alkoxy, nitro, cyano, oxo, or combinations thereof, 
 cycloalkyl having 3 to 10 carbon atoms, which is unsubstituted or substituted one or more times by halogen, hydroxy, oxo, cyano, alkoxy, alkyl having 1 to 4 carbon atoms, 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, alkyl, alkoxy or combinations thereof, 
 aryl having 6 to 14 carbon atoms which is unsubstituted or substituted one or more times by halogen, alkyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, amino, aminomethyl, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, or combinations thereof 
 arylalkyl having 7 to 19 carbon atoms, wherein the aryl portion has 6 to 14 carbon atoms and the alkyl portion, which is branched or unbranched, has 1 to 5 carbon atoms, arylalkyl radical is unsubstituted or substituted, in the aryl portion, one or more times by halogen, trifluoromethyl, CF 3 O, nitro, amino, alkyl, alkoxy, amino, alkylamino, dialkylamino, or combinations thereof, and/or substituted in the alkyl portion by halogen, cyano, methyl, or combinations thereof, 
 a heterocyclic group, which is saturated, partially saturated or unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, which is unsubstituted or substituted one or more times by halogen, alkyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, amino, aminomethyl, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, or combinations thereof, or 
 a heterocycle-alkyl group, wherein the heterocyclic portion is saturated, partially saturated or unsaturated, and has 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, and the alkyl portion which is branched or unbranched and has 1 to 5 carbon atoms, the heterocycle-alkyl group is unsubstituted or substituted one or more times in the heterocyclic portion by halogen, alkyl, alkoxy, cyano, trifluoromethyl, CF 3 O, nitro, oxo, amino, alkylamino, dialkylamino, or combinations thereof and/or substituted in the alkyl portion by halogen, cyano, or methyl or combinations thereof; 
 
       L is a single bond or a divalent aliphatic radical having up to 8 carbon atoms wherein one or more —CH 2 — groups are each optionally replaced by —O—, —S—, —SO 2 —, —SO—, —NR 6 —, —SO 2 NH—, —NHSO 2 —, —CO—, —NR 6 CO—, —CONR 6 —, —NHCONH—, —OCONH—, —NHCOO—, —SCONH—, —SCSNH—, or —NHCSNH—; 
       R 6  is H, or
 alkyl having 1 to 8 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times with halogen, C 1-4 -alkyl, C 1-4 -alkoxy, oxo, or combinations thereof; 
 
       R 7  is alkoxy or alkylthio, in each case having 1 to 4 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen; 
       R 8  is —CO—C 1-4 -alkyl which is branched or unbranched and where the alkyl is unsubstituted or substituted one or more times by halogen, or is 
     
     
       
         
         
             
             
         
       
       R 9  is H or alkyl having 1 to 4 carbon atoms, which is branched or unbranched, and which is unsubstituted or substituted one or more times by halogen; 
       R 10  is alkyl having 1 to 6 carbon atoms, which is branched or unbranched, and which is unsubstituted or substituted one or more times by halogen; 
       R 11  is alkyl having 1 to 6 carbon atoms, which is branched or unbranched, and which is unsubstituted or substituted one or more times by halogen; 
       X and Y are each independently O or S; and 
       A is alkylene having 2 to 7 carbon atoms which is unsubstituted or substituted one or more times by halogen;
 wherein in formula I both of R 3  and R 4  are other than H and in formula II at least one of R 3  and R 4  is other than H; or 
 a pharmaceutically acceptable salt thereof; 
 with the proviso that said compound is not 4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-propylindazol-6-yl)-N-propylamino]thiazole; 
 wherein an optically active compound can be in the form of one of its separate enantiomers or mixtures thereof, including racemic mixtures. 
 
