Heterocyclic compounds having inhibitory activity against HIV integrase

Abstract

A heterocyclic compound of the formula (I): wherein B 1 is —C(R 2 )═ or —N═; R 1′ is H, etc.; one of R 1 and R 2 is -Z 1 -Z 2 -Z 3 -R 5 wherein Z 1 and Z 3 are independently single bond, optionally substituted alkylene, etc.; Z 2 is single bond, optionally substituted alkylene, etc.; R 5 is optionally substituted aryl, optionally substituted heteroaryl, etc., and the other of R 1 and R 2 is H; -A 1 - is —C(—Y)═C(—R A )—C(—R 3 )═C(—R 4 )—, etc. wherein Y is OH, etc.; R A is —COR 7 wherein R 7 is OH, etc.; one of R 3 and R 4 is carboxy, etc., and the other of R 1 and R 2 is H, etc, a prodrug thereof, a pharmaceutically acceptable salt thereof, and a solvate thereof, having an antiviral activity, more particularly, an inhibitory activity against HIV integrase, and a pharmaceutical composition containing the same, especially an anti-HIV drug.

1 . A compound of the general formula (I): 
     
       
         
         
             
             
         
       
       a prodrug, a pharmaceutically acceptable salt or a solvate thereof; wherein: 
       B 1  is —C(R 2 )═ or —N═; 
       one of R 1  and R 2  is a group of the formula: -Z 1 -Z 2 -Z 3 -R 5  wherein
 Z 1  and Z 3  each are independently a single bond, optionally substituted alkylene or optionally substituted alkenylene; 
 Z 2  is a single bond, optionally substituted alkylene, optionally substituted alkenylene, —CH(OH)—, —S—, —SO—, —SO 2 —, —SO 2 N(R 6 )—, —N(R 6 )SO 2 —, —O—, —N(R 6 )—, —N(R 6 )CO—, —CON(R 6 )—, —C(═O)—O—, —O—C(═O)— or —CO—; 
 R 6  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryl or optionally substituted heteroaryl; and 
 R 5  is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl or optionally substituted heterocycle, and the other of R 1  and R 2  is hydrogen or a substituent selected from Substituent Group A; 
 
       R 1′  is hydrogen or a substituent selected from Substituent Group A; 
       -A 1 - is —C(—Y)═C(—R A )—C(—R 3 )═C(—R 4 )—, —C(—Y)═C(—R A )—C(—R 3 )═N—, —C(—Y)═C(—R A )—C(═X)—N(—R 4 )—, —C(—Y)═C(—R A )—N═C(—R 4 )—, —C(—Y)═C(—R A )—C(—R 3 )—C(—R 4 )—, —C(—Y)═C(—R A )—O—C(—R 4 )—, —C(—Y)═C(—R A )C(—R 3 )—O—, —C(—Y)═C(—R A )—O— or —C(—Y)═C(—R A )—C(═X)—O— wherein
 X is oxygen or sulfur; 
 Y is —OH, —SH or —NH 2 ; 
 R A  is —C(=Z)R 7  wherein Z is oxygen or sulfur; and R 7  is a substituent selected from Substituent Group A,
 —NHOH, 
 —N═NR 10  wherein R 10  is hydrogen, alkyl, acyl, aralkyl, aryl or heteroaryl, 
 —NHSO 2 R 12  wherein R 12  is alkyl, aryl, aralkyl, hydroxy or amino, 
 —PO(OH) 2 , 
 —PO(OH)(R 13 ) wherein R 13  is alkyl, aryl or aralkyl, or 
 a group of the formula: 
 
 
     
     
       
         
         
             
             
         
       
