5-hydroxyindole-3-carboxylate derivatives and uses thereof

1. A compound of formula I, or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof:

wherein:

R 1 is H, C 1 -C 6 alkyl, or C 3 -C 7 cycloalkyl, wherein said alkyl and cycloalkyl are optionally substituted with 1 to 2 substituents selected from the group consisting of hydroxyl, nitro, halo, cyano, trifluoromethyl and trifluoromethoxy;

R 2 is C 1 -C 6 alkyl, wherein the alkyl is optionally substituted with 1 to 2 substituents selected from the group consisting of hydroxyl, nitro, halo, cyano, trifluoromethyl and trifluoromethoxy;

X is H, nitro, halo, cyano, trifluoromethyl or trifluoromethoxy;

Y is —NR 3 R 4 ;

Z is

or

wherein p represents an integer from 0 to 4, q represents the integer 0 or 1, and when p represents the integer 0, q represents the integer 0;

R 3 and R 4 are covalently bonded together with the nitrogen to which they are attached to form guanidyl, 5- to 10-membered heterocyclic radical or 5- to 10-membered heteroaryl radical, wherein except for the nitrogen atom to which R 3 and R 4 are attached, said heterocyclic and heteraryl radicals may have optionally 1 to 4 heteroatoms selected from N, O or S, and wherein except for the nitrogen atom to which R 3 and R 4 are attached, said heterocyclic radical may optionally have 1 to 2 carbon-carbon double bond or triple bond, said heterocyclic and heteroaryl radicals can be optionally substituted with 1 to 3 same or different R 8 ;

Ar 2 represents C 6 -C 10 aryl, 5- to 10-membered heteroaryl radical or 5- to 10-membered heterocyclic radical, wherein said heteroaryl and heterocyclic radicals can have 1 to 3 heteroatoms selected from N, O or S and Ar 2 can be optionally substituted with 1 to 3 same or different R 9 ;

R 8 represents C 1 -C 4 alkyl, C 1 -C 4 alkoxyl, halo, hydroxyl, cyano, carboxyl, ester group or nitro; and

R 9 represents C 1 -C 6 alkyl, C 1 -C 6 alkoxyl, hydroxyl, C 1 -C 6 alkyl or C 1 -C 6 alkoxyl which is optionally substituted with hydroxyl, amino or halo, C 1 -C 6 alkylsulfanyl, carboxyl group which can be free or form ester group, amide, or salts, halo, C 1 -C 6 alkylacyl, nitro, cyano, amino, C 1 -C 6 alkylamide group, or amine group substituted with (C 1 -C 6 alkyl) n , where n is 1 or 2.

2. The compound of formula I, or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof according to claim 1 , wherein:

X is H, or halo; and

Ar 2 represents C 6 -C 10 aryl or 5- to 10-membered heteroaryl radical.

3. The compound of formula I, or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof according to claim 2 , wherein:

R 1 is H, C 1 -C 4 alkyl or C 3 -C 7 cycloalkyl;

R 2 is C 1 -C 4 alkyl; and

Ar 2 represents C 6 -C 10 aryl or C 5 -C 10 heteroaryl, wherein the heteroaryl may contain 1 to 2 heteroatom(s) selected from N, O or S.

4. The compound of formula I, or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof according to claim 3 , wherein:

R 1 is C 1 -C 4 alkyl or C 3 -C 7 cycloalkyl;

R 3 and R 4 are covalently bonded together with the nitrogen to which they are attached to form guanidyl, 5- to 6-membered heterocyclic radical or 5- to 6-membered heteroaryl radical, wherein except for the nitrogen atom to which R 3 and R 4 are attached, said heterocyclic and heteroaryl radicals may have optionally 1 to 4 heteroatoms selected from N, O or S, and wherein said heterocyclic and heteroaryl radicals can be optionally substituted with 1 to 3 same or different R 8 ; and

Ar 2 represents phenyl, substituted phenyl or 5- to 6-membered heteroaryl, wherein said heteroaryl radical may have 1 to 2 heteroatoms selected from N, O or S and Ar 2 can be optionally substituted with 1 to 3 same or different R 9 .

