Phenylazole compounds, production process and antioxidants

Abstract

The present invention is directed to compounds represented by the formula (1): B-D-Z (1), wherein B represent the following formula (B-1), A represents an optionally substituted imidazole or pyrazole group; E represents the following formula (1a): X represents an oxygen atom, the formula: SOu, or the formula: N—R 9 ; Y represents a carbon atom or a nitrogen atom; D represents an oxygen atom, a sulfur atom or the formula (1a); Z represents (a chroman-2-yl group, a chroman-4-yl group, a 2,3-dihydrobenzofuran-2-yl group, a 2,3-dihydrobenzofuran-3-yl group, etc.) which is substituted with NHR 10 or OR 11 )] or pharmaceutically acceptable salts thereof, and to antioxidants, therapeutic agents for kidney diseases or cerebrovascular disorder, and retinal oxidative damage inhibitors, which include the compounds as the active ingredient.

1 . A compound represented by the formula (1):
   B-D-Z  (1)   
     [wherein B represents the following formula (B-1): 
     
       
         
         
             
             
         
       
       A represents an imidazolyl or pyrazolyl group represented by the following formula (A-1), (A-2), (A-3) or (A-4): 
     
     
       
         
         
             
             
         
       
     
     (wherein R 4  and R 5  each independently represents a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkoxy group which may be substituted with G1, a C 1-6  alkylsulfonyl group which may be substituted with G1, or a halogen atom; R 6  represents a hydrogen atom, a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkylcarbonyl group which may be substituted with G1, or a benzoyl group which may be substituted with G1, or a tetrahydropyranyl group;
 G1 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom, 
 s represents 0 or an integer of 1 to 3, 
 t represents 0 or an integer of 1 or 2, and 
 R 4 (s) or R 5 (s) may be the same or different when s or t is 2 or more); 
 R 1  represents a halogen atom, a nitro group, a cyano group, a hydroxyl group, a C 1-6  alkyl group which may be substituted with G2, a C 1-6  alkoxy group which may be substituted with G2, a C 1-6  alkylthio group which may be substituted with G2, a C 1-6  alkylcarbonyl group which may be substituted with G2, an amino group (which may be substituted with one or two C 1-6  alkyl groups), a benzoyl group which may be substituted with G2, or a benzyl group which may be substituted with G2; 
 R 2  represents a C 1-6  alkyl group which may be substituted with G2; 
 G2 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, a C 1-6  alkoxycarbonyl group, a nitro group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom; 
 m represents 0 or an integer of 1 to 4, and R 1 (s) may be the same or different when m is 2 or more; 
 o represents an integer of 2; 
 n represents 0 or an integer of 1 to 10, and R 2 (s) may be the same or different when n is 2 or more; 
 in the formula (B-1), the dotted line represents a single bond or a double bond and does not simultaneously represent a double bond; 
 Y represents a carbon atom or a nitrogen atom, which may have a substituent selected from the group consisting of a hydrogen and a hydroxyl or a multiple bond that satisfies a valence; 
 E represents an oxygen atom, a sulfur atom or the 
 
     
       
         
         
             
             
         
       
     
     following formula (1a) when Y represents a carbon atom; (wherein R 60  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group); R 7  and R 8  each independently represents a hydrogen atom, a cyano group, a hydroxyl group, a halogen atom, a C 1-6  alkyl group, a C 1-6  alkoxy group, a C 2-6  alkenyl group, a C 2-6  alkynyl group, a C 2-6  alkenyloxy group, a C 2-6  alkynyloxy group, a C 1-6  acyloxy group, a C 3-6  cycloalkyl group which may be substituted with G2, or a phenyl group which may be substituted with G2;
 j and k independently represent 0 or an integer of 1; 
 l represents 0 or an integer of 1 to 16; 
 R 7 (s) and R 8 (s) may be the same or different when 1 is 2 or more); 
 E represents the formula (1a) when Y represents a nitrogen atom; 
 D represents the formula (1a); 
 Z represents a 2,3-dihydrobenzofuran-2-yl group which is substituted with G3, a 2,3-dihydrobenzofuran-3-yl group which is substituted with G3; 
 G3 represents the formula: NHR 10    
 
     {wherein R 10  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group)}; 
     or the formula: OR 11    
     {wherein R 11  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a hydroxyl group, a C 1-6  alkoxy group, a halogen atom, or a C 1-6  alkyl group)}] 
     or a pharmaceutically acceptable salt thereof. 
   