       wherein Ring C is a nitrogen-containing heteroaromatic ring group optionally substituted by one to four of substituents selected from a group consisting of Substituent Group A and a substituent represented by the formula: -Z 1 -Z 2 -Z 3 -R 5  wherein Z 1 , Z 2 , Z 3  and R 5  are as defined above; 
       R 3  and R 4  each is independently a substituent selected from Substituent Group A or hydrogen; Substituent Group A is a group consisting of halogen, optionally substituted alkoxycarbonyl, carboxy, optionally substituted alkyl, optionally substituted alkoxy, alkoxyalkyl, nitro, hydroxy, hydroxyalkyl, optionally substituted alkenyl, optionally substituted alkynyl, alkylsulfonyl, alkyloxysulfonyl, optionally substituted amino, optionally substituted aminosulfonyl, alkylthio, alkylthioalkyl, haloalkyl, haloalkoxy, haloalkoxyalkyl, cycloalkyl, cycloalkenyl, oxo, thioxo, alkylenedioxy, alkylene, alkenylene, nitroso, azido, amidino, guanidine, cyano, isocyano, mercapto, optionally substituted carbamoyl, optionally substituted carbamoylalkyl, optionally substituted sulfamoyl, sulfoamino, sulfo, formyl, alkylcarbonyl, alkylcarbonyloxy, hydrazino, morpholino, phosphono, phosphinico, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycle, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted heterocycleoxy, optionally substituted arylthio, optionally substituted heteroarylthio, optionally substituted aralkyloxy, optionally substituted heteroaralkyloxy, optionally substituted aralkylthio, optionally substituted heteroaralkylthio, optionally substituted aryloxyalkyl, optionally substituted heteroaryloxyalkyl, optionally substituted arylthioalkyl, optionally substituted heteroarylthioalkyl, optionally substituted arylsulfonyl, optionally substituted heteroarylsulfonyl, optionally substituted aralkylsulfonyl, optionally substituted heteroaralkylsulfonyl, optionally substituted alkylcarbonyl alkyl, optionally substituted arylcarbonyl alkyl, alkylsulfonyloxy, sulfamoyloxy and optionally substituted arylcarbonyl;
 provided that (1) when -A 1 - is —C(—Y)═C(—R A )—C(—R 3 )═C(—R 4 )—, R A  is not the following substituted carbamoyl; (2) when -A 1 - is —C(—Y)═C(—R A )—C(—R 3 )═C(—R 4 )—, R 1′  is hydrogen; and (3) when -A 1 - is —C(—Y)═C(—R A )—N═C(—R 4 )—, R A  is not the following substituted carbamoyl; and that, in the substituted carbamoyl of (1) and (3), its N atom is substituted with both a group of the formula: -L-A 3  wherein L is a single bond or alkylene, alkenylene, cycloalkylene, alkylcycloalkylene, cycloalkylalkylene or alkyl(cycloalkyl)alkylene, each optionally substituted and/or optionally interrupted by a heteroatom, or —O(C═O)— or —C(═O)O—; A 3  is optionally substituted aryl or optionally substituted heterocycle and a group of the formula: —R m  wherein R m  is a hydrogen, optionally substituted alkyl or optionally substituted phenyl at the same time, or “—R m ” and “-L-A 3 ” may be combined together with the adjacent N atom to form an optionally substituted heteroring; 
 provided that when B 1  is C(R 2 )═, A 1  is not —C(—Y)═C(—R A )—C(—R 3 )═N—, —C(—Y)═C(—R A )—C(═X)—N(—R 4 )— or —C(—Y)═C(—R A )—N═C(—R 4 )—. 
 
     
   
   
       2 . A compound of the general formula (II): 
     
       
         
         
             
             
         
       
       a prodrug, a pharmaceutically acceptable salt or a solvate thereof; 
       wherein: 
       B 2  is —C(R 2′ )═ or —N═;
 one of R 1  and R 2′  is a group of the formula: -Z 1 -Z 2 -Z 3 -R 5  wherein Z 1 , Z 2 , Z 3  and R 5  are as defined in  claim 1  and the other of R 1  and R 2′  is hydrogen; 
 
       -A 2 - is —C(—Y)═C(—R B )—C(—R 24 )═C(—R 25 )—, —C(—Y)═C(—R B )—C(—R 24 )═N—, —C(—Y)═C(—R B )—C(═X)—N(—R 25 )—, —C(—Y)═C(—R B )—N═C(—R 25 )—, —C(—Y)═C(—R B )—C(R 24 )—C(—R 25 )—, —C(—Y)═C(—R B )—O—C(—R 25 )—, —C(—Y)═C(—R B )—C(—R 24 )—O—, —C(—Y)═C(—R B )—O— or —C(—Y)═C(—R B )—C(═X)—O— wherein X and Y are as defined in  claim 1 ; 
       R B  is
 —C(═O)R 26  wherein R 26  is hydroxy, alkoxy, alkyl, optionally substituted aryl or optionally substituted heterocycleoxy, 
 —CON(R 8 )(R 9 ) wherein R 8  and R 9  each is independently hydrogen, alkyl, aralkyl or acyl, 
 —NHOH, 
 —N═NR 10  wherein R 10  is hydrogen, alkyl, acyl, aralkyl, aryl or heteroaryl, 
 —NHSO 2 R 12  wherein R 12  is alkyl, aryl, aralkyl, hydroxy or amino, 
 —PO(OH) 2 , 
 —PO(OH)(R 13 ) wherein R 13  is alkyl, aryl or aralkyl, or 
 a group of the formula: 
 
