Hetero-substituted benzimidazole compounds and antiviral uses thereof

A compound of the Formula II:

• 50
• or a pharmaceutically-acceptable prodrug, salt, solvate, hydrate, clathrate, enantiomer, diastereomer, racemate or mixture of stereoisomer thereof, wherein:
• Z1, Z2, Z3 and Z4 are each independently nitrogen or carbon and at least one of Z1, Z2, Z3 and Z4 is carbon;
• R1 and R2 are each independently:
• hydrogen, saturated or unsaturated straight or branched substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloaryl;
• substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted arylalkyl;
• wherein, if present, the substituent is at least one alkanoyl, imide, alkyl, hydroxy, halide, methoxy, ethoxy, carboxylic acid, cyano, amine, amide, alkylamine, acetal, acetylene, aminal, amino acid, amino acid ester, azo, diazo, azide, carbamate, carboxylic acid ester, carboalkoxy ester, cyanohydrin, diazonium salt, glucoside, glucuronide, halocarbon, polyhalocarbon, halocarbonoxy, polyhalocarbonoxy, hydroxylamine, ketone, lactone, nitrile, nitrile oxide, N-oxides, nucleoside linked, oxime, phosphate, phosphinate, phosphonate, phosphonic acid, quaternary ammonium salt, sulfoxide, sulfone, sulfonate ester, sulfinate ester, sulfonic acid, thioacetal, thiocarboxylic acid, thiol, thioaryl, or R1 and R2 may be joined to form a substituted or unsubstituted ring including a heterocycloalkyl, heterocycloaryl or heteroaryl group;
• R3 is hydrogen, halide, saturated or unsaturated straight or branched substituted or unsubstituted alkyl, hydroxy, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
• wherein, if present the substituent is at least one alkanoyl, imide, alkyl, hydroxy, halide, methoxy, ethoxy, carboxylic acid, amine, amide, alkylamine, acetal, acetylene, aminal, amino acid, amino acid ester, azo, diazo, azide, carbamate, carboxylic acid ester, carboalkoxy ester, cyanohydrin, diazonium salt, glucoside, glucuronide, halocarbon, polyhalocarbon, halocarbonoxy, polyhalocarbonoxy, hydroxylamine, ketone, lactone, nitrile, nitrile oxide, N-oxides, nucleoside linked, oxime, phosphate, phosphinate, phosphonate, phosphonic acid, quaternary ammonium salt, sulfoxide, sulfone, sulfonate ester, sulfinate ester, sulfonic acid, thioacetal, thiocarboxylic acid, thiol, or thioaryl;
• R4, R4′, R8, and R8′ are each independently hydrogen, halide, saturated or unsaturated straight or branched substituted or unsubstituted alkyl, hydroxy, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heteroaryl;
• wherein, if present the substituent is at least one alkyl, hydroxy, halide, methoxy, ethoxy, amine, cyano, alkanoyl, imide, amine, amide, alkylamine, amide, carboxylic acid, ester, nitro, sulfide, sulfonyl, sulfonamide, acetal, acetylene, aminal, amino acid, amino acid ester, azo, diazo, azide, halogen, carbamate, carboxylic acid ester, carboalkoxy ester, cyanohydrin, diazonium salt, glucoside, glucuronide, halocarbon, polyhalocarbon, halocarbonoxy, polyhalocarbonoxy, hydroxylamine, ketone, lactone, nitrile, nitrile oxide, N-oxides, nucleoside linked, oxime, phosphate, phosphinate, phosphonate, phosphonic acid, quaternary ammonium salt, sulfoxide, sulfone, sulfonate ester, sulfinate ester, sulfonic acid, thioacetal, thiocarboxylic acid, thiol, or thioaryl.

A compound of the Formula III:

• 51
• or a pharmaceutically-acceptable prodrug, salt, solvate, hydrate, clathrate, enantiomer, diastereomer, racemate or mixture of stereoisomer thereof, wherein:
• Z1, Z2, Z3 and Z4 are each independently nitrogen or carbon and at least one of Z1, Z2, Z3 and Z4 is carbon;
• Z5, Z6, Z7 and Z8 are each independently nitrogen or carbon;
• R1 and R2 are each independently:
• hydrogen, saturated or unsaturated straight or branched substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylamino, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloaryl, substituted or unsubstituted heteroaryl, alkanoyl, or imide, wherein, if present, the substituent is at least one alkyl, alkanoyl, imide, alkoxy, carboxylic acid, amine, amide, alkylamine, cyano, halide, hydroxy, nitro, thiol, acetal, acetylene, aminal, amino acid, amino acid ester, azo, diazo, azide, carbamate, carboxylic acid ester, carboalkoxy ester, cyanohydrin, diazonium salt, glucoside, glucuronide, halocarbon, polyhalocarbon, halocarbonoxy, polyhalocarbonoxy, hydroxylamine, lactone, nitrile, nitrile oxide, N-oxides, nucleoside linked, oxime, quaternary ammonium salt, sulfoxide, sulfone, sulfonate ester, sulfinate ester, sulfonic acid, thioacetal, thiocarboxylic acid, thiol, or thioaryl;
• R4, R4′, R5, R5′, R8, R8′, R9, and R9′ are each independently hydrogen, halide, saturated or unsaturated straight or branched substituted or unsubstituted alkyl, hydroxy, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloaryl or substituted or unsubstituted heteroaryl;
• wherein, if present, the substituent is at least one alkanoyl, imide, alkyl, hydroxy, halide, methoxy, ethoxy, carboxylic acid, cyano, amine, alkylamine, amide, carboxylic acid, ester, nitro, sulfide, sulfonyl, sulfonamide, acetal, acetylene, aminal, amino acid, amino acid ester, azo, diazo, azide, carbamate, carboxylic acid ester, carboalkoxy ester, cyanohydrin, diazonium salt, glucoside, glucuronide, halocarbon, polyhalocarbon, halocarbonoxy, polyhalocarbonoxy, hydroxylamine, ketone, lactone, nitrile, nitrile oxide, N-oxides, nucleoside linked, oxime, phosphate, phosphinate, phosphonate, phosphonic acid, quaternary ammonium salt, sulfoxide, sulfone, sulfonate ester, sulfinate ester, sulfonic acid, thioacetal, thiocarboxylic acid, thiol, or thioaryl;
• and
• R6 is hydrogen, saturated or unsaturated,saturated or unsaturated straight or branched substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylamino, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloaryl or substituted or unsubstituted heteroaryl;
• wherein, if present, the substituent is at least one alkanoyl, imide, alkyl, hydroxy, halide, methoxy, ethoxy, carboxylic acid, cyano, nitro, thiol, alkanoyl, imide, acetal, acetylene, aminal, amino acid, azo, diazo, carbamate, carboalkoxy ester, cyanohydrin, glucoside, glucuronide, halocarbon, polyhalocarbon, halocarbonoxy, polyhalocarbonoxy, ketone, nitrile, nitrile oxide, N-oxides, nucleoside linked, oxime, sulfone, or sulfonic acid.

