Broad Spectrum Antiviral Compositions and Methods

A method of inhibiting virus production comprising contacting a virus-infected cell with a virus production inhibiting amount of a composition comprising a compound of Formula I:

• wherein:
• one of X1 and X2 is N and the other is S;
• X3 and X4 are independently selected from C and N;
• and when X3 is C it is optionally substituted with methyl, ethyl, propyl, i-propyl or n-propyl;
• one of R1 and R2 is H and the other is a 5- or 6-membered aryl or cycloalkyl with 0 to 3 ring heteroatoms independently selected from N and O and substituted with 0 to 3 groups independently selected from:
• ═O, C1-6 straight or branched alkyl optionally substituted with —OR12 or NR7R8, C1-6 straight or branched alkoxy optionally substituted with NR7R8 or —OR12, and C3-6 cycloalkyl optionally substituted with —R12, —OR12 or —NR7R8,
• or R1 and R2 together form a 5- or 6-membered aryl or cycloalkyl with 0 to 3 ring heteroatoms independently selected from N and O and substituted with 0 to 3 groups independently selected from:
• ═O, C1-6 straight or branched alkyl optionally substituted with —OR12 or NR7R8, C1-6 straight or branched alkoxy optionally substituted with NR7R8 or —OR12, and C3-6 cycloalkyl optionally substituted with —R12, —OR12 or —NR7R8;
• R3 is selected from H, halo, —C≡CH, —C≡N, —OH, —OCF3, —OCHF2, C1-4 straight or branched alkoxy, —SO2(C1-6 alkyl), —N(CH3)2, —C(O)NH2, —NHSO2R7, —C(O)NR7R8, and a ring structure comprising a 5- or 6-membered aryl or a 4-, 5-, or 6-membered cycloalkyl with 0 to 3 ring heteroatoms independently selected from N, O and S and substituted with 0 to 2 groups independently selected from ═O, halo, C1-6 straight or branched alkyl optionally substituted with —OR12 or —NR7R8, C1-6 straight or branched alkoxy optionally substituted with —NR7R8 or —OR12, —C(O)—C1-6 alkyl and —C(O)O—C1-6 alkyl;
• R4 is selected from H, halo, —C≡CH, —C≡N, —OH, —OCF3, —OCHF2, C1-4 straight or branched alkoxy, —SO2(C1-6 alkyl), —N(CH3)2, —C(O)NH2, —NHSO2R7, —C(O)NR7R8, a ring structure comprising a 5- or 6-membered aryl or a 4-, 5-, or 6-membered cycloalkyl with 0 to 3 ring heteroatoms independently selected from N, O and S and substituted with 0 to 2 groups independently selected from ═O, halo, C1-6 straight or branched alkyl optionally substituted with —OR12 or —NR7R8, C1-6 straight or branched alkoxy optionally substituted with —NR7R8 or —OR12, —C(O)—C1-6 alkyl and —C(O)O—C1-6 alkyl,
• or the R4 group bonds to X4 to form a 5- or 6-membered aryl or cycloalkyl with 0 to 3 ring heteroatoms independently selected from N, O and S and substituted with 0 to 2 groups independently selected from ═O, halo, C1-6 straight or branched alkyl optionally substituted with —OR12 or —NR7R8, C1-6 straight or branched alkoxy optionally substituted with —NR7R8 or —OR12, —C(O)—C1-6 alkyl and —C(O)O—C1-6 alkyl;
• provided that:
• at least one of R3 and R4 is selected from the group consisting of:
• H, halo, —C≡CH, —C≡N, —OH, —OCF3, —OCHF2, C1-4 straight or branched alkoxy, —SO2(C1-6 alkyl), —N(CH3)2, —C(O)NH2, —NHSO2R7, and —C(O)NR7R8, and
• R3 and R4 are not both H;
• R5 is selected from the group consisting of H, methyl, ethyl, n-propyl, isopropyl, n-butyl, CF3, CH2CF3 and halo;
• R6 is selected from the group consisting of H, methyl, ethyl, n-propyl, isopropyl, n-butyl, CF3, CH2CF3, halo, cyclopropylmethyl and C1-4 alkoxy;
• R7 and R8 are independently selected, in each instance, from H, C1-6 straight or branched alkyl, C3-6 cycloalkyl, cyclopropylmethyl and cyclobutylmethyl;
• and
• R12 is independently selected, in each instance, from H and C1-4 straight or branched alkyl.
• or a pharmaceutically acceptable salt or solvate thereof.