     
     
       
         
         
             
             
         
       
       wherein ring C is as defined in  claim 1 ; 
       one of R 24  and R 25  is 
       carboxy, 
       —N(R 14 )(R 15 ) wherein R 14  and R 15  each is independently
 hydrogen, 
 alkyl, 
 cycloalkyl, 
 —(CH 2 ) 1-3 OR 16  wherein R 16  is hydrogen, alkyl, acyl or aryl, 
 —C(═O)R 17  wherein R 17  is hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted alkyl, haloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl or optionally substituted amino, 
 —C(═S)R 17  wherein R 17  is as defined above, or 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino) or 
 R 14  and R 15  may be combined to form optionally substituted thioamidino or R 14  and R 15  combined with adjacent nitrogen atom form optionally substituted nitrogen containing heterocycle optionally having nitrogen, sulfur and/or oxygen atom in the cycle, 
 
       —(CH 2 ) 0-3 OR 18  wherein R 18  is hydrogen, alkyl acyl or aryl, 
       —(CH 2 ) 1-3 CONHR 19  wherein R 19  is hydrogen, alkyl, acyl or aryl, 
       —SO 3 R 20  wherein R 20  is alkyl or hydroxy, 
       —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, 
       —PO(OH) 2 , 
       —PO(OH)(R 22 ) wherein R 22  is alkyl, 
       haloalkyl, 
       —(CH 2 ) 1-3 COR 23  wherein R 23  is alkyl or optionally substituted aryl, 
       —(CH 2 ) 0-3 CN, 
       —R 41 —COOR 42  wherein R 41  is alkenyl and R 42  is hydrogen or alkyl, 
       —(CH 2 ) 1-3 R 40  wherein R 40  is optionally substituted aryl or optionally substituted heteroaryl, 
       optionally substituted aryl or 
       optionally substituted heteroaryl; and 
       the other of R 24  and R 25  is hydrogen or heterocycle;
 provided that (1) when -A 1 - is —C(—Y)═C(—R A )—C(—R 3 )═C(—R 4 )—, R A  is not the following substituted carbamoyl; (2) when -A 1 - is —C(—Y)═C(—R A )—C(—R 3 )═C(—R 4 )—, R 1′  is hydrogen; and (3) when -A 1 - is —C(—Y)═C(—R A )—N═C(—R 4 )—, R A  is not the following substituted carbamoyl; and that, in the substituted carbamoyl of (1) and (3), its N atom is substituted with both a group of the formula: -L-A 3  wherein L is a single bond or alkylene, alkenylene, cycloalkylene, alkylcycloalkylene, cycloalkylalkylene or alkyl(cycloalkyl)alkylene, each optionally substituted and/or optionally interrupted by a heteroatom, or —O(C═O)— or —C(═O)O—; A 3  is optionally substituted aryl or optionally substituted heterocycle and a group of the formula: —R m  wherein R m  is a hydrogen, optionally substituted alkyl or optionally substituted phenyl at the same time; or “—R m ” and “-L-A 3 ” may be combined together with the adjacent N atom to form an optionally substituted heteroring. 
 