   
       2 . A compound represented by the formula (1):
   B-D-Z  (1)   
     [wherein B represents the following formula (B-1): 
     
       
         
         
             
             
         
       
       A represents an imidazolyl or pyrazolyl group represented by the following formula (A-1), (A-2), (A-3) or (A-4): 
     
     
       
         
         
             
             
         
       
     
     (wherein R 4  and R 5  each independently represents a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkoxy group which may be substituted with G1, a C 1-6  alkylsulfonyl group which may be substituted with G1, or a halogen atom; R 6  represents a hydrogen atom, a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkylcarbonyl group which may be substituted with G1, or a benzoyl group which may be substituted with G1, or a tetrahydropyranyl group;
 G1 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom, 
 s represents 0 or an integer of 1 to 3, 
 t represents 0 or an integer of 1 or 2, and 
 R 4 (s) or R 5 (s) may be the same or different when s or t is 2 or more); 
 R 1  represents a halogen atom, a nitro group, a cyano group, a hydroxyl group, a C 1-6  alkyl group which may be substituted with G2, a C 1-6  alkoxy group which may be substituted with G2, a C 1-6  alkylthio group which may be substituted with G2, a C 1-6  alkylcarbonyl group which may be substituted with G2, an amino group (which may be substituted with one or two C 1-6  alkyl groups), a benzoyl group which may be substituted with G2, or a benzyl group which may be substituted with G2; 
 R 2  represents a C 1-6  alkyl group which may be substituted with G2; 
 G2 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, a C 1-6  alkoxycarbonyl group, a nitro group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom; 
 m represents 0 or an integer of 1 to 4, and R 1 (s) may be the same or different when m is 2 or more; 
 o represents an integer of 1 or 2; 
 when o is 1, n represents 0 or an integer of 1 to 8, when o is 2 n represents 0 or an integer of 1 to 10, and R 2 (s) may be the same or different when n is 2 or more; 
 in the formula (B-1), the dotted line represents a single bond or a double bond and does not simultaneously represent a double bond; 
 Y represents a carbon atom or a nitrogen atom, which may have a substituent selected from the group consisting of a hydrogen and a hydroxyl or a multiple bond that satisfies a valence; 
 E represents an oxygen atom, a sulfur atom or the 
 
     
       
         
         
             
             
         
       
     
     following formula (1a) when Y represents a carbon atom; (wherein R 60  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group); R 7  and R 8  each independently represents a hydrogen atom, a cyano group, a hydroxyl group, a halogen atom, a C 1-6  alkyl group, a C 1-6  alkoxy group, a C 2-6  alkenyl group, a C 2-6  alkynyl group, a C 2-6  alkenyloxy group, a C 2-6  alkynyloxy group, a C 1-6  acyloxy group, a C 3-6  cycloalkyl group which may be substituted with G2, or a phenyl group which may be substituted with G2;
 j and k independently represent 0 or an integer of 1; 
 l represents 0 or an integer of 1 to 16; 
 R 7 (s) and R 8 (s) may be the same or different when 1 is 2 or more); 
 E represents the formula (1a) when Y represents a nitrogen atom; 
 D represents the formula (1a); 
 Z represents a chroman-2-yl group which is substituted with G3, a chroman-4-yl group which is substituted with G3; 
 G3 represents the formula: NHR 10    
 
     {wherein R 10  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group)}; 
     or the formula: OR 11    
     {wherein R 11  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a hydroxyl group, a C 1-6  alkoxy group, a halogen atom, or a C 1-6  alkyl group)}] 
     or a pharmaceutically acceptable salt thereof. 
   