     
   
   
       2 . A compound of  claim 1 , which is of formula III or formula IV: 
     
       
         
         
             
             
         
       
       wherein 
       R 3  is H,
 alkyl having 1 to 8 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times with halogen, cyano, C 1-4 -alkoxy, or combinations thereof, 
 a partially unsaturated carbocycle-alkyl group wherein the carbocyclic portion has 5 to 14 carbon atoms and the alkyl portion which is branched or unbranched has 1 to 5 carbon atoms, and which is unsubstituted or substituted in the carbocyclic portion one or more times by halogen, alkyl, alkoxy, nitro, cyano, oxo, or combinations thereof, and the alkyl portion is optionally substituted by halogen, C 1-4 -alkoxy, cyano or combinations thereof, 
 arylalkyl having 7 to 19 carbon atoms, wherein the aryl portion has 6 to 14 carbon atoms and the alkyl portion, which is branched or unbranched, has 1 to 5 carbon atoms, arylalkyl radical is unsubstituted or substituted, in the aryl portion, one or more times by halogen, trifluoromethyl, CF 3 O, nitro, amino, alkyl, alkoxy, alkylamino, dialkylamino and/or substituted in the alkyl portion by halogen, cyano, or methyl, or 
 heterocyclic-alkyl group, wherein the heterocyclic portion may be partially or fully saturated and has 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, the alkyl portion, which is branched or unbranched, has 1 to 5 carbon atoms, the heterocyclic-alkyl group is unsubstituted or substituted one or more times in the heterocyclic portion by halogen, alkyl, alkoxy, cyano, trifluoromethyl, CF 3 O, nitro, amino, alkylamino, dialkylamino, or combinations thereof and/or substituted in the alkyl portion by halogen, cyano, or methyl or combinations thereof; 
 
       R 4  is H,
 aryl having 6 to 14 carbon atoms and which is unsubstituted or substituted one or more times by halogen, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, OCF 3 , amino, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, 2(-heterocycle)tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, trialkylsilyloxy, R 5 -L-, or combinations thereof, or 
 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, alkyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, amino, aminomethyl, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, trialkylsilyloxy, R 5 -L-, or combinations thereof; 
 
       R 7  is alkoxy or alkylthio, in each case having 1 to 4 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen, 
       R 8  is —CO—C 1-4 -alkyl which is branched or unbranched and where the alkyl is unsubstituted or substituted one or more times by halogen, or is 
     
     
       
         
         
             
             
         
       
       
         or 
         a pharmaceutically acceptable salt thereof; 
         wherein an optically active compound can be in the form of one of its separate enantiomers or mixtures thereof, including racemic mixtures. 
       
     
   
   
       3 . A compound of  claim 1 , which is of the subformula V or VI: 
     
       
         
         
             
             
         
       
       wherein 
       R 1  is H,
 alkyl having 1 to 8 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen, 
 cycloalkyl having 3 to 10 carbon atoms, which is unsubstituted or substituted one or more times by halogen, hydroxy, oxo, cyano, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, or combinations thereof, or 
 a heterocyclic group, which is saturated, partially saturated or unsaturated, having 5 to 10 ring atoms in which at least 1 ring atom is a N, O or S atom, which is unsubstituted or substituted one or more times by halogen, alkyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, amino, aminomethyl, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, or combinations thereof; 
 
       R 2  is H, or
 alkyl having 1 to 4 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen, cyano, and/or C 1-4 -alkoxy, and where one or more —CH 2 CH 2 — groups are optionally replaced in each case by —CH═CH— or —C≡C—; 
 
       R 4  is H,
 aryl having 6 to 14 carbon atoms and which is unsubstituted or substituted one or more times by halogen, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, OCF 3 , amino, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, 2(-heterocycle)tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, trialkylsilyloxy, R 5 -L-, or combinations thereof, or 
 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, alkyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, amino, aminomethyl, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, trialkylsilyloxy, R 5 -L-, or combinations thereof; 
 
       R 7  is alkoxy or alkylthio, in each case having 1 to 4 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen; 
       R 8  is —CO—C 1-4 -alkyl which is branched or unbranched and where the alkyl is unsubstituted or substituted one or more times by halogen, or is 
     
     
       
         
         
             
             
         
       
       and one of B, D and E is N and the other two are C;
 or 
 a pharmaceutically acceptable salt thereof; 
 wherein an optically active compound can be in the form of one of its separate enantiomers or mixtures thereof, including racemic mixtures. 
 
