HCV Helicase Inhibitors and Methods of Use Thereof
AssigneesUWM Research Foundation, Inc., University of Kansas
InventorsJeffrey Aube, Brian Scott Jonathan Blagg, Kevin John Frankowski, David Norman Frick, Kelin Li, Frank John Schoenen
Life of this patent
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Abstract
The present invention discloses thioflavine S and primuline derivatives which inhibit hepatitis C virus helicase and protease activity. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are useful as antiviral agents. The present invention further relates to pharmaceutical compositions containing the aforementioned compounds and methods of treating an HCV infection.
Claims12
1-9. (canceled)
A compound of Formula I or Formula II, or a pharmaceutically acceptable salt, ester or prodrug thereof,
- wherein
- one of R1 or R2 is SO3H, CO2H or a carboxylic acid isostere and the other of R1 or R2 is H;
- each X is independently O, S, NR3, or C═C;
- R of Formula I is a nitro, or substituted or unsubstituted benzothiazole, benzamide, phenylurea, benzenesulfonamide, pyridine-carboxamide, naphthalene-carboxamide, or benzothiazole-carboxamide group;
- R of Formula II is an amino, nitro, or substituted or unsubstituted benzothiazole, benzamide, phenylurea, benzenesulfonamide, pyridine-carboxamide, naphthalene-carboxamide, or benzothiazole-carboxamide group;
- and
- R3 is hydrogen, alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of Formula I or Formula II, or a pharmaceutically acceptable salt, ester or prodrug thereof,
- wherein
- one of R1 or R2 is SO3H, CO2H or a carboxylic acid isostere and the other of R1 or R2 is H;
- each X is independently O, S, NR3, or C═C;
- R is an amino, nitro, or substituted or unsubstituted benzothiazole, benzamide, phenylurea, benzenesulfonamide, pyridine-carboxamide, naphthalene-carboxamide, or benzothiazole-carboxamide group;
- and
- R3 is hydrogen, alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl.
A method for inhibiting hepatitis C virus (HCV) or Dengue Virus (DV) nonstructural protein 3 helicase and protease activity comprising contacting HCV or DV nonstructural protein 3 with a compound of Formula I or Formula II, or a pharmaceutically acceptable salt, ester or prodrug thereof,
- wherein
- one of R1 or R2 is SO3H, CO2H or a carboxylic acid isostere and the other of R1 or R2 is H;
- each X is independently O, S, NR3, or C═C;
- R is an amino, nitro, or substituted or unsubstituted benzothiazole, benzamide, phenylurea, benzenesulfonamide, pyridine-carboxamide, naphthalene-carboxamide, or benzothiazole-carboxamide group;
- and
- R3 is hydrogen, alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl.
A method for inhibiting hepatitis C virus (HCV) or Dengue Virus (DV) replication comprising contacting a biological sample with a compound of Formula I or Formula II, or a pharmaceutically acceptable salt, ester or prodrug thereof,
- wherein
- one of R1 or R2 is SO3H, CO2H or a carboxylic acid isostere and the other of R1 or R2 is H;
- each X is independently O, S, NR3, or C═C;
- R is an amino, nitro, or substituted or unsubstituted benzothiazole, benzamide, phenylurea, benzenesulfonamide, pyridine-carboxamide, naphthalene-carboxamide, or benzothiazole-carboxamide group;
- and
- R3 is hydrogen, alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl.
A method for staining viable cells in situ comprising contacting a population of cells with a compound of Formula I or Formula II so that viable cells are stained,
- wherein
- one of R1 or R2 is SO3H, CO2H or a carboxylic acid isostere and the other of R1 or R2 is H;
- each X is independently O, S, NR3, or C═C;
- R is an amino, nitro, or substituted or unsubstituted benzothiazole, benzamide, phenylurea, benzenesulfonamide, pyridine-carboxamide, naphthalene-carboxamide, or benzothiazole-carboxamide group;
- and
- R3 is hydrogen, alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl.
A method for detecting amyloid beta protein plaques comprising contacting a biopsy sample with a compound of Formula I or Formula II so that amyloid beta protein plaques are stained,
- wherein
- one of R1 or R2 is SO3H, CO2H or a carboxylic acid isostere and the other of R1 or R2 is H;
- each X is independently O, S, NR3, or C═C,
- R is an amino, nitro, or substituted or unsubstituted benzothiazole, benzamide, phenylurea, benzenesulfonamide, pyridine-carboxamide, naphthalene-carboxamide, or benzothiazole-carboxamide group;
- and
- R3 is hydrogen, alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl.
A method for staining or quantifying DNA comprising contacting a DNA sample with a compound of Formula I or Formula II,
- wherein
- one of R1 or R2 is SO3H, CO2H or a carboxylic acid isostere and the other of R1 or R2 is H;
- each X is independently O, S, NR3, or C═C;
- R is an amino, nitro, or substituted or unsubstituted benzothiazole, benzamide, phenylurea, benzenesulfonamide, pyridine-carboxamide, naphthalene-carboxamide, or benzothiazole-carboxamide group;
- R3 is hydrogen, alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, or heterocycloalkyl.
Dependencies are inferred from the claim text.