Inhibitors for excessive accumulation of sodium ion in cells

1 . A medicament for suppressing intracellular excess accumulation of sodium ions, which comprises, as an active ingredient, an aminobenzenesulfonic acid derivative represented by the following general formula (I) or a salt thereof, or a hydrate thereof or a solvate thereof:

wherein R 1 represents hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a halogenated C 1 -C 4 alkyl group, a halogen atom, or a C 6 -C 12 aryl group; R 2 represents hydrogen atom, a C 1 -C 6 alkyl group, or a C 7 -C 12 aralkyl group which may have one or more substituents selected from the group consisting of cyano group, nitro group, a C 1 -C 6 alkoxyl group, a halogen atom, a C 1 -C 6 alkyl group, and amino group; and n represents an integer of from 1 to 4.

2 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , which is used for therapeutic and/or preventive treatment of disorders resulting from ischemia and reperfusion.

3 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , which is characterized to suppress an increase of intracellular sodium content induced by ischemia and reperfusion.

4 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , wherein a substituting position R 1 is position-5.

5 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , wherein n is 2.

6 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , wherein R 2 is hydrogen atom, a C 1 -C 3 alkyl group, or a C 7 -C 12 aralkyl group which may have one or more substituents selected from the group consisting of a C 1 -C 3 alkyl group, a C 1 -C 3 alkoxyl group, and a halogen atom.

7 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , wherein R 2 is hydrogen atom or a C 7 -C 12 aralkyl group which may have one or more C 1 -C 3 alkoxyl groups.

8 . The medicament for suppressing intracellular excess accumulation of sodium ions according to any claim 1 , wherein R 2 is hydrogen atom.

9 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , wherein R 1 is hydrogen atom, a C 1 -C 6 alkyl group, a C 5 -C 6 cycloalkyl group, trifluoromethyl group, a halogen atom, or phenyl group.

10 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , wherein R 1 is a C 1 -C 3 alkyl group, cyclohexyl group, trifluoromethyl group, chlorine atom, bromine atom, or phenyl group.

11 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , wherein R 1 is methyl group or propyl group.

12 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , wherein the active ingredient is selected from the following compounds:

5-methyl-2-(1-piperazinyl)benzenesulfonic acid;

5-trifluoromethyl-2-(1-piperazinyl)benzenesulfonic acid;

5-n-propyl-2-(1-piperazinyl)benzenesulfonic acid;

5-phenyl-2-(1-piperazinyl)benzenesulfonic acid;

5-chloro-2-(1-piperazinyl)benzenesulfonic acid;

5-bromo-2-(1-piperazinyl)benzenesulfonic acid;

5-isopropyl-2-(1-piperazinyl)benzenesulfonic acid;

5-cyclohexyl-2-(1-piperazinyl)benzenesulfonic acid;

5-n-propyl-2-(1-homopiperazinyl)benzenesulfonic acid;

5-n-propyl-2-[4-(2,3,4-trimethoxybenzyl)-1-piperazinyl]benzenesulfonic acid;

5-n-propyl-2-[4-(3,4-dimethoxybenzyl)-1-piperazinyl]benzenesulfonic acid or a salt thereof, or a hydrate thereof or a solvate thereof.

13 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 12 , wherein the active ingredient is selected from the following compounds:

5-methyl-2-(1-piperazinyl)benzenesulfonic acid and 5-n-propyl-2-(1-piperazinyl)-benzenesulfonic acid

or a salt thereof, or a hydrate thereof or a solvate thereof.

14 . The medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 , wherein the active ingredient is 5-methyl-2-(1-piperazinyl)benzenesulfonic acid monohydrate.

15 . A medicament for therapeutic and/or preventive treatment of diseases caused by intracellular excess accumulation of sodium ions (provided that an ischemic heart disease, heart failure, hypertension, and arrhythmia are excluded), which comprises, as an active ingredient, the medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 .

