Antiviral agents and nucleoside analogs for treatment of Zika virus

Patent metadata

Field	Value
Publication number	US-11963972-B2
Application number	US-201716088017-A
Country	US
Kind code	B2
Filing date	Mar 22, 2017
Priority date	Mar 23, 2016
Publication date	Apr 23, 2024
Grant date	Apr 23, 2024

Abstract

The present invention is directed to compounds, compositions and methods for treating or preventing Zika virus. The compounds include pyrimidine and purine nucleosides and prodrugs thereof, including certain N4-hydroxycytidine nucleoside derivatives, sulfasalazine, and various entry inhibitors.

First claim

The invention claimed is:

1. A method for treating a host infected with Zika, preventing an Zika infection, or reducing the biological activity of an Zika infection in a host, comprising administering an effective treatment or preventative amount of a compound or salt thereof to a patient in need of treatment or prevention thereof wherein the compound has one of the following formulas:

2. A method for treating a host infected with Zika, preventing an Zika infection, or reducing the biological activity of an Zika infection in a host, comprising administering an effective treatment or preventative amount of a compound or salt thereof to a patient in need of treatment or prevention thereof wherein the compound has the formula:

or analogs thereof where, at the 2′-position, the methyl group is replaced with Cl, Br, or F.

3. A method for treating a host infected with Zika, preventing an Zika infection, or reducing the biological activity of an Zika infection in a host, comprising administering an effective treatment or preventative amount of a compound or salt thereof to a patient in need of treatment or prevention thereof wherein the compound is sulfasalazine, ipsalazide, balsalazide, or a sulfasalazine analog of the formula:

wherein
X is pyridyl, phenyl, phenyl-substituted by lower alkyl, lower alkoxy, halogen, hydroxy, or nitro, furyl, pyrrolyl, quinolyl, pyrimidyl, thienyl or imidazolyl;
R, R 1 and R 2 are independently H, C 1-6 alkyl, C 1-6 aminoalkyl or

A is H, C 1-6 alkyl, C 1-6 aminoalkyl, amino, alkoxy, halo or CF 3 ; and
n is 0 to 4, wherein
the term pyridyl means 2-pyridyl, 3-pyridyl and 4-pyridyl;
halo is chloro, bromo, iodo, or fluoro; and amino is —NH 2 , —NH—C(NH 2 )—NH or

4. The method of claim 3 , wherein the compound is sulfasalazine.

5. A method for treating a host infected with Zika, preventing an Zika infection, or reducing the biological activity of an Zika infection in a host, comprising administering an effective treatment or preventative amount of a compound or salt thereof to a patient in need of treatment or prevention thereof, wherein the compound is

6. The method of claim 5 , wherein the compound or salt thereof is administered in combination with a second anti-Zika agent.

7. The method of claim 6 , wherein the second anti-Zika agent is galidesivir (BCX4430), an entry inhibitor, a reverse transcriptase inhibitor, a protease inhibitor, or an immune-based therapeutic agent.

8. The method of claim 1 , wherein the compound or salt thereof is administered in combination with a second anti-Zika agent.

9. The method of claim 8 , wherein the second anti-Zika agent is galidesivir (BCX4430), an entry inhibitor, a reverse transcriptase inhibitor, a protease inhibitor, or an immune-based therapeutic agent.

10. The method of claim 2 , wherein the compound or salt thereof is administered in combination with a second anti-Zika agent.

11. The method of claim 10 , wherein the second anti-Zika agent is galidesivir (BCX4430), an entry inhibitor, a reverse transcriptase inhibitor, a protease inhibitor, or an immune-based therapeutic agent.

12. The method of claim 3 , wherein the compound or salt thereof is administered in combination with a second anti-Zika agent.

13. The method of claim 12 , wherein the second anti-Zika agent is galidesivir (BCX4430), an entry inhibitor, a reverse transcriptase inhibitor, a protease inhibitor, or an immune-based therapeutic agent.

Assignees

• Univ Emory

Inventors

• Schinazi Raymond F
• Amblard Franck
• Cox Bryan D
• Bassit Leda
• Zhou Longhu
• Gavegnano Christina

Classifications

• A61K31/7068 Primary

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• A61K31/4706 Primary

  4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine · CPC title

• A61K31/53

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · CPC title

• A61K31/655

  Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds · CPC title

• A61K31/7064

  containing condensed or non-condensed pyrimidines · CPC title