Thiophene compounds and thrombopoietin receptor activators

Abstract

A compound represented by the formula (I) (wherein R 1 , R 2 , R 3 and R 4 are as defined in the description), a tautomer, prodrug or pharmaceutically acceptable salt of the compound or a solvate thereof.

1 - 20 . (canceled) 
     
     
         21 . A compound represented by the formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  is a phenyl group (the phenyl group may be substituted with one or more C 1-6  alkyl groups, one or more C 1-3  alkyl groups (the C 1-3  alkyl groups are substituted with one or more halogen atoms), one or more C 1-3  alkoxy groups (the C 1-3  alkoxy groups may be substituted with one or more halogen atoms) or one or more halogen atoms), 
         R 2  is a hydrogen atom or a C 1-3  alkyl group (the C 1-3  alkyl group may be substituted with one or more halogen atoms), 
         R 3  is a phenyl group or a pyridyl group (the phenyl group and the pyridyl group are substituted with one or more substituents selected from the group consisting of hydrogen atoms, nitro groups, halogen atoms and C 1-3  alkyl groups (the C 1-3  alkyl groups may be substituted with one or more halogen atoms) and with (C═O)R 5  (wherein R 5  is NR 6 R 7  (wherein R 6  is a hydrogen atom or a C 1-3  alkyl group (the C 1-3  alkyl group may be substituted with one or more halogen atoms), and R 7  is a substituted C 1-6  alkyl group (the C 1-6  alkyl group is substituted with one or more halogen atoms, one or more hydroxyl groups, one or more C 1-3  alkoxy groups or one or more C 2-14  aryl groups (the C 2-14  aryl groups may be substituted with one or more C 1-3  alkyl groups, one or more C 1-3  alkoxy groups, one or more carboxyl groups, one or more carbamoyl groups, one or more cyano groups or one or more halogen atoms, and in the case of aryl groups containing one or more nitrogen atoms, may be N-oxides thereof)), a phenyl group, a thienyl group, a pyridyl group or a pyridyl-N-oxide group (the phenyl group, the thienyl group, the pyridyl group and the pyridyl-N-oxide group may be substituted with one or more halogen atoms), or NR 6 R 7  is, as a whole, a nitrogen-containing heterocyclyl group (the nitrogen-containing heterocyclyl group may be substituted with one or more hydrogen atoms, one or more C 1-6  alkyl groups (the C 1-6  alkyl groups may be substituted with one or more halogen atoms), one or more halogen atoms, one or more hydroxyl groups or one or more C 1-3  alkoxy groups (the C 1-3  alkoxy groups may be substituted with one or more halogen atoms))) or a C 1-6  alkyl group (the C 1-6  alkyl group may be substituted with one or more halogen atoms, one or more pyridyl groups, one or more pyridyl-N-oxide groups, one or more furyl groups, one or more thienyl groups or one or more phenyl groups or substituted with one or more cyano groups))), and 
         R 4  is a hydrogen atom or a C 1-3  alkyl group (the C 1-3  alkyl group may be substituted with one or more halogen atoms), a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
       
     
     
         22 . The compound according to  claim 21 , wherein R 2  is a methyl group, and R 4  is a hydrogen atom, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         23 . The compound according to  claim 22 , wherein R 1  is a 3,4-dimethyl-phenyl group, a 4-t-butyl-phenyl group, a 4-trifluoromethyl-phenyl group, a 3-chloro-phenyl group, a 4-chloro-phenyl group, a 4-fluoro-phenyl group, a 3,4-dichloro-phenyl group, a 4-bromo-phenyl group or a 4-trifluoromethoxy-phenyl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         24 . The compound according to  claim 23 , wherein R 6  is a methyl group or an ethyl group, and R 7  is a C 1-6  alkyl group (the C 1-6  alkyl group is substituted with one or more methoxy groups), a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         25 . The compound according to  claim 23 , wherein R 6  is a methyl group or an ethyl group, and R 7  is a C 1-3  alkyl group (the C 1-3  alkyl group is substituted with one or more phenyl groups or one or more pyridyl groups), a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         26 . The compound according to  claim 23 , wherein R 6  is a hydrogen atom, and R 7  is a C 1-6  alkyl group (the C 1-6  alkyl group is substituted with one or more methoxy groups) or a pyridyl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         27 . The compound according to  claim 23 , wherein NR 6 R 7  is, as a whole, represented by one of the formulae (IIIA)-(IIIE): 
       
         
           
           
               
               
           
         
         wherein R 9  is a C 1-3  alkyl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
       
     
     
         28 . The compound according to  claim 23 , wherein R 3  is represented by the formula (IV): 
       
         
           
           
               
               
           
         
         wherein R 6  is a hydrogen atom, R 7  is a C 1-3  alkyl group (the C 1-3  alkyl group may be substituted with one or more hydroxyl groups), and R 8  is a methyl group or a chlorine atom, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
       
     
     
