Host targeted inhibitors of dengue virus and other viruses

• US 9,879,003 B2
• Filed: 03/15/2013
• Issued: 01/30/2018
• Est. Priority Date: 04/11/2012
• Status: Active Grant

• Current Assignee: Dana-Farber Cancer Institute, President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: Dana-Farber Cancer Institute, President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Gray, Nathanael, Yang, Priscilla, Liu, Qingsong, de Wispelaere, Mlissanne
• Primary Examiner(s): DESAI, RITA J
• Application Number:
  US14/391,638
• Publication Number:
  US 20150166532A1
• Time in Patent Office: 1,782 Days
• Field of Search: 546 80, 514290
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Abstract

Novel antiviral compounds of Formulae (I)-(III) are provided: (I) (II) (III) The inventive compounds, pharmaceutical compositions thereof, and kits including the inventive compounds are useful for the prevention and treatment of infectious diseases caused by viruses, for example, by Flaviviridae virus (e.g., Dengue virus (DENY)), Kunjin virus, Japanese encephalitis virus, vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), human cytomegalovirus (HCMV), poliovirus, Junin virus, Ebola virus, Marburg virus (MARV), Lassa fever virus (LASV), Venezuelan equine encephalitis virus (VEEV), or Rift Valley Fever virus (RVFV).

Claims

1. A compound of the formula:

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is a 5-membered or 6-membered, monocyclic heteroaryl ring comprising 1 to 4 ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted with k instances of R^A.

3. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein

4. The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein

5. The compound of claim 1, wherein the compound is of formula:

6. The compound of claim 1, wherein the compound is of formula:

7. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable excipient.

8. The compound of claim 1, wherein the compound is of the formula:

9. The compound of claim 1, wherein the compound is of the formula:

10. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is 5,6- or 6,6-membered bicyclic heteroaryl comprising 1 to 4 ring heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur, and is optionally substituted with k instances of R^A.

11. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein Ring A is quinolinyl or isoquinolinyl and is optionally substituted with k instances of R^A.

12. The compound of claim 1, wherein the compound is of the formula:

13. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein

14. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein

15. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein

16. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein at least one instance of R^A is optionally substituted C_1-6 alkyl or halogen.

17. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein at least one instance of R^A is —

N(R^A1)₂, —

NR^A1C(═

O)N(R^A1)₂, —

NR^A1S(═

O)₂R^A1, or —

S(═

O)₂N(R^A1)₂.

18. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein at least one instance of R^A is optionally substituted heterocyclyl.

19. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein k is 0.

20. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein k is 1 or 2.

21. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^C is optionally substituted C_1-6 alkyl.

22. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^C is —

CH₃.

23. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R^C is hydrogen, halogen, or —

OR^C1.

24. The compound of claim 1, wherein the compound is of the formula:

25. The compound of claim 1, wherein the compound is of formula: