Tetracyclic fused heterocyclic compound and use thereof as hcv polymerase inhibitor

Abstract

The present invention relates to a tetracyclic fused heterocyclic compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.

1 . A compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein 
       
         
           
           
               
               
           
         
       
       is C═C—N or N—C═C,
 G 3 , G 4  and G 5  are each independently a carbon atom or a nitrogen atom, when at least one of G 3 , G 4  and G 5  is a carbon atom, said carbon atom is optionally substituted by R 3 , 
 Q is 
 (1) —(CH 2 ) b — or 
 (2) —(CH 2 ) c -Q 1 -(CH 2 ) d — 
 (wherein b is an integer of 1 to 4,
 c and d are each independently 0 or an integer of 1 to 4, 
 Q 1  is 
 (1′) —O—, 
 (2′) —NH—, 
 (3′) —S—, 
 (4′) —OCO—, 
 (5′) —OCONH—, 
 (6′) —CO—, 
 (7′) —SO—, 
 (8′) —SO 2 —, 
 (9′) —NHCO—, 
 (10′) —NHSO 2 —, 
 (11′) —NHCOO—, 
 (12′) —COO—, 
 (13′) —CONH—, 
 (14′) —SO 2 NH—, 
 (15′) —NHCONH—, 
 (16′) —NHSO 2 NH—, 
 (17′) —CH═CH—, 
 (18′) —CH═N— or 
 (19′) —N═CH—), 
 
 ring A is 
 (1) benzene, 
 (2) cyclopentane or cyclohexane, 
 (3) cyclopentene or cyclohexene or 
 (4) a 5- or 6-membered heterocycle comprising 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom, 
 G 6  is a carbon atom or a nitrogen atom, a broken line in ring A shows a single bond or a double bond, 
 R 1  is 
 (1) a carboxyl group, 
 (2) a carboxylic acid equivalent, 
 (3) —CONR 11 R 12    
 (wherein R 11  and R 12  are each independently
 (1′) a hydrogen atom, 
 (2′) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the following group E, 
 (3′) a C 2-6  alkenyl group optionally substituted by 1 to 3 substituents selected from the following group E, 
 (4′) a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the following group E, 
 (5′) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group E 
 
 (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
 (6′) a C 3-10  cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group E, 
 (7′) —NR 131 R 132 , 
 (8′) —NHCOOR 133 , 
 (9′) —NHCOR 134    
 
 (wherein R 131 , R 132 , R 133  and R 134  are each independently a hydrogen atom or a group selected from the following group F),
 (10′) —CR 135 R 136 -L 100 -R 137 , 
 (11′) —CR 135 R 136 -L 101 -CONR 140 —R 137 , 
 
 
       
         
           
           
               
               
           
         
         (wherein R 135 , R 136 , R 138  and R 139  are each independently
 (1″) a hydrogen atom or 
 (2″) a group selected from the following group G,
 group G: 
 (1′″) cyano group, 
 (2′″) —COOR 142    
 (wherein R 142  is a hydrogen atom or a group selected from the following group F) 
 (3′″) —CONR 143 R 144    
 (wherein R 143  and R 144  are each independently a hydrogen atom, a C 1-6  alkoxy group or a group selected from the following group F) 
 (4′″) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the following group A, 
 (5′″) a C 2-6  alkenyl group optionally substituted by 1 to 3 substituents selected from the following group A, 
 (6′″) a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the following group B, 
 (7′″) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group B 
 
 (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
 (8′″) a C 3-10  cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group B, 
 (9′″) a C 6-14  aryl C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the following group B, 
 (10′″) a heterocycle C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the following group B and 
 (11′″) a C 3-10  cycloalkyl C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the following group B; or 
 R 135  and R 136 , or, R 138  and R 139  are bonded to each other, and optionally form, together with the carbon atom bonded thereto, 
 
