Elimination of hepatitis b virus with antiviral agents

A compound of the following formula:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• when R1 and R1′ are attached to a carbon, they are, independently, hydrogen, halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, C1-6 haloalkoxy, C2-6 alkenyl, cyano, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonyl alkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• when R1 and R1′ are attached to a nitrogen, they are, independently, hydrogen, C2-6 alkoxy, C3-6 alkoxyalkyl, C2-6 alkenyl, alkoxycarbonyl, carbonylalkyl, carbonyl aryl, C1-6 alkyl, heterocyclylalkyl, C2-6 hydroxyalkyl, or S(O)2R′;
• each R′ is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, aryl, heteroaryl, alkylaryl, or arylalkyl, or if two R′ reside on the same nitrogen atom, they can come together to form a C3-6 ring optionally containing a N, O, or S heteroatom;
• the R′ groups can optionally be substituted with one or more substituents, which substituents are, independently, halo, C1-6 haloalkyl, C1-6 hydroxyalkyl, hydroxyl, carboxyl, acyl, aryl, acyloxy, amino, amido, carboxyl derivatives, alkylamino, dialkylamino, arylamino, alkoxy, alkoxyalkyl, aryloxy, nitro, cyano, sulfonic acid, thiol, imine, sulfonyl, sulfanyl, sulfinyl, sulfamonyl, ester, carboxylic acid, amide, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrozine, carbamate, phosphonic acid, or phosphonate;
• u and v are independently 0, 1, 2, 3, 4 or 5;
• I is phenyl, a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, or three heteroatoms, which are, independently, N, O, or S, a C4-14 bicyclic ring;
• alkylheteroaryl, or alkylaryl;
• J is a five-membered heteroaromatic ring containing one, two, or three heteroatoms, which are, independently, N, O, or S, a six or seven-membered ring or a six or seven-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, or S, a five-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, or S;
• or a four-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, or S,
• W is
• R12 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl,
• R13 is C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, alkylaryl, arylalkyl, a C4-14 bicyclic ring;
• or a six-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, or S,
• R13 is optionally substituted with one or more substituents each independently selected from the group consisting of hydrogen, halogen, CF3, SF5, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C(O)R′, C1-6 alkoxy, C1-6 haloalkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, cycloalkyl, arylalkoxycarbonyl, carboxyl, haloalkyl, heterocyclylalkyl, C1-6 hydroxyalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl, where substituents on the substituted aryl and substituted heteroaryl are selected from the group consisting of halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C(O)R′, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and C1-6 alkyl.
• or R12 and R13 together with the nitrogen to which they are attached form a 3 to 4 membered ring optionally substituted with one or more substituents each independently selected from the group consisting of hydrogen, halogen (F, Cl, Br, I), CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, and C1-6 hydroxyalkyl;
• or
• of the following formula:
• or a pharmaceutically acceptable salt or prodrug thereof,
• wherein:
• A is selected from the group consisting of phenyl, a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, or three nitrogen atoms which are, independently, N, O, or S;
• a C4-14 bicyclic ring, alkylheteroaryl, and alkylaryl;
• B is a six or seven-membered ring or a six or seven-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S, a five-membered ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S;
• a four-membered ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S, or a C4-14 bicyclic ring,
• when R1 and R1′ are attached to a carbon, they are, independently, hydrogen, halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, C1-6 haloalkoxy, C2-6 alkenyl, cyano, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonyl alkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• when R1 and R1′ are attached to a nitrogen, they are, independently, hydrogen, C2-6 alkoxy, C3-6 alkoxyalkyl, C2-6 alkenyl, alkoxycarbonyl, carbonylalkyl, carbonyl aryl, C1-6 alkyl, heterocyclylalkyl, C2-6 hydroxyalkyl, or S(O)2R′;
• each R′ is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, aryl, heteroaryl, alkylaryl, or arylalkyl, or if two R′ reside on the same nitrogen atom, they can come together to form a C3-6 ring optionally containing a N, O, or S heteroatom;
• the R′ groups can optionally be substituted with one or more substituents, which substituents are, independently, halo, C1-6 haloalkyl, C1-6 hydroxyalkyl, hydroxyl, carboxyl, acyl, aryl, acyloxy, amino, amido, carboxyl derivatives, alkylamino, dialkylamino, arylamino, alkoxy, alkoxyalkyl, aryloxy, nitro, cyano, sulfonic acid, thiol, imine, sulfonyl, sulfanyl, sulfinyl, sulfamonyl, ester, carboxylic acid, amide, phosphonyl, phosphinyl, phosphoryl, phosphine, thioester, thioether, acid halide, anhydride, oxime, hydrozine, carbamate, phosphonic acid, or phosphonate;
• u and v are independently 0, 1, 2, 3, 4 or 5;
• X is
• R3 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl,
• R2 is C1-6 alkyl, C1-6 haloalkyl, C2-8 alkoxyalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, alkylaryl, arylalkyl, a six-membered ring or a six-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, or S, a seven-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, or S, a five-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, or S;
• a four-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, or S;
• cycloalkyl, alkylheteroaryl, or alkylaryl;
• R2 is optionally substituted with one or more substituents, which each, independently, are halogen, CF3, SF5, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, C1-6 haloalkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• or is optionally substituted with aryl, substituted aryl, heteroaryl, or substituted heteroaryl, where substituents on the substituted aryl and substituted heteroaryl are selected from the group consisting of halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C(O)R′, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and C1-6 alkyl, and
