4-(methylaminophenoxy)pyrdin-3-yl-benzamide derivatives for treating cancer

Abstract

The present invention provides a novel compound having an excellent antitumor effect, stability and metabolic stability. The compound of the present invention is represented by the following general formula (1) wherein R 1 represents a halogen atom, an aryl group, an aryloxy group or a lower alkyl group optionally substituted with one or more halogen atoms; R 2 represents a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group; and; m represents an integer of 1 to 3; provided that when m represents 2 or 3, R 1 s are the same or different.

1 . A compound of the following formula (1) or a salt thereof: 
       
         
           
           
               
               
           
         
         wherein R 1  is a halogen atom, an aryl group, an aryloxy group or a linear or branched alkyl group having 1 to 6 carbon atoms, said lower alkyl group being optionally substituted with one or more halogen atoms; 
         R 2  is a hydrogen atom, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms or a linear or branched alkoxy group having 2 to 6 carbon atoms; and; 
         m is an integer of 1 to 3; 
         provided that when m is 2 or 3, R 1 s are the same or different. 
       
     
     
         2 . The compound according to  claim 1  or a salt thereof, wherein R 2  is a hydrogen atom. 
     
     
         3 . The compound according to  claim 1  or a salt thereof, wherein R 2  is a halogen atom. 
     
     
         4 . The compound according to  claim 1  or a salt thereof, wherein R 2  is linear or branched alkyl group having 1 to 6 carbon atoms. 
     
     
         5 . The compound according to  claim 1  or a salt thereof, wherein R 2  is a linear or branched alkoxy group having 2 to 6 carbon atoms. 
     
     
         6 . The compound according to  claim 1  or a salt thereof, which is selected from the group consisting of:
 N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}-4-phenoxybenzamide, 
 N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}biphenyl-4-carboxamide, 
 N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide, 
 2-fluoro-N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide, 
 2,3,4-trifluoro-N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}benzamide, 
 N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}-4-phenoxybenzamide, 
 N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}biphenyl-4-carboxamide, 
 N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide, 
 2-fluoro-N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamid, 
 N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}-4-phenoxybenzamide], 
 N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}biphenyl-4-carboxamide, 
 N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide, 
 N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}-4-phenoxybenzamide, 
 N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}biphenyl-4-carboxamide, 
 2-fluoro-N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide, 
 2,3,4-trifluoro-N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}benzamide, 
 2,3,4-trifluoro-N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}benzamide, 
 N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide, 
 2-fluoro-N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide, and 
 2,3,4-trifluoro-N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}benzamide. 
 
     
     
         7 . The compound according to  claim 1 , which is selected from the group consisting of:
 N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}-4-phenoxybenzamide,   N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}biphenyl-4-carboxamide,   N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide,   2-fluoro-N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide,   2,3,4-trifluoro-N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}benzamide,   N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}-4-phenoxybenzamide,   N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}biphenyl-4-carboxamide,   N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide,   2-fluoro-N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide,   N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}-4-phenoxybenzamide,   N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}biphenyl-4-carboxamide,   N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide,   N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}-4-phenoxybenzamide,   N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}biphenyl-4-carboxamide,   2-fluoro-N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide,   2,3,4-trifluoro-N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}benzamide,   2,3,4-trifluoro-N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}benzamide,   N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide,   2-fluoro-N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide,   2,3,4-trifluoro-N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}benzamide,   N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}-4-phenoxybenzamide hydrochloride,   2-fluoro-N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide hydrochloride,   2,3,4-trifluoro-N-{6-[2-fluoro-4-(methylamino)phenoxy]pyridin-3-yl}benzamide hydrochloride,   N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide hydrochloride,   2,3,4-trifluoro-N-{6-[2-methyl-4-(methylamino)phenoxy]pyridin-3-yl}benzamide hydrochloride,   N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}-4-phenoxybenzamide hydrochloride,   N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide hydrochloride,   2-fluoro-N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide hydrochloride,   2,3,4-trifluoro-N-{6-[2-methoxy-4-(methylamino)phenoxy]pyridin-3-yl}benzamide hydrochloride,   N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide hydrochloride,   2-fluoro-N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}-4-(trifluoromethyl)benzamide hydrochloride, and   2,3,4-trifluoro-N-{6-[4-(methylamino)phenoxy]pyridin-3-yl}benzamide hydrochloride.   
     
     
         8 . A pharmaceutical composition comprising a compound of the formula (1) or a salt thereof according to  claim 1 , and a pharmacologically acceptable carrier. 
     
     
         9 . A pharmaceutical composition according to  claim 8  for treating cancer. 
     
     
         10 . A compound of the formula (1) or a salt thereof according to  claim 1  for use in the pharmaceutical composition. 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . A method of treating cancer, comprising administering to a patient in need thereof a compound of the formula (1) or a salt thereof according to  claim 1 .