Novel amide derivative and whitening agent

Abstract

Compound represented by formula (I): wherein the symbols are as defined in the description, and salts thereof, are useful as skin whitening agents.

1 . A compound represented by formula (V): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3 , R 4 , and R 5  are each independently a hydrogen atom, an alkyl group having a carbon number of 1 to 3, a hydroxyl group or an alkoxy group having a carbon number of 1 to 3, or R 1  and R 2 , or R 2  and R 3  in combination optionally form a methylenedioxy group, and at least one of R 1 , R 2 , R 3 , R 4  and R 5  is a hydroxyl group; 
 R 6  is a hydroxyl group and R 7  is a hydrogen atom; 
 Z is a hydrogen atom; 
 or a salt thereof, 
 provided that the following compound and salts thereof are excluded: 
 a compound wherein, when R 1 , R 2 , and R 5  are hydrogen atoms, then:
 R 3  and R 4  are hydroxyl groups, or 
 R 3  is a hydroxyl group and R 4  is a methoxy group, 
 or R 3  and R 4  are hydrogen atoms, or 
 R 3  is a methoxy group and R 4  is a hydrogen atom. 
 
 
     
     
         2 . A compound according to  claim 1 , which is represented by any of formulae (32), (33), (34), (35), or (36): 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         3 . A whitening agent, comprising a compound according to  claim 1 , or a salt thereof. 
     
     
         4 . A whitening agent, comprising a compound according to  claim 2 , or a salt thereof. 
     
     
         5 . A method of whitening skin, comprising applying a whitening agent according to  claim 3  to the skin. 
     
     
         6 . A method of whitening skin, comprising applying a whitening agent according to  claim 4  to the skin. 
     
     
         7 . A method of whitening skin, comprising applying to the skin a whitening agent comprising a compound represented by formula (V): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and R 7  are each independently a hydrogen atom, an alkyl group having a carbon number of 1 to 3, a hydroxyl group or an alkoxy group having a carbon number of 1 to 3, or R 1  and R 2 , or R 2  and R 3  in combination optionally form a methylenedioxy group, provided that at least one of R 1 , R 2 , R 3 , R 4  and R 5  is a hydroxyl group; 
 Z is a hydrogen atom; 
 or a salt thereof, 
 provided that the following compound and salts thereof are excluded: 
 a compound wherein, when R 1 , R 2 , R 5  and R 7  are hydrogen atoms, and R 6  is a hydroxyl group, then:
 R 3  and R 4  are hydroxyl groups, or 
 R 3  is a hydroxyl group and R 4  is a methoxy group, or 
 R 3  and R 4  are hydrogen atoms, or 
 R 3  is a methoxy group and R 4  is a hydrogen atom. 
 
 
     
     
         8 . A compound represented by formula (IV): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 4 , and R 5  are each independently a hydrogen atom, an alkyl group having a carbon number of 1 to 3, a hydroxyl group or an alkoxy group having a carbon number of 1 to 3, or R 1  and R 2  in combination optionally form a methylenedioxy group; 
 R 3  is a hydroxyl group; 
 R 6  is a hydroxyl group; 
 R 7  is a hydrogen atom; 
 X is a methylene group, an ethylene group, or a vinylene group; 
 Z is a hydrogen atom; 
 or a salt thereof, 
 provided that the following compound and salts thereof are excluded: 
 a compound wherein, when X is a vinylene group, and R 1 , R 2 , and R 5  are hydrogen atoms, then
 R 4  is a hydrogen atom, a methoxy group, or a hydroxyl group. 
 
 
     
     
         9 . A compound according to  claim 8 , which is represented by any of formulae (4), (6), (7), (8), (9), (14), (15), (17), (22), or (23): 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         10 . A compound which is represented by any of formulae (5), (10), (16), (18), (19), (20), or (21): 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         11 . A whitening agent, comprising a compound according to  claim 8 , or a salt thereof. 
     
     
         12 . A whitening agent, comprising a compound according to  claim 9 , or a salt thereof. 
     
     
         13 . A whitening agent, comprising a compound according to  claim 10 , or a salt thereof. 
     
     
         14 . A method of whitening skin, comprising applying a whitening agent of  claim 11  to the skin. 
     
     
         15 . A method of whitening skin, comprising applying a whitening agent of  claim 12  to the skin. 
     
     
         16 . A method of whitening skin, comprising applying a whitening agent of  claim 13  to the skin. 
     
     
         17 . A method of whitening skin, comprising applying to the skin a whitening agent, comprising a compound represented by formula (I′): 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3 , R 4  and R 5  are each independently a hydrogen atom, an alkyl group having a carbon number of 1 to 3, a hydroxyl group or an alkoxy group having a carbon number of 1 to 3, or R 1  and R 2 , or R 2  and R 3  in combination optionally form a methylenedioxy group, and at least one of R 1 , R 2 , R 3 , R 4  and R 5  is a hydroxyl group; 
 X is a methylene group, an ethylene group, or a vinylene group; 
 Y is a divalent group represented by formula: 
 
       
         
           
           
               
               
           
         
         Z is a hydrogen atom, a hydroxycarbonyl group or an alkoxycarbonyl group having a carbon number of 1 to 3, and when Z is other than a hydrogen atom and a carbon atom bonded to Z contains an asymmetric center, the stereochemistry thereof may be any of (S), (R) and (SR); 
         Ar is a substituent represented by formula (II): 
       
       
         
           
           
               
               
           
         
       
       wherein:
 R 6  and R 7  are each independently a hydrogen atom, an alkyl group having a carbon number of 1 to 3, a hydroxyl group or an alkoxy group having a carbon number of 1 to 3, and * is a moiety bonded to Y; 
 provided that the following compounds and salts thereof are excluded: 
 (1) a compound wherein, when X is a vinylene group, Y is an ethylene group, R 1 , R 2 , R 5  and R 7  are hydrogen atoms, and R 6  is a hydroxyl group, then
 R 3  is a hydroxyl group and R 4  is a hydrogen atom, or 
 R 3  is a hydroxyl group and R 4  is a methoxy group, or 
 R 3  and R 4  are hydroxyl groups; and 
 
 (2) a compound wherein, when X is a vinylene group, Y is an ethylene group, and R 1 , R 2 , R 5 , R 6  and R 7  are hydrogen atoms, then
 R 3  and R 4  are hydroxyl groups. 
 
 
     
     
         18 . A method of  claim 17 , wherein said compound represented by the formula (I′) is a compound represented by any of formulae (12), (13), (30), or (31): 
       
         
           
           
               
               
           
         
       
     
     
         19 . A compound represented by any of formulae (25), (26), (27), (28), or (29): 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         20 . A whitening agent, comprising a compound according to  claim 19 , or a salt thereof. 
     
     
         21 . A method of whitening skin, comprising applying a whitening agent according to  claim 20  to the skin. 
     
     
         22 . A method of whitening skin, comprising applying to the skin a whitening agent, comprising a compound represented by formula (24): 
       
         
           
           
               
               
           
         
       
       a salt thereof.