 (1″) a C 3-10  cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group B or 
 (2″) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group B 
 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom),
 R 137  is 
 (1″) a hydrogen atom, 
 (2″) a carboxyl group, 
 (3″) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the following group E, 
 (4″) a C 2-6  alkenyl group optionally substituted by 1 to 3 substituents selected from the following group E, 
 (5″) a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the following group E, 
 (6″) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group E 
 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom) or
 (7″) a C 3-10  cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group E, 
 R 140  and R 141  are each independently 
 (1″) a hydrogen atom or 
 (2″) a C 1-6  alkyl group, 
 L 100  is 
 (1″) a bond, 
 (2″) —CO—, 
 (3″) —CH 2 O—, 
 (4″) —CH 2 NH—, 
 (5″) —CH 2 NHCO—, 
 (6″) a C 1-6  alkylene optionally substituted by hydroxyl group or 
 (7″) a C 2-6  alkenylene, 
 L 101  and L 102  are each independently 
 (1″) a bond, 
 (2″) —CO—, 
 (3″) a C 1-6  alkylene optionally substituted by hydroxyl group or 
 (4″) a C 2-6  alkenylene, 
 L 103  is 
 (1″) a bond or 
 (2″) a C 1-6  alkylene, 
 L 104  is a C 1-6  alkylene, 
 L 105  is 
 (1″) a bond or 
 (2″) a C 1-6  alkylene, 
 L 106  is 
 (1″) a bond, 
 (2″) a C 1-6  alkylene, 
 (3″) —NH—, 
 (4″) —NH—CH 2 — or 
 (5″) —CH 2 —CONH—, 
 ring D 3 , ring D 4  and ring D 5  are each independently 
 (1″) a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the following group E, 
 (2″) a C 3-10  cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group E or 
 (3″) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group E 
 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom))), 
         (4) —COOR 103    
         (wherein R 103  is a group selected from the following group C or a glucuronic acid residue), 
       
       
         
           
           
               
               
           
         
         (wherein ring D 6  is a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group E 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom), 
         ring D 7  is a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the following group E), 
         R 2  may substitute at a substitutable position on carbon atom or nitrogen atom constituting Q and is 
         (1) a hydrogen atom, 
         (2) a group selected from the following group E, 
         (3) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the following group E, 
         (4) a C 2-6  alkenyl group optionally substituted by 1 to 3 substituents selected from the following group E, 
       
       
         
           
           
               
               
           
         
         {wherein L 1  and L 2  are each independently
 (1′) a bond, 
 (2′) C 1-6  alkylene, 
 (3′) C 2-6  alkenylene, 
 (4′) —(CH 2 ) u1 —O—(CH 2 ) v1 —, 
 (5′) —(CH 2 ) u1 —S—(CH 2 ) v1 —, 
 (6′) —(CH 2 ) u1 —NR L1 —(CH 2 ) v1 —, 
 (7′) —(CH 2 ) u1 —CO—(CH 2 ) v1 —, 
 (8′) —(CH 2 ) u1 —CONR L2 —(CH 2 ) v1 —, 
 (9′) —(CH 2 ) u1 —NR L2 CO 2 —(CH 2 ) v1 —, 
 (10′) —(CH 2 ) u1 —NR L2 CONR L3 —(CH 2 ) v1 —, 
 (11′) —(CH 2 ) u1 —NR L2 CO 2 —(CH 2 ) v1 —, 
 (12′) —(CH 2 ) u1 —NR L2 SO 2 —(CH 2 ) v1 —, 
 (13′) —(CH 2 ) u1 —SO 2 —(CH 2 ) u1 —, 
 (14′) —(CH 2 ) u1 —SO 2 NR L2 —(CH 2 ) v1 — or 
 (15′) —(CH 2 ) u1 —N + R L2 R L2′ —(CH 2 ) v1 —, 
 
         (wherein u, v, u1 and v1 are each independently 0 or an integer of 1 to 6,
 R L1  is 
 (1″) a hydrogen atom, 
 (2″) a group selected from the following group C, 
 (3″) —COR L11 , 
 (4″) —CONR L11 R L12 , 
 (5″) —COOR L11  or 
 (6″) —SO 2 R L13    
 
