Compounds exhibiting thrombopoietin receptor agonism

Abstract

Pharmaceutical compositions containing as an active ingredient compounds of the general formula (I), prodrugs of the same, pharmaceutically acceptable salts of both, or solvates of them and exhibiting thrombopoietin receptor agonism: X 1 —Y 1 -Z 1 -W 1   (I) wherein X 1 is optionally substituted aryl, optionally substituted heteroaryl or the like; Y 1 is —NR A CO—(CH 2 ) 0-2 — or the like (wherein R A is a hydrogen or the like); Z 1 is optionally substituted phenylene or the like; and W 1 is a group represented by the below formula: wherein R 1 , R 2 , R 3 , and R 4 are each independently a hydrogen atom, optionally substituted lower alkyl or the like, a broken line (---) represents the presence or absence of bond.

1 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism which contains as an active ingredient a compound of the general formula (I):
   X 1 —Y 1 -Z 1 -W 1   (I)   wherein X 1  is optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl;   Y 1  is —NR A CO—(CR C R D ) 0-2 —, —NR A CO—(CH 2 ) 0-2 —V—, —NR A CR C ═CR D —, —V—(CH 2 ) 1-5 —NR A CO—(CH 2 ) 0-2 —, —V—(CH 2 ) 1-5 —CONR A —(CH 2 ) 0-2 —, —CONR A —(CH 2 ) 0-2 —, —(CH 2 ) 0-2 —NR A —SO 2 —(CH 2 ) 0-2 —, —(CH 2 ) 0-2 —, SO 2 —NR A —(CH 2 ) 0-2 —, —NR A —(CH 2 ) 0-2 , —NR A —CO—NR A —, —NR A —CS—NR A —, —N═C(—SR A )—NR A , —NR A CSNR A CO—, —N═C(—SR A )—NR A CO—, —NR A —(CH 2 ) 1-2 —NR A —CO—, —NR A CONR A NR B CO—, or —N═C(—NR A R A )—NR A —CO—,   wherein R A  is each independently a hydrogen atom or lower alkyl; R B  is a hydrogen atom or phenyl; R C  and R D  are each independently a hydrogen atom, halogen atom, optionally substituted lower alkyl, optionally substituted lower alkyloxy, optionally substituted lower alkylthio, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, optionally substituted non-aromatic heterocyclic group, or optionally substituted amino; V is an oxygen atom or a sulfur atom;   Z 1  is optionally substituted phenylene, optionally substituted monocyclic heteroarylene, optionally substituted monocyclic non-aromatic heterocycle-diyl, or optionally substituted monocyclic cycloalkane-diyl;   W 1  is a group represented by the formula:   
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 7 , and R 8  are each independently a hydrogen atom, halogen atom, optionally substituted lower alkyl, optionally substituted lower alkyloxy, optionally substituted lower alkylthio, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, optionally substituted nonaromatic heterocyclic group, or optionally substituted amino; 
       R 5 , R 6 , and R 9  are each independently a hydrogen atom, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, or optionally substituted non-aromatic heterocyclic group; 
       A 1  is a optionally substituted aryl or optionally substituted heteroaryl; 
       a broken line (---) represents the presence or absence of a bond, 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       2 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism of  claim 1 , wherein X 1  is optionally substituted heteroaryl. 
   
   
       3 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism of  claim 1 , wherein X 1  is a group represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 10  and R 11  are each independently a hydrogen atom, optionally substituted lower alkyl, carboxy, lower alkyloxycarbonyl, halogen atom, optionally substituted aminocarbonyl, optionally substituted heteroaryl, or optionally substituted aryl; 
       R 12  is a hydrogen atom or lower alkyl. 
     
   
   
       4 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism which contains a compound of  claim 1 , wherein X 1  is a group represented by the formula: 
     
       
         
         
             
             
         
       
     
   
   
       5 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism of any one of  claims 1  to  4 , wherein Y 1  is —NHCO—, —CONH—, —NHCH 2 —, —NHCO—CH═CH—, or —NHSO 2 —. 
   
   
       6 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism of any one of  claims 1  to  4 , wherein Y 1  is —NHCO—. 
   
   
       7 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism of any one of  claims 1  to  4 , wherein Z 1  is 1,4-phenylene optionally substituted with halogen atom or lower alkyl. 
   
   
       8 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism of any one of  claims 1  to  4 , wherein R 1  is a hydrogen atom or lower alkyl. 
   
   
       9 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism of any one of  claims 1  to  4 , wherein R 2  is a hydrogen atom, lower alkyl, halogen atom, lower alkyloxy, lower alkylthio, or optionally substituted amino. 
   
   
       10 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism of any one of  claims 1  to  4 , wherein W 1  is a group represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 13  is a hydrogen atom, lower alkyl, lower alkyloxy, lower alkylthio, or halogen atom; 
       R 14  and R 15  are each independently a hydrogen atom, or optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl, each substituted by one or more substituent(s) selected from substituent group A; 
       a broken line (---) represents the presence or absence of a bond; 
       substituent group A consists of a halogen atom, halo(lower)alkyl, optionally substituted amino, carboxy, lower alkylthio, lower alkylsilyl, or lower alkyloxy. 
     
   
   
       11 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism of any one of  claims 1  to  4 , wherein W 1  is a group represented by the formula: 
     
       
         
         
             
             
         
       
       R 13  is a hydrogen atom, lower alkyl, lower alkyloxy, lower alkylthio, or halogen atom; 
       R 26  is a hydrogen atom or lower alkyl; 
       a broken line (---) represents the presence or absence of a bond; 
     
   
   
       12 . A pharmaceutical composition exhibiting thrombopoietin receptor agonism of any one of  claims 1  to  4 , which is a platelet production modifier. 
   
   
       13 . A pharmaceutical composition for platelet production modification, comprising at least one compound according to  claim 1  and at least one of an excipient, binder, penetrant, disintegrator, or lubricant. 
   
   
       14 . A method for modifying a platelet production of a mammal, including a human, which comprises administration to said mammal of a compound of any one of  claims 1  to  4  in a pharmaceutically effective amount. 
   
   
       15 . A compound represented by the general formula (II):
   X 2 —Y 2 -Z 2 -W 2   (II)   wherein X 2  is optionally substituted 5-member heteroaryl or optionally substituted pyridyl:   Y 2  is —NR A CO—(CR C R D ) 0-2 —, —NR A CO—(CH 2 ) 0-2 —V—, —NR A CO—CR C ═CR D —, —V—(CH 2 ) 1-5 —NR A CO—(CH 2 ) 0-2 —, —V—(CH 2 ) 1-5 —CONR A —(CH 2 ) 0-2 —, —CONR A —(CH 2 ) 0-2 , —(CH 2 ) 0-2 —NR A SO 2 —(CH 2 ) 0-2 —, —(CH 2 ) 0-2 —SO 2 —NR A —(CH 2 ) 0-2 —, —NR A —(CH 2 ) 0-2 —, —NR A —CO—NR A —, —NR A —CS—NR A —, —N═C(—SR A )—NR A —, —NR A CSNR A —CO—, —N═C(—SR A )—NR A CO—, —NR A —(CH 2 ) 1-2 —NR A —CO—, —NR A CONR A NR B —CO—, or —N═C(—NR A R A )—NR A —CO—,   wherein R A  is each independently a hydrogen atom or lower alkyl; R B  is a hydrogen atom or phenyl; R C  and R D  are each independently a hydrogen atom, halogen atom, optionally substituted lower alkyl, optionally substituted lower alkyloxy, optionally substituted lower alkylthio, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroaryl-alkyl, optionally substituted non-aromatic heterocyclic group, or optionally substituted amino; V is an oxygen atom or a sulfur atom;   Z 2  is optionally substituted phenylene, optionally substituted 2,5-pyridine-diyl, optionally substituted 2,5-thiophene-diyl, or optionally substituted 2,5-furan-diyl;   W 2  is a group represented by the formula:   
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 7 , and R 8  are each independently a hydrogen atom, halogen atom, optionally substituted lower alkyl, optionally substituted lower alkyloxy, optionally substituted lower alkylthio, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, optionally substituted nonaromaticheterocyclic group, or optionally substituted amino; 
       R 5 , R 6 , and R 9  are each independently a hydrogen atom, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, or optionally substituted non-aromatic heterocyclic group; 
       A 2  is a optionally substituted aryl or optionally substituted heteroaryl; 
       a broken line (---) represents the presence or absence of a bond, 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       16 . A compound of  claim 15 , wherein X 2  is a group represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 10  and R 11  are each independently a hydrogen atom, optionally substituted lower alkyl, carboxy, lower alkyloxycarbonyl, halogen atom, optionally substituted aminocarbonyl, optionally substituted heteroaryl, or optionally substituted aryl, 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       17 . A compound in of  claim 15  or  16 , wherein X 2  is a group represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 16  is a hydrogen atom, optionally substituted lower alkyl, carboxy, lower alkyloxycarbonyl, halogen atom, or optionally substituted amino carbonyl; 
       R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , and R 23  are each independently a hydrogen atom, optionally substituted lower alkyl by one or more substituent(s) selected from substituent group B, cycloalkyl, optionally substituted alkyoxy by one or more substituent(s) selected from substituent group B, alkylthio, halogen atom, optionally substituted phenyl by one or more substituent(s) selected from substituent group C, optionally substituted heteroaryl by one or more substituent(s) selected from substituent group C, or optionally substituted nonaromatic heterocyclic group by one or more substituent(s) selected from substituent group C; 
       substituent group B consists of hydroxy, alkyloxy, halogen atom, carboxy, lower alkyloxycarbonyl, aryloxycarbonyl, optionally substituted amino, optionally substituted phenyl by one or more substituent(s) selected from substituent group C, non-aromatic heterocyclic group, or heteroaryl; 
       substituent group C consists of hydroxy, alkyl, halogen atom, halo(lower)alkyl, carboxy, lower alkyloxycarbonyl, alkyloxy, optionally substituted amino, non-aromaticheterocyclic group, or heteroaryl; or 
       R 16  and R 17  taken together may form —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —OCH 2 —, or —SCH 2 —; 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       18 . A compound of any one of  claims 15  or  16 , wherein Y 2  is —NHCO—;
 its prodrug, or pharmaceutically acceptable salts or solvates thereof.   
   
