US 7,332,486 B2Granted

Phosphodiesterase 4 inhibitors

AssigneeMemory Pharmaceuticals Corporation

InventorsAshok Tehim, Allen T. Hopper, Ruiping Liu, Hans-Jurgen Ernst Hess, Yajing Rong

Life of this patent

Estimating the term…

Abstract

PDE4 inhibition is achieved by novel compounds of the Formula I: wherein R1 and R2 are as defined herein.

Claims33

Dependent claims

A compound of Formula I:

wherein,
R1 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 —CH2— 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;
R2 is aryl having 6 to 14 carbon atoms, which is substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, phenoxy, benzyloxy, —NR3R4, —CO—NH—SO2—R5, —SO2—NH—CO—R5 or combinations thereof, wherein said aryl is substituted by at least one of benzyloxy, —NR3R4, —CO—NH—SO2—R5 or —SO2—NH—CO—R5,
arylalkyl having 7 to 16 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, phenoxy, benzyloxy, —NR3R4, —CO—NH—SO2—R5, —SO2—NH—CO—R5 or combinations thereof, wherein said arylalkyl is substituted by at least one of benzyloxy, —NR3R4, —CO—NH—SO2—R5, or —SO2—NH—CO—R5,
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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, —NR3R4, —CO—NH—SO2—R5, —SO2—NH—CO—R5 or combinations thereof, wherein said heteroaryl is substituted by at least one of morpholinyl, piperazinyl, —NR3R4, —CO—NH—SO2—R5, or —SO2—NH—CO—R5, 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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, —NR3R4, —CO—NH—SO2—R5, —SO2—NH—CO—R5 or combinations thereof, wherein said heteroarylalkyl is substituted by at least one of morpholinyl, piperazinyl, —NR3R4, —CO—NH—SO2—R5, or —SO2—NH—CO—R5;
R3 is cycloalkyl having 3 to 8 carbon atoms which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, C1-4 alkoxy, cyano or combinations thereof,
cycloalkylalkyl having 4 to 12 C atoms, which is unsubstituted or substituted one or more times by C1-4 alkyl, halogenated C1-4 alkyl, C1-4 alkoxy, cyano, halogen, or combinations thereof,
aryl having 6 to 14 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, or combinations thereof,
C1-4-alkylsulphonyl, or
C1-4-alkyl-CO—O—C1-4-alkylene;
R4 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
R5 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 —CH2— groups is each independently optionally replaced by —O—, —S—, or —NH—, and wherein optionally one or more —CH2CH2— 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, C1-4 alkyl, halogenated C1-4 alkyl, C1-4 alkoxy, cyano or combinations thereof,
cycloalkylalkyl having 4 to 12 C atoms, which is unsubstituted or substituted one or more times by C1-4 alkyl, halogenated C1-4 alkyl, C1-4 alkoxy, cyano, halogen, or combinations thereof,
aryl having 6 to 14 carbon atoms which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, phenoxy, benzyloxy, or combinations thereof,
arylalkyl having 7 to 16 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, phenoxy, benzyloxy, —NR3R4, 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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, —NR3R4, 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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C1-4-alkylamino, di-C1-4-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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, or combinations thereof;
or a pharmaceutically acceptable salt thereof.

24 more elements

A compound of Formula I′:

wherein,
R1is 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 —CH2—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;
R2 is aryl having 6 to 14 carbon atoms, which is substituted one or more times by halogen, C1-14 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, phenoxy, benzyloxy, —3R4, —CO—NH—SO2—R5 or combinations thereof, wherein said aryl is substituted by at least one of benzyloxy, or —3R4, 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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, —NR3R4 or combinations thereof, wherein said heteroaryl is substituted by at least one of morpholinyl, piperazinyl, and —NR3R4;
R3 is cycloalkyl having 3 to 8 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, C1-4 alkoxy, cyano or combinations thereof,
aryl having 6 to 14 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, or combinations thereof,
C1-4-alkylsulphonyl, or
C1-4-alkyl—CO—O—C1-4-alkylene;
R4 is H or alkyl having 1 to 4 carbon atoms which is straight chain or branched;
and
R5 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 —CH2— groups is each independently optionally replaced by —O—, —S—, or —NH, and wherein optionally one or more —CH2CH2— 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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, or combinations thereof;
or a pharmaceutically acceptable salt thereof.

15 more elements

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-trifluoromethyl-purine,
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-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)sulfonylamino-carbonylphenyl]-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 methane sulfonic acid salt,
and pharmaceutically acceptable salts thereof.

