Methods and compositions for inhibition of polymerase

Patent metadata

Field	Value
Publication number	US-9492452-B2
Application number	US-201414531471-A
Country	US
Kind code	B2
Filing date	Nov 3, 2014
Priority date	Oct 15, 2010
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

The present invention is directed to methods and compositions for inhibition of viral nucleic acid polymerases, such as RNA and DNA polymerases, and methods and compositions that are useful for treating viral infections in subjects. The methods comprise administering to the subject a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or hydrate thereof, or a composition comprising a compound of formula I, or a pharmaceutically acceptable salt or hydrate thereof, and a pharmaceutically acceptable carrier. The composition or method may optionally comprise one or more additional anti-viral agents.

First claim

What is claimed is:

1. A method of treating a viral infection, comprising administering to a subject in need thereof a therapeutically effective amount of a compound having the following structure:

or a pharmaceutically acceptable salt or hydrate thereof; wherein the virus is a member of a virus family selected from the group consisting of orthomyxoviridae, paramyxoviridae, arenaviridae, bunyaviridae, flaviviridae, filoviridae, togaviridae, picornaviridae, poxviridae, adenoviridae, and coronaviridae virus families.

2. The method of claim 1 , wherein said subject is a mammal.

3. The method of claim 1 , wherein the subject is a human.

4. The method of claim 1 , wherein the virus is selected from the group consisting of adenovirus, rhinovirus, polio, measles, Ebola, Coxsackie, small pox, yellow fever, Dengue fever, influenza A, influenza B, lassa, lymphocytic choriomeningitis, junin, machupo, guanarito, hantavirus, Rift Valley Fever, La Crosse, California encephalitis, Crimean-Congo, Marburg, Japanese Encephalitis, Kyasanur Forest, Eastern equine encephalitis, Western equine encephalitis, severe acute respiratory syndrome (SARS), parainfluenza, Tacaribe, vaccinia, and pichinde viruses.

5. The method of claim 1 , wherein the virus is selected from the group consisting of Ebola, yellow fever, Marburg, influenza A and influenza B viruses.

6. The method of claim 1 , wherein the virus is Ebola virus.

7. The method of claim 6 , wherein said subject is a human.

8. The method of claim 1 , further comprising co-administering to the subject an effective amount of an anti-viral agent.

9. The method of claim 8 , wherein the anti-viral agent is a neuraminidase inhibitor.

10. The method of claim 8 , wherein the anti-viral agent is selected from the group consisting of laninamivir, oseltamivir, zanamivir, and peramivir.

11. The method of claim 8 , wherein the anti-viral agent is peramivir.

12. The method of claim 1 , wherein the compound is administered intravenously, intraperitoneally, intramuscularly, or orally.

13. The method of claim 1 , wherein the therapeutically effective amount is delivered in a single dose per day or more than one dose per day.

14. The method of claim 13 , wherein the total dose per day is about 5 to about 50 mg/kg, about 50 to about 80 mg/kg, about 80 to about 150 mg/kg, about 250 to about 350 mg/kg, about 350 to about 550 mg/kg, about 450 to about 550 mg/kg, about 550 to about 700 mg/kg, or about 700 to about 100 mg/kg.

15. The method of claim 13 , wherein the total dose per day is 10 mg/kg, 30 mg/kg, 100 mg/kg, 150 mg/kg, 250 mg/kg, or 300 mg/kg.

16. A method of suppressing a viral infection, comprising administering to a subject in need thereof a therapeutically effective amount of a compound having the following structure:

or a pharmaceutically acceptable salt or hydrate thereof; wherein the virus is a member of a virus family selected from the group consisting of orthomyxoviridae, paramyxoviridae, arenaviridae, bunyaviridae, flaviviridae, filoviridae, togaviridae, picornaviridae, poxviridae, adenoviridae, and coronaviridae virus families.

17. The method of claim 16 , wherein said subject is a mammal.

18. The method of claim 16 , wherein the subject is a human.

19. The method of claim 16 , wherein the virus is selected from the group consisting of adenovirus, rhinovirus, polio, measles, Ebola, Coxsackie, small pox, yellow fever, Dengue fever, influenza A, influenza B, lassa, lymphocytic choriomeningitis, junin, machupo, guanarito, hantavirus, Rift Valley Fever, La Crosse, California encephalitis, Crimean-Congo, Marburg, Japanese Encephalitis, Kyasanur Forest, Eastern equine encephalitis, Western equine encephalitis, severe acute respiratory syndrome (SARS), parainfluenza, Tacaribe, vaccinia, and pichinde viruses.

20. The method of claim 16 , wherein the virus is selected from the group consisting of Ebola, yellow fever, Marburg, influenza A and influenza B viruses.

21. The method of claim 16 , wherein the virus is Ebola virus.

22. The method of claim 21 , wherein said subject is a human.

23. The method of claim 16 , further comprising co-administering to the subject an effective amount of an anti-viral agent.

24. The method of claim 23 , wherein the anti-viral agent is a neuraminidase inhibitor.

25. The method of claim 23 , wherein the anti-viral agent is selected from the group consisting of laninamivir, oseltamivir, zanamivir, and peramivir.

26. The method of claim 23 , wherein the anti-viral agent is peramivir.

27. The method of claim 16 , wherein the compound is administered intravenously, intraperitoneally, intramuscularly, or orally.

28. The method of claim 16 , wherein the therapeutically effective amount is delivered in a single dose per day or more than one dose per day.

29. The method of claim 28 , wherein the total dose per day is about 5 to about 50 mg/kg, about 50 to about 80 mg/kg, about 80 to about 150 mg/kg, about 250 to about 350 mg/kg, about 350 to about 550 mg/kg, about 450 to about 550 mg/kg, about 550 to about 700 mg/kg, or about 700 to about 100 mg/kg.

30. The method of claim 28 , wherein the total dose per day is 10 mg/kg, 30 mg/kg, 100 mg/kg, 150 mg/kg, 250 mg/kg, or 300 mg/kg.

Assignees

• Biocryst Pharm Inc

Inventors

• Bantia Shanta
• Kotian Pravin L
• Babu Yarlagadda S

Classifications

• A61P31/14

  for RNA viruses · CPC title

• C07H7/06

  Heterocyclic radicals · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K31/351

  not condensed with another ring · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title