Alkylamine derivative

Abstract

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.

The invention claimed is: 
     
       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. 
     
     
       10. The compound according to claim 1, wherein
 R 1  and R 2  represent a hydrogen atom,   R 4  and R 5  represent a hydrogen atom,   X represents NH,   Y represents C═O,   G represents R 7 -substituted phenyl, which may further be substituted with one or two R 8 ,   R 7  represents sulfo, and   Q represents COOH.   
     
     
       11. The compound according to claim 1, wherein
 R 1  and R 2  represent a hydrogen atom,   R 4  and R 5  represent a hydrogen atom,   X represents NH,   Y represents C═O,   G represents R 7 -substituted phenyl, which is substituted with two R 8 ,   R 7  represents sulfo, and   Q represents COOH.   
     
     
       12. The compound according to claim 1, wherein
 R 1  and R 2  represent a hydrogen atom,   R 4  and R 5  represent a hydrogen atom,   X represents NH,   Y represents C═O,   G represents R 7 -substituted phenyl, which is not substituted with R 8 ,   R 7  represents sulfo, and   Q represents COOH.   
     
     
       13. The compound represented by the following formula: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
       14. A sodium salt of the compound according to claim 13. 
     
     
       15. The compound represented by the following formula: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
       16. A sodium salt of the compound according to claim 15. 
     
     
       17. The compound represented by the following formula: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
       18. A sodium salt of the compound according to claim 17. 
     
     
       19. The compound represented by the following formula: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
       20. A sodium salt of the compound according to claim 19.