95 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/636,979Filed 8 Aug 2003 · us provisional application
Priority: 8 Aug 2002
Published: US 2007/0093510 A126 Apr 2007
Granted: 19 Feb 2008
Term ends: Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 473/34
Nitrogen atom: attached in position 6, e.g. adenine
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 11/00
Drugs for disorders of the respiratory system
A61P 25/00
Drugs for disorders of the nervous system

Family

Application60/401,765Us provisional application · filed 8 Aug 2002
US 2007/0093510 A1Pre-grant publication · published 26 Apr 2007
US 7,332,486 B2This patent

From the US filing history. Foreign family members aren’t listed.

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

A compound of Formula I:

wherein,
R1 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 —CH2— 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;
R2 is aryl having 6 to 14 carbon atoms, which is substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, phenoxy, benzyloxy, —NR3R4, —CO—NH—SO2—R5, —SO2—NH—CO—R5 or combinations thereof, wherein said aryl is substituted by at least one of benzyloxy, —NR3R4, —CO—NH—SO2—R5 or —SO2—NH—CO—R5,
arylalkyl having 7 to 16 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, phenoxy, benzyloxy, —NR3R4, —CO—NH—SO2—R5, —SO2—NH—CO—R5 or combinations thereof, wherein said arylalkyl is substituted by at least one of benzyloxy, —NR3R4, —CO—NH—SO2—R5, or —SO2—NH—CO—R5,
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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, —NR3R4, —CO—NH—SO2—R5, —SO2—NH—CO—R5 or combinations thereof, wherein said heteroaryl is substituted by at least one of morpholinyl, piperazinyl, —NR3R4, —CO—NH—SO2—R5, or —SO2—NH—CO—R5, 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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, —NR3R4, —CO—NH—SO2—R5, —SO2—NH—CO—R5 or combinations thereof, wherein said heteroarylalkyl is substituted by at least one of morpholinyl, piperazinyl, —NR3R4, —CO—NH—SO2—R5, or —SO2—NH—CO—R5;
R3 is cycloalkyl having 3 to 8 carbon atoms which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, C1-4 alkoxy, cyano or combinations thereof,
cycloalkylalkyl having 4 to 12 C atoms, which is unsubstituted or substituted one or more times by C1-4 alkyl, halogenated C1-4 alkyl, C1-4 alkoxy, cyano, halogen, or combinations thereof,
aryl having 6 to 14 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, or combinations thereof,
C1-4-alkylsulphonyl, or
C1-4-alkyl-CO—O—C1-4-alkylene;
R4 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
R5 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 —CH2— groups is each independently optionally replaced by —O—, —S—, or —NH—, and wherein optionally one or more —CH2CH2— 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, C1-4 alkyl, halogenated C1-4 alkyl, C1-4 alkoxy, cyano or combinations thereof,
cycloalkylalkyl having 4 to 12 C atoms, which is unsubstituted or substituted one or more times by C1-4 alkyl, halogenated C1-4 alkyl, C1-4 alkoxy, cyano, halogen, or combinations thereof,
aryl having 6 to 14 carbon atoms which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, phenoxy, benzyloxy, or combinations thereof,
arylalkyl having 7 to 16 carbon atoms, which is unsubstituted or substituted one or more times by halogen, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, nitro, methylenedioxy, ethylenedioxy, amino, C1-4 alkylamino, di-C1-4-alkylamino, C1-4-hydroxyalkyl, C1-4-hydroxyalkoxy, carboxy, cyano, —C(O)—NHOH, —C(O)—NH2, C2-4-alkanoyl, C2-4-alkoxycarbonyl, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, phenoxy, benzyloxy, —NR3R4, 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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, —C(O)—NHOH, —C(O)—NH2, C1-4-alkylthio, C1-4-alkylsulphinyl, C1-4-alkylsulphonyl, morpholinyl, piperazinyl, —NR3R4, 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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C1-4-alkylamino, di-C1-4-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, C1-4 alkyl, halogenated C1-4 alkyl, hydroxy, C1-4-alkoxy, halogenated C1-4 alkoxy, cyano, trifluoromethyl, nitro, oxo, amino, C1-4-alkylamino, di-C1-4-alkylamino, carboxy, alkoxycarbonyl, or combinations thereof;
or a pharmaceutically acceptable salt thereof.

24 more elements

Facts

Application

10/636,979Filed 8 Aug 2003 · us provisional application

Priority

8 Aug 2002

Published

US 2007/0093510 A126 Apr 2007

Granted

19 Feb 2008

Term ends

Not estimatedThe source records don’t support an estimate.

Classification19 codes

C07D 473/34
Nitrogen atom: attached in position 6, e.g. adenine
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 11/00
Drugs for disorders of the respiratory system
A61P 25/00
Drugs for disorders of the nervous system