   
       19 . A compound of any one of  claims 15  or  16 , wherein Z 2  is 1,4-phenylene optionally substituted with halogen atom or lower alkyl;
 its prodrug, or pharmaceutically acceptable salts or solvates thereof.   
   
   
       20 . A compound of any one of  claims 15  or  16 , wherein R 1  is a hydrogen atom or lower alkyl;
 its prodrug, or pharmaceutically acceptable salts or solvates thereof.   
   
   
       21 . A compound of any one of  claims 15  or  16 , wherein R 2  is a hydrogen atom, lower alkyl, halogen atom, lower alkyloxy, lower alkylthio, or optionally substituted amino;
 its prodrug, or their pharmaceutically acceptable salts or solvates thereof.   
   
   
       22 . A compound of any one of  claims 15  or  16 , wherein W 2  is a group represented by the formula: 
     
       
         
         
             
             
         
       
       wherein, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8  and A 2  are as defined in  claim 15 ; provided that R 2  is not imidazolyl, triazolyl, or tetrazolyl; 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       23 . A compound of any one of  claims 15  or  16 , wherein W 2  is a group represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 13  is a hydrogen atom, lower alkyl, lower alkyloxy, lower alkylthio, or halogen atom; 
       R 14  and R 15  are each independently a hydrogen atom, or optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl, each substituted by one or more substituent(s) selected from substituent group A; 
       substituent group A consists of a halogen atom, halo(lower)alkyl, optionally substituted amino, carboxy, lower alkylthio, lower alkylsilyl, or lower alkyloxy; 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       24 . A compound of any one of  claims 15  or  16 , wherein W2 is a group represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 13  is a hydrogen atom, lower alkyl, lower alkyloxy, lower alkylthio, or halogen atom; 
       R 26  is a hydrogen atom or lower alkyl; 
       a broken line (---) represents the presence or absence of a bond; 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       25 . (canceled) 
   
   
       26 . (canceled) 
   
   
       27 . A compound represented by the general formula (IV-B): 
     
       
         
         
             