   
       3 . A compound represented by the formula (1):
   B-D-Z  (1)   
     [wherein B represents the following formula (B-1): 
     
       
         
         
             
             
         
       
       A represents an imidazolyl or pyrazolyl group represented by the following formula (A-1), (A-2), (A-3) or (A-4): 
     
     
       
         
         
             
             
         
       
     
     (wherein R 4  and R 5  each independently represents a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkoxy group which may be substituted with G1, a C 1-6  alkylsulfonyl group which may be substituted with G1, or a halogen atom; R 6  represents a hydrogen atom, a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkylcarbonyl group which may be substituted with G1, or a benzoyl group which may be substituted with G1, or a tetrahydropyranyl group;
 G1 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom, 
 s represents 0 or an integer of 1 to 3, 
 t represents 0 or an integer of 1 or 2, and 
 R 4 (s) or R 5 (s) may be the same or different when s or t is 2 or more); 
 R 1  represents a halogen atom, a nitro group, a cyano group, a hydroxyl group, a C 1-6  alkyl group which may be substituted with G2, a C 1-6  alkoxy group which may be substituted with G2, a C 1-6  alkylthio group which may be substituted with G2, a C 1-6  alkylcarbonyl group which may be substituted with G2, an amino group (which may be substituted with one or two C 1-6  alkyl groups), a benzoyl group which may be substituted with G2, or a benzyl group which may be substituted with G2; 
 R 2  represents a C 1-6  alkyl group which may be substituted with G2; 
 G2 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, a C 1-6  alkoxycarbonyl group, a nitro group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom; 
 m represents 0 or an integer of 1 to 4, and R 1 (s) may be the same or different when m is 2 or more; 
 o represents an integer of 1 or 2; 
 when o is 1, n represents 0 or an integer of 1 to 8, when o is 2 n represents 0 or an integer of 1 to 10, and R 2 (s) may be the same or different when n is 2 or more; 
 in the formula (B-1), the dotted line represents a single bond or a double bond and does not simultaneously represent a double bond; 
 Y represents a carbon atom or a nitrogen atom, which may have a substituent selected from the group consisting of a hydrogen and a hydroxyl or a multiple bond that satisfies a valence; 
 E represents an oxygen atom, a sulfur atom or the 
 
     
       
         
         
             
             
         
       
     
     following formula (1a) when Y represents a carbon atom; 
     (wherein R 60  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group); R 7  and R 8  each independently represents a hydrogen atom, a cyano group, a hydroxyl group, a halogen atom, a C 1-6  alkyl group, a C 1-6  alkoxy group, a C 2-6  alkenyl group, a C 2-6  alkynyl group, a C 2-6  alkenyloxy group, a C 2-6  alkynyloxy group, a C 1-6  acyloxy group, a C 3-6  cycloalkyl group which may be substituted with G2, or a phenyl group which may be substituted with G2;
 j and k independently represent 0 or an integer of 1; 
 l represents 0 or an integer of 1 to 16; 
 R 7 (s) and R 8 (s) may be the same or different when 1 is 2 or more); 
 E represents the formula (1a) when Y represents a nitrogen atom; 
 D represents the formula (1a); 
 Z represents a thiochroman-2-yl group which is substituted with G3, a 2,3-dihydrobenzothiophene-2-yl group which is substituted with G3, a thiochroman-4-yl group which is substituted with G3, a 2,3-dihydrobenzothiophene-3-yl group which is substituted with G3, or a 1,3-benzoxathiol-2-yl group which is substituted with G3; 
 G3 represents the formula: NHR 10    
 
     {wherein R 10  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group)}; 
     or the formula: OR 11    
     {wherein R 11  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a hydroxyl group, a C 1-6  alkoxy group, a halogen atom, or a C 1-6  alkyl group)}] 
     or a pharmaceutically acceptable salt thereof. 
   