         (wherein R L11  and R L12  are each independently a hydrogen atom or a group selected from the following group C, and R L13  is a group selected from the following group C),
 R L2 , R L2′  and R L3  are each independently 
 (1″) a hydrogen atom, 
 (2″) a group selected from the following group C, 
 (3″) —COR L11  or 
 (4″) —SO 2 R L13    
 
         (wherein R L11  and R L13  are as defined above)),
 L 3  is 
 (1′) —CHR L14 — or 
 (2′) —NR L14 — 
 
         (wherein R L14  and R L13  are as defined above)),
 L 3  is 
 (1′) —CHR L14 — or 
 (2′) —NR L14 — 
 
         (wherein R L4  is a group selected from the following group F),
 ring D 1  and ring D 2  are each independently 
 (1′) a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the following group E, 
 (2′) a C 3-10  cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group E or 
 (3′) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group E 
 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom)}, 
         R 3  is 
         (1) a hydrogen atom, 
         (2) a halogen atom, 
         (3) a C 1-6  alkanoyl group, 
         (4) a carboxyl group, 
         (5) a cyano group, 
         (6) a nitro group, 
         (7) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the following group A, 
         (8) —OR 101    
         (wherein R 101  is a hydrogen atom or a group selected from the following group C), 
         (9) —NR 102 R 119    
         (wherein R 102  and R 119  are each independently a hydrogen atom, a C 1-6  alkanoyl group or a C 1-6  alkylsulfonyl group), 
         (10) —COOR 103    
         (wherein R 103  is a group selected from the following group C or a glucuronic acid residue), 
         (11) —CONR 104 R 105    
         (wherein R 104  and R 105  are each independently a hydrogen atom, a hydroxyl group, a cyano group, a C 1-6  alkoxy group or a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the following group A), 
         (12) —SO 2 R 106    
         (wherein R 106  is a hydroxyl group, an amino group, a C 1-6  alkyl group or a C 1-6  alkylamino group), 
         (13) —NHCOR 107    
         (wherein R 107  is an amino group or a C 1-6  alkylamino group), 
         (14) —C(═NR 108 )—NH 2    
         (wherein R 108  is a hydrogen atom, a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the following group A, a hydroxyl group or a C 1-6  alkoxy group), 
         (15) —P(═O)(OR 109 ) 2    
         (wherein R 109  are each independently a hydrogen atom or a group selected from the following group C), 
         (16) —P(═O)(OR 110 )NR 111 R 112    
         (wherein R 110 , R 111  and R 112  are each independently a hydrogen atom or a group selected from the following group C), 
         (17) —CONHCO—R 113    
         (wherein R 113  is a group selected from the following group C), 
         (18) —CONHSO 2 —R 114    
         (wherein R 114  is a group selected from the following group C), 
         (19) —SO 2 NHCO—R 115    
         (wherein R 115  is a group selected from the following group C) or 
         (20) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group B 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom), 
         R 4  may substitute at a substitutable position on carbon atom or nitrogen atom constituting Q and each is independently 
         (1) a halogen atom, 
         (2) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the following group A, 
         (3) —OR 116    
         (wherein R 116  is a hydrogen atom or a group selected from the following group C), 
         (4) —NR 117 R 118    
         (wherein R 117  and R 118  are each independently a hydrogen atom, a C 1-6  alkanoyl group or a group selected from the following group C), 
         (5) a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the following group B or 
         (6) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group B 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom), 
         a is 0, 1 or 2, 
         R 5  and R 6  are each independently 
         (1) a hydrogen atom, 
         (2) a halogen atom, 
         (3) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the following group A, 
         (4) —OR 120    
         (wherein R 120  is a hydrogen atom or a group selected from the following group C) or 
         (5) —NR 121 R 122    
         (wherein R 121  and R 122  are each independently a hydrogen atom, a C 1-6  alkanoyl group or a group selected from the following group C), 
         ring Cy is 
         (1) a C 3-10  cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group B, 
         (2) a C 3-10  cycloalkenyl group optionally substituted by 1 to 5 substituents selected from the following group B or 
         (3) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group B 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom), 
         X is 
         (1) a group selected from the following group D, 
         (2) a C 2-6  alkenyl group optionally substituted by 1 to 3 substituents selected from the following group A or 
       
