Triazolopyridine compound, and action thereof as prolyl hydroxylase inhibitor or erythropoietin production-inducing agent

Abstract

The present invention provides a triazolopyridine compound having a prolyl hydroxylase inhibitory action and an erythropoietin production-inducing ability. The present invention relates to a compound represented by the following formula [I]: wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof, or a solvate thereof, as well as a prolyl hydroxylase inhibitor or erythropoietin production-inducing agent containing the compound. The compound of the present invention shows a prolyl hydroxylase inhibitory action and an erythropoietin production-inducing ability and is useful as a prophylactic or therapeutic agent for various diseases and pathologies (disorders) caused by decreased production of erythropoietin.

1 . A compound represented by the following formula [I], or a pharmaceutically acceptable salt thereof, or a solvate thereof: 
       
         
           
           
               
               
           
         
         wherein 
         the partial structural formula: 
       
       
         
           
           
               
               
           
         
         is a group represented by any of the following formulas: 
       
       
         
           
           
               
               
           
         
         R 1  is 
         (1) a hydrogen atom, 
         (2) a C 1-6  alkyl group, 
         (3) a C 6-14  aryl group, 
         (4) a C 3-8  cycloalkyl group, 
         (5) a C 6-14  aryl-C 1-6  alkyl group, or 
         (6) a C 3-8  cycloalkyl-C 1-6  alkyl group; 
         R 2  is 
         (1) a hydrogen atom, 
         (2) a C 1-10  alkyl group, 
         (3) a C 6-14  aryl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B, 
         (4) a C 3-8  cycloalkyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B, 
         (5) a C 3-8  cycloalkenyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B, 
         (6) a heteroaryl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B (wherein the heteroaryl has, besides carbon atom, 1 to 6 hetero atoms selected from nitrogen atom, oxygen atom and sulfur atom), 
         (7) a C 6-14  aryl-C 1-6  alkyl group (wherein C 6-14  aryl is optionally substituted by the same or different 1 to 5 substituents selected from the following group B), or 
         (8) a C 3-8  cycloalkyl-C 1-6  alkyl group (wherein C 3-8  cycloalkyl is optionally substituted by the same or different 1 to 5 substituents selected from the following group B); 
         R 3  is 
         (1) a hydrogen atom, 
         (2) a halogen atom, 
         (3) a C 1-6  alkyl group, 
         (4) a C 6-14  aryl group, 
         (5) a C 3-8  cycloalkyl group, or 
         (6) a C 6-14  aryl-C 1-6  alkyl group; and 
         R 4  and R 5  are each independently 
         (1) a hydrogen atom, or 
         (2) a C 1-6  alkyl group, 
         group B: 
         (a) a halogen atom, 
         (b) a C 1-6  alkyl group, 
         (c) a C 3-8  cycloalkyl group, 
         (d) a cyano group, and 
         (e) a halo-C 1-6  alkyl group. 
       
     
     
         2 . The compound according to  claim 1  wherein the partial structural formula: 
       
         
           
           
               
               
           
         
         is a group represented by the following formula 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a solvate thereof. 
       
     
     
         3 . The compound according to  claim 1 , wherein the partial structural formula: 
       
         
           
           
               
               
           
         
         is a group represented by the following formula 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a solvate thereof. 
       
     
     
         4 . The compound according to  claim 1 , wherein the partial structural formula: 
       
         
           
           
               
               
           
         
         is a group represented by the following formula 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a solvate thereof. 
       
     
     
         5 . The compound according to  claim 1 , wherein the partial structural formula: 
       
         
           
           
               
               
           
         
         is a group represented by the following formula 
       
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, or a solvate thereof. 
       
     
     
         6 . The compound according to  claim 1 , wherein both R 4  and R 5  are hydrogen atoms, or a pharmaceutically acceptable salt thereof, or a solvate thereof. 
     
     
         7 . The compound according to  claim 1 , wherein R 3  is a hydrogen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof. 
     
     
         8 . The compound according to  claim 1 , wherein R 1  is a hydrogen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof. 
     