             
         
       
       wherein R 28 , R 29 , and R 30  are each independently a hydrogen atom, optionally substituted lower alkyl by one or more substituent(s) selected from substituent group B, cycloalkyl, optionally substituted alkyoxy by one or more substituent(s) selected from substituent group B, alkylthio, halogen atom, optionally substituted phenyl by one or more substituent(s) selected from substituent group C, optionally substituted heteroaryl by one or more substituent(s) selected from substituent group C, or optionally substituted nonaromatic heterocyclic group by one or more substituent(s) selected from substituent group C; 
       substituent group B consists of hydroxy, alkyloxy, halogen atom, carboxy, lower alkyloxycarbonyl, aryloxycarbonyl, optionally substituted amino, optionally substituted phenyl by one or more substituent(s) selected from substituent group C, non-aromatic heterocyclic group, or heteroaryl; 
       substituent group C consists of hydroxy, alkyl, halogen atom, halo(lower)alkyl, carboxy, lower alkyloxycarbonyl, alkyloxy, optionally substituted amino, non-aromatic heterocyclic group, or heteroaryl; 
       R 31  and R 32  are each independently a hydrogen atom, lower alkyl, halogen atom, haro(lower)alkyl, lower alkyloxy, halo(lower)alkyloxy, or hydroxy; 
       W4 is a group represented by the formula: 
     
     
       
         
         
             
             
         
       
       wherein R 13  is a hydrogen atom, lower alkyl, lower alkyloxy, lower alkylthio, or halogen atom; 
       R 14  and R 15  are each independently a hydrogen atom, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, or optionally substituted non-aromatic heterocyclic group, each substituted by one or more substituent(s) selected 
       from substituent group A; 
       substituent group A consists of a halogen atom, halo(lower)alkyl, optionally substituted amino, carboxy, lower alkylthio, lower alkylsilyl, or lower alkyloxy; 
       R 24  is a hydrogen atom or lower alkyl; 
       T is —CH2-, —CH2CH2-, —CH2CH2CH2-, —OCH2-, or —SCH2-; 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       28 . A pharmaceutical composition containing as the active ingredient a compound of any one of  claims 15  or  27 . 
   
   
       29 . A pharmaceutical composition containing as the active ingredient a compound of any one of  claims 15  or  27 , which is exhibiting thrombopoietin receptor agonism. 
   
   
       30 . A platelet production modifier which contains as the active ingredient a compound of any one of  claims 15  or  27 . 
   
   
       31 . A pharmaceutical composition for platelet production modification, comprising at least one compound according to any one of  claims 15  or  27  and at least one of an excipient, binder, penetrant, disintegrator, or lubricant. 
   
   
       32 . A method for modifying a platelet production of a mammal, including a human, which comprises administration to said mammal of a compound of any one of  claims 15  or  27  in a pharmaceutically effective amount. 
   
   
       33 . A compound represented by the general formula (II):
   X 2 —Y 2 -Z 2 -W 2   (II)   wherein X 2  is optionally substituted 5-membered heteroaryl or optionally substituted pyridyl;   Y 2  is —NR A CO—(CR C R D ) 0-2 —, —NR A CO—(CH 2 ) 0-2 —V—, —NR A CO—CR C ═CR D —, —V—(CH 2 ) 1-5 —NR A CO—(CH 2 ) 0-2 —, —V—(CH 2 ) 1-5 —CONR A —(CH 2 ) 0-2 —, —CONR A —(CH 2 ) 0-2 , —(CH 2 ) 0-2 —NR A SO 2 —(CH 2 ) 0-2 —, —(CH 2 ) 0-2 —SO 2 —NR A —(CH 2 ) 0-2 —, —NR A —(CH 2 ) 0-2 —, —NR A —CO—NR A —, —NR A —CS—NR A —, —N═C(—SR A )—NR A —, —NR A CSNR A CO—, —N═C(—SR A )—NR A CO—, —NR A —(CH 2 ) 1-2 —NR A —CO—, —NR A CONR A NR B —CO—, or —N═C(—NR A R A )—NR A —CO—,   wherein R A  is each independently a hydrogen atom or lower alkyl; R B  is a hydrogen atom or phenyl; R C  and R D  are each independently a hydrogen atom, halogen atom, optionally substituted lower alkyl, optionally substituted lower alkyloxy, optionally substituted lower alkylthio, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, optionally substituted non-aromatic heterocyclic group, or optionally substituted amino;   V is an oxygen atom or a sulfur atom;   Z 2  is optionally substituted phenylene, optionally substituted 2,5-pyridine-diyl, optionally substituted 2,5-thiophene-diyl, or optionally substituted 2,5-furan-diyl;   W 2  is a group represented by the formula:   
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 7 , and R 8  are each independently a hydrogen atom, halogen atom, optionally substituted lower alkyl, optionally substituted lower alkyloxy, optionally substituted lower alkylthio, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, optionally substituted non-aromatic heterocyclic group, or optionally substituted amino; R 5 , R 6 , and R 9  are each independently a hydrogen atom, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, or optionally substituted non-aromatic heterocyclic group; 
       A 2  is optionally substituted aryl or optionally substituted heteroaryl; 
       a broken line (---) represents the presence or absence of a bond, provided that, 
       1) when X 2  is thiazolyl optionally substituted with alkyl, or benzothiazolyl optionally substituted with alkoxyl or diethylamino; Z 2  is 1,4-phenylene; and 
       W 2  is a group represented by the formula: 
     
