Antiviral compounds

A method of treating a Pneumoviridae virus infection in a human in need thereof, the method comprising administering to the human a therapeutically effective amount of a compound of Formula (II):

• or a pharmaceutically acceptable salt thereof, wherein
• Base is
• R1A and R2A are each independently:
• (A) C1-12 alkyl optionally substituted with 1 to 3 R1B,
• (B) 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, wherein the 3 to 6 membered heterocyclyl is optionally substituted with 1 to 3 R1C, or
• (C) phenyl, wherein
• each R1B is independently halogen, —OH, —NH2, C1-6 alkoxy, methoxyethoxy, or 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, and
• each R1C is independently C1-3 alkyl,
• R3 is —N(H)R3A or —N═C(R3B)(R3C);
• R3A is H, —CH2OP(O)(OH)2, or —C(O)R3D, wherein
• R3D is C1-6 alkyl optionally substituted with 1 methoxy, or 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with C1-3 alkyl;
• R3B is H or C1-3 alkyl;
• R3C is —N(R3C1)(R3C2);
• R3C1 and R3C2 are each independently H or C1-6 alkyl;
• or
• R3C1 and R3C2 together with the atom to which they are attached form a 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with C1-6 alkyl;
• R4A is O or S;
• and
• R4B and R4C are each independently
• (A) —OH;
• (B) —OR4B1, wherein
• R4B1 is C1-6 alkyl optionally substituted with 1 to 3 R4B2 groups, or C6-12 aryl, wherein
• each R4B2 group is independently C1-6 alkoxy, —S—R4B3, or —S(O)2—R4B3, and
• each R4B3 group is independently C1-6 alkyl;
• (C)
• wherein
• m is 0, 1, 2, 3, 4, or 5;
• and
• each R4D is independently C1-3 alkyl optionally substituted with 1 to 3 R4D1 groups, C1-3 alkoxy optionally substituted with 1 to 3 R4D2 groups, or —C(O)N(R4D3)2, wherein
• each R4D1 group is independently —NH2 or —C(O)OR4D3,
• each R4D2 is independently C1-3 alkoxy, and
• each R4D3 is independently C1-3 alkyl;
• (D)
• wherein
• R4E1 and R4E2 are each independently H or C1-6 alkyl,
• R4F1 and R4F2 are each independently H or C1-6 alkyl, or R4F1 and R4F2 together are oxo,
• R4G is C1-12 alkyl optionally substituted with 1 to 3 R4G1 C3-7 cycloalkyl optionally substituted with 1 to 3 R4G2, 3 to 8 membered heterocyclyl having 1 to 3 heteroatoms selected from N, O and S, optionally substituted with 1 to 3 R4G3, or —C(O)R4G4,
• each R4G1 is independently —OH, C1-6 alkyl, C1-3 alkoxy, —(CH2OCH2)1-5—CH3, —N(R4G8)2, —OP(O)(OH)2, C3-7 cycloalkyl optionally substituted with 1 to 3 R4G9, 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with 1 to 3 R4G10, or phenyl,
• each R4G2 is independently C1-6 alkyl, C1-3 haloalkyl, or —NH2,
• each R4G3 is independently halogen or C1-3 alkyl;
• each R4G4 is independently C1-12 alkyl,
• each R4G8 is independently C1-6 alkyl,
• each R4G9 is independently C1-3 haloalkyl, or —NH2, and
• each R4G10 is independently C1-3 haloalkyl;
• or
• (E) —(OP(O)(OH))1-2—OH;
• and
• R5A and R5B are each C1-6 alkyl substituted with —OP(O)(OH)2.

A method of treating a Picornaviridae virus infection in a human in need thereof, the method comprising administering to the human a therapeutically effective amount of a compound of Formula (II):

• or a pharmaceutically acceptable salt thereof, wherein
• Base is
• R1A and R2A are each independently:
• (A) C1-12 alkyl optionally substituted with 1 to 3 R1B,
• (B) 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, wherein the 3 to 6 membered heterocyclyl is optionally substituted with 1 to 3 R1C, or
• (C) phenyl, wherein
• each R1B is independently halogen, —OH, —NH2, C1-6 alkoxy, methoxyethoxy, or 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, and
• each R1C is independently C1-3 alkyl,
• R3 is —N(H)R3A or —N═C(R3B)(R3C);
• R3A is H, —CH2OP(O)(OH)2, or —C(O)R3D, wherein
• R3D is C1-6 alkyl optionally substituted with 1 methoxy, or 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with C1-3 alkyl;
• R3B is H or C1-3 alkyl;
• R3C is —N(R3C1)(R3C2);
• R3C1 and R3C2 are each independently H or C1-6 alkyl;
• or
• R3C1 and R3C2 together with the atom to which they are attached form a 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with C1-6 alkyl;
• R4A is O or S;
• and
• R4B and R4C are each independently
• (A) —OH;
• (B) —OR4B1, wherein
• R4B1 is C1-6 alkyl optionally substituted with 1 to 3 R4B2 groups, or C6-12 aryl, wherein
• each R4B2 group is independently C1-6 alkoxy, —S—R4B3, or —S(O)2—R4B3, and
• each R4B3 group is independently C1-6 alkyl;
• (C)
• wherein
• m is 0, 1, 2, 3, 4, or 5;
• and
• each R4D is independently C1-3 alkyl optionally substituted with 1 to 3 R4D1 groups, C1-3 alkoxy optionally substituted with 1 to 3 R4D2 groups, or —C(O)N(R4D3)2, wherein
• each R4D1 group is independently —NH2 or —C(O)OR4D3,
• each R4D2 is independently C1-3 alkoxy, and
• each R4D3 is independently C1-3 alkyl;
• (D)
• wherein
• R4E1 and R4E2 are each independently H or C1-6 alkyl,
• R4F1 and R4F2 are each independently H or C1-6 alkyl, or R4F1 and R4F2 together are oxo,
• R4G is C1-12 alkyl optionally substituted with 1 to 3 R4G1 C3-7 cycloalkyl optionally substituted with 1 to 3 R4G2, 3 to 8 membered heterocyclyl having 1 to 3 heteroatoms selected from N, O and S, optionally substituted with 1 to 3 R4G3, or —C(O)R4G4,
• each R4G1 is independently —OH, C1-6 alkyl, C1-3 alkoxy, —(CH2OCH2)1-5—CH3, —N(R4G8)2, —OP(O)(OH)2, C3-7 cycloalkyl optionally substituted with 1 to 3 R4G9, 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with 1 to 3 R4G10, or phenyl,
• each R4G2 is independently C1-6 alkyl, C1-3 haloalkyl, or —NH2,
• each R4G3 is independently halogen or C1-3 alkyl;
• each R4G4 is independently C1-12 alkyl,
• each R4G8 is independently C1-6 alkyl,
• each R4G9 is independently C1-3 haloalkyl, or —NH2, and
• each R4G10 is independently C1-3 haloalkyl;
• or
• (E) —(OP(O)(OH))1-2—OH;
• and
• R5A and R5B are each C1-6 alkyl substituted with —OP(O)(OH)2.

