Benzimidazole compounds and antiviral uses thereof

A compound of the Formula I:

• or a pharmaceutically-acceptable prodrug, salt, solvate, hydrate, enantiomer, diastereomer, racemate or mixture of stereoisomer thereof, wherein:
• R1 and R2 are joined to form a substituted or unsubstituted ring wherein, when R1 and R2 form a substituted ring, the substituent is at least one unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, amide, amine, sulfonamide, ester, hydroxy, halide, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
• R3 is substituted or unsubstituted 2-benzimidazolyl;
• 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, methyl ester, ethyl ester, C1–C2 amide, carboxylic acid, or sulfonamide;
• X is a bond, methylene, or ethylene;
• Y is nitrogen;
• and
• n is 1.

A compound of the Formula I:

• or a pharmaceutically-acceptable prodrug, salt, solvate, hydrate, enantiomer, diastereomer, racemate or mixture of stereoisomer thereof, wherein:
• R1 and R2 are joined to form a substituted or unsubstituted ring wherein, when R1 and R2 form a substituted ring, the substituent is at least one unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, amide, amine, sulfonamide, ester, hydroxy, halide, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
• R3 is substituted or unsubstituted 2-benzimidazolyl;
• 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, methyl ester, ethyl ester, C1–C2 amide, carboxylic acid, or sulfonamide;
• wherein said substituted or unsubstituted 2-benzimidazolyl is substituted with at least one C1–C4 alkyl, C1–C4 alkoxy, C1–C4 sulfide, C1–C4 sulfonyl, nitro, fluoride, chloride, or bromide;
• X is a methylene;
• Y is nitrogen;
• and
• n is 1.

A compound of the Formula I:

• or a pharmaceutically-acceptable salt, solvate, or hydrate, wherein:
• R1 and R2 are joined to form a substituted or unsubstituted ring, said substituted ring is a substituted heterocycloalkyl or a substituted 5, 6, 7 or 8 membered-heteroaryl,
• wherein, when R1 and R2 form said substituted ring, the substituent is at least one unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, amide, amine, sulfonamide, ester, hydroxy, halide, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, or unsubstituted heteroaryl;
• R3 is substituted or unsubstituted 2-benzimidazolyl;
• 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, methyl ester, ethyl ester, C1–C2 amide, carboxylic acid, or sulfonamide;
• X is a bond, straight chain or branched substituted or unsubstituted alkyl, -(alkyl)N—, -(alkyl)O—, —C═N—, carbonyl, phosphorus, or sulfur;
• Y is nitrogen;
• and
• n is an integer from 0 to 4;
• wherein said compound is an enantiomer or diastereomer.

A compound of the Formula I:

• or a pharmaceutically-acceptable prodrug, salt, solvate, hydrate, enantiomer, diastereomer, racemate or mixture of stereoisomer thereof, wherein:
• R1 and R2 are joined to form a substituted or unsubstituted ring wherein, when R1 and R2 form a substituted ring, the substituent is at least one unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, amide, amine, sulfonamide, ester, hydroxy, halide, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
• R3 is substituted or unsubstituted 2-benzimidazolyl;
• 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, methyl ester, ethyl ester, C1–C2 amide, carboxylic acid, or sulfonamide;
• wherein at least one of R4, R4′, R8, and R8′ is not hydrogen;
• X is a bond, straight chain or branched substituted or unsubstituted alkyl, -(alkyl)N—, -(alkyl)O—, —C═N—, carbonyl, phosphorus, or sulfur;
• Y is nitrogen;
• and
• n is an integer from 0 to 4.

A compound having the formula:

• 1-(1H-Benzimidazol-2-ylmethyl)-2-morpholin-4-ylmethyl-1H-benzimidazole-5-carboxylic acid methyl ester;
• 1-(1H-Benzimidazol-2-ylmethyl)-2-morpholin-4-ylmethyl-1H-benzimidazole-6-carboxylic acid methyl ester;
• {1-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-piperidin-3-yl}-methanol;
• {1-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-pyrrolidin-2-yl}-methanol;
• 2-{1-[1-(1H-benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-piperidin-2-yl}-ethanol;
• [1,2,4]Oxadiazol-3-ylmethyl-2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-ylmethyl]-1H-benzoimidazole;
• 1-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-4-(3-trifluoromethyl-phenyl)piperazine;
• 1-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-4-(4-trifluoromethyl-phenyl)piperazine;
• 1-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-4-pyridin-2-ylpiperazine;
• (R)-{1-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-pyrrolidin-2-yl}-methanol;
• (S)-1-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-pyrrolidine-2-carboxylic acid methyl ester;
• (S)-1-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-pyrrolidine-2-carboxylic acid amide;
• 2-{4-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-piperazin-1-yl}-acetamide;
• 1-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-piperidine-3-carboxylic acid 1-(1H-benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl ester;
• or
• 1-[1-(1H-Benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl]-pyrrolidine-2-carboxylic acid 1-(1H-benzoimidazol-2-ylmethyl)-1H-benzoimidazol-2-ylmethyl ester.

A compound having the Formula II:

• or a pharmaceutically-acceptable prodrug, salt, solvate, hydrate, enantiomer, diastereomer, racemate or mixture of stereoisomer thereof, wherein:
• R1 and R2 are joined to form a substituted or unsubstituted ring wherein, when R1 and R2 form a substituted ring, the substituent is at least one unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, amide, amine, sulfonamide, ester, hydroxy, halide, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
• R3 is substituted or unsubstituted 2-benzimidazolyl;
• 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, amine, C1–C4 alkylamine, C1–C4 amide, carboxylic acid, ester, nitro, C1–C4 sulfide, C1–C4 sulfonyl, or sulfonamide.

A compound of the Formula IV:

• or a pharmaceutically-acceptable prodrug, salt, solvate, hydrate, enantiomer, diastereomer, racemate or mixture of stereoisomer thereof, wherein:
• —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 unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, amide, amine, sulfonamide, ester, hydroxy, halide, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterocycloaryl or substituted or unsubstituted heteroaryl;
• 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;
• 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.

A pharmaceutical composition in solid form comprising a compound of the Formula I:

• or a pharmaceutically-acceptable prodrug, salt, solvate, hydrate, enantiomer, diastereomer, racemate or mixture of stereoisomer thereof, wherein:
• R1 and R2 are joined to form a substituted or unsubstituted ring wherein, when R1 and R2 form a substituted ring, the substituent is at least one unsubstituted lower alkyl, substituted or unsubstituted lower alkoxy, amide, amine, sulfonamide, ester, hydroxy, halide, substituted or unsubstituted aryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
• R3 is substituted or unsubstituted 2-benzimidazolyl;
• 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, methyl ester, ethyl ester, C1–C2 amide, carboxylic acid, or sulfonamide;
• X is a bond, straight chain or branched substituted or unsubstituted alkyl, -(alkyl)N—, -(alkyl)O—, —C═N—, carbonyl, phosphorus, or sulfur;
• Y is nitrogen;
• and
• n is an integer from 0 to 4;
• a pharmaceutically acceptable carrier.