Inhibitors of hepatitis b virus

Abstract

The present invention relates to compounds that are inhibitors of hepatitis B virus (HBV). Compounds of this invention are useful alone or in combination with other agents for treating, ameliorating, preventing or curing HBV infection and related conditions. The present invention also relates to pharmaceutical compositions containing the compounds.

1 . A compound of general formula (I): 
       
         
           
           
               
               
           
         
       
       wherein:
 Cy is aryl or heteroaryl; 
 X is O, NH, N—C 1-6 alkyl, S, SO or SO 2 ; 
 Y, Y′, Y″ and Y′″ are each independently a single bond or C 1-6 alkanediyl optionally substituted with one or more R 3 ; 
 Z is CR 4  or N; 
 W is a single bond or NR 5 , wherein if W is a single bond, Z is N, and if W is NR 5 , Z is CR 4 ; 
 A is NR 6 , O, S or C 1-6 alkanediyl optionally substituted with one or more R 3 ; 
 R 1  is H or C 1-6 alkyl; 
 R 2  is selected from H, OH and C 1-6 alkyl; 
 R 3  is selected from H, OH, C 1-6 alkyl, C 3-8 cycloalkyl and halogen or two geminal R 3  form together with the atom to which they are attached a spiro-C 3-8 cycloalkyl or a spiro-C 3-8 heterocycloalkyl or R 3  is O forming together with the carbon atom to with it is bonded a C═O; 
 R 4  is H or C 1-6 alkyl; 
 or when W is NR 5  and Z is CR 4 , R 2  and R 4  may optionally form a C 1-6 alkanediyl bridge; 
 R 5  is selected from H, C 1-6 alkyl, C 1-6 alkylaryl, C 1-6 alkylheteroaryl and C 1-6 alkyl-C 3-8 cycloalkyl wherein each of said C 1-6 alkyl, C 1-6 alkylaryl, C 1-6 alkylheteroaryl or C 1-6 alkyl-C 3-8 cycloalkyl is optionally substituted with one or more substituents each independently selected from: OH, halogen, haloC 1-6 alkyl, cyano and NH 2 ; 
 R 6  is selected from:
 hydrogen; 
 OH; 
 C(O)R 7 ; 
 C(O)OR 7 ; 
 C(O)NHR 7 ; 
 C(O)N(R 7 ) 2 ; 
 SO 2 R 7 ; 
 SO 2 NH(R 7 ); 
 SO 2 N(R 7 ) 2; 
 C 1-6 alkyl optionally substituted with one or more substituents each independently selected from the group consisting of: OH, halogen, CN, NH 2 , NH(R 7 ), N(R 7 ) 2 , aryl, heteroaryl, 3-7 membered saturated ring and 5-7 membered unsaturated ring, each of said saturated or unsaturated ring optionally containing one or more heteroatoms selected from the group consisting of O, N and S and each of said aryl, heteroaryl, 3-7 membered saturated or 5-7 membered unsaturated ring being optionally substituted with one or more substituents each independently selected from OH, halogen, haloC 1-6 alkyl, CN, haloC 1-6 alkoxy and C 1-6 alkoxy; 
 aryl or heteroaryl ring, each of said aryl or heteroaryl ring being optionally substituted with one or more substituents each independently selected from: OH, halogen, haloC 1-6 alkyl, CN, haloC 1-6 alkoxy, C 1-6 alkoxy, C 1-6 alkyl, and NH 2 ; and 
 a 3-8 membered saturated or partially unsaturated cyclic or bicyclic ring optionally containing one or more heteroatoms each independently selected from the group consisting of: 0, S and N, the 3-8 membered saturated or partially unsaturated cyclic or bicyclic ring being optionally substituted with one, two or more substituents each independently selected from the group consisting of: OH, halogen, CN, C 1-6 alkyl, hydroxyC 1-6 alkyl, C(O)OR 7 , C(O)R 7 , haloC 1-6 alkyl, haloC 1-6 alkoxy and C 1-6 alkoxy; 
 
 R 7  is selected from the group consisting of: C 1-9 alkyl, C 3-8 cycloalkyl, aryl, heteroaryl and 3-8 membered saturated or partially saturated heterocyclic ring, wherein each of said C 1-9 alkyl, C 3-8 cycloalkyl, aryl, heteroaryl or 3-8 membered saturated or partially saturated heterocyclic ring is optionally substituted with one or more substituents each independently selected from the group consisting of: OH, halogen, CN, C 1-6 alkyl, hydroxyC 1-6 alkyl, haloC 1-6 alkyl, haloC 1-6 alkoxy, C 1-6 alkoxy, NH 2 , OC(═O)C 1-6 alkyl, OP(═O)(OH) 2 , aryl, heteroaryl and NHC(═O)C 1-6 alkyl; 
 Ra, Rb, Rc and Rd are each independently selected from the group consisting of: hydrogen, halogen, CN, C 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkyl and haloC 1-6 alkoxy; 
 
       and pharmaceutically acceptable salts, tautomers, stereoisomers thereof. 
     