     
   
   
       4 . A compound of  claim 3 , wherein D is N and B and E are C. 
   
   
       5 . A compound of  claim 3 , wherein R 4  is pyridyl or phenyl which are unsubstituted or substituted one or more times by halogen, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, alkoxyalkoxy, nitro, methylenedioxy, ethylenedioxy, trifluoromethyl, OCF 3 , amino, aminoalkyl, aminoalkoxy dialkylamino, hydroxyalkyl, hydroxamic acid, tetrazole-5-yl, 2(-heterocycle)tetrazole-5-yl, hydroxyalkoxy, carboxy, alkoxycarbonyl, cyano, acyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, trialkylsilyloxy, R 5 -L-, or combinations thereof. 
   
   
       6 . A compound of  claim 1 , which is:
 7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-(4-pyridylmethyl)]aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-(3-pyridylmethyl)]aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-phenyl-N-(4-pyridylmethyl)]aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-(3-cyanophenyl)-N-(3-pyridylmethyl)]aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-phenyl-N-(3-pyridylmethyl)]aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-(3-cyanophenyl)-N-(4-pyridylmethyl)]aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-(4-acetylphenyl)-N-(3-pyridylmethyl)]aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-(4-carboxyphenyl)-N-(3-pyridylmethyl)]aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-(4-(2H-tetrazol-5-yl)phenyl)-N-(3-pyridylmethyl]aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-(4-carboxy-3-chlorophenyl)-N-(3-pyridylmethyl)]aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-[N-(3-carboxy-5-fluorophenyl)-N-(3-pyridylmethyl)]aminobenzofuran,   1-Cyclopentyl-6-[N-(3-(1,1-dimethylethoxycarbonyl)phenyl)-N-(3-pyridylmethyl)]-1H-aminoindazole,   2-Acetyl-7-methoxy-4-(N-(4-cyanophenyl)-N-(3-pyridylmethyl))aminobenzofuran,   2-Acetyl-7-methoxy-4-(N-phenyl-N-(4-pyridylmethyl))aminobenzofuran,   1-Cyclopentyl-6-(N-phenyl-N-(3-pyridylmethyl))aminoindazole,   1-Cyclopentyl-6-(N-(3-carboxyphenyl)-N-(3-pyridylmethyl))aminoindazole,   2-Acetyl-7-methoxy-4-(N-(3-carboxyphenyl)-N-(3-pyridylmethyl))aminobenzofuran,   7-Methoxy-2-(2-methyl-(1,3-dioxolane-2-yl))-4-(N-(4-cyanophenyl)-N-(3-pyridylmethyl))-aminobenzofuran,   2-Acetyl-7-methoxy-4-(N-(3-cyanophenyl)-N-(3-pyridylmethyl))aminobenzofuran,   2-Acetyl-7-methoxy-4-(N-phenyl-N-(3-pyridylmethyl))aminobenzofuran,   2-Acetyl-7-methoxy-4-(N-(3-cyanophenyl)-N-(4-pyridylmethyl))aminobenzofuran,   2-Acetyl-7-methoxy-4-(N-(4-acetylphenyl)-N-(3-pyridylmethyl))aminobenzofuran,   2-Acetyl-7-methoxy-4-[N-(4-carboxyphenyl)-N-(3-pyridylmethyl)]aminobenzofuran,   2-Acetyl-7-methoxy-4-[N-(4-(2H-tetrazol-5-yl)phenyl)-N-(3-pyridylmethyl]aminobenzofuran,   2-Acetyl-7-methoxy-4-[N-(4-carboxy-3-chlorophenyl)-N-(3-pyridylmethyl)]aminobenzofuran,   2-Acetyl-7-methoxy-4-[N-(3-carboxy-5-fluorophenyl)-N-(3-pyridylmethyl)]aminobenzofuran,   6-Amino-1-cyclopentyl-3-ethyl-6-[N-3-(1,1-dimethylethoxycarbonyl)phenyl]-N-(3-pyridylmethyl)amino-1H-indazole,   1-Cyclopentyl-3-ethyl-6-[N-(3-carboxyphenyl)-N-(3-pyridylmethyl)]amino-1H-indazole,   2-Acetyl-7-methoxy-N-(4-phenylsulfonylaminocarbonylphenyl)-N-(3-pyridylmethyl]-4-aminobenzofuran,   or   pharmaceutically acceptable salts thereof,
 wherein optically active compounds can be in the form of their separate enantiomers or mixtures thereof, including racemic mixtures. 
   