   
       4 . A compound represented by the formula (1):
   B-D-Z  (1)   
     [wherein B represents the following formula (B-1): 
     
       
         
         
             
             
         
       
       A represents an imidazolyl or pyrazolyl group represented by the following formula (A-1), (A-2), (A-3) or (A-4): 
     
     
       
         
         
             
             
         
       
     
     (wherein R 4  and R 5  each independently represents a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkoxy group which may be substituted with G1, a C 1-6  alkylsulfonyl group which may be substituted with G1, or a halogen atom; R 6  represents a hydrogen atom, a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkylcarbonyl group which may be substituted with G1, or a benzoyl group which may be substituted with G1, or a tetrahydropyranyl group;
 G1 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom, 
 s represents 0 or an integer of 1 to 3, 
 t represents 0 or an integer of 1 or 2, and 
 R 4 (s) or R 5 (s) may be the same or different when s or t is 2 or more); 
 R 1  represents a halogen atom, a nitro group, a cyano group, a hydroxyl group, a C 1-6  alkyl group which may be substituted with G2, a C 1-6  alkoxy group which may be substituted with G2, a C 1-6  alkylthio group which may be substituted with G2, a C 1-6  alkylcarbonyl group which may be substituted with G2, an amino group (which may be substituted with one or two C 1-6  alkyl groups), a benzoyl group which may be substituted with G2, or a benzyl group which may be substituted with G2; 
 R 2  represents a C 1-6  alkyl group which may be substituted with G2; 
 G2 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, a C 1-6  alkoxycarbonyl group, a nitro group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom; 
 m represents 0 or an integer of 1 to 4, and R 1 (s) may be the same or different when m is 2 or more; 
 o represents an integer of 1 or 2; 
 when o is 1, n represents 0 or an integer of 1 to 8, when o is 2 n represents 0 or an integer of 1 to 10, and R 2 (s) may be the same or different when n is 2 or more; 
 in the formula (B-1), the dotted line represents a single bond or a double bond and does not simultaneously represent a double bond; 
 Y represents a carbon atom or a nitrogen atom, which may have a substituent selected from the group consisting of a hydrogen and a hydroxyl or a multiple bond that satisfies a valence; 
 E represents an oxygen atom, a sulfur atom or the 
 
     
       
         
         
             
             
         
       
     
     following formula (1a) when Y represents a carbon atom; (wherein R 60  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group); R 7  and R 8  each independently represents a hydrogen atom, a cyano group, a hydroxyl group, a halogen atom, a C 1-6  alkyl group, a C 1-6  alkoxy group, a C 2-6  alkenyl group, a C 2-6  alkynyl group, a C 2-6  alkenyloxy group, a C 2-6  alkynyloxy group, a C 1-6  acyloxy group, a C 3-6  cycloalkyl group which may be substituted with G2, or a phenyl group which may be substituted with G2;
 j and k independently represent 0 or an integer of 1; 
 l represents 0 or an integer of 1 to 16; 
 R 7 (s) and R 8 (s) may be the same or different when 1 is 2 or more); 
 E represents the formula (1a) when Y represents a nitrogen atom; 
 D represents an oxygen atom, a sulfur atom; 
 Z represents a chroman-2-yl group which is substituted with G3, a chroman-4-yl group which is substituted with G3, a 2,3-dihydrobenzofuran-2-yl group which is substituted with G3, a 2,3-dihydrobenzofuran-3-yl group which is substituted with G3, a thiochroman-2-yl group which is substituted with G3, a 2,3-dihydrobenzothiophene-2-yl group which is substituted with G3, a thiochroman-4-yl group which is substituted with G3, a 2,3-dihydrobenzothiophene-3-yl group which is substituted with G3, or a 1,3-benzoxathiol-2-yl group which is substituted with G3; 
 G3 represents the formula: NHR 10    
 
     {wherein R 10  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group)}; 
     or the formula: OR 11    
     [wherein R 11  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a hydroxyl group, a C 1-6  alkoxy group, a halogen atom, or a C 1-6  alkyl group)}] 
     or a pharmaceutically acceptable salt thereof. 
   
