THERAPEUTIC AGENT FOR GLAUCOMA CONTAINING ADENOSINE DERIVATIVE AS ACTIVE INGREDIENT

1 . A composition for treating glaucoma or ocular hypertension comprising a pharmacologically effective amount of a compound represented by the following formula (1) or a salt thereof as an active ingredient:

wherein

X represents CH or N;

R 1 represents a hydrogen atom, a hydroxy group, a halogen atom, an alkyl group, an alkoxy group, a cycloalkyl group, a cycloalkoxy group, a (cycloalkyl)alkoxy group, or

R 2 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkylcarbonyl group or an alkyloxycarbonyl group; and

R a and R b are the same or different and represent a hydrogen atom, a hydroxy group, a halogen atom, an alkyl group, an alkoxy group, a cycloalkyl group or a cycloalkoxy group, and a pharmacologically acceptable ophthalmic carrier.

2 . The composition according to claim 1 , wherein in the formula (1),

X represents CH or N;

R 1 represents a hydroxy group, an alkoxy group, a cycloalkoxy group, a (cycloalkyl)alkoxy group, or

R 2 represents an alkyl group or a cycloalkyl group; and

R a and R b are the same or different and represent a hydrogen atom, a halogen atom or an alkoxy group.

3 . The composition according to claim 1 , wherein in the formula (1),

X represents CH or N;

R 1 represents a methoxy group, an ethoxy group, an isopropoxy group, an isobutoxy group, a cyclobutoxy group, a (cyclopropyl)methoxy group, a 4-fluorophenyloxy group, a 2-methoxyphenyloxy group, a 4-methoxyphenyloxy group or a 3,4-difluorophenyloxy group; and

R 2 represents an ethyl group or a cyclopropyl group.

4 . The composition according to claim 1 , wherein the compound represented by the formula (1) is selected from the group consisting of

4-{(3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid methyl ester;

4-{(3-[6-amino-9-((2R,3R,4S,5S)-5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid methyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid isobutyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-cyclohexane-1-carboxylic acid methyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid ethyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid isopropyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid 4-fluorophenyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid 2-methoxyphenyl ester;

4-{3-[(6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid 4-methoxyphenyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid 3,4-difluorophenyl ester; and

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid cyclobutyl ester.

5 . The composition according to claim 1 , wherein the composition is in a dosage form which is an eye drop or an ophthalmic ointment.

6 . A method for treating glaucoma or ocular hypertension, comprising administering to a patient a pharmacologically effective amount of a compound represented by the following formula (1) or a salt thereof as an active ingredient to a patient:

wherein

X represents CH or N;

R 1 represents a hydrogen atom, a hydroxy group, a halogen atom, an alkyl group, an alkoxy group, a cycloalkyl group, a cycloalkoxy group, a (cycloalkyl)alkoxy group, or

R 2 represents a hydrogen atom, an alkyl group, a cycloalkyl group, an alkylcarbonyl group or an alkyloxycarbonyl group; and

R a and R b are the same or different and represent a hydrogen atom, a hydroxy group, a halogen atom, an alkyl group, an alkoxy group, a cycloalkyl group or a cycloalkoxy group.

7 . The method according to claim 6 , wherein in the formula (1),

X represents CH or N;

R 1 represents a hydroxy group, an alkoxy group, a cycloalkoxy group, a (cycloalkyl)alkoxy group, or

R 2 represents an alkyl group or a cycloalkyl group; and

R a and R b are the same or different and represent a hydrogen atom, a halogen atom, or an alkoxy group.

8 . The method according to claim 6 , wherein in the formula (1),

X represents CH or N;

R 1 represents a methoxy group, an ethoxy group, an isopropoxy group, an isobutoxy group, a cyclobutoxy group, a (cyclopropyl)methoxy group, a 4-fluorophenyloxy group, a 2-methoxyphenyloxy group, a 4-methoxyphenyloxy group or a 3,4-difluorophenyloxy group; and

R 2 represents an ethyl group or a cyclopropyl group.

9 . The method according to claim 6 , wherein the compound represented by the formula (1) is selected from the group consisting of

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid methyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid methyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid isobutyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-cyclohexane-1-carboxylic acid methyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid ethyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-ethylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid isopropyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid 4-fluorophenyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid 2-methoxyphenyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid 4-methoxyphenyl ester;

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid 3,4-difluorophenyl ester; and

4-{3-[6-amino-9-((2R,3R,4S,5S)-5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl]-2-propynyl}-piperidine-1-carboxylic acid cyclobutyl ester.

10 . The method according to claim 6 , wherein the compound is administered in a dosage form which is an eyedrop or an ophthalmic ointment.

11 - 16 . (canceled)

17 . The composition according to claim 2 , wherein the composition is in a dosage form which is an eyedrop or an ophthalmic solution.

18 . The composition according to claim 3 , wherein the composition is in a dosage form which is an eyedrop or an ophthalmic solution.

19 . The composition according to claim 4 , wherein the composition is in a dosage form which is an eyedrop or an ophthalmic solution.

20 . The method according to claim 7 , wherein the compound is administered in a dosage form which is an eyedrop or an ophthalmic ointment.

21 . The method according to claim 8 , wherein the compound is administered in a dosage form which is an eyedrop or an ophthalmic ointment.

22 . The method according to claim 9 , wherein the compound is administered in a dosage form which is an eyedrop or an ophthalmic ointment.