5. The compound of formula I, or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof according to claim 4 , wherein:

R 1 is methyl, ethyl, propyl, isopropyl, or cyclopropyl;

Y is —NR 3 R 4 ; and

Z is

or

wherein p represents an integer from 0 to 2, q represents the integer 0 or 1, and when p is 0, q is 0;

R 3 and R 4 are covalently bonded together with the nitrogen to which they are attached to form guanidyl, 4-morpholino, 4-methyl-1-piperazinyl, 1-piperidino, 1-pyrrolidinyl, 1H-1,2,4-triazol-1-yl, 1-imidazolyl, 2-methyl-1-imidazolyl or 1H-tetrazol-1-yl.

6. The compound of formula I, or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof according to claim 5 , wherein:

Z is

or

wherein p represents the integer from 0 to 2 and q represents the integer 0;

R 3 and R 4 are covalently bonded together with the nitrogen to which they are attached to form guanidyl, 4-morpholino, 4-methyl-1-piperazinyl, 1-piperidino, 1-pyrrolidinyl, 1H-1,2,4-triazol-1-yl, 1-imidazolyl, 2-methyl-1-imidazolyl or 1H-tetrazol-1-yl; and

Ar 2 represents phenyl or phenyl optionally substituted with 1 to 3 same or different R 9 .

7. The compound of formula I, or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof according to claim 1 , wherein:

Ar 2 represents phenyl, substituted phenyl or 5- to 6-membered heteroaryl, wherein the heteroaryl and heterocyclic radicals may contain 1 to 3 heteroatoms selected from N, O or S and Ar 2 can be optionally substituted with 1 to 3 same or different R 9 .

8. The compound of formula I, or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof according to claim 7 , wherein:

Ar 2 represents phenyl or phenyl group substituted with 1 to 3 halo.

9. The compound of formula I, or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof according to claim 1 , wherein:

X is H, or bromine.

10. A compound or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof according to claim 1 , selected from the group consisting of:

Ethyl 6-bromo-5-hydroxy-1-methyl-2-[(2-methylphenyl)sulfinylmethyl]-4-(morpholinomethyl)-1H-indole-3-carboxylate;

Ethyl 6-bromo-2-[(4-fluorophenyl)sulfinylmethyl]-5-hydroxy-1-methyl-4-(morpholinomethyl)-1H-indole-3-carboxylate;

Ethyl 6-bromo-2-[(3-chlorophenyl)sulfinylmethyl]-5-hydroxy-1-methyl-4-(morpholinomethyl)-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-(morpholinomethyl)-2-[(4-fluorobenzyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-2-[(3,4-difluorophenyl)sulfinylmethyl]-5-hydroxy-4-[(4-methyl-1-piperazinyl)methyl]-1H-indole-3-carboxylate dihydrochloride;

Ethyl 6-bromo-2-[(2-furylmethyl)sulfinylmethyl]-5-hydroxy-1-methyl-4-(1-pyrrolidinylmethyl)-1H-indole-3-carboxylate;

Ethyl 5-hydroxy-2-[(3-methoxyphenyl)sulfonylmethyl]-1-methyl-4-(1-pyrrolidinylmethyl)-1H-indole-3-carboxylate;

Ethyl 2-[(3-furylmethyl)sulfinylmethyl]-5-hydroxy-1-methyl-4-(piperidinomethyl)-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-(1-pyrrolidinylmethyl)-2-[(4-trifluoromethylphenyl)sulfonylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-5-hydroxy-4-(1-pyrrolidinylmethyl)-2-[(3-trifluoromethylphenyl)sulfonylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-(1-pyrrolidinylmethyl)-2-[(4-fluorobenzyl)sulfonylmethyl]-1H-indole-3-carboxylate;

Ethyl 1-cyclopropyl-5-hydroxy-4-(1-pyrrolidinylmethyl)-2-[(2-furylmethyl)sulfonylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-(1-piperidinomethyl)-2-[(4-fluorobenzyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-2-[(3-fluorobenzyl)sulfinylmethyl]-5-hydroxy-1-methyl-4-(4-morpholinomethyl)-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-4-[(1-imidazolyl)methyl]-1-methyl-2-(phenylsulfinylmethyl)-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-5-hydroxy-4-(1-imidazolylmethyl)-2-[(4-fluorophenyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-2-[(3,4-difluorophenyl)sulfinylmethyl]-5-hydroxy-4-(1-imidazolylmethyl)-1H-indole-3-carboxylate;