     
         9 . The compound according to  claim 1 , wherein R 2  is
 (1) a C 1-10  alkyl group,   (2) a C 6-14  aryl group optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group B,   (3) a C 6-14  aryl-C 1-6  alkyl group (wherein C 6-14  aryl is optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group B), or   (4) a C 3-8  cycloalkyl-C 1-6  alkyl group (wherein C 3-8  cycloalkyl is optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group B), or a pharmaceutically acceptable salt thereof, or a solvate thereof.   
     
     
         10 . The compound according to  claim 2 , wherein both R 4  and R 5  are hydrogen atoms, or a pharmaceutically acceptable salt thereof, or a solvate thereof. 
     
     
         11 . The compound according to  claim 10 , wherein R 3  is a hydrogen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof. 
     
     
         12 . The compound according to  claim 11 , wherein R 1  is a hydrogen atom, or a pharmaceutically acceptable salt thereof, or a solvate thereof. 
     
     
         13 . The compound according to  claim 12 , wherein R 2  is
 (1) a C 1-10  alkyl group, or   (2) a C 6-14  aryl-C 1-6  alkyl group (wherein C 6-14  aryl is optionally substituted by the same or different 1 to 5 substituents selected from the above-mentioned group B),   or a pharmaceutically acceptable salt thereof, or a solvate thereof.   
     
     
         14 . A compound represented by the following formula [I-1] or a pharmaceutically acceptable salt thereof, or a solvate thereof: 
       
         
           
           
               
               
           
         
         wherein the partial structural formula: 
       
       
         
           
           
               
               
           
         
         is a group represented by: 
       
       
         
           
           
               
               
           
         
         R 11  is 
         (1) a hydrogen atom, 
         (2) a C 1-6  alkyl group, 
         (3) a phenyl group, 
         (4) a C 3-8  cycloalkyl group, 
         (5) a phenyl-C 1-6  alkyl group, or 
         (6) a C 3-8  cycloalkyl-C 1-6  alkyl group; 
         R 21  is 
         (1) a hydrogen atom, 
         (2) a C 1-10  alkyl group, 
         (3) a phenyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B, 
         (4) a C 3-8  cycloalkyl group, 
         (5) a C 3-8  cycloalkenyl group, 
         (6) a thienyl group optionally substituted by the same or different 1 to 5 substituents selected from the following group B, 
         (7) a phenyl-C 1-6  alkyl group (wherein phenyl is optionally substituted by the same or different 1 to 5 substituents selected from the following group B), or 
         (8) a C 3-8  cycloalkyl-C 1-6  alkyl group; 
         R 31  is 
         (1) a hydrogen atom, 
         (2) a halogen atom, 
         (3) a C 1-6  alkyl group, 
         (4) a phenyl group, 
         (5) a C 3-8  cycloalkyl group, or 
         (6) a phenyl-C 1-6  alkyl group; and 
         R 41  and R 51  are each independently 
         (1) a hydrogen atom, or 
         (2) a C 1-6  alkyl group 
         group B: 
         (a) a halogen atom, 
         (b) a C 1-6  alkyl group, 
         (c) a C 3-8  cycloalkyl group, 
         (d) a cyano group, and 
         (e) a halo-C 1-6  alkyl group. 
       
     
     
         15 .- 25 . (canceled) 
     
     
         26 . A pharmaceutical composition comprising the compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, or a solvate thereof, and a pharmaceutically acceptable carrier. 
     
     
         27 .- 34 . (canceled) 
     
     
         35 . A method of inhibiting prolyl hydroxylase, comprising administering an effective amount of the compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal. 
     
     
         36 . A method of inducing erythropoietin production, comprising administering an effective amount of the compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal. 
     
     
         37 . A method of treating anemia, comprising administering an effective amount of the compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal. 
     
     
         38 . A method of treating renal anemia, comprising administering an effective amount of the compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, or a solvate thereof to a mammal. 
     
     
         39 . A commercial package comprising the pharmaceutical composition according to  claim 26  and a written matter associated therewith, the written matter stating that the pharmaceutical composition can or should be used for the treatment or prophylaxis of a disease selected from anemia and renal anemia. 
     
     
         40 . A kit comprising the pharmaceutical composition according to  claim 26  and a written matter associated therewith, the written matter stating that the pharmaceutical composition can or should be used for the treatment or prophylaxis of a disease selected from anemia and renal anemia.