• R2 and R3 can come together with the nitrogen to which they are attached to form a 6-10 membered bicyclic or bridged ring, a 3 to 8 saturated ring, or a 5 membered unsaturated ring;
• such bicyclic, bridged, saturated and unsaturated rings optionally containing one or more additional heteroatoms, where each is, independently, O, S or N, and optionally being substituted with one or more substituents, wherein each, independently, is halogen (including F, Cl, Br, I), CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• or
• of the following formula:
• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• R1 and R1′ are as defined with respect to Formula I,
• u and v are independently 0, 1, 2, 3, 4 or 5;
• C is phenyl, a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, or three heteroatoms which are, independently, N, O, or S;
• a C4-14 bicyclic ring, alkylaryl, or alkylheteroaryl;
• D is phenyl, a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, or three heteroatoms, which are, independently, N, O, or S, or a C4-14 bicyclic ring,
• Y is
• R4 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl;
• R5 is alkylaryl, arylalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, or a six-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, or S;
• R5 is optionally substituted with one or more substituents, each of which is, independently, halogen, CF3, SF5, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, C1-6 haloalkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, cycloalkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• or is optionally substituted with aryl, substituted aryl, heteroaryl, or substituted heteroaryl, where substituents on the substituted aryl and substituted heteroaryl are selected from the group consisting of halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C(O)R′, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and C1-6 alkyl,
• wherein, if C is phenyl, D is not phenyl or a 5-membered ring heteroaryl, or if C is phenyl and D is phenyl or a 5-membered ring heteroaryl, then R5 is not alkylaryl, alkenyl, or a six-membered bridged ring;
• or when Y is
• R4 and R5 together with the nitrogen to which they are attached form a 3 to 4 membered ring optionally substituted with one or more substituents, each of which is, independently, halogen, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′), C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• or
• of the following formula:
• or a pharmaceutically acceptable salt or prodrug thereof, wherein R1 and R1′ are as defined with respect to Formula I,
• u and v are independently 0, 1, 2, 3, 4 or 5;
• E is a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, or three heteroatoms, where each is, independently, N, O, or S;
• a C4-14 bicyclic ring, alkylheteroaryl, or alkylaryl;
• F is a five-membered heteroaromatic ring containing one, two, or three heteroatoms which are, independently, N, O, or S, or a C4-14 bicyclic ring,
• Z is
• R8 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl,
• R9 is C1-6 alkyl, C1-6 haloalkyl, C2-8 alkoxyalkyl, a six-membered ring or a six-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms, which are independently N, O, or S, a seven-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S, a five-membered ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S;
• a four-membered ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S, or a three membered ring;
• R9 is optionally substituted with one or more substituents, each of which is independently halogen, CF3, SF5, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, C1-6 haloalkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, cycloalkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• or is optionally substituted with aryl, substituted aryl, heteroaryl, or substituted heteroaryl, where substituents on the substituted aryl and substituted heteroaryl are selected from the group consisting of halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C(O)R′, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and C1-6 alkyl, and
• R8 and R9 can come together with the nitrogen to which they are attached to form a 6-10 membered bicyclic or bridged ring or a 3 to 8 saturated ring;
• such bicyclic, bridged and saturated ring moiety optionally containing one or more additional heteroatoms which, independently, are O, S or N and optionally being substituted with one or more substituents, each, independently, is halogen, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• or
• of the following formula:
• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• G is phenyl, a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, or three heteroatoms, which are, independently, N, O, or S;
• a C4-14 bicyclic ring, alkylheteroaryl, or alkylaryl;
• H is phenyl, a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a six-membered non-aromatic ring optionally containing one, two, or three heteroatoms, which are, independently, N, O, or S;
• or a C4-14 bicyclic ring;
• when R1 and R1′ are attached to a carbon they are, independently, hydrogen, halogen, CF3, hydroxy, SF5, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, cyano, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• when R1 and R1′ are attached to a nitrogen they are, independently, hydrogen, C1-6 alkoxy, C3-6 alkoxyalkyl, alkoxycarbonyl, carbonylalkyl, carbonyl aryl, C1-6 alkyl, C2-6 alkynyl, C2-6 alkenyl, heterocyclylalkyl, C1-6 hydroxyalkyl, or S(O)2R′;
• each R′ is independently H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, aryl, heteroaryl, alkylaryl, or arylalkyl, or if two R′ reside on the same nitrogen atom they can come together to form a C3-6 alkyl ring optionally containing a N, O, or S;
• wherein the R′ groups can be substituted with one or more C1-6 hydroxyalkyl, aminoalkyl, or alkoxyalkyl substituents;
• u and v are independently 0, 1, 2, 3, 4 or 5;
• W is
• R10 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl,