     
         2 . The compound according to  claim 1  having general formula (Ia): 
       
         
           
           
               
               
           
         
       
       wherein Cy, Y, Y′, Y″, A, R 1 , R 2 , Ra, Rb, Rc and Rd are as defined in  claim 1  and X is O, S, NH or N—C 1-6 alkyl; and pharmaceutically acceptable salts, tautomers, stereoisomers thereof. 
     
     
         3 . The compound according to  claim 1  or  2 , wherein: Cy is phenyl, X is O, NH or S, A is CH 2 , R 1  is CH 3 , R 2  and R 3  are hydrogen, and pharmaceutically acceptable salts, tautomers, stereoisomers thereof. 
     
     
         4 . The compound according to  claim 1  having general formula (Ib): 
       
         
           
           
               
               
           
         
       
       wherein Cy, Y, Y′, Y″, A, R 1 , R 2 , R 4 , R 5 , Ra, Rb, Rc and Rd are as defined in  claim 1  and X is O, S, NH or N—C 1-6 alkyl; and pharmaceutically acceptable salts, tautomers, stereoisomers thereof. 
     
     
         5 . The compound according to  claim 1  or  4  wherein: Cy is phenyl, X is O, NH or S, Y is CH 2 , Y′ is CH 2 , Y″ is CH 2  and A is CH 2 , O or NR 6 , and pharmaceutically acceptable salts, tautomers, stereoisomers thereof. 
     
     
         6 . The compound according to any one of  claims 1 ,  2 ,  4  or  5 , wherein: A is NR 6 , O or C 1-4 alkanediyl; R 6  is selected from the group consisting of: hydrogen, C(O)R 7 , C(O)OR 7 , C(O)NHR 7 , SO 2 R 7 , SO 2 NH(R 7 ), aryl, heteroaryl, C 1-6 alkyl, said C 1-6 alkyl being optionally substituted with one or more substituents each independently selected from the group consisting of: halogen, CN and phenyl; R 7  is C 1-6 alkyl, C 3-8 cycloalkyl, aryl, heteroaryl or a 3-8 membered saturated heterocyclic ring and R 7  is optionally substituted with one or more substituents each independently selected from the group consisting of: OP(═O)(OH) 2 , NH 2 , OC(═O)CH 3 , methyl, OH, aryl, heteroaryl, NHC(═O)C 1-6 alkyl and halogen and pharmaceutically acceptable salts, tautomers, stereoisomers thereof. 
     
     
         7 . The compound according to any one of  claims 1 ,  2 ,  4  or  5 , wherein A is NR 6 , R 6  is C(O)R 7  and R 7  is selected from the group consisting of: C 1-6 alkyl, C 3-8 cycloalkyl, aryl, heteroaryl and 3-8 membered saturated or partially saturated heterocyclic ring, wherein each of said C 1-6 alkyl, C 3-8 cycloalkyl, aryl, heteroaryl or 3-8 membered saturated or partially saturated heterocyclic ring is optionally substituted with one or more substituents each independently selected from the group consisting of: OH, halogen, CN, C 1-6 alkyl, hydroxyC 1-6 alkyl, haloC 1-6 alkyl, haloC 1-6 alkoxy, C 1-6 alkoxy, NH 2 , aryl, heteroaryl and pharmaceutically acceptable salts, tautomers, stereoisomers thereof. 
     
