Substituted isoquinoline derivative

1. An isoquinoline-6-sulfonamide compound of Formula (1), a salt thereof, or a solvate of the compound or the salt:

wherein

X and Y each independently is a direct bond, NH, CH═CH, O, or S;

R 1 and R 2 each independently is a hydrogen atom, a halogen atom, a cyano group, an alkyl group, a halogenoalkyl group, an alkenyl group, an alkoxy group, an alkylthio group, a hydroxyl group, a mercapto group, a nitro group, an aryl group, an amino group, or an aminoalkylthio group;

R 3 and R 4 each independently is a hydrogen atom, an alkyl group, an alkenyl group, an amino group, an alkylamino group, a dialkylamino group, an aminoalkyl group, a halogenoalkyl group, an alkanoyl group, an aminoalkanoyl group, an alkylaminoalkanoyl group, an alkoxycarbonyl group, a hydroxyl group, or a mercapto group, or R 3 and R 4 together form an alkylene group or an alkenylene group, which may be bridged between two carbon atoms to an arbitrary position; and

l, m, and n represent an integer number of 1 to 4.

2. The compound, salt, or solvate of claim 1 , wherein in Formula (1),

X and Y are each independently a direct bond, NH, CH═CH, O, or S;

R 1 and R 2 are each independently a hydrogen atom, a halogen atom, a cyano group, a C 1-3 alkyl group, a halogeno C 1-8 alkyl group, a C 2-8 alkenyl group, a C 1-8 alkoxy group, a C 1-8 alkylthio group, a hydroxyl group, a mercapto group, a nitro group, a phenyl group, an amino group, or an amino C 1-8 alkylthio group;

R 3 and R 4 are each independently a hydrogen atom, a C 1-8 alkyl group, a C 2-8 alkenyl group, an amino group, an amino C 1-8 alkyl group, a halogeno C 1-8 alkyl group, a C 1-8 alkylamino group, a di-C 1-8 alkylamino group, a C 2-8 alkanoyl group, an amino C 2-8 alkanoyl group, a C 1-8 alkoxycarbonyl group, a hydroxyl group, or a mercapto group, or R 3 and R 4 together form a bridged C 1-3 alkylene group or alkenylene group;

l and m are each independently 1 to 3; and

n is 2 or 3.

3. The compound, salt, or solvate of claim 1 , wherein in Formula (1),

X is a direct bond or NH;

Y is a direct bond, NH, CH═CH, or O;

R 1 and R 2 are each independently a hydrogen atom, a halogen atom, a C 1-8 alkyl group, a nitro group, a cyano group, a hydroxyl group, a halogeno C 1-8 alkyl group, a phenyl group, or an amino C 1-8 alkylthio group;

R 3 and R 4 are a hydrogen atom, a C 1-8 alkyl group, an amino group, a C 1-8 alkylamino group, an amino C 1-8 alkyl group, a halogeno C 1-8 alkyl group, an amino C 1-8 alkanoyl group, a C 1-8 alkylamino group, or a C 1-8 alkanoyl group, or R 3 and R 4 together form a bridged C 1-3 alkylene group;

l and m are each independently 1 to 3; and

n is 2 or 3.

4. The compound, salt, or solvate of claim 1 , wherein in Formula (1),

X is a direct bond or NH;

Y is a direct bond, NH, CH═CH, or O;

R 1 and R 2 are each independently a hydrogen atom, a halogen atom, a nitro group, an aminoalkylthio group, a C 1-6 alkyl group, or a halogeno C 1-6 alkyl group;

R 3 and R 4 are a hydrogen atom, a C 1-6 alkyl group, a halogeno C 1-6 alkyl group, an amino group, a C 1-8 alkylamino group, or an amino C 1-8 alkanoyl group, or R 3 and R 4 together form a bridged C 1-3 alkylene group;

l and m are each independently 1 to 3; and

n is 2 or 3.

5. The compound, salt, or solvate of claim 1 , wherein in Formula (1),

X is a direct bond or NH;

Y is a direct bond, CH═CH, or O;

R 1 and R 2 are each independently a hydrogen atom, a halogen atom, an aminoalkylthio group, or a C 1-6 alkyl group;

R 3 and R 4 are a hydrogen atom, a C 1-6 alkyl group, a halogeno C 1-6 alkyl group, or an amino group, or R 3 and R 4 together form a bridged C 1-3 alkylene group;

l and m are each independently 1 to 3; and

n is 2 or 3.