A compound of the Formula IV:

• 53
• or a pharmaceutic ally-acceptable prodrug, salt, solvate, hydrate, clathrate, enantiomer, diastereomer, racemate or mixture of stereoisomer thereof, wherein:
• Z1, Z2, Z3 and Z4 are each independently nitrogen or carbon and at least one of Z1, Z2, Z3 and Z4 is carbon;
• Z5, Z6, Z7 and Z8 are each independently nitrogen or carbon;
• —R1—N—R2— form a saturated or unsaturated substituted or unsubstituted heterocycloalkyl ring, substituted or unsubstituted heteroaryl ring, wherein, if present, the substituent is at least one substituted or unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, amides, sulfonamides, esters, hydroxy, halide, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloaryl or substituted or unsubstituted heteroaryl;
• wherein, if present, the substituent is at least one alkanoyl, imide, alkyl, hydroxy, halide, methoxy, ethoxy, carboxylic acid, cyano, carbonyl, nitro, acetal, acetylene, aminal, amino acid, amino acid ester, azo, diazo, azide, carbamate, carboxylic acid ester, carboalkoxy ester, cyanohydrin, diazonium salt, glucoside, glucuronide, halocarbon, polyhalocarbon, halocarbonoxy, polyhalocarbonoxy, hydroxylamine, ketone, lactone, nitrile, nitrile oxide, N-oxides, nucleoside linked, oxime, phosphate, phosphinate, phosphonate, phosphonic acid, quaternary ammonium salt, sulfoxide, sulfone, sulfonate ester, sulfinate ester, sulfonic acid, thioacetal, thiocarboxylic acid, thiol, or thioaryl;
• R4, R4′, R5, R5′, R8, R8′, R9, and R9′ are each independently hydrogen, halide, saturated or unsaturated straight or branched substituted or unsubstituted alkyl, hydroxy, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloaryl or substituted or unsubstituted heteroaryl;
• wherein, if present, the substituent is at least one alkanoyl, imide, alkyl, hydroxy, halide, methoxy, ethoxy, carboxylic acid, cyano, amine, alkylamine, amide, carboxylic acid, ester, nitro, sulfide, sulfonyl, or sulfonamide, acetal, acetylene, aminal, amino acid, amino acid ester, azo, diazo, azide, carbamate, carboxylic acid ester, carboalkoxy ester, cyanohydrin, diazonium salt, glucoside, glucuronide, halocarbon, polyhalocarbon, halocarbonoxy, polyhalocarbonoxy, hydroxylamine, ketone, lactone, nitrile, nitrile oxide, N-oxides, nucleoside linked, oxime, phosphate, phosphinate, phosphonate, phosphonic acid, quaternary ammonium salt, sulfoxide, sulfone, sulfonate ester, sulfinate ester, sulfonic acid, thioacetal, thiocarboxylic acid, thiol, or thioaryl;
• and
• R6 is hydrogen, saturated or unsaturated straight or branched substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylamino, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocycloaryl or substituted or unsubstituted heteroaryl;
• wherein, if present, the substituent is at least one alkanoyl, imide, alkyl, hydroxy, halide, methoxy, ethoxy, carboxylic acid, cyano, nitro, alkanoyl, imide, acetal, acetylene, aminal, amino acid, amino acid ester, azo, diazo, azide, carbamate, carboxylic acid ester, carboalkoxy ester, cyanohydrin, diazonium salt, glucoside, glucuronide, halocarbon, polyhalocarbon, halocarbonoxy, polyhalocarbonoxy, hydroxylamine, ketone, lactone, nitrile, nitrile oxide, N-oxides, nucleoside linked, oxime, phosphate, phosphinate, phosphonate, phosphonic acid, quaternary ammonium salt, sulfoxide, sulfone, sulfonate ester, sulfinate ester, sulfonic acid, thioacetal, thiocarboxylic acid, thiol, or thioaryl.