       
         
           
           
               
               
           
         
         wherein ring B is 
         (1′) a C 6-14  aryl group, 
         (2′) a C 3-10  cycloalkyl group or 
         (3′) a heterocyclic group comprising 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom, 
         each Z is independently
 (1′) a group selected from the following group D, 
 (2′) a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the following group D, 
 (3′) a C 3-10  cycloalkyl group optionally substituted by 1 to 5 substituents selected from the following group D, 
 (4′) a C 6-14  aryl C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the following group D, 
 (5′) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the following group D 
 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom) or
 (6′) a heterocycle C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the following group D 
 
         (wherein said heterocycle C 1-6  alkyl group is a C 1-6  alkyl group substituted by “a heterocyclic group optionally substituted by 1 to 5 substituents selected from group D” as defined above),
 w is an integer of 1 to 3, 
 Y is 
 (a) C 1-6  alkylene, 
 (b) C 2-6  alkenylene or 
 (c) —Y 1 —(CH 2 ) m —Y 2 —(CH 2 ) n — 
 
         (wherein m and n are each independently 0 or an integer of 1 to 6,
 Y 1  and Y 2  are each independently 
 (1′) a bond, 
 (2′) —O—, 
 (3′) —NR y1 —, 
 (4′) —S—, 
 (5′) —CO—, 
 (6′) —SO—, 
 (7′) —SO 2 —, 
 (8′) —CO 2 —, 
 (9′) —OCO—, 
 (10′) —CONR y2 —, 
 (11′) —NR y2 CO—, 
 (12′) —SO 2 NR y2 —, 
 (13′) —NR y2 SO 2 —, 
 (14′) —NR y2 CO 2 —, 
 (15′) —OCONR y2 —, 
 (16′) —NR y2 CONR y3 —, 
 (17′) —CR y2 R y5 — or 
 (18′) —CH═CH— 
 
         (wherein R y1  is
 (1″) a hydrogen atom, 
 (2″) a group selected from the following group C, 
 (3″) —(CH 2 ) s —COOR y11 , 
 (4″) —(CH 2 ) s —CONR y11 R y12 , 
 (5″) (CH 2 ) s —COR y11  or 
 (6″) —(CH 2 ) s —SO 2 R y13    
 
         (wherein s is 0 or an integer of 1 to 6, R y11  and R y12  are each independently a hydrogen atom or a group selected from the following group C, R y13  is a group selected from the following group C),
 R y2  and R y3  are each independently 
 (1″) a hydrogen atom, 
 (2″) a group selected from the following group C, 
 (3″) —COR y11  or 
 (4″) —SO 2 R y13  (wherein R y11  and R y13  are as defined above), 
 R y4  and R y5  are each independently 
 (1″) a hydrogen atom, 
 (2″) a carboxyl group, 
 (3″) a group selected from group F, 
 (4″) —OR y14  or 
 (5″) —NHR y15    
 
         (wherein R y14  is a group selected from the following group C, R y15  is a hydrogen atom, a C 1-6  alkyl group, a C 1-6  alkanoyl group, a C 6-14  aryl C 1-6  alkyloxycarbonyl group or a C 1-6  alkoxycarbonyl group)))
 group A: 
 