6. A compound selected from the group consisting of the following, a salt thereof, or a solvate thereof:

6-(piperazin-1-ylsulfonyl)isoquinoline,

(R)-6-(3-aminopyrrolidin-1-ylsulfonyl)isoquinoline,

6-(1,4-diazepan-1-ylsulfonyl)isoquinoline,

6-(4-aminopiperidin-1-ylsulfonyl)isoquinoline,

5-bromo-6-(1,4-diazepan-1-ylsulfonyl)isoquinoline,

6-(1,4-diazepan-1-ylsulfonyl)-8-fluoroisoquinoline,

6-{(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-ylsulfonyl}isoquinoline,

(R,Z)-6-(2-methyl-2,3,4,5-tetrahydro-1,4-diazocin-1 (8H)-ylsulfonyl)isoquinoline,

6-(morpholin-1-ylsulfonyl)isoquinoline,

(S)-6-{3-(N-methylamino)pyrrolidin-1-ylsulfonyl}isoquinoline,

(S)-6-{3-(N-butylamino)pyrrolidin-1-ylsulfonyl}isoquinoline,

(S)-6-(2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(S)-6-(2-methylpiperazin-1-ylsulfonyl)isoquinoline,

(R)-6-(2-methyl-1,4-diazocan-1-ylsulfonyl)isoquinoline,

(S)-5-bromo-6-(2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

6-(3-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

6-(7-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-6-(2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-6-(2-ethyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-6-(2-ethyl-1,4-diazocan-1-ylsulfonyl)isoquinoline,

6-(1,4-diazocan-1-ylsulfonyl)isoquinoline,

6-(2,2-dimethyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-5-bromo-6-(2-methyl-1,4-diazocan-1-ylsulfonyl)isoquinoline,

(S)-6-(2-methyl-1,4-diazocan-1-ylsulfonyl)isoquinoline,

(R)-6-(2-methyl-1,4-diazepan-1-ylsulfonyl)-7-fluoroisoquinoline,

(S)-6-(2-fluoromethyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(S)-6-(2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-5-bromo-6-(2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-6-(6-methyl-1,4-diazocan-1-ylsulfonyl)isoquinoline,

(R)-6-(7-methyl-1,4-diazocan-1-ylsulfonyl)isoquinoline,

(S)-6-(7-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-6-(2-methyl-1,4-diazonan-1-ylsulfonyl)isoquinoline,

(R)-6-(7-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(2R,7R)-6-(2,7-dimethyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(2S,7R)-6-(2,7-dimethyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-6-(8-methyl-1,4-diazocan-1-ylsulfonyl)isoquinoline,

(R)-6-(2-methyl-1,5-diazocan-1-ylsulfonyl)isoquinoline,

(R)-6-(2-methyl-1,4-diazocan-1-ylsulfonyl)-5-nitroisoquinoline,

(2R,6R)-6-(2,6-dimethylpiperazin-1-ylsulfonyl)isoquinoline,

(2S,7S)-6-(2,7-dimethyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(S)-6-(2-methyl-1,5-diazocan-1-ylsulfonyl)isoquinoline,

(R)-6-(5-methyl-1,4,7-oxadiazonan-4-ylsulfonyl)isoquinoline,

(R)-6-(2-methyl-1,4,7-triazonan-1-ylsulfonyl)isoquinoline,

6-(4-glycyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(S)-6-(4-glycyl-2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-6-(4-glycyl-2-methyl-1,4-diazocan-1-ylsulfonyl)isoquinoline,

(R)-6-(4-sarkosyl-2-methyl-1,4-diazocan-1-ylsulfonyl)isoquinoline,

(S)-5-methyl-6-(2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(S)-1-(2-aminoethylthio)-6-(2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-1-(2-aminoethylthio)-6-(7-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline,

(R)-1-(2-aminoethylthio)-6-(2-methyl-1,4-diazocan-1-ylsulfonyl)isoquinoline,

6-(1,4-diazepan-1-ylsulfonyl)isoquinolin-1(2H)-one,

1-amino-6-(1,4-diazepan-1-ylsulfonyl)isoquinoline,

1-nitrile-6-(1,4-diazepan-1-ylsulfonyl)isoquinoline,

(S)-6-(2-(4-aminobutyl)-1,4-diazepin-1-ylsulfonyl)isoquino line,

6-(4-methoxycarbonylpiperidin-1-ylsulfonyl)isoquinoline,

(S)-6-(3-hydroxypyrrolidin-1-ylsulfonyl)isoquinoline, and

5-phenyl-6-(1,4-diazepan-1-ylsulfonyl)isoquinoline.