     
         8 . The compound of general formula (I) according to  claim 1  being selected from the following list:
 N-(3,4-difluorophenyl)-2-methyl-6,7,8,9,9a,10-hexahydro-2H-pyrido[1,2-e]pyrrolo[3,4-b][1,4,5]oxathiazepine-1-carboxamide 4,4-dioxide; 
 N-(3,4-difluorophenyl)-2-methyl-2,6,7,8,9,9a,10,11-octahydropyrido[1,2-b]pyrrolo[3,4-f][1,2,5]thiadiazepine-1-carboxamide 4,4-dioxide; 
 N-(3,4-difluorophenyl)-2-methyl-6,7,7a,8-tetrahydro-2H-azeto[1,2-e]pyrrolo[3,4-b][1,4,5]oxathiazepine-1-carboxamide 4,4-dioxide; 
 trans-N-(3,4-difluorophenyl)-7-methyl-1,3a,4,9a-tetrahydro-3H,7H-furo[3,4-f]pyrrolo[3,4-b][1,4,5]oxathiazepine-8-carboxamide 5,5-dioxide; 
 cis-N-(3,4-difluorophenyl)-9-methyl-3,4,5,6-tetrahydro-2H,9H-3,5-methanopyrrolo[3,4-b][1,4,5]oxathiazonine-8-carboxamide 1,1-dioxide; 
 cis-N-(3,4-difluorophenyl)-2-methyl-5a,6,7,8,8a,9-hexahydro-2H,5H-cyclopenta[f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-7-methyl-N-(3,4,5-trifluorophenyl)-1,3a,4,9a-tetrahydro-3H,7H-furo[3,4-f]pyrrolo[3,4-b][1,4,5]oxathiazepine-8-carboxamide 5,5-dioxide; 
 (5aR,8aR)—N-(3,4-difluorophenyl)-2-methyl-5a,6,7,8,8a,9-hexahydro-2H,5H-cyclopenta[f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 (5aS,8aS)—N-(3,4-difluorophenyl)-2-methyl-5a,6,7,8,8a,9-hexahydro-2H,5H-cyclopenta[f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-Ethyl 7-methyl-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 cis-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2,7-dimethyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-Ethyl 8-((3,4-difluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 cis-Ethyl 8-((4-fluoro-3-methylphenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 cis-Ethyl 8-((3-chloro-4-fluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 cis-Ethyl 8-((3-(difluoromethyl)-4-fluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 cis-Ethyl 8-((3-cyano-4-fluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 cis-2-(isopropylsulfonyl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(methylsulfonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(cyclopropylsulfonyl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(N-isopropylsulfamoyl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl 7-methyl-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 N 2 ,7-dimethyl-N 8 -(3,4,5-trifluorophenyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2,8(3H)-dicarboxamide 5,5-dioxide; 
 tert-butyl 7-methyl-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aR,10aS)—N-(3,4-difluorophenyl)-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,2′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aS)—N8-(3,4-difluorophenyl)-N1,7-dimethyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,2′-f][1,4,5]oxathiazocine-1,8-dicarboxamide 5,5-dioxide; 
 ethyl (3aR,10aS)-8-((3,4-difluorophenyl)carbamoyl)-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,2′-f][1,4,5]oxathiazocine-1-carboxylate 5,5-dioxide; 
 cis-2-methyl-N-(3,4,5-trifluorophenyl)-5a,6,7,8,8a,9-hexahydro-2H,5H-cyclopenta[f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 N-(3,4-difluorophenyl)-2,8a-dimethyl-5a,6,7,8,8a,9-hexahydro-2H,5H-cyclopenta[f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-N-(3,4-difluorophenyl)-8a-hydroxy-2-methyl-5a,6,7,8,8a,9-hexahydro-2H,5H-cyclopenta[f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 (3aS,10aS)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 ethyl (3aR,10aR)-7-methyl-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 ethyl (3aS,10aS)-7-methyl-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 tert-butyl (3aS,10aS)-7-methyl-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 tert-butyl (3aR,10aR)-7-methyl-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (5aS,8aR) N-(3,4-difluorophenyl)-2-methyl-5a,6,7,8,8a,9-hexahydro-2H,5H-cyclopenta[f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 (5aR,8aS) N-(3,4-difluorophenyl)-2-methyl-5a,6,7,8,8a,9-hexahydro-2H,5H-cyclopenta[f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 (3aS,10aS) ethyl 8-((3,4-difluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aR,10aR) ethyl 8-((3,4-difluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aS,10aS) ethyl 8-((4-fluoro-3-methylphenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aR,10aR) ethyl 8-((4-fluoro-3-methylphenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aS,10aS) ethyl 8-((3-chloro-4-fluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aR,10aR) ethyl 8-((3-chloro-4-fluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aS,10aS) ethyl 8-((3-(difluoromethyl)-4-fluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aR,10aR) ethyl 8-((3-(difluoromethyl)-4-fluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aS,10aS) ethyl 8-((3-cyano-4-fluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aR,10aR) ethyl 8-((3-cyano-4-fluorophenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(pyridin-3-yl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(1,3,4-oxadiazol-2-yl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(oxazole-2-carbonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methylisoxazole-3-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-2-(6-hydroxynicotinoyl)-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7-methyl-2-nicotinoyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-2-isonicotinoyl-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(5-oxo-4,5-dihydropyrazine-2-carbonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(1-methyl-1H-pyrazole-4-carbonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(thiazole-2-carbonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(6-oxo-1,6-dihydropyrimidin-2-yl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(4-amino-1,2,5-oxadiazole-3-carbonyl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(4-amino-1,2,5-oxadiazole-3-carbonyl)-N-(4-fluoro-3-methylphenyl)-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methyl-1,3,4-thiadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(1,2,4-oxadiazole-3-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(oxazole-5-carbonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(oxazole-4-carbonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(3-methyloxetane-3-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(L-alanyl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(L-seryl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(L-threonyl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(7-methyl-5,5-dioxido-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocin-2(3H)-yl)-2-oxoethyl acetate; 
 cis-2-(2-hydroxyacetyl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(7-methyl-5,5-dioxido-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocin-2(3H)-yl)-2-oxoethyl dihydrogen phosphate; 
 cis-7-methyl-2-(2,2,2-trifluoroethyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(cyanomethyl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(5-fluoropyrimidin-2-yl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(2-chloropyridin-4-yl)-N-(4-fluoro-3-methylphenyl)-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 ethyl (3R,6R)-10-methyl-9-((3,4,5-trifluorophenyl)carbamoyl)-3,4,6,7-tetrahydro-10H-3,6-methanopyrrolo[3,4-b][1,4,5,8]oxathiadiazecine-5(2H)-carboxylate 1,1-dioxide; 
 cis-7-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(cyanomethyl)-N-(4-fluoro-3-methylphenyl)-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(2,2,2-trifluoroethyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(pyridin-2-yl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(pyrazin-2-yl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-7-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(5-hydroxypyrimidin-2-yl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-(3aR,10aR)-7-methyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7,10a-dimethyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7,10a-dimethyl-2-(5-methyloxazole-4-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7,10a-dimethyl-2-(2-methyltetrahydrofuran-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-7,10a-dimethyl-2-(3-methyloxetane-3-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis-2-(2-oxabicyclo[2.1.1]hexane-1-carbonyl)-N-(4-fluoro-3-methylphenyl)-7,10a-dimethyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aS,10aS) ethyl 7,10a-dimethyl-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aR,10aR) ethyl 7,10a-dimethyl-8-((3,4,5-trifluorophenyl)carbamoyl)-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aS,10aS) ethyl 8-((4-fluoro-3-methylphenyl)carbamoyl)-7,10a-dimethyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aR,10aR) ethyl 8-((4-fluoro-3-methylphenyl)carbamoyl)-7,10a-dimethyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aS,10aS) N-(4-fluoro-3-methylphenyl)-7,10a-dimethyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR) N-(4-fluoro-3-methylphenyl)-7,10a-dimethyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)-7-methyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(3-chloro-4-fluorophenyl)-7-methyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-((R)-tetrahydrofuran-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-((S)-tetrahydrofuran-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)-2-(5-amino-1,3,4-oxadiazole-2-carbonyl)-7-methyl-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(3-methyl-1,2,4-oxadiazole-5-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(oxazole-4-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(1,2,5-oxadiazole-3-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)-7-methyl-2-(oxazole-4-carbonyl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methyl-1,3,4-thiadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(oxetane-3-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)-2-(2-oxabicyclo[2.1.1]hexane-1-carbonyl)-N-(4-fluoro-3-methylphenyl)-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(oxetane-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(2-methyltetrahydrofuran-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(2-methyloxazole-4-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methyloxazole-4-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)-2-(2,5-dimethyloxazole-4-carbonyl)-N-(4-fluoro-3-methylphenyl)-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(3-chloro-4-fluorophenyl)-7-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)-7-methyl-2-(3-methyl-1,2,4-oxadiazol-5-yl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)—N-(3-chloro-4-fluorophenyl)-7-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aR)-7-methyl-2-(5-methyl-1,3,4-oxadiazol-2-yl)-N-(3,4,5-trifluorophenyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 ethyl (3aR,10aR)-8-((4-fluoro-3-methylphenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-c:3′,4′-g][1,6,2]dithiazocine-2(3H)-carboxylate 5,5-dioxide; 
 ethyl (3aR,10aR)-8-((4-fluoro-3-methylphenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-c:3′,4′-g][1,6,2]dithiazocine-2(3H)-carboxylate 5,5,9-trioxide; 
 ethyl (3aR,10aR)-8-((4-fluoro-3-methylphenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-c:3′,4′-g][1,6,2]dithiazocine-2(3H)-carboxylate 5,5,9,9-tetraoxide; 
 (3aR,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-c:3′,4′-g][1,6,2]dithiazocine-8-carboxamide 5,5-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-2-methyl-8-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-2-methyl-8-(3-methyloxetane-3-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-2-methyl-8-(2-methyltetrahydrofuran-2-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-8-(2-oxabicyclo[2.1.1]hexane-1-carbonyl)-N-(4-fluoro-3-methylphenyl)-2-methyl-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-2-methyl-8-(5-methyloxazole-4-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-2-methyl-8-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-2-methyl-8-(3-methyloxetane-3-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-2-methyl-8-(2-methyltetrahydrofuran-2-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-8-(2-oxabicyclo[2.1.1]hexane-1-carbonyl)-N-(4-fluoro-3-methylphenyl)-2-methyl-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-2-methyl-8-(5-methyloxazole-4-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-2-methyl-7-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[3,4-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-2-methyl-7-(3-methyloxetane-3-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[3,4-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-2-methyl-8-(2-methyltetrahydrofuran-2-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-7-(2-oxabicyclo[2.1.1]hexane-1-carbonyl)-N-(4-fluoro-3-methylphenyl)-2-methyl-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[3,4-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 cis-N-(4-fluoro-3-methylphenyl)-2-methyl-7-(5-methyloxazole-4-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[3,4-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-2-methyl-7-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[3,4-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-2-methyl-7-(3-methyloxetane-3-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[3,4-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-2-methyl-8-(2-methyltetrahydrofuran-2-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[4,3-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-7-(2-oxabicyclo[2.1.1]hexane-1-carbonyl)-N-(4-fluoro-3-methylphenyl)-2-methyl-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[3,4-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-2-methyl-7-(5-methyloxazole-4-carbonyl)-5,5a,6,7,8,9,9a,10-octahydro-2H-pyrido[3,4-f]pyrrolo[3,4-b][1,4,5]oxathiazocine-1-carboxamide 4,4-dioxide; 
 trans-tert-butyl 8-((4-fluoro-3-methylphenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methyloxazole-4-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(2-methyltetrahydrofuran-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 trans-N-(4-fluoro-3-methylphenyl)-7-methyl-2-(3-methyloxetane-3-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 trans-2-(2-oxabicyclo[2.1.1]hexane-1-carbonyl)-N-(4-fluoro-3-methylphenyl)-7-methyl-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 tert-butyl (3aS,10aR)-8-((4-fluoro-3-methylphenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 tert-butyl (3aR,10aS)-8-((4-fluoro-3-methylphenyl)carbamoyl)-7-methyl-3a,4,10,10a-tetrahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-2(3H)-carboxylate 5,5-dioxide; 
 (3aS,10aR)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 (3aR,10aS)—N-(4-fluoro-3-methylphenyl)-7-methyl-2-(5-methyl-1,3,4-oxadiazole-2-carbonyl)-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis 2-benzyl-N-(4-fluoro-3-methylphenyl)-7-methyl-3-oxo-2,3,3a,4,10,10a-hexahydro-1H,7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazocine-8-carboxamide 5,5-dioxide; 
 cis/trans ethyl 7-methyl-8-((3,4,5-trifluorophenyl)carbamoyl)-1,3a,4,10,11,11a-hexahydro-7H-dipyrrolo[3,4-b:3′,4′-f][1,4,5]oxathiazonine-2(3H)-carboxylate 5,5-dioxide; 
 cis ethyl 8-((4-fluoro-3-methylphenyl)carbamoyl)-7-methyl-3a,4,7,9,10,10a-hexahydro-1H-dipyrrolo[3,4-c:3′,4′-g][1,2,6]thiadiazocine-2(3H)-carboxylate 5,5-dioxide; 
 
