Methods and compositions of treating a flaviviridae family viral infection
Clemizole and clemizole analog compounds, and pharmaceutical compositions of the same, are useful in methods of treating a host infected with a virus from the Flaviviridae family of viruses, methods of inhibiting HCV replication in a host, methods of inhibiting the binding of NS4B polypeptide to the 3′UTR of HCV negative strand RNA in a host, and methods of treating liver fibrosis in a host.
1. A compound having the structure shown in Formula III-C
or a pharmaceutically acceptable salt, a tautomer, or a prodrug thereof,
A 1 is a substituted or an unsubstituted, 5 or 6 membered, non aromatic heterocycle containing one basic nitrogen atom or a substituted or an unsubstituted 6 membered heteroaryl containing one basic nitrogen atom, wherein substituted refers to a substitution selected from the group consisting of: alkyl, alkenyl, oxo, aryl, heterocyclo, carbocyclo, halo, hydroxy, alkoxy, aryloxy, alkanoyl, aroyl, alkylester, arylester, cyano, nitro, amido, amino, substituted amino, lactam, urea, urethane, and sulfonyl;
wherein R 5 is a substituted or an unsubstituted C 1 -C 3 alkyl or 5 membered heteroaryl group, wherein substituted refers to a substitution selected from the group consisting of: aryl, heteroaryl, heterocyclo, carbocyclo, halo, hydroxy, protected hydroxy, alkoxy, acyl, aryloxy, alkylester, arylester, alkanoyl, aroyl, carboxy, protected carboxy, cyano, nitro, amino, substituted amino, (monosubstituted)amino, (disubstituted)amino, protected amino, amido, lactam, urea, urethane, and sulfonyl;
R 6 is hydrogen or a substituted or an unsubstituted C 1 -C 3 alkyl, wherein substituted refers to a substitution selected from the group consisting of: aryl, heteroaryl, heterocyclo, carbocyclo, halo, hydroxy, protected hydroxy, alkoxy, acyl, aryloxy, alkylester, arylester, alkanoyl, aroyl, carboxy, protected carboxy, cyano, nitro, amino, substituted amino, (monosubstituted)amino, (disubstituted)amino, protected amino, amido, lactam, urea, urethane, and sulfonyl; and
R 35 is hydrogen or a substituted or an unsubstituted C 1 -C 3 alkyl, wherein substituted refers to a substitution selected from the group consisting of: aryl, heteroaryl, heterocyclo, carbocyclo, halo, hydroxy, protected hydroxy, alkoxy, acyl, aryloxy, alkylester, arylester, alkanoyl, aroyl, carboxy, protected carboxy, cyano, nitro, amino, substituted amino, (monosubstituted)amino, (disubstituted)amino, protected amino, amido, lactam, urea, urethane, and sulfonyl.
2. A composition, comprising the following compound,
or a pharmaceutically acceptable salt, a tautomer, or a prodrug thereof.
3. A compound having the structure shown in Formula III-C
or a pharmaceutically acceptable salt, a tautomer, or a prodrug thereof,
wherein A 1 is a 6 membered, non aromatic heterocycle containing one basic nitrogen atom;
wherein R 5 is a C 1 -C 4 alkyl or 5 membered heteroaryl group;
wherein R 6 is hydrogen or a C 1 -C 4 alkyl; and
wherein R 35 is hydrogen or a C 1 -C 3 alkyl.
4. A compound having the structure shown in Formula III-C
or a pharmaceutically acceptable salt, a tautomer, or a prodrug thereof,
wherein A 1 is a 6 membered heteroaryl containing one basic nitrogen atom;
wherein R 5 is a C 1 -C 4 alkyl or 5 membered heteroaryl group;
wherein R 6 is hydrogen or a C 1 -C 4 alkyl; and
wherein R 35 is hydrogen or a C 1 -C 3 alkyl.
5. A compound having the structure shown in Formula III-C
or a pharmaceutically acceptable salt, a tautomer, or a prodrug thereof,
wherein A 1 is a 5 or 6 membered, non aromatic heterocycle containing one basic nitrogen atom or a 6 membered heteroaryl containing one basic nitrogen atom;
wherein R 5 is a C 1 -C 4 alkyl;
wherein R 6 is a C 1 -C 4 alkyl; and
wherein R 35 is a C 1 -C 3 alkyl.