Methyllactam ring compound and pharmaceutical use thereof

Abstract

An object of the present invention is to provide a methyllactam ring compound that has an SGLT1 inhibitory activity and is useful for a drug, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising it, and pharmaceutical use thereof. A compound of Formula [I]:or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising it, and pharmaceutical use thereof is provided.

1 - 11 . (canceled) 
     
     
         12 . A method of preparing a compound of Formula [17]: 
       
         
           
           
               
               
           
         
         the method comprising a step C1-1, comprising reacting a compound of Formula [15]: 
       
       
         
           
           
               
               
           
         
         with a compound of Formula [16]: 
       
       
         
           
           
               
               
           
         
         in a solvent and in the presence of a base, wherein
 L 3  is a leaving group; 
 P C1  and P C2  are each independently a carboxyl protecting group; and 
 each R 3  is independently methoxy or ethoxy. 
 
       
     
     
         13 . The method of  claim 12 , wherein
 the base of step C1-1 is selected from the group consisting of potassium tert-butoxide, sodium methoxide, sodium ethoxide, lithium diisopropylamide, potassium hexamethyldisilazane, potassium carbonate, cesium carbonate, and sodium hydride;   the solvent of step C1-1 is selected from the group consisting of an ether solvent, an alcohol solvent, and a polar solvent; and   the reacting of step C1-1 is carried out at a temperature from −78° C. to 100° C.   
     
     
         14 . A method of preparing compound of Formula [10]: 
       
         
           
           
               
               
           
         
         or salt thereof, the method comprising a step B1-4, comprising removing a P N2  group from a compound of Formula [9]: 
       
       
         
           
           
               
               
           
         
         in a solvent, wherein
 each P N2  group is an amine protecting group or the two P N2  groups are combined with the nitrogen atom to which they are attached to form 2,5-dimethylpyrrole; and 
 L 1  is a leaving group. 
 
       
     
     
         15 . The method of  claim 14 , wherein
 the removing of step B1-4 is carried out by hydroxylamine or hydroxylamine hydrochloride;   the solvent of step B1-4 is selected from the group consisting of an alcohol, water, or a mixture thereof; and   the removing of step B1-4 is carried out at a temperature from 40° C. to 150° C.   
     
     
         16 . The method of  claim 14 , wherein the compound of Formula [9] is obtained by a step B1-3, comprising introducing L 1  into a compound of Formula [8]: 
       
         
           
           
               
               
           
         
         in a solvent and in the presence of a base, wherein
 each P N2  group is an amine protecting group or the two P N2  groups are combined with the nitrogen atom to which they are attached to form 2,5-dimethylpyrrole. 
 
       
     
     
         17 . The method of  claim 16 , wherein
 the base of step B1-3 is selected from the group consisting of n-butyllithium, lithium diisopropylamide, lithium hexamethyldisilazide, and lithium tetramethylpiperidide;   L 1  is iodine and is introduced by an iodizing agent selected from the group consisting of iodine, iodine monochloride, N-iodosuccinimide, and 1-chloro-2-iodoethane;   the two P N2  groups are combined with nitrogen atom to which they are attached to form 2,5-dimethylpyrrole;   the solvent of step B1-3 is selected from the group consisting of an ether solvent, a hydrocarbon solvent, or a mixture of the foregoing; and   the introducing is carried out at a temperature from −100° C. to 40° C.   
     
     
         18 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein
 each L 1  and L 3  is independently a leaving group; 
 P C1  and P C2  are each independently a carboxyl protecting group; 
 each P N2  group is an amine protecting group or the two P N2  groups are combined with the nitrogen atom to which they are attached to form 2,5-dimethylpyrrole; and 
 each R 3  is independently methoxy or ethoxy. 
 
       
     
     
         19 . The compound of  claim 18 , wherein
 L 1  is chlorine, bromine, or iodine;   L 3  is chlorine or bromine;   P C1  and P C2  are each independently methyl, ethyl, tert-butyl, or benzyl; and   the two P N2  groups are combined with the nitrogen atom to which they are attached to form 2,5-dimethylpyrrole.   
     
     
         20 . A compound of Formula [10], or a salt thereof:
 wherein   L 1  is a leaving group.   
       
         
           
           
               
               
           
         
       
     
     
         21 . The compound of  claim 20 , or a salt thereof, wherein L 1  is chlorine, bromine, or iodine.