Methods and compositions of treating a Flaviviridae family viral infection

A pharmaceutical composition comprising a compound as shown in Formula II-a, or a pharmaceutically acceptable salt, a stereoisomer a tautomer, or a prodrug thereof:

• wherein R1 is
• wherein V is selected from the group consisting of:
• alkyl, cycloalkyl, heterocyclo, aryl, and heteroaryl, and m is 0, 1 or 2;
• R3 is —OH, —O(CH2)nX, or —(CH2)nX, wherein n is 1, 2, 3, or 4, and X is selected from the group consisting of:
• —NH2, —NH(alkyl), —N(alkyl)2, —OH, —O-alkyl, —O-aryl, —SO2(alkyl), —SO2 NH2, —SO2 NH(alkyl), NHSO2(alkyl)
• each of R4-R7 are independently selected from the group consisting of:
• —H, —Br, —Cl, —F, —I, —CH3, —CN, —OH, —OCH3, —NO2, —NH2, —NHCO(alkyl), —NHCO(aryl),
• or, optionally, R4 and R5, R5 and R6, or R6 and R7 are joined together with a bond to form a 5, 6, or 7 -membered ring;
• or optionally, R4 and R5, R5 and R6, or R6 and R7 are joined together to form a 1,2-(methylenedioxy)benzene ring system;
• provided that the compound of Formula II-a is not

A compound having the structure shown in Formula III

• or a pharmaceutically acceptable salt, a stereoisomer, a tautomer or a prodrug thereof, wherein
• m is 1 or 2;
• V is an unsubstituted or a monosubstituted phenyl, cyclohexyl, or a 6-membered heterocyclo group, where the heterocyclo group contains 1 nitrogen atom;
• R3 is —O-L-X;
• L is an unsubstituted or a monosubstituted C1-C5 alkylene;
• X is selected from the group consisting of:
• —N(R20)2, 4-substituted phenyl;
• R5 is hydrogen, alkyl, halo, a substituted or an unsubstituted 5, 6, 7 membered heterocyclo, or —NR21R22;
• each R20 is independently selected from a substituted or an unsubstituted C1-C3 alkyl;
• R21 and R22 are each independently selected from hydrogen, a substituted or an unsubstituted C1-C3 alkyl, C3-C8 cycloalkyl, aryl, heteroaryl group, —COR16, or —SO2R16, or R21 and R22 together with the nitrogen atom to which they are attached form a 5-7 membered substituted or unsubstituted heterocyclo group;
• and
• R16 is substituted or unsubstituted C1-C3 alkyl.

A pharmaceutical composition comprising the compound as shown in formula III and a pharmaceutically acceptable carrier, excipient, or diluent:

• or a pharmaceutically acceptable salt, a stereoisomer, a tautomer or a prodrug thereof, wherein m is 1 or 2;
• V is an unsubstituted or a monosubstituted phenyl, cyclohexyl, or a 6-membered heterocyclo group, where the heterocyclo group contains 1 nitrogen atom;
• R3 is —O-L-X;
• L is an unsubstituted or a monosubstituted C1-C5 alkylene;
• X is selected from the group consisting of:
• —N(R20)2, 4-substituted phenyl,
• R5 is hydrogen, alkyl, halo, a substituted or an unsubstituted 5, 6, 7 membered heterocyclo, or —NR21R22;
• each R20 is independently selected from a substituted or an unsubstituted C1-C3 alkyl;
• R21 and R22 are each independently selected from hydrogen, a substituted or an unsubstituted C1-C3 alkyl, C3-C8 cycloalkyl, aryl, heteroaryl group, —COR16, or —SO2R16, or R21and R22 together with the nitrogen atom to which they are attached form a 5-7 membered substituted or unsubstituted heterocyclo group;
• and
• R16 is substituted or unsubstituted C1-C3 alkyl.

A compound having the structure shown in Formula II-a, or a pharmaceutically acceptable salt or a stereoisomer thereof:

• wherein R1 is —H;
• R3 is selected from the group consisting of:
• —OH, —O(CH2)nX, or —(CH2)nX, wherein n is 1, 2, 3, or 4, and X is —NH2, —NH(alkyl), —N(alkyl)2, —OH, —O-alkyl, —O-aryl, —SO2(alkyl), —SO2NH2, —SO2 NH(alkyl), NHSO2(alkyl),
• each of R4-R7 are independently selected from the group consisting of:
• —H, —Br, —CI, —F, —I, —CH3, —CN, -OH, -OCH3, —NO2, —NH2, —NHCO(alkyl), —NHCO(aryl),
• or, optionally, R4 and R5, R5 and R6, or R6 and R7 are joined together with a bond to form a 5, 6, or 7-membered ring;
• or, optionally, R4 and R5, R5 and R6, or R6 and R7 are joined together to form a 1,2-(methylenedioxy)benzene ring system;
• provided that the compound of Formula II-a is not

A pharmaceutical composition comprising a compound as shown in Formula II-a, or a pharmaceutically acceptable salt, a stereoisomer, a tautomer, or a prodrug thereof:

• wherein R1 is selected from the group consisting of:
• —H;
• R3 is selected from the group consisting of:
• —OH, —O(CH2)nX, or —(CH2)nX, wherein n is 1, 2, 3, or 4, and X is —NH2, —NH(alkyl), —N(alkyl)2, —OH, —O-alkyl, —O-aryl, —SO2(alkyl), —SO2 NH2, —SO2 NH(alkyl), NHSO2(alkyl),
• each of R4-R7 are independently selected from the group consisting of:
• —H, —Br, —CI, —F, —I, —CH3, —CN, —OH, —OCH3, —NO2, —NH2, —NHCO(alkyl), —NHCO(aryl),
• or, optionally, R4 and R5, R5 and R6, or R6 and R7 are joined together with a bond to form a 5, 6, or 7-membered ring;
• or, optionally, R4 and R5, R5 and R6, or R6 and R7 are joined together to form a 1,2-(methylenedioxy)benzene ring system;
• provided that the compound of Formula II-a is not