2,4,6-triamino-1,3,5-triazine derivative

Abstract

This invention relates to an anti-dementia agent which uses a BEC 1 potassium channel inhibitor as the active ingredient. It was proved that the BEC 1 potassium channel inhibitor has an action to improve learning disorder and is useful as a preventive or therapeutic agent for diseases, preferably dementia, in which the BEC 1 potassium channel is considered to be concerned. Illustratively, it was confirmed by an in vivo test that the BEC 1 potassium channel inhibitor has an action to improve learning disorder. Also, it was found that a compound having 2,4,6-triamino-1,3,5-triazine has a BEC 1 potassium channel inhibitory action.

1 . An anti-dementia agent which comprises a substance having BEC 1 potassium channel inhibitory action as the active ingredient. 
     
     
         2 . The anti-dementia agent wherein the substance having BEC 1 potassium channel inhibitory action is a 2,4,6-triamino-1,3,5-triazine derivative represented by a formula (I) or a pharmaceutically acceptable salt thereof 
       
         
           
           
               
               
           
         
       
       (symbols in the formula are as follows
 R 1  and R 2 : the same or different from each other, and each represents H, OH, an alkyl-O—, an aryl-CO—, H 2 N, an alkyl-NH which may be substituted with OH, an (alkyl) 2 N, a hydrocarbon radical which may be substituted or a hetero ring which may be substituted, or R 1 , R 2  and the adjacent N may together form a nitrogen-containing hetero ring and said ring may be substituted, 
 R 3 , R 4 , R 5  and R 6 : the same or different from one another, and each represents (i) H, (ii) CN, (iii) NO 2 , (iv) a halogen, (v) a lower alkyl which may be substituted with (1) CN, (2) a halogen or (3) OH, (vi) a cycloalkyl, (vii) an aryl which may be substituted with a lower alkyl, (ix) a hetero ring which may be substituted with a lower alkyl, (x) R 7 R 8 N— (R 7  and R 8 : the same or different from each other, and each represents (1) H or (2) a lower alkyl which may be substituted with an aryl or R 9 —O—CO— (R 9 : (1) H or a lower alkyl which may be substituted with an aryl), (xi) R 10 -T 1 - (R 10 : (1) H, (2) a lower alkyl which may be substituted with an aryl, an HO—C 1-10  alkylene-O— or HO or (3) an aryl, T 1 : O or S), or (xii) R 11 -T 2 - (R 11 : (1) OH, (2) R 7 R 8 N—, (3) a lower alkyl-O—, (4) a lower alkyl, (5) an aryl or (6) a hetero ring, (T 2 : CO or SO 2 )), 
 further, R 3 , R 4  and the adjacent C, or R 5 , R 6  and the adjacent C, may together form a hetero ring or cyclic hydrocarbon ring, and the ring may be condensed with a benzene ring). 
 
     
     
         3 . A BEC 1 potassium channel described in SEQ ID NO:2 inhibitor, which comprises, as the active ingredient, a 2,4,6-triamino-1,3,5-triazine derivative represented by the formula (I) or a pharmaceutically acceptable salt thereof. 
     
     
         4 . A 2,4,6-triamino-1,3,5-triazine derivative represented by a formula (II) or a pharmaceutically acceptable salt thereof 
       
         
           
           
               
               
           
         
       
       (symbols in the formula are as follows
 R 1  and R 2 : the same or different from each other, and each represents H, OH, an alkyl-O—, an aryl-CO—, H 2 N, an alkyl-NH which may be substituted with OH, an (alkyl) 2 N, a hydrocarbon radical which may be substituted or a hetero ring which may be substituted, or R 1 , R 2  and the adjacent N may together form a nitrogen-containing hetero ring and said ring may be substituted, 
 R 3 , R 4 , R 5  and R 6 : the same or different from one another, and each represents (i) H, (ii) CN, (iii) NO 2 , (iv) a halogen, (v) a lower alkyl which may be substituted with (1) CN, (2) a halogen or (3) OH, (vi) a cycloalkyl, (vii) an aryl which may be substituted with a lower alkyl, (ix) a hetero ring which may be substituted with a lower alkyl, (x) R 7 R 8 N— (R 7  and R 8 : the same or different from each other, and each represents (1) H or (2) a lower alkyl which may be substituted with an aryl or R 9 —O—CO— (R 9 : (1) H or a lower alkyl which may be substituted with an aryl), (xi) R 10 -T 1 - (R 10 : (1) H, (2) a lower alkyl which may be substituted with an aryl, an HO—C 1-10  alkylene-O— or HO or (3) an aryl, T 1 : O or S), or (xii) R 11 -T 2 - (R 11 : (1) OH, (2) R 7 R 8 N—, (3) a lower alkyl-O—, (4) a lower alkyl, (5) an aryl or (6) a hetero ring (T 2 : CO or SO 2 )), 
 further, R 3 , R 4  and the adjacent C, or R 5 , R 6  and the adjacent C, may together form a hetero ring or cyclic hydrocarbon ring, and the ring may be condensed with a benzene ring), 
 
       excluding a case in which R 1  and R 2  in the aforementioned formula (II) are the same or different from each other, and each represents (i) H, NH 2 , a cyclohexyl, phenyl which may be substituted, R a —(CH 2 ) 2 — (R a : HS, HO, R 7 R 8 N, COOH, an ethoxy, CN, morpholino or chloro), an alkyl which may be substituted with a substituent group of the following (a) to (e) ((a), HOOC, (b) an alkyl-O—CO—, (c) phenyl which may be substituted, (d) R 7 R 8 NCONHCO or (e) R 7 R 8 NCONHCO—), an alkenyl, phenyl-S—, phenyl-SO 2 —, phenyl-NHCS— which may be substituted, phenyl-NHCO— which may be substituted, an alkyl-O—CO—, H 2 NCS, chloro-COCH 2 — or 1,3,4-oxadiazol-2-ylmethyl which may be substituted, or R 1 , R 2  and the adjacent C together form pyrazol-1-yl, indol-1-yl, indazol-2-yl, piperidin-1-yl or morpholin-4-yl and R 3 , R 4 , R 5  and R 6  are the same or different from one another and each represents H, a halogen, NO 2 , acetyl, HO, a lower alkyl-O—, HOOC—, a lower alkyl-O—CO—, H 2 NSO 2 — or a lower alkyl). 
     
     
         5 . A pharmaceutical composition which comprises the 2,4,6-triamino-1,3,5-triazine derivative or a pharmaceutically acceptable salt thereof described in  claim 4 .