Glutamate derivatives or salts thereof

1. A glutamate compound represented by formula (I):

wherein:

R 1 , R 2 , R 3 , R 4 and R 5 each independently represents a group selected from hydrogen atom, a halogeno group, hydroxyl group, nitro group, amino group, a C 1-6 alkyl group which may have a substituent(s), a C 1-6 alkoxy group which may have a substituent(s), a mono- or di-C 1-6 alkylamino group which may have a substituent(s), sulfo group, and a group:

provided that at least one of R 1 , R 2 and R 3 is sulfo group or a group selected from:

R 6 is hydrogen atom, hydroxyl group or a C 1-6 alkyl group which may have a substituent(s);

R 7 is hydrogen atom or a C 1-6 alkyl group which may have a substituent(s);

X is methylene group or oxygen atom; and,

E is a C 1-6 alkoxy group which may have a substituent(s), a mercapto group which may have a substituent(s), or a group:

wherein in formula (IIb), Z represents a divalent C 1-6 hydrocarbon group which may have a substituent(s) and E 2 represents hydrogen atom or a C 1-6 alkyl group;

provided that:

when E is methoxy group, ethoxy group or benzyloxy group and X is methylene group, in a group:

R 7 is not methyl group, ethyl group or benzyl group:

and,

when E is butoxy group and X is methylene group, in a group:

R 7 does not represent a group:

or a pharmaceutically acceptable salt thereof.

2. A glutamate compound represented by formula (I):

wherein:

R 1 , R 2 , R 3 , R 4 and R 5 each independently represents a group selected from hydrogen atom, a halogeno group, hydroxyl group, nitro group, amino group, a C 1-6 alkyl group which may have a substituent(s), a C 1-6 alkoxy group which may have a substituent(s) or a mono- or di-C 1-6 alkylamino group which may have a substituent(s), sulfo group, and a group:

provided that at least one of R 1 , R 2 and R 3 is sulfo group or a group selected from:

R 6 is hydrogen atom, hydroxyl group or a C 1-6 alkyl group which may have a substituent(s);

R 7 is hydrogen atom or a C 1-6 alkyl group which may have a substituent(s);

X is methylene group or oxygen atom; and,

E is a C 1-6 alkoxy group which may have a substituent(s), a mercapto group which may have a substituent(s), or a group;

wherein in formula (IIb), Z represents a divalent C 1-6 hydrocarbon group which may have a substituent(s) and E 2 represents hydrogen atom or a C 1-6 alkyl group;

provided that:

(i) when X is methylene group, R 3 is a carboxylic acid group and R 1 , R 2 , R 4 , R 5 and R 6 are hydrogen atom, then, E is not methoxy group;

(ii) when X is methylene group, R 2 is a carboxylic acid group, R 5 is fluorine atom and R 1 , R 3 , R 4 and R 6 are hydrogen atom, then, E is not methoxy group; and,

(iii) when E is methoxy group, ethoxy group or benzyloxy group and X is methylene group, then, in a group:

R 7 is not methyl group, ethyl group or benzyl group; and,

when E is butoxy group and X is methylene group, in a group:

R 7 is not a group:

or a pharmaceutically acceptable salt thereof.

3. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according to any one of claims 1 and 2 , wherein:

E is a C 1-6 alkoxy group or a group:

-0Z-E 1   (IIa)

wherein in formula (IIa), Z represents a divalent C 1-6 hydrocarbon group which may have a substituent(s), E 1 represents a C 1-6 acyloxy group which may have a substituent(s), a C 1-6 alkoxycarbonyloxy group which may have a substituent(s), an amino group which may have a substituent(s), carboxyl group, a C 1-6 alkoxycarbonyl group which may have a substituent(s), a halogen atom, an aryl group, a heteroaryl group, a C 1-6 alkoxy group which may have a substituent(s) or a carbamoyl group which may have a substituent(s), or Z and E 1 may be combined together to form a ring.

4. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 1 , R 3 , R 4 and R 5 each independently represents a group selected from hydrogen atom, a halogeno group, hydroxyl group, nitro group, amino group, a C 1-6 alkyl group which may have a substituent(s), a C 1-6 alkoxy group which may have a substituent(s), and a mono- or di-C 1-6 alkylamino group which may have a substituent(s):

R 2 represents sulfo group or a group selected from:

and,

R 6 and R 7 each independently represents hydrogen atom or methyl group.

5. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 1 , R 3 , R 4 and R 5 each independently represents a group selected from hydrogen atom, a halogeno group, hydroxyl group, nitro group, amino group, a C 1-3 alkyl group which may have a substituent(s), a C 1-3 alkoxy group which may have a substituent(s), and a mono- or di-C 1-3 alkylamino group which may have a substituent(s):

R 2 is sulfo group or a group selected from:

and,

R 6 and R 7 each independently represents hydrogen atom or methyl group.

6. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according to claim 1 , wherein:

R 1 , R 3 , R 4 and R 5 each independently represents a group selected from hydrogen atom, chloro or bromo group, hydroxyl group, nitro group, amino group, methyl group and methoxy group;

R 2 is sulfo group or a group selected from:

R 6 is hydrogen atom or methyl group;

R 7 is hydrogen atom; and,

X is methylene group.

7. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 2 is sulfo group, a carboxylic acid group or a phosphonic acid group.

8. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according to claim 7 , wherein R 4 is a halogeno group.

9. A pharmaceutical composition, comprising a glutamate compound or pharmaceutically acceptable salt thereof, according to claim 1 .

10. A method for agonizing CaSR activity, comprising contacting CaSR with a glutamate compound

or a pharmaceutically acceptable salt thereof according to claim 1 .

11. The method according to claim 10 , wherein in formula (I):

E is a C 1-6 alkoxy group which may have a substituent(s), and said group is a group:

-0Z-E 1   (IIa)

wherein in formula (IIa), Z represents a divalent C 1-6 hydrocarbon group which may have a substituent(s), E 1 represents a C 1-6 acyloxy group which may have a substituent(s), a C 1-6 alkoxycarbonyloxy group which may have a substituent(s), an amino group which may have a substituent(s), carboxyl group, a C 1-6 alkoxycarbonyl group which may have a substituent(s), a halogen atom, an aryl group, a heteroaryl group, a C 1-6 alkoxy group which may have a substituent(s) or a carbamoyl group which may have a substituent(s), or Z and E 1 may be combined together to form a ring.

12. The pharmaceutical composition according to claim 9 , which is a therapeutic agent for diseases improved by CaSR activation.

13. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according claim 2 , wherein:

R 1 , R 3 , R 4 and R 5 each independently represents a group selected from hydrogen atom, a halogeno group, hydroxyl group, nitro group, amino group, a C 1-6 alkyl group which may have a substituent(s), a C 1-6 alkoxy group which may have a substituent(s), and a mono- or di-C 1-6 alkylamino group which may have a substituent(s):

R 2 represents sulfo group or a group selected from:

and,

R 6 and R 7 each independently represents hydrogen atom or methyl group.

14. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according to claim 2 , wherein:

R 1 , R 3 , R 4 and R 5 each independently represents a group selected from hydrogen atom, a halogeno group, hydroxyl group, nitro group, amino group, a C 1-3 alkyl group which may have a substituent(s), a C 1-3 alkoxy group which may have a substituent(s), and a mono- or di-C 1-3 alkylamino group which may have a substituent(s):

R 2 is sulfo group or a group selected from:

and,

R 6 and R 7 each independently represents hydrogen atom or methyl group.

15. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according to claim 2 , wherein:

R 1 , R 3 , R 4 and R 5 each independently represents a group selected from hydrogen atom, chloro or bromo group, hydroxyl group, nitro group, amino group, methyl group and methoxy group;

R 2 is sulfo group or a group selected from:

R 6 is hydrogen atom or methyl group;

R 7 is hydrogen atom; and,

X is methylene group.

16. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according to claim 2 , wherein R 2 is sulfo group, a carboxylic acid group or a phosphonic acid group.

17. The glutamate compound of formula (I) or pharmaceutically acceptable salt thereof, according to claim 16 , wherein R 4 is a halogeno group.

18. A pharmaceutical composition, comprising a glutamate compound or pharmaceutically acceptable salt thereof, according to claim 2 .