16 . A medicament for therapeutic and/or preventive treatment of cardiovascular diseases caused by intracellular excess accumulation of calcium ions that occurs successively after intracellular excess accumulation of sodium ions, which comprises, as an active ingredient, the medicament for suppressing intracellular excess accumulation of sodium ions according to claim 1 .

17 . The therapeutic and/or preventive medicament according to claim 16 , wherein the cardiovascular diseases caused by intracellular excess accumulation of calcium ions that occurs successively after intracellular excess accumulation of sodium ions is an ischemic heart disease, heart failure, hypertension, or arrhythmia.

18 . The therapeutic and/or preventive medicament according to claim 17 , wherein the ischemic heart disease is myocardial infarct or angina pectoris.

19 . A medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations, which comprises, as an active ingredient, an aminobenzenesulfonic acid derivative represented by the following general formula (I) or a salt thereof, or a hydrate thereof or a solvate thereof:

wherein R 1 represents hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a halogenated C 1 -C 4 alkyl group, a halogen atom, or a C 6 -C 12 aryl group; R 2 represents hydrogen atom, a C 1 -C 6 alkyl group, or a C 7 -C 12 aralkyl group which may have one or more substituents selected from the group consisting of cyano group, nitro group, a C 1 -C 6 alkoxyl group, a halogen atom, a C 1 -C 6 alkyl group, and amino group; and n represents an integer of from 1 to 4.

20 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 19 , wherein a substituting position R 1 is position-5.

21 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 19 , wherein n is 2.

22 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 19 , wherein R 2 is hydrogen atom, a C 1 -C 3 alkyl group, or a C 7 -C 12 aralkyl group which may have one or more substituents selected from the group consisting of a C 1 -C 3 alkyl group, a C 1 -C 3 alkoxyl group, and a halogen atom.

23 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 19 , wherein R 2 is hydrogen atom or a C 7 -C 12 aralkyl group which may have one or more C 1 -C 3 alkoxyl groups.

24 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 19 , wherein R 2 is hydrogen atom.

25 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 19 , wherein R 1 is hydrogen atom, a C 1 -C 6 alkyl group, a C 5 -C 6 cycloalkyl group, trifluoromethyl group, a halogen atom, or phenyl group.

26 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 19 , wherein R 1 is a C 1 -C 3 alkyl group, cyclohexyl group, trifluoromethyl group, chlorine atom, bromine atom, or phenyl group.

27 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 19 , wherein R 1 is methyl group or propyl group.

28 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 19 , wherein the active ingredient is selected from the following compounds:

5-methyl-2-(1-piperazinyl)benzenesulfonic acid;

5-trifluoromethyl-2-(1-piperazinyl)benzenesulfonic acid;

5-n-propyl-2-(1-piperazinyl)benzenesulfonic acid;

5-phenyl-2-(1-piperazinyl)benzenesulfonic acid;

5-chloro-2-(1-piperazinyl)benzenesulfonic acid;

5-bromo-2-(1-piperazinyl)benzenesulfonic acid;

5-isopropyl-2-(1-piperazinyl)benzenesulfonic acid;

5-cyclohexyl-2-(1-piperazinyl)benzenesulfonic acid;

5-n-propyl-2-(1-homopiperazinyl)benzenesulfonic acid;

5-n-propyl-2-[4-(2,3,4-trimethoxybenzyl)-1-piperazinyl]benzenesulfonic acid;

5-n-propyl-2-[4-(3,4-dimethoxybenzyl)-1-piperazinyl]benzenesulfonic acid or a salt thereof, or a hydrate thereof or a solvate thereof.

29 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 28 , wherein the active ingredient is selected from the following compounds:

5-methyl-2-(1-piperazinyl)benzenesulfonic acid and 5-n-propyl-2-(1-piperazinyl)-benzenesulfonic acid

or a salt thereof, or a hydrate thereof or a solvate thereof.

30 . The medicament for therapeutic and/or preventive treatment of cardiac disorders resulting from cardiosurgery operations according to claim 19 , wherein the active ingredient is

5-methyl-2-(1-piperazinyl)benzenesulfonic acid monohydrate.