     
   
   
       3 . The compound of  claim 1  represented by the general formula (III): 
     
       
         
         
             
             
         
       
       the prodrug, the pharmaceutically acceptable salt or the solvate thereof; 
       wherein 
       R 8  is independently hydrogen, alkyl, aralkyl or acyl; 
       one of R 1  and R 2′  is a group of the formula: -Z 1 -Z 2 -Z 3 -R 5  wherein Z 1 , Z 2 , Z 3  and R 5  are as defined in  claim 1  and the other of R 1  and R 2′  is hydrogen; 
       Y is as defined in  claim 1 ; 
       one of R 27  and R 28  is
 carboxy, 
 N(R 14 )(R 15 ) wherein R 14  and R 15  each is independently
 hydrogen, 
 alkyl, 
 cycloalkyl, 
 —(CH 2 ) 1-3 OR 6  wherein R 16  is hydrogen, alkyl, acyl or aryl, 
 —C(═O)R 17  wherein R 17  is hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted alkyl, haloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl or optionally substituted amino, 
 —C(═S)R 17  wherein R 17  is as defined above, or —SO 2 R 2  wherein R 21  is alkyl or optionally substituted amino, 
 R 14  and R 15  may be combined to form optionally substituted thioamidino group, or 
 R 14  and R 15  are combined together with the adjacent nitrogen to form an optionally substituted nitrogen-containing heterocycle optionally containing nitrogen, sulfur or oxygen atom in its ring, 
 
 —(CH 2 ) 0-3 OR 18  wherein R 18  is hydrogen, alkyl, acyl or aryl, 
 —(CH 2 ) 1-3 CONHR 19  wherein R 19  is hydrogen, alkyl, acyl or aryl, 
 —SO 3 R 20  wherein R 20  is alkyl or hydroxy, 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, 
 —PO(OH) 2 , 
 —PO(OH)(R 22 ) wherein R 22  is alkyl, 
 haloalkyl, 
 —(CH 2 ) 1-3 COR 23  wherein R 23  is alkyl or optionally substituted aryl, 
 —(CH 2 ) 0-3 CN, 
 —R 41 —COOR 42  wherein R 41  is alkenyl and R 42  is hydrogen or alkyl, 
 —(CH 2 ) 1-3 R 40  wherein R 40  is optionally substituted aryl or optionally substituted heteroaryl, 
 optionally substituted aryl or 
 optionally substituted heteroaryl; and 
 
       the other of R 27  and R 28  is hydrogen or heterocycle. 
     
   
   
       4 - 6 . (canceled) 
   
   
       7 . The compound of  claim 1 , represented by the general formula (VI): 
     
       
         
         
             
             
         
       
       the prodrug, the pharmaceutically acceptable salt or the solvate thereof; 
       wherein Y, R A , R 1  and R 2  are as defined in  claim 1 ; and 
       one of R 27  and R 28  is
 carboxy, 
 —N(R 14 )(R 15 ) wherein R 14  and R 15  each is independently
 hydrogen, 
 alkyl, 
 cycloalkyl, 
 —(CH 2 ) 1-3 OR 16  wherein R 16  is hydrogen, alkyl, acyl or aryl, 
 —C(═O)R 17  wherein R 17  is hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted alkyl, haloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl or optionally substituted amino, 
 —C(═S)R 17  wherein R 17  is as defined above, or —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, 
 R 14  and R 15  may be combined to form optionally substituted thioamidino group, or 
 R 14  and R 15  are combined together with the adjacent nitrogen to form an optionally substituted nitrogen-containing heterocycle optionally containing nitrogen, sulfur or oxygen atom in its ring, 
 
 —(CH 2 ) 0-3 OR 18  wherein R 18  is hydrogen, alkyl, acyl or aryl, 
 —(CH 2 ) 1-3 CONHR 19  wherein R 19  is hydrogen, alkyl, acyl or aryl, 
 —SO 3 R 20  wherein R 20  is alkyl or hydroxy, 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, 
 —PO(OH)(R 22 ) wherein R 22  is alkyl, 
 haloalkyl, 
 —(CH 2 ) 1-3 COR 23  wherein R 23  is alkyl or optionally substituted aryl, 
 —(CH 2 ) 0-3 CN, 
 —R 41 —COOR 42  wherein R 41  is alkenyl and R 42  is hydrogen or alkyl, 
 —(CH 2 ) 1-3 R 40  wherein R 40  is optionally substituted aryl or optionally substituted heteroaryl, 
 optionally substituted aryl or 
 optionally substituted heteroaryl; and 
 
       the other of R 27  and R 28  is hydrogen or heterocycle. 
     
   
   
       8 . The compound of  claim 1 , represented by the general formula (VII): 
     
       
         
         
             
             
         
       
       the prodrug, the pharmaceutically acceptable salt or the solvate thereof; 
       wherein Y, R A , R 1 , R 2  and R 4  are as defined in  claim 1 . 
     