     
       
         
         
             
             
         
       
       R 2  is not optionally substituted imidazolyl, optionally substituted triazolyl, or optionally substituted tetrazolyl, 
       2) when X 2  is 2-pyridyl; Y 2  is —NHCO—CH═CH—, or —NHCSNHCO—; Z 2  is 1,4-phenylene; and W 2  is a group represented by the formula: 
     
     
       
         
         
             
             
         
       
       R 2  is not triazolyl, 
       3) when X 2  is benzothiazolyl; Y 2  is —NHCO—CH═CH—; Z 2  is 1,4-phenylene; and 
       W 2  is a group represented by the formula: 
     
     
       
         
         
             
             
         
       
       R 2  is not 2-pyridyl or carboxymethyl, 
       4) when X 2  is benzothiazolyl; Y 2  is —NHCO—; and Z 2  is 1,4-phenylene; 
       W 2  is not a group represented by the formula: 
     
     
       
         
         
             
             
         
       
       5) when X 2  is thiazolyl optionally substituted with methyl, t-butyl, or unsubstituted phenyl, or benzothiazolyl optionally substituted with alkyl or diethylaminoethyl; Z 2  is optionally substituted phenylene; and W 2  is —CH═O, Y 2  is not —NHCO—(CH 2 ) 0-2 —, —NHCO—CH═CH—, —NHCO—CH 2 —O—, or —NHCO—CH 2 —NMe-, 
       6) when Y 2  is —NH—CH 2 —; Z 2  is 1,4-phenylene; W 2  is optionally substituted tetrazolyl wherein 2-position is substituted phenyl, X 2  is not thiadiazolyl, thiazolyl, benzothiazolyl, oxadiazazolyl, imidazolyl, or oxazolyl, 
       7) when X 2  is optionally substituted benzothiazolyl; Z 2  is 1,4-phenylene; and 
       W 2  is a group represented by the formula: 
     
     
       
         
         
             
             
         
       
       Y 2  is not —NHCO—, —NH—CH 2 —, —NEt-CH 2 —, or —NH— 
       8) when X 2  is optionally substituted benzothiazolyl; Y 2  is —NH—; and Z 2  is 1,4-phenylene; W 2  is not —CH 2 COOH or —CH 2 COOEt, 
       9) when X 2  is optionally substituted benzothiazolyl; Y 2  is —NH—; and Z 2  is 2,5-pyridinediyl; 
       W 2  is not —COOH or —CONH 2 , 
       10) when X 2  is optionally substituted benzothiazolyl; 
       Z 2  is phenylene optionally substituted with methyl or chlorine atom; and W 2  is —COOH, —COOEt, or —CONH 2 , Y 2  is not —NH—, —NH—CH 2 —, —NH—CO—, or —NH—SO 2 —, its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       34 . A compound of  claim 33  wherein X 2  is represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 10  and R 11  are each independently a hydrogen atom, optionally substituted lower alkyl, carboxy, lower alkyloxycarbonyl, halogen atom, optionally substituted aminocarbonyl, optionally substituted heteroaryl, or optionally substituted aryl; 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       35 . A compound of  claim 33  or  34  wherein X 2  is represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 16  is a hydrogen atom, optionally substituted lower alkyl, carboxy, lower alkyloxycarbonyl, halogen atom, or optionally substituted aminocarbonyl; 
       R 17 , R 18 , R 19 , R 20 , R 21 , R 22 , and R 23  are each independently a hydrogen atom, optionally substituted lower alkyl by one or more substituent(s) selected from substituent group B, cycloalkyl, optionally substituted alkyoxy by one or more substituent(s) selected from substituent group B, alkylthio, halogen atom, optionally substituted phenyl by one or more substituent(s) selected from substituent group C, optionally substituted heteroaryl by one or more substituent(s) selected from substituent group C, or optionally substituted nonaromatic heterocyclic group by one or more substituent(s) selected from substituent group C; 
       substituent group B consists of hydroxy, alkyloxy, halogen atom, carboxy, lower alkyloxycarbonyl, aryloxycarbonyl, optionally substituted amino, optionally substituted phenyl by one or more substituent(s) selected from substituent group C, non-aromatic heterocyclic group, and heteroaryl; 
       substituent group C consists of hydroxy, alkyl, halogen atom, halo(lower)alkyl, carboxy, lower alkyloxycarbonyl, alkyloxy, optionally substituted amino, non-aromatic heterocyclic group, and heteroaryl; or 
       R 16  and R 17  taken together may form —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —OCH 2 —, or SCH 2 —; 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       36 . A compound of any one of  claims 33  or  34 , wherein Y 2  is —NHCO—;
 its prodrug, or pharmaceutically acceptable salts or solvates thereof.   
   