   
   
       7 . A compound of  claim 1 , wherein:
 each aryl group is, independently, a phenyl, naphthyl or biphenyl group optionally substituted one or more times by halogen, alkyl, hydroxy, alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, alkylamino, dialkylamino, hydroxyalkyl, hydroxyalkoxy, carboxy, cyano, acyl, alkoxycarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, phenoxy, or combinations thereof;   each heteroaryl group is, independently, a furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, dithialyl, oxathialyl, isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, oxatriazolyl, dioxazolyl, oxathiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, oxazinyl, isoxazinyl, oxathiazinyl, oxadiazinyl, benzofuranyl, isobenzofuranyl, thionaphthenyl, isothionaphthenyl, indolyl, isoindolyl, indazolyl, benzisoxazolyl, benzoxazolyl, benzthiazolyl, benzisothiazolyl, purinyl, benzopyranyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, naphthyridinyl, or benzoxazinyl group optionally substituted in one or more places by halogen, aryl, alkyl, alkoxy, carboxy, methylene, cyano, trifluoromethyl, nitro, amino, alkylamino, dialkylamino, or combinations thereof; and   each heterocycle group is, independently, a heteroaryl group as stated above or a tetrahydrofuranyl, piperidinyl, or pyrrolidinyl group optionally substituted as stated above.   
   
   
       8 . A compound of  claim 1 , wherein:
 R 1  is an alkyl group having 2 to 4 carbon atoms which is optionally substituted by fluorine or chlorine or is cyclopentyl or cyclohexyl;   R 2  is H or alkyl having 1 to 4 carbon atoms;   R 3  is hydrogen; alkyl having 1 to 4 carbon atoms; substituted or unsubstituted benzyl, phenethyl, or phenpropyl; or substituted or unsubstituted pyridylmethyl, furanylmethyl, thienylmethyl, pyrrolylmethyl, pyrimidinylmethyl, thiazolylmethyl, isoquinolinylmethyl or quinolinylmethyl; and   R 4  is phenyl, naphthyl, biphenyl, furanyl, pyrazinyl, pyrimidinyl, pyridyl, quinolinyl, or isoquinolinyl, which in each case is unsubstituted or is substituted one or more times by OH, F, Cl, CF 3 , alkyl, alkoxy, CN, vinyl, CH 2 OH, CONHOH, CONH 2 , methylenedioxy or COOH, or   R 4  is phenyl, naphthyl, or biphenyl which in each case is optionally substituted by R 5 —, R 5 —O—, R 5 —CO—, R 5 —NH—CO—, R 5 —SO 2 —NH—, R 5 —SO 2 —NH-alkylene-O—, NH 2 -alkyl-NH—CO—, R 5 -alkylene-NH—CO—, alkyl-CO—NH-alkyl-, methyl, ethyl, Cl, F, CN, OCH 3 , CF 3 , amino, nitro, HOCH 2  COOH, or combinations thereof;   R 7  is alkoxy having 1 to 4 carbon atoms, which is branched or unbranched and which is unsubstituted or substituted one or more times by halogen;   R 8  is —CO—C 1-4 -alkyl;   R 9  is —CH 3 ;   X and Y are each O or S; and   A is —CH 2 CH 2 —.   
   