       and pharmaceutically acceptable salts, tautomers, stereoisomers thereof. 
     
     
         9 . A compound or a pharmaceutically acceptable salt, tautomer, stereoisomer thereof as defined in any one of previous claims for medical use. 
     
     
         10 . A compound or a pharmaceutically acceptable salt, tautomer, stereoisomer thereof as defined in  claim 9  for use in the treatment and/or prevention of an HBV infection and/or a condition related to an HBV infection. 
     
     
         11 . The compound or pharmaceutically acceptable salt, tautomer, stereoisomer thereof for use according to  claim 10 , wherein said condition related to an HBV infection is selected from the group consisting of: chronic hepatitis B, HBV/HDV co-infection, HBV/HCV co-infection, HBV/HIV co-infection, inflammation, necrosis, cirrhosis, hepatocellular carcinoma, hepatic decompensation and hepatic injury from an HBV infection. 
     
     
         12 . The compound or pharmaceutically acceptable salt, tautomer, stereoisomer thereof for use according to  claim 10  or  11 , wherein said use is in treating, eradicating, reducing, slowing or inhibiting an HBV infection in an individual in need thereof, and/or in reducing the viral load associated with an HBV infection in an individual in need thereof, and/or in reducing reoccurrence of an HBV infection in an individual in need thereof, and/or in inducing remission of hepatic injury from an HBV infection in an individual in need thereof, and/or in prophylactically treating an HBV infection in an individual afflicted with a latent HBV infection. 
     
     
         13 . The compound or pharmaceutically acceptable salt, tautomer, stereoisomer thereof for use according according to any one of  claims 9 - 12 , wherein said use is in combination with at least one further therapeutic agent. 
     