         (1) a halogen atom, 
         (2) a C 1-6  alkoxy C 1-6  alkoxy group, 
         (3) a cyano group, 
         (4) —OR a1 , 
         (5) —SR a1 , 
         (6) —NR a1 R a2 , 
         (7) —COOR a1 , 
         (8) —CONR a1 R a2 , 
         (9) —SO 3 H, 
         (10) —SO 2 NR a1 R a2 , 
         (11) —NHCOR a1 , 
         (12) —NHSO 2 R a3 , 
         (13) —NHCO 2 R a4 , 
         (14) —COR a1  and 
         (15) —N + R a1 R a2 R a3    
         (wherein R a1  and R a2  are each a hydrogen atom, a C 1-6  alkyl group or a benzyl group, R a3  is a C 1-6  alkyl group and R a4  is a C 1-6  alkyl group)
 group B: 
 
         (1) a halogen atom, 
         (2) a cyano group, 
         (3) a nitro group, 
         (4) a C 1-6  alkyl group, 
         (5) a C 2-6  alkenyl group optionally substituted by carboxyl group, 
         (6) a halogenated C 1-6  alkyl group, 
         (7) —(CH 2 ) r —OR b1 , 
         (8) —(CH 2 ) r —SR b1 , 
         (9) —(CH 2 ) r —NR b1 R b2 , 
         (10) —(CH 2 ) r —COOR b1 , 
         (11) —(CH 2 ) r —CONR b1 R b2 , 
         (12) —(CH 2 ) r —COR b1 , 
         (13) —(CH 2 ) r —NR b1 —COR b2 , 
         (14) —(CH 2 ) r —NR b1 —SO 2 R b3 , 
         (15) —(CH 2 ) r —SO 2 R b3 , 
         (16) —(CH 2 ) r —SO 2 NR b1 R b2 , 
         (17) —(CH 2 ) r —CONR b1 —SO 2 R b3 , 
         (18) —(CH 2 ) r —SO 2 NR b1 —COR b2 , 
         (19) —(CH 2 ) r —NR b1 —COOR b3 , 
         (20) —(CH 2 ) r —NR b1 —CONR b2 R b4 , 
         (21) —O—(CH 2 ) r —COOR b1  and 
         (22) —CO—(CH 2 ) r —R b5    
         (wherein R b1 , R b2  and R b4  are each independently a hydrogen atom or a C 1-6  alkyl group, R b3  is a C 1-6  alkyl group, R b5  is a heterocyclic group and r is 0 or an integer of 1 to 6) 
         (1) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A, 
         (2) a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, 
         (3) a C 6-14  aryl C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, 
         (4) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the aforementioned group B and 
         (5) a heterocycle C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B
 group D: 
 
         (a) a hydrogen atom, 
         (b) a halogen atom, 
         (c) a cyano group, 
         (d) a nitro group, 
         (e) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A, 
         (f) —(CH 2 ) t —OR d1 ,
 wherein R d1  is 
 (1) a hydrogen atom, 
 (2) a group selected from the following group F, 
 (3) a C 2-6  alkenyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or 
 (4) a C 2-6  alkynyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A, 
 hereinafter each t is independently 0 or an integer of 1 to 6, 
 
         (g) —(CH 2 ) t —S(O) q —R d2 ,
 wherein R d2  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 q is 0, 1, 2 or 3, 
 
         (h) —(CH 2 ) t —NR d3 R d4 ,
 wherein R d3  and R d4  are each independently 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (i) —(CH 2 ) t —COOR d5 ,
 wherein R d5  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (j) —(CH 2 ) t —CONR d6 R d7 ,
 wherein R d6  and R d7  are each independently 
 (1) a hydrogen atom, 
 (2) a hydroxyl group, 
 (3) a group selected from the following group F or 
 (4) a C 1-6  alkoxy group, 
 
         (k) —(CH 2 ) t —COR d8 ,
 wherein R d8  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (l) —(CH 2 ) t —NR d9 CO—R d10 ,
 wherein R d9  is 
 (1) a hydrogen atom, 
 (2) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or 
 (3) a C 1-6  alkanoyl group, 
 R d10  is 
 (1) an amino group, 
 (2) a C 1-6  alkylamino group or 
 (3) a group selected from the following group F, 
 