         29 . The compound according to  claim 23 , wherein R 6  is a hydrogen atom, and R 7  is a methyl group, an ethyl group or a normal propyl group (the methyl group, the ethyl group and the normal propyl group are substituted with one or more pyridyl groups, one or more pyridyl-N-oxide groups, one or more furyl groups, one or more pyrazinyl groups, one or more imidazolyl groups, one or more pyrazolyl groups or one or more isoxazolyl groups (the pyridyl groups, the pyridyl-N-oxide groups, the furyl groups, the pyrazinyl groups, the imidazolyl groups, the pyrazolyl groups and the isoxazolyl groups may be substituted with one or more methyl groups, one or more methoxy groups, one or more carboxyl groups or one or more halogen atoms)), a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         30 . The compound according to  claim 21 , wherein R 1  is a 3,4-dimethyl-phenyl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         31 . The compound according to  claim 21 , wherein R 1  is a 3,4-dichloro-phenyl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         32 . The compound according to  claim 21 , wherein R 1  is a 4-chloro-phenyl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         33 . The compound according to  claim 21 , wherein R 1  is a 4-trifluoromethyl-phenyl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         34 . The compound according to  claim 21 , wherein R 1  is a 4-bromo-phenyl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         35 . The compound according to  claim 21 , wherein R 1  is a 4-trifluoromethoxy-phenyl group, a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
     
     
         36 . A pharmaceutical composition comprising at least one compound of  claim 21 , a tautomer, prodrug or pharmaceutically acceptable salt of the compound, as an active ingredient. 
     
     
         37 . The pharmaceutical composition of  claim 36 , which comprises the active ingredient and at least one pharmaceutically acceptable additive. 
     
     
         38 . A platelet increasing agent comprising an effective amount of at least one compound of  claim 21 . 
     
     
         39 . Medicament comprising the compound according to  claim 21 , a tautomer, prodrug or pharmaceutically acceptable salt of the compound, as an active ingredient. 
     
     
         40 . A compound represented by the formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  is a phenyl group (the phenyl group may be substituted with one or more C 1-6  alkyl groups, one or more C 1-3  alkyl groups (the C 1-3  alkyl groups are substituted with one or more halogen atoms), one or more C 1-3  alkoxy groups (the C 1-3  alkoxy groups may be substituted with one or more halogen atoms) or one or more halogen atoms), 
         R 2  is a hydrogen atom or a C 1-3  alkyl group (the C 1-3  alkyl group may be substituted with one or more halogen atoms), 
         R 3  is a phenyl group or a pyridyl group (the phenyl group and the pyridyl group are substituted with one or more substituents selected from the group consisting of hydrogen atoms, nitro groups, halogen atoms and C 1-3  alkyl groups (the C 1-3  alkyl groups may be substituted with one or more halogen atoms) and with (C═O)R 5  (wherein R 5  is NR 6 R 7  (wherein R 6  is a C 1-3  alkyl group (the C 1-3  alkyl group may be substituted with one or more halogen atoms), and R 7  is a C 1-6  alkyl group (the C 1-6  alkyl group may be substituted with one or more halogen atoms, one or more hydroxyl groups, one or more C 1-3  alkoxy groups or one or more C 2-14  aryl groups (the C 2-14  aryl groups may be substituted with one or more C 1-3  alkyl groups, one or more C 1-3  alkoxy groups, one or more carboxyl groups, one or more carbamoyl groups, one or more cyano groups or one or more halogen atoms, and in the case of aryl groups containing one or more nitrogen atoms, may be N-oxides thereof)), a phenyl group, a thienyl group, a pyridyl group or a pyridyl-N-oxide group (the phenyl group, the thienyl group, the pyridyl group and the pyridyl-N-oxide group may be substituted with one or more halogen atoms), or NR 6 R 7  is, as a whole, a nitrogen-containing heterocyclyl group (the nitrogen-containing heterocyclyl group may be substituted with one or more hydrogen atoms, one or more C 1-6  alkyl groups (the C 1-6  alkyl groups may be substituted with one or more halogen atoms), one or more halogen atoms, one or more hydroxyl groups or one or more C 1-3  alkoxy groups (the C 1-3  alkoxy groups may be substituted with one or more halogen atoms))) or a C 1-6  alkyl group (the C 1-6  alkyl group may be substituted with one or more halogen atoms, one or more pyridyl groups, one or more pyridyl-N-oxide groups, one or more furyl groups, one or more thienyl groups or one or more phenyl groups or substituted with one or more cyano groups))), and 
         R 4  is a hydrogen atom or a C 1-3  alkyl group (the C 1-3  alkyl group may be substituted with one or more halogen atoms), a tautomer, prodrug or pharmaceutically acceptable salt of the compound. 
       
     
     
         41 . A pharmaceutical composition comprising at least one compound of  claim 40 , a tautomer, prodrug or pharmaceutically acceptable salt of the compound, as an active ingredient. 
     
     
         42 . The pharmaceutical composition of  claim 41 , which comprises the active ingredient and at least one pharmaceutically acceptable additive.