     
         14 . The compound or pharmaceutically acceptable salt, tautomer, stereoisomer thereof for use according to  claim 13 , wherein the at least one further therapeutic agent is selected from the group consisting of: a therapeutic vaccine; an RNA interference therapeutic/antisense oligonucleotide; an immunomodulator; a STING agonist; a RIG-I modulator; a NKT modulator; an IL agonist; an interleukin or another immune acting protein; a therapeutic and prophylactic vaccine; an immune checkpoint modulator/inhibitor; an HBV entry inhibitor; a cccDNA modulator; an inhibitor of HBV protein expression; an agent targeting HBV RNA; a capsid assembly inhibitor/modulator; a core or X protein targeting agent; a nucleotide analogue; a nucleoside analogue; an interferon or a modified interferon; an HBV antiviral of distinct or unknown mechanism; a cyclophilin inhibitor; a sAg release inhibitor; an HBV polymerase inhibitor; a dinucleotide; a SMAC inhibitor; a HDV targeting agent; a viral maturation inhibitor; a reverse transcriptase inhibitor and an HBV RNA destabilizer or another small-molecule inhibitor of HBV protein expression; or a combination thereof; wherein said therapeutic vaccine is preferably selected from: HBsAG-HBIG, HB-Vac, ABX203, NASVAC, GS-4774, GX-110 (HB-110E), CVI-HBV-002, RG7944 (INO-1800), TG-1050, FP-02 (Hepsyn-B), AIC649, VGX-6200, KW-2, TomegaVax-HBV, ISA-204, NU-500, INX-102-00557, HBV MVA and PepTcell; wherein said RNA interference therapeutic is preferably selected from: TKM-HBV (ARB-1467), ARB-1740, ARC-520, ARC-521, BB-HB-331, REP-2139, ALN-HBV, ALN-PDL, LUNAR-HBV, GS3228836 and GS3389404; wherein said immunomodulator is preferably a TLR agonist, preferably a TLR7, TLR8 or TLR9 agonist, preferably being selected from: RG7795 (RO-6864018), GS-9620, SM360320 (9-benzyl-8-hydroxy-2-(2-methoxy-ethoxy)adenine), AZD 8848 (methyl [3-({[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-pyrin-9-yl)propyl][3-(4-morpholinyl)propyl]amino}methyl)phenyl]acetate) and ARB-1598; wherein said RIG-I modulator is preferably SB-9200; wherein said IL agonist or other immune acting protein is preferably INO-9112 or recombinant IL12; wherein said immune checkpoint modulator/inhibitor is preferably BMS-936558 (Opdivo (nivolumab)) or pembrolizumab; wherein said HBV entry inhibitor is preferably Myrcludex B, IVIG-Tonrol or GC-1102; wherein said cccDNA modulator is preferably selected from: a direct cccDNA inhibitor, an inhibitor of cccDNA formation or maintenance, a cccDNA epigenetic modifier and an inhibitor of cccDNA transcription; wherein said capsid assembly inhibitor/modulator, core or X protein targeting agent, direct cccDNA inhibitor, inhibitor of cccDNA formation or maintenance, or cccDNA epigenetic modifier is preferably selected from: BAY 41-4109, NVR 3-778, GLS-4, NZ-4 (W28F), Y101, ARB-423, ARB-199, ARB-596, AB-506, JNJ-56136379, ASMB-101 (AB-V102), ASMB-103, CHR-101, CC-31326, AT-130 and R07049389; wherein said interferon or modified interferon is preferably selected from: interferon alpha (IFN-α), pegylated interferon alpha (PEG-IFN-α), interferon alpha-2a, recombinant interferon alpha-2a, peginterferon alpha-2a (Pegasys), interferon alpha-2b (Intron A), recombinant interferon alpha-2b, interferon alpha-2b XL, peginterferon alpha-2b, glycosylated interferon alpha-2b, interferon alpha-2c, recombinant interferon alpha-2c, interferon beta, interferon beta-1a, peginterferon beta-1a, interferon delta, interferon lambda (IFN-λ), peginterferon lambda-1, interferon omega, interferon tau, interferon gamma (IFN-γ), interferon alfacon-1, interferon alpha-n1, interferon alpha-n3, albinterferon alpha-2b, BLX-883, DA-3021, PI 101 (also known as AOP2014), PEG-infergen, Belerofon, INTEFEN-IFN, albumin/interferon alpha 2a fusion protein, rHSA-IFN alpha 2a, rHSA-IFN alpha 2b, PEG-IFN-SA and interferon alpha biobetter; wherein said HBV antiviral of distinct or unknown mechanism is selected from: AT-61 ((E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide), AT130 ((E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide), analogues thereof, REP-9AC (REP-2055), REP-9AC′ (REP-2139), REP-2165 and HBV-0259; wherein said cyclophilin inhibitor is preferably selected from: OCB-030 (NVP-018), SCY-635, SCY-575 and CPI-431-32; wherein said HBV polymerase inhibitor is preferably selected from: entecavir (Baraclude, Entavir), lamivudine (3TC, Zeffix, Heptovir, Epivir, and Epivir-HBV), telbivudine (Tyzeka, Sebivo), clevudine, besifovir, adefovir (hepsera), tenofovir, preferably said tenofovir is in a salt form selected from: tenofovir disoproxil fumarate (Viread), tenofovir alafenamide fumarate (TAF), tenofovir disoproxil orotate (DA-2802), tenofovir disopropxil aspartate (CKD-390), AGX-1009, and CMX157; wherein said dinucleotide is preferably SB9200; wherein said SMAC inhibitor is preferably Birinapant; wherein said HDV targeting agent is preferably Lonafamib; wherein said HBV RNA destabilizer or other small-molecule inhibitor of HBV protein expression is preferably RG7834 or AB-452. 
     
