Compounds exhibiting thrombopoietin receptor agonism

Abstract

A compound represented by the general formula (I): wherein R 1 is a hydrogen atom, a halogen atom, or the like; R 2 , R 3 , and R 4 are each independently a hydrogen atom, a halogen atom, C1-C15 alkyl optionally substituted with one or more C1-C12 alkyloxy or the like, or the like; R 5 is a hydrogen atom or the like; R 6 and R 7 are a hydrogen atom or the like; R 8 is C1-C3 alkyl or the like; R 9 is a hydrogen atom or the like), a prodrug, a pharmaceutically acceptable salt, or solvate thereof.

1 - 12 . (canceled) 
   
   
       13 . A compound represented by the general formula (III): 
     
       
         
         
             
             
         
       
     
     wherein R E  is C1-C15 alkyl optionally substituted with one or two substituent(s) selected from substituent group C, C2-C15 alkynyl optionally substituted with one or two substituent(s) selected from substituent group C, or C1-C15 alkyloxy optionally substituted with one or two substituent(s) selected from substituent group C;
 Z is straight-chain C1-C4 alkylene optionally substituted with C1-C8 alkyl, which may contain an optionally substituted heteroatom(s) or straight-chain C2-C4 alkenylene optionally substituted with C1-C8 alkyl, which may contain an optionally substituted heteroatom(s) 
 R 6  and R 7  are each independently halogen atom or C1-C3 alkyl; 
 R 8  is halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy; 
 substituent group C consists of halogen atom, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, naphthyl, pyridyl, oxolanyl, cyano, C1-C8 alkyloxy, C2-C8 alkenyloxy, C2-C8 alkynyloxy, C3-C8 cycloalkyl-C1-C8 alkyloxy, phenyl-C1-C8 alkyloxy, naphthyl-C1-C8 alkyloxy, C1-C8 alkyloxy-C1-C8 alkyloxy, (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy, di(C1-C8 alkyloxy)C1-C8 alkyloxy, oxolanyl-C1-C8 alkyloxy, haloC1-C8 alkyloxy, C3-C8 cycloalkyloxy, amino optionally substituted with C1-C8 alkyl, C1-C8 alkylthio, and C1-C8 alkylthio-C1-C8 alkyloxy; 
 
     a pharmaceutically acceptable salt, or solvate thereof. 
   
   
       14 . A compound of  claim 13 , wherein both of R 6  and R 7  are fluorine atom or chlorine atom, a pharmaceutically acceptable salt, or solvate thereof. 
   
   
       15 . A compound of  claim 13 , wherein R 8  is methyl or methyloxy, a pharmaceutically acceptable salt, or solvate thereof. 
   
   
       16 . A compound of  claim 13 , wherein Z is C1-C4 alkylene, —O—(C1-C3 alkylene)- or —(C1-C3 alkylene)-O—, a pharmaceutically acceptable salt, or solvate thereof. 
   
   
       17 . A compound of any one of  claims 13  to  16 , wherein R E  is C1-C10 alkyl optionally substituted with one or two substituent(s) selected from substituent group C, C2-CG 0 alkynyl optionally substituted with one or two substituent(s) selected from substituent group C, or C1-C10 alkyloxy optionally substituted with one or two substituent(s) selected from substituent group C, a pharmaceutically acceptable salt, or solvate thereof. 
   
   
       18 . A compound of  claim 13 , wherein both of R 6  and R 7  are fluorine atom or chlorine atom, R 8  is methyl or methyloxy, R E  is C1-C8 alkyl optionally substituted with one or two C1-C6 alkyloxy, Z is C1-C2 alkylene, a pharmaceutically acceptable salt, or solvate thereof. 
   
   
       19 - 23 . (canceled) 
   
   
       24 . A pharmaceutical composition containing a compound as an active ingredient, a pharmaceutically acceptable salt, or solvate thereof of any one of  claims 13  to  16  or  18 . 
   
   
       25 . A pharmaceutical composition containing a compound as an active ingredient, a pharmaceutically acceptable salt, or solvate thereof of any one of  claims 13  to  16  or  18 , in an amount effective for exhibiting thrombopoietin receptor agonism. 
   
   
       26 . A pharmaceutical composition containing a compound as an active ingredient, a pharmaceutically acceptable salt, or solvate thereof of any one of  claims 13  to  16  or  18 , in an amount effective for modifying platelet production. 
   
   
       27 . (canceled) 
   
   
       28 . A method for treating or preventing hemopathy in a mammal, including a human, in need thereof, comprising
 administering to said mammal a compound, a pharmaceutically acceptable salt, or solvate thereof of any one of  claims 13  to  16  or  18  in an amount effective for modifying platelet production.