A method for the treatment or prophylaxis of an exacerbation of a respiratory condition by a viral infection in a human in need thereof, the method comprising administering to the human a therapeutically effective amount of a compound of Formula (II):

• or a pharmaceutically acceptable salt thereof, wherein
• Base is
• R1A and R2A are each independently:
• (A) C1-12 alkyl optionally substituted with 1 to 3 R1B,
• (B) 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, wherein the 3 to 6 membered heterocyclyl is optionally substituted with 1 to 3 R1C, or
• (C) phenyl, wherein
• each R1B is independently halogen, —OH, —NH2, C1-6 alkoxy, methoxyethoxy, or 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, and
• each R1C is independently C1-3 alkyl,
• R3 is —N(H)R3A or —N═C(R3B)(R3C);
• R3A is H, —CH2OP(O)(OH)2, or —C(O)R3D, wherein
• R3D is C1-6 alkyl optionally substituted with 1 methoxy, or 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with C1-3 alkyl;
• R3B is H or C1-3 alkyl;
• R3C is —N(R3C1)(R3C2);
• R3C1 and R3C2 are each independently H or C1-6 alkyl;
• or
• R3C1 and R3C2 together with the atom to which they are attached form a 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with C1-6 alkyl;
• R4A is O or S;
• and
• R4B and R4C are each independently
• (A) —OH;
• (B) —OR4B1, wherein
• R4B1 is C1-6 alkyl optionally substituted with 1 to 3 R4B2 groups, or C6-12 aryl, wherein
• each R4B2 group is independently C1-6 alkoxy, —S—R4B3, or —S(O)2—R4B3, and
• each R4B3 group is independently C1-6 alkyl;
• (C)
• wherein
• m is 0, 1, 2, 3, 4, or 5;
• and
• each R4D is independently C1-3 alkyl optionally substituted with 1 to 3 R4D1 groups, C1-3 alkoxy optionally substituted with 1 to 3 R4D2 groups, or —C(O)N(R4D3)2, wherein
• each R4D1 group is independently —NH2 or —C(O)OR4D3,
• each R4D2 is independently C1-3 alkoxy, and
• each R4D3 is independently C1-3 alkyl;
• (D)
• wherein
• R4E1 and R4E2 are each independently H or C1-6 alkyl,
• R4F1 and R4F2 are each independently H or C1-6 alkyl, or R4F1 and R4F2 together are oxo,
• R4G is C1-12 alkyl optionally substituted with 1 to 3 R4G1 C3-7 cycloalkyl optionally substituted with 1 to 3 R4G2, 3 to 8 membered heterocyclyl having 1 to 3 heteroatoms selected from N, O and S, optionally substituted with 1 to 3 R4G3, or —C(O)R4G4,
• each R4G1 is independently —OH, C1-6 alkyl, C1-3 alkoxy, —(CH2OCH2)1-5—CH3, —N(R4G8)2, —OP(O)(OH)2, C3-7 cycloalkyl optionally substituted with 1 to 3 R4G9, 3 to 6 membered heterocyclyl having 1 to 3 heteroatoms independently selected from N, O and S, optionally substituted with 1 to 3 R4G10, or phenyl,
• each R4G2 is independently C1-6 alkyl, C1-3 haloalkyl, or —NH2,
• each R4G3 is independently halogen or C1-3 alkyl;
• each R4G4 is independently C1-12 alkyl,
• each R4G8 is independently C1-6 alkyl,
• each R4G9 is independently C1-3 haloalkyl, or —NH2, and
• each R4G10 is independently C1-3 haloalkyl;
• or
• (E) —(OP(O)(OH))1-2—OH;
• and
• R5A and R5B are each C1-6 alkyl substituted with —OP(O)(OH)2
• wherein the respiratory condition is chronic obstructive pulmonary disease.