   
   
       9 . The compound of  claim 1 , represented by the general formula (VIII): 
     
       
         
         
             
             
         
       
       the prodrug, the pharmaceutically acceptable salt or the solvate thereof; 
       wherein Y, R A , R 1 , R 2  and R 3  are as defined in  claim 1 . 
     
   
   
       10 . The compound of  claim 1 , represented by the general formula (IX): 
     
       
         
         
             
             
         
       
       the prodrug, the pharmaceutically acceptable salt or the solvate thereof; 
       wherein Y, R A , R 1  and R 2  are as defined in  claim 1 . 
     
   
   
       11 . The compound of  claim 1 , represented by the general formula (X): 
     
       
         
         
             
             
         
       
       the prodrug, the pharmaceutically acceptable salt or the solvate thereof; 
       wherein X, Y, R A , R 1  and R 2  are as defined in  claim 1 . 
     
   
   
       12 . The compound of  claim 1 , the prodrug, the pharmaceutically acceptable salt or
 the solvate thereof;   wherein R 3  or R 4  is
 a carboxy or 
 —N(R 14 )(R 15 ) wherein R 14  and R 15  each is independently
 hydrogen, 
 alkyl, 
 acyl, 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, or 
 R 14  and R 15  may be combined together with the adjacent nitrogen atom to form nitrogen-containing heterocycle optionally containing sulfur in its ring. 
 
   
   
   
       13 . The compound of  claim 1 , the prodrug, the pharmaceutically acceptable salt or
 the solvate thereof;   wherein R 3  or R 4  is
 —N(R 14 )(R 15 ) wherein R 14  and R 15  each is independently
 hydrogen, 
 alkyl, 
 acyl, 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, or 
 R 14  and R 15  may be combined together with the adjacent nitrogen atom to form a nitrogen-containing heterocycle optionally containing sulfur in its ring. 
 
   
   
   
       14 - 18 . (canceled) 
   
   
       19 . The compound of  claim 1 , represented by the formula: 
     
       
         
         
             
             
         
       
       the pharmaceutically acceptable salt or the solvate thereof; 
       wherein: 
       R B  is —C(═O)R 26  wherein R 26  is hydroxy, alkoxy, alkyl, alkoxyalkyl, cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl or optionally substituted heterocycleoxy or
 —CON(R 8 )(R 9 ) wherein R 8  and R 9  each is independently hydrogen, alkyl or alkoxy; 
 
       R 1  is a group of the formula: -Z 2 -R 5  wherein Z 2  is optionally substituted alkylene; R 5  is optionally substituted aryl; 
       R 28  is carboxy,
 —N(R 14 )(R 15 ) wherein R 14  and R 15  each is independently
 hydrogen, 
 alkyl, 
 cycloalkyl, 
 —(CH 2 ) 1-3 OR 6  wherein R 16  is hydrogen, alkyl, acyl or aryl, 
 —C(═O)R 17  wherein R 17  is hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted alkyl, haloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl or optionally substituted amino, 
 —C(═S)R 17  wherein R 17  is as defined above, 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, 
 R 14  and R 15  may be combined to form an optionally substituted thioamidino group, or 
 R 14  and R 15  may be combined together with the adjacent nitrogen to form optionally substituted nitrogen containing heterocycle optionally having nitrogen, sulfur and/or oxygen in its ring, 
 
 —(CH 2 ) 0-3 OR 18  wherein R 18  is hydrogen, alkyl, acyl or aryl, 
 —(CH 2 ) 1-3 CONHR 19  wherein R 19  is hydrogen, alkyl, acyl or aryl, 
 —SO 3 R 20  wherein R 20  is alkyl or hydroxy, 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, 
 —PO(OH) 2 , 
 —PO(OH)(R 22 ) wherein R 22  is alkyl, 
 haloalkyl, 
 —(CH 2 ) 1-3 COR 23  wherein R 23  is alkyl or optionally substituted aryl, 
 —(CH 2 ) 0-3 CN, 
 —R 41 —COOR 42  wherein R 41  is alkenyl, R 42  is hydrogen or alkyl, 
 —(CH 2 ) 1-3 R 40  wherein R 40  is optionally substituted aryl or optionally substituted heteroaryl, 
 optionally substituted alkenyl, 
 optionally substituted alkynyl, 
 optionally substituted aryl or 
 optionally substituted heteroaryl. 
 