   
       37 . A compound of any one of  claims 33  or  34 , wherein Z 2  is 1,4-phenylene optionally substituted with halogen atom or lower alkyl;
 its prodrug, or pharmaceutically acceptable salts or solvates thereof.   
   
   
       38 . A compound of any one of  claims 33  or  34 , wherein R 1  is a hydrogen atom or lower alkyl;
 its prodrug, or pharmaceutically acceptable salts or solvates thereof.   
   
   
       39 . A compound of any one of  claims 33  or  34 , wherein R 2  is a hydrogen atom, lower alkyl, halogen atom, lower alkyloxy, lower alkylthio, or optionally substituted amino;
 its prodrug, or pharmaceutically acceptable salts or solvates thereof.   
   
   
       40 . A compound of any one of  claims 33  or  34 , wherein W 2  is a group represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 1 , R 2 , R 3 , R 4 , R 7 , and R 8  are each independently a hydrogen atom, halogen atom, optionally substituted lower alkyl, optionally substituted lower alkyloxy, optionally substituted lower alkylthio, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, optionally substituted nonaromaticheterocyclic group, or optionally substituted amino; 
       R 5 , R 6 , and R 9  are each independently a hydrogen atom, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroarylalkyl, or optionally substituted non-aromatic heterocyclic group; 
       A 2  is a optionally substituted aryl or optionally substituted heteroaryl; 
       provided that R 2  is not imidazolyl, triazolyl, or tetrazolyl; 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       41 . A compound of any one of  claims 33  or  34 , wherein W 2  is a group represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 13  is a hydrogen atom, lower alkyl, lower alkyloxy, lower alkylthio, or halogen atom; 
       R 14  and R 15  are each independently a hydrogen atom, or optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl, each substituted by one or more substituent(s) selected from substituent group A; 
       substituent group A consists of a halogen atom, halo(lower)alkyl, optionally substituted amino, carboxy, lower alkylthio, lower alkylsilyl, or lower alkyloxy; 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       42 . A compound of any one of  claims 33  or  34 , wherein W 2  is a group represented by the formula: 
     
       
         
         
             
             
         
       
       wherein R 13  is a hydrogen atom, lower alkyl, lower alkyloxy, lower alkylthio, or halogen atom; 
       R 26  is a hydrogen atom or lower alkyl; 
       a broken line (---) represents the presence or absence of a bond; 
       its prodrug, or pharmaceutically acceptable salts or solvates thereof. 
     
   
   
       43 . A pharmaceutical composition containing as an active ingredient a compound of any one of  claims 33  or  34 . 
   
   
       44 . A pharmaceutical composition containing as an active ingredient a compound of any one of  claims 33  or  34 , which exhibits thrombopoietin receptor agonism. 
   
   
       45 . A composition for use as a platelet production modifier which contains as an active ingredient a compound of any one of  claims 33  or  34 . 
   
   
       46 . A pharmaceutical composition for platelet production modification, comprising at least one compound according to  claim 33  or  34  and at least one of an excipient, binder, penetrant, disintegrator, or lubricant. 
   
   
       47 . A method for modifying the platelet production of a mammal, including a human, which comprises administration to said mammal of a compound of any one of  claims 33  or  34  in a pharmaceutically effective amount.