Inhibitors of Bunyaviridae and uses thereof

Patent metadata

Field	Value
Publication number	US-12357589-B2
Application number	US-202418662947-A
Country	US
Kind code	B2
Filing date	May 13, 2024
Priority date	May 12, 2020
Publication date	Jul 15, 2025
Grant date	Jul 15, 2025

Abstract

The present disclosure provides inhibitors of bunyavirus of the formula:

wherein the variables are defined herein. These inhibitors may be used to treat an infection of Rift Valley phlebovirus, hantavirus, and La Crosse virus, or Crimean-Congo Hemorrhagic fever.

First claim

What is claimed:

1. A method of treating Rift Valley fever in a patient comprising administering to the patient a therapeutically effective amount of a compound according to the formula:

wherein:
represents a single or double bond;
R 7 and R 8 are each independently oxo or hydroxy;
R 9 and R 10 are each independently hydrogen, alkyl (C≤6) , or substituted alkyl (C≤6) ; and
R 11 is aryl (C≤12) , substituted aryl (C≤12) , or —X 4 —Y 4 ;
wherein:
X 4 is arenediyl (C≤12) or substituted arenediyl (C≤12) ; and
Y 4 is aryloxy (C≤12) or substituted aryloxy (C≤12) ;

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the compound is administered intravenously, intraarterially, orally, buccally, nasally, ocularly, rectally, vaginally, topically, intramuscularly, intradermally, cutaneously, or subcutaneously.

3. The method of claim 1 further comprising administering a second anti-viral therapy.

4. A method of inhibiting the replication of a bunyavirus comprising contacting the cell with an effective amount of a compound according to the formula:

wherein:
represents a single or double bond;
R 7 and R 8 are each independently oxo or hydroxy;
R 9 and R 10 are each independently hydrogen, alkyl (C≤6) , or substituted alkyl (C≤6) ; and
R 11 is aryl (C≤12) , substituted aryl (C≤12) , or —X 4 —Y 4 ;
wherein:
X 4 is arenediyl (C≤12) or substituted arenediyl (C≤12) ;
Y 4 is aryloxy (C≤12) or substituted aryloxy (C≤12) ;

or a pharmaceutically acceptable salt thereof.

5. The method of claim 4 , wherein the bunyavirus is Rift Valley phlebovirus.

6. The method of claim 4 , wherein the bunyavirus is orthohantavirus.

7. The method of claim 4 , wherein the bunyavirus is La Crosse arbovirus.

8. The method of claim 4 , wherein the bunyavirus is Crimean-Congo hemorrhagic fever orthoairovirus.

9. The method of claim 4 , wherein the method is sufficient to treat Rift Valley fever in a patient.

10. The method of claim 4 , wherein the method is sufficient to treat an infection of hantavirus in a patient.

11. The method of claim 4 , wherein the method is sufficient to treat La Crosse encephalitis in a patient.

12. The method of claim 4 , wherein the method is sufficient to treat Crimean-Congo Hemorrhagic fever in a patient.

13. The method of claim 1 , wherein R 7 is hydroxy.

14. The method of claim 1 , wherein R 8 is oxo.

15. The method of claim 1 , wherein R 9 is alkyl (C≤6) .

16. The method of claim 1 , wherein R 10 is alkyl (C≤6) .

17. The method of claim 1 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt thereof.

18. The method of claim 4 , wherein R 7 is hydroxy and R 8 is oxo.

19. The method of claim 4 , wherein R 9 is alkyl (C≤6) and R 10 is alkyl (C≤6) .

20. The method of claim 4 , wherein the compound is further defined as:

or a pharmaceutically acceptable salt thereof.

Assignees

• Univ Saint Louis
• National And Kapodistrian Univ Of Athens

Inventors

• Tavis John Edwin
• Zoidis Grigoris
• Pinto Amelia
• Brien James

Classifications

• A61K31/341 Primary

  not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine · CPC title

• A61K31/165

  having aromatic rings, e.g. colchicine, atenolol, progabide · CPC title

• A61K31/215

  of carboxylic acids · CPC title

• A61K31/381

  having five-membered rings · CPC title

• A61P31/14

  for RNA viruses · CPC title