Remedies and/or preventives for diabetic ischemic heart diseases

1 . A method for therapeutic and/or prophylactic treatment of heart failure or arrhythmia in diabetic ischemic heart disease, which comprises administering to a patient in need thereof a therapeutically effective amount of an aminobenzenesulfonic acid derivative represented by the following general formula (I)

(wherein R 1 represents hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a C 1 -C 4 halogenated 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 alkoxy group, a halogen atom, a C 1 -C 6 alkyl group, and amino group; and n represents an integer of from 1 to 4, or a salt thereof, or a hydrate thereof, or a solvate thereof.

2 . The method according to claim 1 , characterized in that the diabetic ischemic heart disease is diabetic cardiomyopathy.

3 . The method according to claim 1 , characterized in that said derivative inhibits a leak of calcium ion from sarcoplasmic reticulum in the diabetic ischemic heart disease.

4 . A method for therapeutic and/or prophylactic treatment of a disease caused by a leak of calcium ion from sarcoplasmic reticulum, which comprises administering to a patient in need thereof a therapeutically effective amount of an aminobenzenesulfonic acid derivative represented by the following general formula (I)

(wherein R 1 represents hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a C 1 -C 4 halogenated 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 alkoxy group, a halogen atom, a C 1 -C 6 alkyl group, and amino group; and n represents an integer of from 1 to 4, or a salt thereof, or a hydrate thereof, or a solvate thereof.

5 . A method for therapeutic and/or prophylactic treatment of diabetic ischemic heart disease, which method improves a cardiac dysfunction in diabetic ischemic heart disease, and which comprises administering to a patient in need thereof a therapeutically effective amount of an aminobenzenesulfonic acid derivative represented by the following general formula (I)

(wherein R 1 represents hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a C 1 -C 4 halogenated 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 alkoxy group, a halogen atom, a C 1 -C 6 alkyl group, and amino group; and n represents an integer of from 1 to 4, or a salt thereof, or a hydrate thereof, or a solvate thereof.

6 . The method according to claim 5 , characterized in that the diabetic ischemic heart disease is diabetic cardiomyopathy.

7 . The method according to claim 5 , characterized in that the cardiac dysfunction is cardiac dysfunction resistant to acidosis.

8 . A method for therapeutic and/or prophylactic treatment of a disease caused by a cardiac dysfunction resistant to acidosis, which comprises administering to a patient in need thereof a therapeutically effective amount of an aminobenzenesulfonic acid derivative represented by the following general formula (I)

(wherein R 1 represents hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a C 1 -C 4 halogenated 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 alkoxy group, a halogen atom, a C 1 -C 6 alkyl group, and amino group; and n represents an integer of from 1 to 4, or a salt thereof, or a hydrate thereof, or a solvate thereof.

9 . The method according to any one of claims 1 , 4 , 5 or 8 , wherein the substitution position of R 1 is 5-position.

10 . The method according to any one of claims 1 , 4 , 5 or 8 , wherein n is 2.

11 . The method according to any one of claims 1 , 4 , 5 or 8 , 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 alkoxy group, and a halogen atom.

12 . The method according to any one of claims 1 , 4 , 5 or 8 , wherein R 2 is hydrogen atom 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 alkoxy group.

13 . The method according to any one of claims 1 , 4 , 5 or 8 , wherein R 2 is hydrogen atom.

14 . The method according to any one of claims 1 , 4 , 5 or 8 , 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.

15 . The method according to any one of claims 1 , 4 , 5 or 8 , wherein R 1 is a C 1 -C 3 alkyl group, cyclohexyl group, trifluoromethyl group, chlorine atom, bromine atom, or phenyl group.

16 . The method according to any one of claims 1 , 4 , 5 or 8 , wherein R 1 is methyl group or propyl group.

17 . The method according to any one of claims 1 , 4 , 5 or 8 , wherein the derivative 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; and

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

18 . The method according to claim 17 , wherein the derivative is selected from the following compounds: 5-methyl-2-(1-piperazinyl)benzenesulfonic acid; and 5-n-propyl-2-(1-piperazinyl)benzenesulfonic acid.

19 . The method according to any one of claims 1 , 4 , 5 or 8 , wherein the derivative is 5-methyl-2-(1-piperazinyl)benzenesulfonic acid monohydrate.

20 . A method for inhibiting a leak of calcium ion from sarcoplasmic reticulum in diabetic ischemic heart disease, which comprises administering to a patient in need thereof a therapeutically effective amount of an aminobenzenesulfonic acid derivative represented by the following general formula (I)

(wherein R 1 represents hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a C 1 -C 4 halogenated 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 alkoxy group, a halogen atom, a C 1 -C 6 alkyl group, and amino group; and n represents an integer of from 1 to 4, or a salt thereof, or a hydrate thereof, or a solvate thereof.

21 . A method for acidosis-resistant improvement of cardiac dysfunction in diabetic ischemic heart disease, which comprises administering to a patient in need thereof a therapeutically effective amount of an aminobenzenesulfonic acid derivative represented by the following general formula (I)

(wherein R 1 represents hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a C 1 -C 4 halogenated 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 alkoxy group, a halogen atom, a C 1 -C 6 alkyl group, and amino group; and n represents an integer of from 1 to 4, or a salt thereof, or a hydrate thereof, or a solvate thereof.

22 . The method according to claim 20 or 21 , wherein the substitution position of R 1 is 5-position.

23 . The method according to claim 20 or 21 , wherein n is 2.

24 . The method according to claim 20 or 21 , 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 alkoxy group, and a halogen atom.

25 . The method according to claim 20 or 21 , wherein R 2 is hydrogen atom, 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 alkoxy group.

26 . The method according to claim 20 or 21 , wherein R 2 is hydrogen atom.

27 . The method according to claim 20 or 21 , 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.

28 . The method according to claim 20 or 21 , wherein R 1 is a C 1 -C 3 alkyl group, cyclohexyl group, trifluoromethyl group, chlorine atom, bromine atom, or phenyl group.

29 . The method according to claim 20 or 21 , wherein R 1 is methyl group or propyl group.

30 . The method according to claim 20 or 21 , wherein the derivative 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; and

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

31 . The method according to claim 30 , wherein the derivative is selected from the following compounds:

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

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

32 . The method according to claim 20 or 21 , wherein the derivative is 5-methyl-2-(1-piperazinyl)benzenesulfonic acid monohydrate.