Ethyl 6-bromo-2-[(4-fluorophenyl)sulfinylmethyl]-5-hydroxy-4-[(1-imidazolyl)methyl]-1-methyl-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-4-[(1-imidazolyl)methyl]-1-methyl-2-[(2-fluorophenyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 2-(benzylsulfinylmethyl)-6-bromo-1-cyclopropyl-5-hydroxy-4-[(1-imidazolyl)methyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-5-hydroxy-4-[(1-imidazolyl)methyl]-2-[(4-thiazolylmethyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-5-hydroxy-4-[(1-imidazolyl)methyl]-2-[(2-furylmethyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-[(2-methyl-1-imidazolyl)methyl]-2-[(3,4-difluorophenyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-[(2-methyl-1-imidazolyl)methyl]-2-[(3-methylphenyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-[(2-methyl-1-imidazolyl)methyl]-2-[(2-methoxyphenyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-2-[(2,6-dichlorophenyl)sulfinylmethyl]-5-hydroxy-4-[(2-methyl-1-imidazolyl)methyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-2-[(4-fluorophenyl)sulfinylmethyl]-5-hydroxy-4-[(2-methyl-1-imidazolyl)methyl]-1H-indole-3-carboxylate;

Ethyl 5-hydroxy-1-methyl-4-[(2-methyl-1-imidazolyl)methyl]-2-[(4-methylphenyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-2-(phenylsulfinylmethyl)-4-[(1H-1,2,4-triazol-1-yl)methyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-[(1H-1,2,4-triazol-1-yl)methyl]-2-[(4-fluorobenzyl)sulfinylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-5-hydroxy-4-[(1-imidazolyl)methyl]-[2-(2-furylmethyl)sulfonylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-4-[(1-imidazolyl)methyl]-1-methyl-2-[(4-fluorobenzyl)sulfonylmethyl]-1H-indole-3-carboxylate;

Ethyl 1-cyclopropyl-5-hydroxy-4-[(1-imidazolyl)methyl]-2-[(4-methylphenyl)sulfonylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-5-hydroxy-4-[(2-methyl-1-imidazolyl)methyl]-2-[(2-fluorobenzyl)sulfonylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-[(2-methyl-1-imidazolyl)methyl]-2-(phenylsulfonylmethyl)-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-[(2-methyl-1-imidazolyl)methyl]-2-(benzylsulfonylmethyl)-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-4-[(1-imidazolyl)methyl]-1-methyl-2-[(4-trifluoromethylphenyl)sulfinyl-methyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-5-hydroxy-4-[(2-methyl-1-imidazolyl)methyl]-2-(benzylsulfonylmethyl)-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-[(2-methylimidazolyl)methyl]-2-[(1-adamantanyl)sulfonylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-[(2-methyl-1-imidazolyl)methyl]-2-[(4-trifluoromethylphenyl)sulfonylmethyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-1-cyclopropyl-5-hydroxy-4-[(2-methyl-1-imidazolyl)methyl]-2-[(4-thiazolylmethyl)sulfinylmethyl]-1H-indole-3-carboxylate hydrochloride;

Ethyl 6-bromo-1-cyclopropyl-5-hydroxy-4-[(2-methyl-1-imidazolyl)methyl]-2-[(2-fluorobenzyl)sulfinyl methyl]-1H-indole-3-carboxylate;

Ethyl 6-bromo-5-hydroxy-1-methyl-4-[(2-methyl-1-imidazolyl)methyl]-2-[(4-fluorobenzyl)sulfinylmethyl]-1H-indole-3-carboxylate; and

Ethyl 6-bromo-5-hydroxy-1-methyl-4-[(2-methyl-1-imidazolyl)methyl]-2-[(4-fluorobenzyl)sulfonylmethyl]-1H-indole-3-carboxylate.

11. A pharmaceutical composition, comprising the compound or racemic mixture or optical isomers or pharmaceutically acceptable salts thereof according to claim 1 as active ingredient and pharmaceutically acceptable excipient.