     
         15 . A pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt, tautomer, stereoisomer thereof as defined in any one of  claims 1 - 8 , alone or in combination with at least one further therapeutic agent, and at least one pharmaceutically acceptable excipient. 
     
     
         16 . The pharmaceutical composition according to  claim 15 , wherein the at least one further therapeutic agent is selected from the group consisting of: a therapeutic vaccine; an RNA interference therapeutic/antisense oligonucleotide; an immunomodulator; a STING agonist; a RIG-I modulator; a NKT modulator; an IL agonist; an interleukin or another immune acting protein; a therapeutic and prophylactic vaccine; an immune checkpoint modulator/inhibitor; an HBV entry inhibitor; a cccDNA modulator; an inhibitor of HBV protein expression; an agent targeting HBV RNA; a capsid assembly inhibitor/modulator; a core or X protein targeting agent; a nucleotide analogue; a nucleoside analogue; an interferon or a modified interferon; an HBV antiviral of distinct or unknown mechanism; a cyclophilin inhibitor; a sAg release inhibitor; an HBV polymerase inhibitor; a dinucleotide; a SMAC inhibitor; a HDV targeting agent; a viral maturation inhibitor; a reverse transcriptase inhibitor and an HBV RNA destabilizer or another small-molecule inhibitor of HBV protein expression; or a combination thereof; wherein said therapeutic vaccine is preferably selected from: HBsAG-HBIG, HB-Vac, ABX203, NASVAC, GS-4774, GX-110 (HB-110E), CVI-HBV-002, RG7944 (INO-1800), TG-1050, FP-02 (Hepsyn-B), AIC649, VGX-6200, KW-2, TomegaVax-HBV, ISA-204, NU-500, INX-102-00557, HBV MVA and PepTcell; wherein said RNA interference therapeutic is preferably selected from: TKM-HBV (ARB-1467), ARB-1740, ARC-520, ARC-521, BB-HB-331, REP-2139, ALN-HBV, ALN-PDL, LUNAR-HBV, GS3228836 and GS3389404; wherein said immunomodulator is preferably a TLR agonist, preferably a TLR7, TLR8 or TLR9 agonist, preferably being selected from: RG7795 (RO-6864018), GS-9620, SM360320 (9-benzyl-8-hydroxy-2-(2-methoxy-ethoxy)adenine), AZD 8848 (methyl [3-({[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-pyrin-9-yl)propyl][3-(4-morpholinyl)propyl]amino}methyl)phenyl]acetate) and ARB-1598; wherein said RIG-I modulator is preferably SB-9200; wherein said IL agonist or other immune acting protein is preferably INO-9112 or recombinant IL12; wherein said immune checkpoint modulator/inhibitor is preferably BMS-936558 (Opdivo (nivolumab)) or pembrolizumab; wherein said HBV entry inhibitor is preferably Myrcludex B, IVIG-Tonrol or GC-1102; wherein said cccDNA modulator is preferably selected from: a direct cccDNA inhibitor, an inhibitor of cccDNA formation or maintenance, a cccDNA epigenetic modifier and an inhibitor of cccDNA transcription; wherein said capsid assembly inhibitor/modulator, core or X protein targeting agent, direct cccDNA inhibitor, inhibitor of cccDNA formation or maintenance, or cccDNA epigenetic modifier is preferably selected from: BAY 41-4109, NVR 3-778, GLS-4, NZ-4 (W28F), Y101, ARB-423, ARB-199, ARB-596, AB-506, JNJ-56136379, ASMB-101 (AB-V102), ASMB-103, CHR-101, CC-31326, AT-130 and R07049389; wherein said interferon or modified interferon is preferably selected from: interferon alpha (IFN-α), pegylated interferon alpha (PEG-IFN-u), interferon alpha-2a, recombinant interferon alpha-2a, peginterferon alpha-2a (Pegasys), interferon alpha-2b (Intron A), recombinant interferon alpha-2b, interferon alpha-2b XL, peginterferon alpha-2b, glycosylated interferon alpha-2b, interferon alpha-2c, recombinant interferon alpha-2c, interferon beta, interferon beta-1a, peginterferon beta-1a, interferon delta, interferon lambda (IFN-k), peginterferon lambda-1, interferon omega, interferon tau, interferon gamma (IFN-γ), interferon alfacon-1, interferon alpha-n1, interferon alpha-n3, albinterferon alpha-2b, BLX-883, DA-3021, PI 101 (also known as AOP2014), PEG-infergen, Belerofon, INTEFEN-IFN, albumin/interferon alpha 2a fusion protein, rHSA-IFN alpha 2a, rHSA-IFN alpha 2b, PEG-IFN-SA and interferon alpha biobetter; wherein said HBV antiviral of distinct or unknown mechanism is selected from: AT-61 ((E)-N-(1-chloro-3-oxo-1-phenyl-3-(piperidin-1-yl)prop-1-en-2-yl)benzamide), AT130 ((E)-N-(1-bromo-1-(2-methoxyphenyl)-3-oxo-3-(piperidin-1-yl)prop-1-en-2-yl)-4-nitrobenzamide), analogues thereof, REP-9AC (REP-2055), REP-9AC′ (REP-2139), REP-2165 and HBV-0259; wherein said cyclophilin inhibitor is preferably selected from: OCB-030 (NVP-018), SCY-635, SCY-575 and CPI-431-32; wherein said HBV polymerase inhibitor is preferably selected from: entecavir (Baraclude, Entavir), lamivudine (3TC, Zeffix, Heptovir, Epivir, and Epivir-HBV), telbivudine (Tyzeka, Sebivo), clevudine, besifovir, adefovir (hepsera), tenofovir, preferably said tenofovir is in a salt form selected from: tenofovir disoproxil fumarate (Viread), tenofovir alafenamide fumarate (TAF), tenofovir disoproxil orotate (DA-2802), tenofovir disopropxil aspartate (CKD-390), AGX-1009, and CMX157; wherein said dinucleotide is preferably SB9200; wherein said SMAC inhibitor is preferably Birinapant; wherein said HDV targeting agent is preferably Lonafamib; wherein said HBV RNA destabilizer or other small-molecule inhibitor of HBV protein expression is preferably RG7834 or AB-452. 
     
