Alkylamine derivative
A composition containing a compound represented by General Formula (I) below (see the definition in the specification for the symbols in the formula) or a salt thereof has an excellent CaSR agonistic effect and provides a pharmaceutical agent, a CaSR agonistic agent, a prophylactic or therapeutic agent for a disease that can be ameliorated through CaSR activation as well as seasonings and an agent for imparting kokumi.
1. A compound of Formula (I) or a salt thereof:
wherein R 1 and R 2 , each independently, represent a hydrogen atom, or unsubstituted C 1-6 alkyl;
R 3 represents a hydrogen atom;
R 4 and R 5 , each independently, represent a hydrogen atom, substituted or unsubstituted C 1-6 alkyl;
X represents CH 2 , an oxygen atom, NH, or a sulfur atom;
Y represents C═O, SO, SO 2 , or C═S;
R 6 represents a hydrogen atom;
G represents R 7 -substituted phenyl or R 7 -substituted pyridyl, where the R 7 -substituted phenyl or the R 7 -substituted pyridyl may further be substituted with one or two R 8 ;
R 7 represents sulfo or carboxyl;
R 8 represents substituted or unsubstituted C 1-6 alkyl, halogeno, hydroxy, substituted or unsubstituted C 1-6 alkoxy, sulfo, or C 1-3 alkylcarbonylamino, where they may be different when more than one R 8 exist;
Q represents a hydrogen atom, substituted or unsubstituted C 1-6 alkyl, carboxyl, CONR e R f , CONHNHR g , COR h , phenyl, or substituted or unsubstituted oxadiazolyl;
R e and R f , each independently, represent a hydrogen atom, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 1-6 alkylsulfonyl, phenylsulfonyl, substituted or unsubstituted C 3-8 cycloalkyl, or hydroxy, or alternatively, R e and R f may integrally form morpholino;
R g represents substituted or unsubstituted C 1-6 alkylcarbonyl; and
R h represents substituted or unsubstituted C 1-6 alkoxy,
provided that when X is methylene or an oxygen atom, Y is C═O, all of R 1 -R 5 are hydrogen atoms, and G is R 7 -substituted phenyl optionally substituted with one or two R 8 , then, Q is a group other than carboxyl or COR h .
2. The compound according to claim 1 , or a salt thereof, wherein R 8 represents substituted or unsubstituted C 1-6 alkyl, halogeno, hydroxy, substituted or unsubstituted C 1-6 alkoxy, nitro, or sulfo,
Q represents a hydrogen atom, substituted or unsubstituted C 1-6 alkyl (wherein the substituent on said substituted C 1-6 alkyl is selected from the group consisting of phenyl, carbamoyl, and cyano), carboxyl, CONR e R f , CONHNHR g , COR h , phenyl, or substituted or unsubstituted oxadiazolyl (wherein the substituent on said substituted oxadiazolyl is selected from the group consisting of C 1-6 alkyl, C 1-6 alkyl substituted with phenyl, phenyl substituted with halogen, phenyl substituted with C 1-6 alkyl, and thiazolyl);
R e and R f , each independently, represent a hydrogen atom, substituted or unsubstituted C 1-6 alkyl (wherein the substituent on said substituted C 1-6 alkyl is selected from the group consisting of phenyl, phenyl substituted with C 1-6 alkyl, phenyl substituted with halogen, and imidazolyl), C 1-6 alkylsulfonyl, phenylsulfonyl, substituted or unsubstituted C 3-8 cycloalkyl, or hydroxy, or alternatively, R e and R f may integrally form morpholino;
R g represents substituted or unsubstituted C 1-6 alkylcarbonyl; and
R h represents substituted or unsubstituted C 1-6 alkoxy,
provided that when X is methylene or an oxygen atom, Y is C═O, all of R 1 -R 5 are hydrogen atoms, and G is R 7 -substituted phenyl optionally substituted with one or two R 8 , then, Q is a group other than carboxyl or COR h .
3. A pharmaceutical composition, comprising:
the compound or a pharmaceutically acceptable salt thereof according to claim 1 or 2 as an active ingredient; and
a pharmaceutically acceptable excipient.
4. The compound according to claim 1 , wherein G represents R 7 -substituted phenyl or R 7 -substituted pyridyl, where the R 7 -substituted phenyl or the R 7 -substituted pyridyl is not further substituted with one or two R 8 .
5. The pharmaceutical composition according to claim 3 , wherein G represents R 7 -substituted phenyl or R 7 -substituted pyridyl, where the R 7 -substituted phenyl or the R 7 -substituted pyridyl is not further substituted with one or two R 8 .
6. The compound according to claim 1 , wherein
X represents NH,
Y represents C═O or C═S,
G represents R 7 -substituted phenyl, which may further be substituted with one or two R 8 ,
R 7 represents sulfo or carboxyl,
R 8 represents C 1-6 alkyl, halogen, hydroxy, C 1-3 alkylcarbonylamino or sulfo, where they may be different when more than one R 8 exist, and
Q represents carboxyl, CONR e R f , CONHNHR g or COR h .
7. The compound according to claim 1 , wherein G is phenyl, X is NH, Y is CO, and Q is COOH.
8. The compound according to claim 2 , wherein
X represents NH,
Y represents C═O or C═S,
G represents R 7 -substituted phenyl, which may further be substituted with one or two R 8 ,
R 7 represents sulfo or carboxyl,
R 8 represents C 1-6 alkyl, halogeno, hydroxy, C 1-3 alkylcarbonylamino or sulfo, where they may be different when more than one R 8 exist, and
Q represents carboxyl, CONR e R f , CONHNHR g or COR h .
9. The compound according to claim 2 , wherein G is phenyl, X is NH, Y is CO, and Q is COOH.