Novel heterocyclic compounds having anti-HBV activity

A compound of Formula II

• wherein n is zero, 1, 2, or 3;
• A is S, O, or N(CH3);
• B and B′ are either both H or jointly oxo;
• R1 and R2 are, independently, H, CH3, CF3, or CH3O;
• R3 is H;
• or R3 is a 5- or 6-membered ring, said ring optionally containing one or more double bonds, optionally containing 1-3 ring heteroatoms independently selected from O, N, and S, and optionally substituted with one or two groups independently selected from CH3, OCH3, CO2CH3, OC(O)CH3, CN, and halo, wherein all methyl groups are optionally substituted with 1, 2, or 3 halogen atoms;
• or R3 is C1-6 alkyl, C1-6 alkanoyl, C1-6 alkenyl, C1-6 alkoxy, C1-6 alkenoxy, wherein said alkyl groups, the alkyl moieties of said alkanoyl and said alkoxy groups, said alkenyl groups, and the alkenyl moieties of said alkenoxy groups may be straight-chain, branched, or cyclic, and may optionally be substituted as follows:
• a) with one, two, or three halogen atoms;
• b) with one or two substituents independently selected from hydroxy, carboxyl, cyano, benzyl, benzoyl, and benzoyloxy;
• c) with one saturated, unsaturated, or aromatic 5- or 6-membered ring containing 0-3 heteroatoms selected from N, O, and S, said ring optionally substituted with one or two groups independently selected from CH3, OCH3, C(O)CH3, CO2CH3, OC(O)CH3, CN, and halo, wherein all methyl groups are optionally substituted with 1, 2, or 3 halogen atoms;
• and
• d) with one group selected from C1-6 alkanoyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbamoyl, ethylcarbamoylmethyl methylcarbamoylmethyl, 2-hydroxy-2-phenyl-ethylcarbamoylmethyl, or N-phthalimido;
• or R3 is R4NHC(O), R4NHC(S), or R4NHCH2C(O), wherein R4 is C1-6 alkyl, wherein said alkyl group may be straight-chain, branched, or cyclic, and is optionally substituted as described for R3 alkyl groups, or R4 is a five- or 6-membered aromatic ring containing 0-3 heteroatoms independently selected from O, N, and S, all R4 optionally substituted with one or two substituents independently selected from halo, methyl, and benzyl, wherein all rings are optionally substituted with one or two groups independently selected from CH3, OCH3, CO2CH3, OC(O)CH3, CN, and halo, wherein all methyl groups are optionally substituted with 1, 2, or 3 halogen atoms;
• and
• R5 is H or C3 alkyl;
• or
• R3 and R5, together with the ring carbon atoms to which they are attached, form an additional fused 5- or 6-membered cycloalkyl group;
• provided that when A is O or S, then R1, R2, R3, B, and B′ are not all H, and further provided that when A is S and R1 is methyl, then R2, R3, B, and B′ are not all H.

A method of treating an HBV infection, comprising providing in a person in need of treatment thereof a therapeutically effective concentration of a compound of Formula I or a compound of formula II, where formula I is

• wherein A is S, O, or N(CH3);
• R1 and R2 are, independently, H, CH3, CF3, or CH3O;
• R3 is H;
• or R3 is a 5- or 6-membered ring, said ring optionally containing one or more double bonds, optionally containing 1-3 ring heteroatoms independently selected from O, N, and S, and optionally substituted with one or two groups independently selected from CH3, OCH3, CO2CH3, OC(O)CH3, CN, and halo, wherein all methyl groups are optionally substituted with 1, 2, or 3 halogen atoms;
• or R3 is C1-6 alkyl, C1-6 alkanoyl, C1-6 alkenyl, Cl-6 alkoxy, C1-6 alkenoxy, wherein said alkyl groups, the alkyl moieties of said alkanoyl and said alkoxy groups, said alkenyl groups, and the alkenyl moieties of said alkenoxy groups may be straight-chain, branched, or cyclic, and can all optionally be substituted as follows:
• a) with one, two, or three halogen atoms;
• b) with one or two substituents independently selected from hydroxy, carboxyl, cyano, benzyl, benzoyl, and benzoyloxy;
• c) with one saturated, unsaturated, or aromatic 5- or 6-membered ring containing 0-3 heteroatoms selected from N, O, and S, said ring optionally substituted with one or two groups independently selected from CH3, OCH3, C(O)CH3, CO2CH3, OC(O)CH3, CN, and halo, wherein all methyl groups are optionally substituted with 1, 2, or 3 halogen atoms;
• and
• d) with one group selected from C1-6 alkanoyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbamoyl, ethylcarbamoylmethyl methylcarbamoylmethyl, 2-hydroxy-2-phenyl-ethylcarbamoylmethyl, or N-phthalimido;
• or R3 is R4NHC(O), R4NHC(S), or R4NHCH2C(O), wherein R4 is C1-6 alkyl, wherein said alkyl group may be straight-chain, branched, or cyclic, and is optionally substituted as described for R3 alkyl groups, or R4 is a five- or 6-membered aromatic ring containing 0-3 heteroatoms independently selected from O, N, and S, all R4 optionally substituted with one or two substituents independently selected from halo, methyl, and benzyl, wherein all rings are optionally substituted with one or two groups independently selected from CH3, OCH3, CO2CH3, OC(O)CH3, CN, and halo, wherein all methyl groups are optionally substituted with 1, 2, or 3 halogen atoms;
• and m and n are, independently, 1 or 2, provided that m and n are not both 2.
• and where formula II is
• wherein n is zero, 1, 2, or 3;
• A is S, O, or N(CH3);
• B and B′ are either both H or jointly oxo;
• R1 and R2 are, independently, H, CH3, CF3, or CH3O;
• R3 is H;
• or R3 is a 5- or 6-membered ring, said ring optionally containing one or more double bonds, optionally containing 1-3 ring heteroatoms independently selected from O, N, and S, and optionally substituted with one or two groups independently selected from CH3, OCH3, CO2CH3, OC(O)CH3, CN, and halo, wherein all methyl groups are optionally substituted with 1, 2, or 3 halogen atoms;
• or R3 is C1-6 alkyl, C1-6 alkanoyl, C1-6 alkenyl, C1-6 alkoxy, C1-6 alkenoxy, wherein said alkyl groups, the alkyl moieties of said alkanoyl and said alkoxy groups, said alkenyl groups, and the alkenyl moieties of said alkenoxy groups may be straight-chain, branched, or cyclic, and may optionally be substituted as follows:
• a) with one, two, or three halogen atoms;
• b) with one or two substituents independently selected from hydroxy, carboxyl, cyano, benzyl, benzoyl, and benzoyloxy;
• c) with one saturated, unsaturated, or aromatic 5- or 6-membered ring containing 0-3 heteroatoms selected from N, O, and S, said ring optionally substituted with one or two groups independently selected from CH3, OCH3, C(O)CH3, CO2CH3, OC(O)CH3, CN, and halo, wherein all methyl groups are optionally substituted with 1, 2, or 3 halogen atoms;
• and
• d) with one group selected from C1-6 alkanoyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbamoyl, ethylcarbamoylmethyl methylcarbamoylmethyl, 2-hydroxy-2-phenyl-ethylcarbamoylmethyl, or N-phthalimido;
• or R3 is R4NHC(O), R4NHC(S), or R4NHCH2C(O), wherein R4 is C1-6 alkyl, wherein said alkyl group may be straight-chain, branched, or cyclic, and is optionally substituted as described for R3 alkyl groups, or R4 is a five- or 6-membered aromatic ring containing 0-3 heteroatoms independently selected from O, N, and S, all R4 optionally substituted with one or two substituents independently selected from halo, methyl, and benzyl, wherein all rings are optionally substituted with one or two groups independently selected from CH3, OCH3, CO2CH3, OC(O)CH3, CN, and halo, wherein all methyl groups are optionally substituted with 1, 2, or 3 halogen atoms;
• and
• R5 is H or C3 alkyl;
• or
• R3 and R5, together with the ring carbon atoms to which they are attached, form an additional fused 5- or 6-membered cycloalkyl group.