   
       9 . A compound of  claim 1 , wherein:
 R 3  is arylalkyl or heteroarylalkyl, in each case substituted or unsubstituted; and   R 4  is H or is-aryl or heteroaryl, in each case substituted or unsubstituted.   
   
   
       10 . A compound of  claim 1 , wherein:
 R 1  is cycloalkyl; and   R 2  is H or C 2 H 5 .   
   
   
       11 . A compound of  claim 1 , wherein:
 R 1  is cycloalkyl;   R 2  is H or C 2 H 5 ;   R 3  is arylalkyl or heteroarylalkyl, in each case substituted or unsubstituted; and   R 4  is H or is aryl or heteroaryl, in each case substituted or unsubstituted.   
   
   
       12 . A compound of  claim 1 , wherein:
 R 1  is cyclopentyl;   R 2  is H or C 2 H 5 ;   R 3  is arylalkyl or heteroarylalkyl, in each case substituted or unsubstituted; and   R 4  is H or is aryl or heteroaryl, in each case substituted or unsubstituted.   
   
   
       13 . A compound of  claim 1 , wherein:
 R 1  is cyclopentyl;   R 2  is H or C 2 H 5 ;   R 3  is pyridyl which is substituted or unsubstituted; and   R 4  is H or is aryl or heteroaryl, in each case substituted or unsubstituted.   
   
   
       14 . A compound of  claim 1 , wherein:
 R 1  is cyclopentyl;   R 2  is H or C 2 H 5 ;   R 3  is pyridyl which is substituted or unsubstituted; and   R 4  is phenyl which is substituted or unsubstituted.   
   
   
       15 . A compound of  claim 1 , wherein:
 R 3  is arylalkyl or heteroarylalkyl, in each case substituted or unsubstituted; and   R 4  is H or is aryl or heteroaryl, in each case substituted or unsubstituted.   
   
   
       16 - 21 . (canceled) 
   
   
       22 . A method according to  claim 1 , wherein said method is for enhancing cognition and/or treating psychosis in a patient. 
   
   
       23 . A method according to  claim 1 , wherein said compound is administered in an amount of 0.01-100 mg/kg of body weight/day. 
   
   
       24 . A method according to  claim 22 , wherein said patient is a human. 
   
   
       25 . A method of  claim 22 , wherein the patient is suffering from cognition impairment or decline. 
   
   
       26 . A method according to  claim 22 , wherein said patient is suffering from memory impairment. 
   
   
       27 . (canceled) 
   
   
       28 . A method according to  claim 26 , wherein said patient is suffering from memory impairment due to dementia. 
   
   
       29 . A method according to  claim 22 , wherein said patient is suffering from a psychosis. 
   
   
       30 . A method according to  claim 29 , wherein said patient is suffering from schizophrenia, bipolar or manic depression, or major depression. 
   
   
       31 . (canceled) 
   
   
       32 . (canceled) 
   
   
       33 . A method according to  claim 1 , wherein said method is for treating a patient suffering from an allergic or inflammatory disease. 
   
   
       34 . A method according to  claim 1 , wherein said method is for treating a patient suffering from neurodegeneration resulting from a disease or injury. 
   
   
       35 . A method according to  claim 34 , wherein the disease or injury is stroke, spinal cord injury, Alzheimer's disease, multiple sclerosis, amylolaterosclerosis (ALS), or multiple systems atrophy (MSA). 
   
   
       36 . A method according to  claim 26 , 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, depression, aging, head trauma, stroke, CNS hypoxia, cerebral senility, multiinfarct dementia, an acute neuronal disease, HIV, cardiovascular disease head trauma or age-related cognitive decline.