7. A pharmaceutical composition, comprising:

the compound, salt, or solvate of claim 1 ; and

a diluent.

8. A method for treating glaucoma, hypertension, or spinal cord injury the method comprising:

administering an effective amount of a composition comprising the compound, salt, or solvate of claim 1 .

9. The compound, salt, or solvate of claim 2 , wherein in Formula (1),

X is a direct bond or NH;

Y is a direct bond, NH, CH═CH, or O;

R 1 and R 2 are each independently a hydrogen atom, a halogen atom, a C 1-8 alkyl group, a nitro group, a cyano group, a hydroxyl group, a halogeno C 1-8 alkyl group, a phenyl group, or an amino C 1-8 alkylthio group;

R 3 and R 4 are a hydrogen atom, a C 1-8 alkyl group, an amino group, a C 1-8 alkylamino group, an amino C 1-8 alkyl group, a halogeno C 1-8 alkyl group, an amino C 1-8 alkanoyl group, a C 1-8 alkylamino group, or a C 1-8 alkanoyl group, or R 3 and R 4 together form a bridged C 1-3 alkylene group;

l and m are each independently 1 to 3; and

n is 2 or 3.

10. The compound, salt, or solvate of claim 2 , wherein in Formula (1),

X is a direct bond or NH;

Y is a direct bond, NH, CH═CH, or O;

R 1 and R 2 are each independently a hydrogen atom, a halogen atom, a nitro group, an aminoalkylthio group, a C 1-6 alkyl group, or a halogeno C 1-6 alkyl group;

R 3 and R 4 are a hydrogen atom, a C 1-6 alkyl group, a halogeno C 1-6 alkyl group, an amino group, a C 1-8 alkylamino group, or an amino C 1-8 alkanoyl group, or R 3 and R 4 together form a bridged C 1-3 alkylene group;

l and m are each independently 1 to 3; and

n is 2 or 3.

11. The compound, salt, or solvate of claim 3 , wherein in Formula (1),

X is a direct bond or NH;

Y is a direct bond, NH, CH═CH, or O;

R 1 and R 2 are each independently a hydrogen atom, a halogen atom, a nitro group, an aminoalkylthio group, a C 1-6 alkyl group, or a halogeno C 1-6 alkyl group;

R 3 and R 4 are a hydrogen atom, a C 1-6 alkyl group, a halogeno C 1-6 alkyl group, an amino group, a C 1-8 alkylamino group, or an amino C 1-8 alkanoyl group, or R 3 and R 4 together form a bridged C 1-3 alkylene group;

l and m are each independently 1 to 3; and

n is 2 or 3.

12. The compound, salt, or solvate of claim 2 , wherein in Formula (1),

X is a direct bond or NH;

Y is a direct bond, CH═CH, or O;

R 1 and R 2 are each independently a hydrogen atom, a halogen atom, an aminoalkylthio group, or a C 1-6 alkyl group;

R 3 and R 4 are a hydrogen atom, a C 1-6 alkyl group, a halogeno C 1-6 alkyl group, or an amino group, or R 3 and R 4 together form a bridged C 1-3 alkylene group;

l and m are each independently 1 to 3; and

n is 2 or 3.

13. The compound, salt, or solvate of claim 3 , wherein in Formula (1),

X is a direct bond or NH;

Y is a direct bond, CH═CH, or O;

R 1 and R 2 are each independently a hydrogen atom, a halogen atom, an aminoalkylthio group, or a C 1-6 alkyl group;

R 3 and R 4 are a hydrogen atom, a C 1-6 alkyl group, a halogeno C 1-6 alkyl group, or an amino group, or R 3 and R 4 together form a bridged C 1-3 alkylene group;

l and m are each independently 1 to 3; and

n is 2 or 3.

14. The compound, salt, or solvate of claim 4 , wherein in Formula (1),

X is a direct bond or NH;

Y is a direct bond, CH═CH, or O;

R 1 and R 2 are each independently a hydrogen atom, a halogen atom, an aminoalkylthio group, or a C 1-6 alkyl group;

R 3 and R 4 are a hydrogen atom, a C 1-6 alkyl group, a halogeno C 1-6 alkyl group, or an amino group, or R 3 and R 4 together form a bridged C 1-3 alkylene group;

l and m are each independently 1 to 3; and

n is 2 or 3.