   
       5 . A compound represented by the formula (1):
   B-D-Z  (1)   
     [wherein B represents the following formula (B-2): 
     
       
         
         
             
             
         
       
       A represents an imidazolyl or pyrazolyl group represented by the following formula (A-1), (A-2), (A-3) or (A-4): 
     
     
       
         
         
             
             
         
       
     
     (wherein R 4  and R 5  each independently represents a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkoxy group which may be substituted with G1, a C 1-6  alkylsulfonyl group which may be substituted with G1, or a halogen atom; R 6  represents a hydrogen atom, a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkylcarbonyl group which may be substituted with G1, or a benzoyl group which may be substituted with G1, or a tetrahydropyranyl group;
 G1 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom, 
 s represents 0 or an integer of 1 to 3, 
 t represents 0 or an integer of 1 or 2, and 
 R 4 (s) or R 5 (s) may be the same or different when s or t is 2 or more); 
 R 1  represents a halogen atom, a nitro group, a cyano group, a hydroxyl group, a C 1-6  alkyl group which may be substituted with G2, a C 1-6  alkoxy group which may be substituted with G2, a C 1-6  alkylthio group which may be substituted with G2, a C 1-6  alkylcarbonyl group which may be substituted with G2, an amino group (which may be substituted with one or two C 1-6  alkyl groups), a benzoyl group which may be substituted with G2, or a benzyl group which may be substituted with G2; 
 G2 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, a C 1-6  alkoxycarbonyl group, a nitro group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom; 
 m represents 0 or an integer of 1 to 4, and R 1 (s) may be the same or different when m is 2 or more; 
 D represents an oxygen atom, a sulfur atom or the following formula (1a): 
 
     
       
         
         
             
             
         
       
     
     (wherein R 60  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group); R 7  and R 8  each independently represents a hydrogen atom, a cyano group, a hydroxyl group, a halogen atom, a C 1-6  alkyl group, a C 1-6  alkoxy group, a C 2-6  alkenyl group, a C 2-6  alkynyl group, a C 2-6  alkenyloxy group, a C 2-6  alkynyloxy group, a C 1-6  acyloxy group, a C 3-6  cycloalkyl group which may be substituted with G2, or a phenyl group which may be substituted with G2;
 j and k independently represent 0 or an integer of 1, and j and k represent 0 when B is (B-2); 
 l represents 0 or an integer of 1 to 16; 
 R 7 (s) and R 8 (s) may be the same or different when 1 is 2 or more); 
 X represents an oxygen atom, the formula: SOu (wherein u represents 0 or an integer of 1 or 2) or the formula: N—R 9  (wherein R 9  represents a hydrogen atom, a C 1-6  alkyl group which may be substituted with G2, or a benzyl group which may be substituted with G2); 
 Z represents a chroman-2-yl group which is substituted with G3, a chroman-4-yl group which is substituted with G3, a 2,3-dihydrobenzofuran-2-yl group which is substituted with G3, a 2,3-dihydrobenzofuran-3-yl group which is substituted with G3, a thiochroman-2-yl group which is substituted with G3, a 2,3-dihydrobenzothiophene-2-yl group which is substituted with G3, a thiochroman-4-yl group which is substituted with G3, a 2,3-dihydrobenzothiophene-3-yl group which is substituted with G3, or a 1,3-benzoxathiol-2-yl group which is substituted with G3; 
 G3 represents the formula: NHR 10    
 
     {wherein R 10  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group)); 
     or the formula: OR 11    
     {wherein R 11  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a hydroxyl group, a C 1-6  alkoxy group, a halogen atom, or a C 1-6  alkyl group)}] 
     or a pharmaceutically acceptable salt thereof. 
   
   
       6 . A compound represented by the formula (1):
   B-D-Z  (1)   
     [wherein B represents the following formula (B-3): 
     
       
         
         
             
             
         
       
       A represents an imidazolyl or pyrazolyl group represented by the following formula (A-1), (A-2), (A-3) or (A-4), or may represent a hydrogen atom or R 1 : 
     
     
       
         
         
             
             
         
       