     
         17 . The pharmaceutical composition according to  claim 15  or  16  for use in the treatment and/or prevention of an HBV infection and/or condition related to an HBV infection. 
     
     
         18 . The pharmaceutical composition for use according to  claim 17 , wherein said condition related to an HBV infection is selected from the group consisting of: chronic hepatitis B, HBV/HDV co-infection, HBV/HCV co-infection, HBV/HIV co-infection, inflammation, necrosis, cirrhosis, hepatocellular carcinoma, hepatic decompensation and hepatic injury from an HBV infection. 
     
     
         19 . The pharmaceutical composition for use according to  claim 17  or  18 , wherein said use is in treating, eradicating, reducing, slowing or inhibiting an HBV infection in an individual in need thereof, and/or in reducing the viral load associated with an HBV infection in an individual in need thereof, and/or in reducing reoccurrence of an HBV infection in an individual in need thereof, and/or in inducing remission of hepatic injury from an HBV infection in an individual in need thereof, and/or in prophylactically treating an HBV infection in an individual afflicted with a latent HBV infection. 
     
     
         20 . A process for the synthesis of the compound of formula I or the pharmaceutically acceptable salt, tautomer, solvate, or stereoisomer thereof as defined in any one of  claims 1 - 8 , said process comprising at least one of the following steps: 
       
         
           
           
               
               
           
         
         cyclisation of a compound of formula (4) in the presence of an appropriate base such as Cs 2 CO 3  to obtain a compound of formula (5), wherein Cy, X, Y, Y′, Y″, Y′″, A, R 1 , R 2 , Ra, Rb, Rc and Rd are as defined in any one of  claims 1 - 8 ; or 
       
       
         
           
           
               
               
           
         
         cyclisation of a compound of formula (4a) in the presence of an appropriate base such as Cs 2 CO 3  to obtain a compound of formula (5a), wherein Cy, X, Y, Y′, Y″, Y′″, A, R 1 , R 2 , R 4 , Ra, Rb, Rc and Rd are as defined in any one of  claims 1 - 8 .