         (m) —(CH 2 ) t —NR d11 SO 2 —R d12 ,
 wherein R d11  is 
 (1) a hydrogen atom, 
 (2) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or 
 (3) a C 1-6  alkanoyl group, 
 R d12  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (n) —(CH 2 ) t —SO 2 —NR d13 R d14 ,
 wherein R d13  and R d14  are each independently 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (o) —(CH 2 ) t —CONR d15 —SO 2 R d16 ,
 wherein R d15  and R d16  are each independently 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (p) —(CH 2 ) t —SO 2 NR d17 —COR d18 ,
 wherein R d17  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 R d18  is a group selected from the following group F, 
 
         (q) —(CH 2 ) t —NR d19 —COOR d20 ,
 wherein R d19  and R d20  are each independently 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (r) —(CH 2 ) t —NR d21 —CONR d22 R d23 ,
 wherein R d21 , R d22  and R d23  are each independently 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (s) —(CH 2 ) t —C(═NR d24 )NH 2 ,
 wherein R d24  is 
 (1) a hydrogen atom, 
 (2) a hydroxyl group, 
 (3) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or 
 (4) C 1-6  alkoxy group, 
 
         (t) —(CH 2 ) t —O—(CH 2 ) p —COR d25 ,
 wherein R d25  is 
 (1) an amino group, 
 (2) a C 1-6  alkylamino group or 
 (3) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, 
 p is 0 or an integer of 1 to 6, 
 
         (u) —(CH 2 ) t —O—(CH 2 ) p —NR d26 R d27 ,
 wherein R d26  and R d27  are each independently 
 (1) a hydrogen atom or 
 (2) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A, 
 p is 0 or an integer of 1 to 6, 
 
         (v) —(CH 2 ) t —O—COOR d28 ,
 wherein R d28  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, and 
 
         (w) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the aforementioned group B 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom)
 group E: 
 
         (a) a halogen atom, 
         (b) a cyano group, 
         (c) a nitro group, 
         (d) an azido group, 
         (e) —OP(═O)(OH) 2 , 
         (f) —OR e1 ,
 wherein R e1  is 
 (1) a hydrogen atom, 
 (2) a group selected from the following group F, 
 (3) a C 2-6  alkenyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or 
 (4) a C 2-6  alkynyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A, 
 
         (g) —S(O) q —R e2  
 wherein R e2  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 q is 0, 1, 2 or 3, 
 
         (h) —NR e3 R e4 ,
 wherein R e3  and R e4  are each independently 
 (1) a hydrogen atom, 
 (2) a cyano group or 
 (3) a group selected from the following group F, 
 
         (i) —COOR e5 ,
 wherein R e5  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (j) —CONR e6 R e7 ,
 wherein R e6  and R e7  are each independently 
 (1) a hydrogen atom, 
 (2) a hydroxyl group, 
 (3) a group selected from the following group F or 
 (4) a C 1-6  alkoxy group, 
 
         (k) —COR e8 ,
 wherein R e8  is a group selected from the following group F, 
 
         (l) —NR e9 CO—R e10 ,
 wherein R e9  is 
 (1) a hydrogen atom, 
 (2) a C 1-6  alkyl group or 
 (3) a C 1-6  alkanoyl group, 
 R e10  is 
 (1) a hydrogen atom, 
 (2) an amino group, 
 (3) a C 1-6  alkylamino group, 
 (4) a C 2-6  alkenyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A or 
 (5) a group selected from the following group F, 
 
         (m) —NR e11 SO 2 —R e12 ,
 wherein R e11  is 
 (1) a hydrogen atom, 
 (2) a C 1-6  alkyl group or 
 (3) a C 1-6  alkanoyl group, 
 R e12  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (n) —SO 2 —NR e13 R e14 ,
 wherein R e13  and R e14  are each independently 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (o) —CONR e15 —SO 2 R e16 ,
 wherein R e15  and R e16  are each independently 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (p) —SO 2 NR e17 —COR e18 ,
 wherein R e17  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 R e18  is a group selected from the following group F, 
 