     
   
   
       20 . The compound of  claim 19 , the pharmaceutically acceptable salt or the solvate thereof, wherein:
 R B  is —C(═O)R 26  wherein R 26  is hydroxy, alkoxy, alkyl, alkoxyalkyl, cycloalkyl or optionally substituted heterocycleoxy;   R 1  is a group of the formula: -Z 2 -R 5  wherein Z 2  is methylene; R 5  is phenyl optionally substituted by halogen;   R 28  is
 carboxy, 
 —N(R 14 )(R 15 ) wherein R 14  and R 15  each is independently
 hydrogen, 
 alkyl, 
 cycloalkyl, 
 —(CH 2 ) 1-3 OR 6  wherein R 16  is hydrogen, alkyl, acyl or aryl, 
 —C(═O)R 17  wherein R 17  is hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted alkyl, haloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl or optionally substituted amino, 
 —C(═S)R 17  wherein R 17  is as defined above, 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, 
 R 14  and R 15  may be combined together to form optionally substituted thioamidino group, or 
 R 14  and R 15  may be combined together with the adjacent nitrogen atom to form an optionally substituted nitrogen-containing heterocycle optionally possessing sulfur and/or oxygen in its ring, 
 
 —(CH 2 ) 0-3 OR 18  wherein R 18  is hydrogen, alkyl, acyl or aryl, 
 —(CH 2 ) 1-3 CONHR 19  wherein R 19  is hydrogen, alkyl, acyl or aryl, 
 —SO 3 R 20  wherein R 20  is alkyl or hydroxy, 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, 
 —PO(OH) 2 , 
 —PO(OH)(R 22 ) wherein R 22  is alkyl, 
 haloalkyl, 
 —(CH 2 ) 1-3 COR 23  wherein R 23  is alkyl or optionally substituted aryl, 
 —(CH 2 ) 0-3 CN, 
 —R 41 —COOR 42  wherein R 41  is alkenyl and R 42  is hydrogen or alkyl, 
 —(CH 2 ) 1-3 R 40  wherein R 40  is optionally substituted aryl or optionally substituted heteroaryl, 
 optionally substituted alkenyl, 
 optionally substituted alkynyl, 
 optionally substituted aryl or 
 optionally substituted heteroaryl. 
   
   
   
       21 . The compound of  claim 1 , represented by the formula: 
     
       
         
         
             
             
         
       
       the pharmaceutically acceptable salt or the solvate thereof; 
       wherein: 
       R B  is a group of the formula: —C(═O)R 26  wherein R 26  is hydroxy, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted alkoxyalkyl, optionally substituted cycloalkyl or optionally substituted heterocycleoxy; 
       R 1  is a group of the formula: —CH 2 —R 5  wherein R 5  is phenyl optionally substituted by halogen; and 
       R 28  is carboxy, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted amino, optionally substituted carbamoyl, optionally substituted acyl, optionally substituted aralkyloxycarbonyl, optionally substituted heteroring, optionally substituted (heteroring)alkyl or optionally substituted aryl. 
     
   
   
       22 . The compound of  claim 19 , the pharmaceutically acceptable salt or the solvate thereof, wherein
 R B  is a group of the formula: —C(═O)R 26  wherein R 26  is hydroxy, alkoxy or optionally substituted heterocycleoxy;   R 1  is a group of the formula: —CH 2 —R 5  wherein R 5  is phenyl optionally substituted by halogen; and   R 28  is a group shown below:   
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       23 . The compound of  claim 22 , the pharmaceutically acceptable salt or the solvate thereof, wherein R B  is —C(═O)R 26  wherein R 26  is alkoxy. 
   
   
       24 . The compound of  claim 22 , the pharmaceutically acceptable salt or the solvate thereof, wherein R B  is —C(═O)R 26  wherein R 26  is alkoxy and R 28  is carboxy. 
   
   
       25 . A compound of the formula: 
     
       
         
         
             
             
         
       
       a pharmaceutically acceptable salt or a solvate thereof. 
     
   
   
       26 . The compound of the formula (I-3) of  claim 25 , an alkali metal salt, alkali earth metal salt or amine salt thereof. 
   
   
       27 . The compound of the formula (I-3) of  claim 25 , a meglumine salt or solvate thereof. 
   