• R11 is C1-6 alkyl, C1-6 haloalkyl, C2-8 alkoxyalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, alkylaryl, arylalkyl, phenyl, a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a six-membered ring or a six-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S, a seven-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S, a five-membered heteroaromatic ring containing one, two, or three heteroatoms, which are, independently, N, O, or S, a five-membered ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S;
• a four-membered ring containing zero, one, or two heteroatoms, which are, independently, N, O, or S;
• a three membered ring, alkylheteroaryl, or alkylaryl;
• wherein R11 is optionally substituted with one or more substituents selected from the group consisting of halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, C1-6 haloalkoxy, C2-6 alkenyl, cyano, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, C1-6 hydroxyalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl, where substituents on the substituted aryl and substituted heteroaryl are selected from the group consisting of halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C(O)R′, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and C1-6 alkyl;
• and
• R10 and R11 can come together with the nitrogen to which they are attached form a 6-10 membered bicyclic or bridged ring or a 3 to 8 saturated ring;
• such bicyclic, bridged or saturated ring moiety optionally containing one or more additional heteroatoms, which are each, independently, O, S or N, and optionally substituted with one or more substituents, each of which is, independently, halogen, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• or
• of the following formula:
• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• R1 and R1′ are as defined with respect to Formula I,
• u and v are independently 0, 1, 2, 3, 4 or 5;
• K is a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, or three heteroatoms which are, independently, N, O, or S;
• a C4-14 bicyclic ring, alkylheteroaryl, or alkylaryl;
• L is a five-membered heteroaromatic ring containing one, two, or three heteroatoms which are, independently, N, O, or S, a six or seven-membered ring or a six or seven-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, or S, a five-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, or S;
• a four-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, or S, or a C4-14 bicyclic ring,
• W is
• R14 is H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, or C2-6 alkynyl,
• R15 is C1-6 alkyl, C1-6 haloalkyl, C2-8 alkoxyalkyl, a six-membered ring or a six-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, or S, a seven-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, S, or Se, a five-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, S or Se;
• a four-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, S, or Se;
• R15 is optionally substituted with one or more substituents which are, independently, halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, C1-6 haloalkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, cycloalkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, or C1-6 hydroxyalkyl;
• or is optionally substituted with aryl, substituted aryl, heteroaryl, or substituted heteroaryl, where substituents on the substituted aryl and substituted heteroaryl are selected from the group consisting of halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C(O)R′, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and C1-6 alkyl, or
• R14 and R15 can come together with the nitrogen to which they are attached form a 6-10 membered bicyclic or bridged ring or a 3 to 8 membered saturated ring;
• such bicyclic, bridged and saturated ring moiety optionally containing one or more additional heteroatoms which are, independently, O, S or N, and optionally being substituted with one or more substituents each independently selected from the group consisting of halogen, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, and C1-6 hydroxyalkyl;
• of the following formula:
• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• R1 and R1′ are as defined with respect to Formula I,
• u and v are independently 0, 1, 2, 3, 4 or 5;
• M is phenyl, a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, or three heteroatoms which are, independently, N, O, S, or Se, a C4-14 bicyclic ring, alkylheteroaryl, or alkylaryl,
• N is phenyl, a six-membered heteroaromatic ring containing one, two, or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, or three heteroatoms independently selected from the group consisting of N, O, S, and Se, a six or seven-membered ring or a six or seven-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, S, or Se, a five-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, S, or Se;
• a four-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, S or Se;
• or a C4-14 bicyclic ring,
• V is
• and
• R16 is C1-6 alkyl, C1-6 haloalkyl, C2-8 alkoxyalkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, a six-membered ring or a six-membered bridged or spiro-fused ring containing zero, one, or two heteroatoms which are, independently, N, O, S, or Se, a five-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, S, or Se;
• a four-membered ring containing zero, one, or two heteroatoms which are, independently, N, O, S, or Se;
• alkylaryl, arylalkyl, alkylheteroaryl, or alkylaryl,
• wherein R16 is optionally substituted with one or more substituents selected from the group consisting of halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C1-6 alkoxy, C1-6 haloalkoxy, C2-6 alkenyl, cyano, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C1-6 alkyl, arylalkoxycarbonyl, carboxy, C1-6 haloalkyl, heterocyclylalkyl, C1-6 hydroxyalkyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl, where substituents on the substituted aryl and substituted heteroaryl are selected from the group consisting of halogen, SF5, CF3, hydroxy, N(R′)S(O)2R′, S(O)2R′, S(O)2N(R′)2, C(O)R′, C1-6 alkoxy, cyano, azido, C2-6 alkynyl, C3-6 alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, and C1-6 alkyl.