         (q) —NR e19 —COOR e20 ,
 wherein R e19  and R e20  are each independently 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (r) —NR e21 —CONR e22 R e23  
 wherein R e21 , R e22  and R e23  are each independently 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (s) —NHCO—COOR e24  
 wherein R e24  is 
 (1) a hydrogen atom or 
 (2) a group selected from the following group F, 
 
         (t) —NHCO—CONR e25  
 wherein R e25  and R e26  are each independently 
 (1) a hydrogen atom, 
 (2) a hydroxyl group or 
 (3) a group selected from the following group F, 
 
         (u) —CONH—COOH, 
       
       
         
           
           
               
               
           
         
         (y) a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, 
         (z) a C 3-10  cycloalkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, 
         (aa) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the aforementioned group B 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom), 
         (bb) a C 3-10  cycloalkylidene group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, and 
         (cc) a heterocycle ylidene group optionally substituted by 1 to 5 substituents selected from the aforementioned group B 
         (wherein said heterocycle ylidene group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom), 
         when group E is a substituent on a C 6-14  aryl group, a C 3-10  cycloalkyl group or a heterocyclic group, it may be 
         (dd) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A, 
         (ee) a C 2-6  alkenyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A, 
         (ff) a C 2-6  alkynyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A, 
         (gg) C 1-6  alkylidene group optionally substituted by 1 to 3 substituents selected from the aforementioned group A, 
         (hh) a C 6-14  aryl C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, 
         (ii) a C 3-10  cycloalkyl C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, or 
         (jj) a heterocycle C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B
 group F: 
 
         (1) a C 1-6  alkyl group optionally substituted by 1 to 3 substituents selected from the aforementioned group A, 
         (2) a C 6-14  aryl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, 
         (3) a heterocyclic group optionally substituted by 1 to 5 substituents selected from the aforementioned group B 
         (wherein said heterocyclic group comprises 1 to 4 heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom), 
         (4) a C 3-10  cycloalkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, 
         (5) a C 6-14  aryl C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B, 
         (6) a heterocycle C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B 
         (wherein said heterocycle C 1-6  alkyl group is a C 1-6  alkyl group substituted by “a heterocyclic group optionally substituted by 1 to 5 substituents selected from group B” as defined above) and 
         (7) a C 3-10  cycloalkyl C 1-6  alkyl group optionally substituted by 1 to 5 substituents selected from the aforementioned group B. 
       
     
     
         2 .- 52 . (canceled) 
     
     
         53 . A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         54 .- 60 . (canceled) 
     
     
         61 . A pharmaceutical composition comprising (a) a compound of  claim 1  or a pharmaceutically acceptable salt thereof, and (b) at least one pharmaceutical agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant. 
     
     
         62 . A pharmaceutical composition comprising (a) a compound of  claim 1  or a pharmaceutically acceptable salt thereof, and (b) interferon. 
     
     
         63 . (canceled) 
     
     
         64 . (canceled) 
     
     
         65 . A method for treating hepatitis C, which comprises administering an effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt thereof to a mammal. 
     
     
         66 . The method of  claim 65 , further comprising administering an effective amount of at least one pharmaceutical agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant to the mammal. 
     
     
         67 . The method of  claim 65 , further comprising administering an effective amount of interferon to the mammal. 
     
     
         68 . A method for inhibiting hepatitis C virus polymerase, which comprises administering an effective amount of a compound of  claim 1  or a pharmaceutically acceptable salt thereof to a mammal. 
     
     
         69 . The method of  claim 68 , further comprising administering an effective amount of at least one pharmaceutical agent selected from the group consisting of a different antiviral agent, an antiinflammatory agent and an immunostimulant to the mammal. 
     
     
         70 . The method of  claim 68 , further comprising administering an effective amount of interferon to the mammal.