   
       28 . A pharmaceutical composition comprising the compound of  claim 1 , a prodrug, a pharmaceutically acceptable salt or a solvate thereof together with a pharmaceutically acceptable carrier or diluent. 
   
   
       29 - 33 . (canceled) 
   
   
       34 . A mixed composition for anti-HIV comprising the pharmaceutical composition of  claim 28  together with a reverse transcriptase inhibitor and/or a protease inhibitor. 
   
   
       35 . (canceled) 
   
   
       36 . A method for preventing or treating AIDS or AIDS related complications, which comprises administering an effective amount of the pharmaceutical composition of  claim 28  to a patient in need thereof. 
   
   
       37 . A method for preparing a pharmaceutical composition for preventing or treating AIDS or AIDS-related complications, which comprises mixing the compound of  claim 1  with a pharmaceutically acceptable carrier or diluent. 
   
   
       38 . A process for preparing Compound (III-1-B), which comprises reacting Compound (G-I) and Compound (G-II) in the presence of an acid catalyst as represented by the following scheme: 
     
       
         
         
             
             
         
       
       wherein Q is halogen; n is an integer 0 to 3; X 1  is hydrogen or protective group of phenolic hydroxy; R 26  is hydroxy, alkoxy, alkyl, alkoxyalkyl, cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycleoxy or —N(R 8 )(R 9 ) wherein R 8  and R 9  each is independently hydrogen, alkyl or alkoxy; 
       Y 1  is
 hydrogen, 
 halogen, 
 carboxy, 
 alkoxycarbonyl, 
 optionally substituted carbamoyl, 
 —N(R 14 )(R 15 ) wherein R 14  and R 15  each is independently
 hydrogen, 
 alkyl, 
 cycloalkyl, 
 —(CH 2 ) 1-3 OR 16  wherein R 16  is hydrogen, alkyl, acyl or aryl, 
 —C(═O)R 17  wherein R 17  is hydrogen, hydroxy, optionally substituted alkoxy, optionally substituted alkyl, haloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl or optionally substituted amino, 
 —C(═S)R 17  wherein R 17  is as defined above, 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, 
 R 14  and R 15  may be combined to form an optionally substituted thioamidino group, or 
 R 14  and R 15  may be combined together with the adjacent nitrogen to form optionally substituted nitrogen containing heterocycle optionally possessing nitrogen, sulfur and/or oxygen in its ring, 
 
 —(CH 2 ) 0-3 OR 18  wherein R 18  is hydrogen, alkyl, acyl or aryl, 
 —(CH 2 ) 1-3 CONHR 19  wherein R 19  is hydrogen, alkyl, acyl or aryl, 
 —SO 3 R 20  wherein R 20  is alkyl or hydroxy, 
 —SO 2 R 21  wherein R 21  is alkyl or optionally substituted amino, 
 —PO(OH) 2 , 
 —PO(OH)(R 22 ) wherein R 22  is alkyl, 
 haloalkyl, 
 —(CH 2 ) 1-3 COR 23  wherein R 23  is alkyl or optionally substituted aryl, 
 —(CH 2 ) 0-3 CN, 
 —R 41 —COOR 42  wherein R 41  is alkenyl and R 42  is hydrogen or alkyl, 
 —(CH 2 ) 1-3 R 40  wherein R 40  is optionally substituted aryl or optionally substituted heteroaryl, 
 optionally substituted aryl or 
 optionally substituted heteroaryl. 
 
     
   
   
       39 . The process of  claim 38 , wherein (Q)n is F; R 26  is alkoxy; Y 1  is hydrogen, halogen, carboxy or alkoxycarbonyl; and X 1  is an ether type protecting group or an ester type protecting group. 
   
   
       40 . The process of  claim 38 , wherein (Q)n is p-F; R 26  is methoxy; Y 1  is hydrogen, halogen, carboxy or methoxycarbonyl; X 1  is hydrogen, alkyl or aralkyl. 
   
   
       41 . The process of  claim 38 , in which the reaction is carried out in the presence of an acid catalyst and an oxidizing reagent. 
   
   
       42 . A pharmaceutical composition comprising the compound of  claim 25 , a prodrug, a pharmaceutically acceptable salt or a solvate thereof, together with a pharmaceutically acceptable carrier or diluent.