     
     (wherein R 4  and R 5  each independently represents a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkoxy group which may be substituted with G1, a C 1-6  alkylsulfonyl group which may be substituted with G1, or a halogen atom; R 6  represents a hydrogen atom, a C 1-6  alkyl group which may be substituted with G1, a C 1-6  alkylcarbonyl group which may be substituted with G1, or a benzoyl group which may be substituted with G1, or a tetrahydropyranyl group;
 G1 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom, 
 s represents 0 or an integer of 1 to 3, 
 t represents 0 or an integer of 1 or 2, and 
 R 4 (s) or R 5 (s) may be the same or different when s or t is 2 or more); 
 R 1  represents a halogen atom, a nitro group, a cyano group, a hydroxyl group, a C 1-6  alkyl group which may be substituted with G2, a C 1-6  alkoxy group which may be substituted with G2, a C 1-6  alkylthio group which may be substituted with G2, a C 1-6  alkylcarbonyl group which may be substituted with G2, an amino group (which may be substituted with one or two C 1-6  alkyl groups), a benzoyl group which may be substituted with G2, or a benzyl group which may be substituted with G2; 
 R 3  represents a hydrogen atom, a C 1-6  alkyl group which may be substituted with G2, a C 1-6  alkylcarbonyl group which may be substituted with G2, a benzoyl group which may be substituted with G2, or a benzyl group which may be substituted with G2; 
 G2 represents a cyano group, a formyl group, a hydroxyl group, a C 1-6  alkoxy group, a C 1-6  alkoxycarbonyl group, a nitro group, an amino group, a monomethylamino group, a dimethylamino group or a halogen atom; 
 p represents 0 or an integer of 1 to 4, and R 1 (s) may be the same or different when p is 2 or more; 
 q and r each independently represents an integer of 1 
 
     
       
         
         
             
             
         
       
       D represents an oxygen atom, a sulfur atom or the following formula (1a): 
     
     (wherein R 60  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group); R 7  and R 8  each independently represents a hydrogen atom, a cyano group, a hydroxyl group, a halogen atom, a C 1-6  alkyl group, a C 1-6  alkoxy group, a C 2-6  alkenyl group, a C 2-6  alkynyl group, a C 2-6  alkenyloxy group, a C 2-6  alkynyloxy group, a C 1-6  acyloxy group, a C 3-6  cycloalkyl group which may be substituted with G2, or a phenyl group which may be substituted with G2;
 j and k independently represent 0 or an integer of 1, and j and k represent 0 when B is (B-2); 
 l represents 0 or an integer of 1 to 16; 
 R 7 (s) and R 8 (s) may be the same or different when 1 is 2 or more); 
 Z represents a chroman-2-yl group which is substituted with G3, a chroman-4-yl group which is substituted with G3, a 2,3-dihydrobenzofuran-2-yl group which is substituted with G3, a 2,3-dihydrobenzofuran-3-yl group which is substituted with G3, a thiochroman-2-yl group which is substituted with G3, a 2,3-dihydrobenzothiophene-2-yl group which is substituted with G3, a thiochroman-4-yl group which is substituted with G3, a 2,3-dihydrobenzothiophene-3-yl group which is substituted with G3, or a 1,3-benzoxathiol-2-yl group which is substituted with G3; 
 G3 represents the formula: NHR 10    
 
     {wherein R 10  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group)}; 
     or the formula: OR 11    
     {wherein R 11  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a hydroxyl group, a C 1-6  alkoxy group, a halogen atom, or a C 1-6  alkyl group)}] 
     or a pharmaceutically acceptable salt thereof. 
   
   
       7 . The compound according to any one of  claims 1  to  6 , 
     
       
         
         
             
             
         
       
     
     wherein Z represents a group represented by the following formula (Z-1), (Z-2), (Z-3), (Z-4) or (Z-5): 
     [wherein * represents an asymmetric carbon atom; X 1  represents an oxygen atom or a sulfur atom; R 12  to R 32  each independently represents a hydrogen atom or a C 1-6  alkyl group, and G3 represents the formula: NHR 10    
     {wherein R 10  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a nitro group, a halogen atom, a hydroxyl group, a C 1-6  alkoxy group, or a C 1-6  alkyl group)}; 
     or the formula: OR 11    
     {wherein R 11  represents a hydrogen atom, a C 1-6  alkylcarbonyl group, or a benzoyl group (which may be substituted with a hydroxyl group, a C 1-6  alkoxy group, a halogen atom, or a C 1-6  alkyl group)}] 
     or a pharmaceutically acceptable salt thereof. 
   
   
       8 . A pharmaceutical composition comprising, one or more compounds or pharmaceutically acceptable salts thereof according to any one of  claims 1  to  7  and an excipient.