Flavivirus inhibitors and methods of their use
Methods of treating, preventing, and/or ameliorating a Flavivirus infection in a subject are disclosed. The methods comprise administering to the subject a therapeutically effective amount of a Flavivirus inhibitor, e.g., a Flavivirus serine protease inhibitor. These methods are useful in treating, preventing, and/or ameliorating Flavivirus infections such as, for example, West Nile Virus, Dengue Virus, and Japanese Encephalitis Virus.
1. A method of treating a Flavivirus infection in a subject, comprising administering to the subject a therapeutically effective amount of the compound of the following formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 is hydroxyl;
R 2 , R 3 , R 4 , R 5 , and R 6 are each independently selected from hydrogen, hydroxyl, substituted or unsubstituted C 1-4 alkyl, substituted or unsubstituted C 1-4 heteroalkyl, substituted or unsubstituted C 2-4 alkenyl, substituted or unsubstituted C 2-4 heteroalkenyl, substituted or unsubstituted C 2-4 alkenyl, substituted or unsubstituted C 2-4 heteroalkynyl, or halogen;
A is
B is
and
R 7 is hydrogen.
2. The method of claim 1 , wherein the Flavivirus is the West Nile Virus.
3. The method of claim 1 , wherein the Flavivirus is Dengue Virus serotype DEN-1, Dengue Virus serotype DEN-2, Dengue Virus serotype DEN-3, or Dengue Virus serotype DEN-4.
4. The method of claim 1 , wherein the Flavivirus is Japanese Encephalitis Virus.
5. A compound of the following formula:
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R 1 is hydroxyl;
R 2 , R 3 , R 4 , R 5 , and R 6 are each independently selected from hydrogen, hydroxyl, substituted or unsubstituted C 1-4 alkyl, substituted or unsubstituted C 1-4 heteroalkyl, substituted or unsubstituted C 2-4 alkenyl, substituted or unsubstituted C 2-4 heteroalkenyl, substituted or unsubstituted C 2-4 alkynyl, substituted or unsubstituted C 2-4 heteroalkynyl, or halogen;
A is
B is
and
R 7 is hydrogen.
6. The compound of claim 5 , wherein R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen.
7. The method of claim 1 , wherein R 2 , R 3 , R 4 , R 5 , and R 6 are hydrogen.