Serotonin 5-ht3 receptor agonist

Abstract

A serotonin 5-HT3 receptor agonist containing a compound represented by the general formula (1) [R 1 , R 3 and R 5 represent hydrogen atom, a lower alkyl group, a lower alkenyl group, a halogen atom, hydroxyl group, amino group, a lower alkoxy group, carboxyl group, carbamoyl group, or nitro group, R 2 and R 4 represent a halogen atom, hydroxyl group, or amino group, R 6 represents hydrogen atom, a lower alkyl group, or a lower alkenyl group, R 7 represents hydrogen atom, a lower alkyl group, a lower alkenyl group, or an aralkyl group, and m and n are integers of 1 to 3] or a physiologically acceptable salt thereof as an active ingredient and having both a serotonin 5-HT3 receptor antagonistic action and a serotonin 5-HT3 receptor activating action.

1 . A serotonin 5-HT3 receptor agonist containing a compound represented by the general formula (1) or a physiologically acceptable salt thereof as an active ingredient: 
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 3  and R 5  may be the same or different, and represent hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower alkenyl group, a halogen atom, hydroxyl group, a substituted or unsubstituted amino group, a lower alkoxy group, carboxyl group, carbamoyl group, or nitro group, R 2  and R 4  may be the same or different, and represent a halogen atom, hydroxyl group, or a substituted or unsubstituted amino group, R 6  represents hydrogen atom, a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted lower alkenyl group, R 7  represents hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower alkenyl group, or a substituted or unsubstituted aralkyl group, and m and n may be the same and different, and represent an integer of 1 to 3. 
   
   
       2 . A serotonin 5-HT3 receptor agonist containing a compound represented by general formula (2) or a physiologically acceptable salt thereof as an active ingredient: 
     
       
         
         
             
             
         
       
     
     wherein R 8  and R 9  may be the same or different, and represent a halogen atom, hydroxyl group, or a substituted or unsubstituted amino group, R 10  represents hydrogen atom, a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted lower alkenyl group, and R 11  represents hydrogen atom, a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted lower alkenyl group. 
   
   
       3 . A compound represented by the general formula (1) according to  claim 1  or a salt thereof, provided that a compound wherein R 2  and R 4  both represent chlorine atom, and a compound wherein R 1 , R 2 , R 3 , R 4  and R 5  all represent chlorine atom are excluded. 
   
   
       4 . A compound represented by the general formula (2) according to  claim 2  or a salt thereof, provided that a compound wherein R 8  and R 9  both represent chlorine atom is excluded. 
   
   
       5 . A compound represented by the general formula (3): 
     
       
         
         
             
             
         
       
     
     wherein R 12 , R 13 , R 14 , R 15  and R 16  may be the same or different, and represent hydrogen atom, a halogen atom, a lower alkoxy group, trifluoromethyl group, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower alkenyl group, or a substituted or unsubstituted amino group, any two groups among R 12 , R 13 , R 14 , R 15  and R 16  may bind to each other to form a cyclic structure (the cyclic structure is a 5- to 7-membered cyclic structure consisting only of carbon atoms or a 5- to 7-membered cyclic structure consisting of carbon atoms and one or two hetero atoms, and may have one or more the same or different substituents on the ring), R 17  represents hydrogen atom, a substituted or unsubstituted lower alkyl group, or a substituted or unsubstituted lower alkenyl group, R 18  and R 19  may be the same or different, and represent a substituted or unsubstituted lower alkyl group, a lower alkenyl group, or an aralkyl group, X −  represents a physiologically acceptable anion species, and m and n may be the same and different, and represent an integer of 1 to 3, provided that the sum of n+m=5. 
   
   
       6 . A serotonin 5-HT3 receptor agonist comprising the compound represented by the general formula (3) according to  claim 5  as an active ingredient. 
   
   
       7 . A medicament for prophylactic and/or therapeutic treatment of a disease associated with the serotonin 5-HT3 receptor, which comprises the serotonin 5-HT3 receptor agonist according to  claim 1 . 
   
   
       8 . The medicament according to  claim 7 , which is an antiemetic drug. 
   
   
       9 . The medicament according to  claim 8 , which is used for prophylactic and/or therapeutic treatment of emesis caused by a cancer treatment including administration of an anticancer agent and/or radiation irradiation. 
   
   
       10 . A medicament for prophylactic and/or therapeutic treatment of a disease associated with the serotonin 5-HT3 receptor, which comprises the serotonin 5-HT3 receptor agonist according to  claim 2 . 
   
   
       11 . The medicament according to  claim 10 , which is an antiemetic drug. 
   
   
       12 . The medicament according to  claim 11 , which is used for prophylactic and/or therapeutic treatment of emesis caused by a cancer treatment including administration of an anticancer agent and/or radiation irradiation. 
   
   
       13 . A medicament for prophylactic and/or therapeutic treatment of a disease associated with the serotonin 5-HT3 receptor, which comprises the serotonin 5-HT3 receptor agonist according to  claim 6 . 
   
   
       14 . The medicament according to  claim 13 , which is an antiemetic drug. 
   
   
       15 . The medicament according to  claim 14 , which is used for prophylactic and/or therapeutic treatment of emesis caused by a cancer treatment including administration of an anticancer agent and/or radiation irradiation.