Methods of treating severe acute respiratory syndrome

Patent metadata

Field	Value
Publication number	US-12582633-B2
Application number	US-202117995604-A
Country	US
Kind code	B2
Filing date	Apr 8, 2021
Priority date	Apr 10, 2020
Publication date	Mar 24, 2026
Grant date	Mar 24, 2026

Abstract

The disclosure is directed to methods of using dantrolene or a dantrolene prodrug, or a pharmaceutically acceptable salt thereof, to treat Severe Acute Respiratory Syndrome.

First claim

What is claimed:

1 . A method of treating Severe Acute Respiratory Syndrome in a subject comprising administering to the subject dantrolene or a pharmaceutically acceptable salt thereof or by administering a dantrolene prodrug or a pharmaceutically acceptable salt thereof, wherein the dantrolene prodrug is a compound of Formula I:

wherein R is —P(O)(OH) 2 or —P(O)(OR 1 )(OR 2 ); R 1 is H, —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; and R 2 is —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl.

2 . The method of claim 1 , comprising administering dantrolene to the subject.

3 . The method of claim 1 , comprising administering a pharmaceutically acceptable salt of dantrolene to the subject.

4 . The method of claim 1 , comprising administering dantrolene sodium to the subject.

5 . The method of claim 1 , wherein the administration results in at least a 1-point decrease in the subject's WHO Ordinal Scale score, as compared to baseline.

6 . The method of claim 1 , wherein the administration results in an improvement in the subject's Sequential Organ Failure Assessment daily score, as compared to baseline.

7 . The method of claim 1 , wherein the administration results in a reduction of time to normalization of fever in the subject, as compared to the amount of time to normalization of fever in a control subject.

8 . The method of claim 1 , wherein the administration results in a reduction of time to normalization of oxygen saturation in the subject, as compared to the amount of time to normalization of oxygen saturation in a control subject.

9 . A method for inhibiting replication of SARS-COV in a subject comprising administering to the subject dantrolene, or a pharmaceutically acceptable salt thereof or by administering a dantrolene prodrug or a pharmaceutically acceptable salt thereof, wherein the dantrolene prodrug is a compound of Formula I:

wherein R is —P(O)(OH) 2 or —P(O)(OR 1 )(OR 2 ); R 1 is H, —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; and R 2 is —C 1-26 alkyl, aryl C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl.

10 . The method of claim 9 , comprising administering dantrolene to the subject.

11 . The method of claim 9 , comprising administering a pharmaceutically acceptable salt of dantrolene to the subject.

12 . The method of claim 9 , comprising administering dantrolene sodium to the subject.

13 . A method for inhibiting replication of SARS-COV in a host cell, for inhibiting entry of SARS-COV into a host cell, for inhibiting SARS-COV virion maturation in a host cell, or for inhibiting release of SARS-COV from a host cell comprising administering to the host cell dantrolene, or a pharmaceutically acceptable salt thereof or by administering a dantrolene prodrug or a pharmaceutically acceptable salt thereof, wherein the dantrolene prodrug is a compound of Formula I:

wherein R is —P(O)(OH) 2 or —P(O)(OR 1 )(OR 2 ); R 1 is H, —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; and R 2 is —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl.

14 . The method of claim 13 , comprising administering dantrolene to the host cell.

15 . The method of claim 13 , comprising administering a pharmaceutically acceptable salt of dantrolene to the host cell.

16 . The method of claim 13 , comprising administering dantrolene sodium to the host cell.

17 . A method for reducing the infectivity of SARS-COV by administering to a host cell dantrolene, or a pharmaceutically acceptable salt thereof or by administering a dantrolene prodrug or a pharmaceutically acceptable salt thereof, wherein the dantrolene prodrug is a compound of Formula I:

wherein R is —P(O)(OH) 2 or —P(O)(OR 1 )(OR 2 ); R 1 is H, —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl; and R 2 is —C 1-26 alkyl, aryl, C 1-6 alkC(O)O—C 1-26 alkyl, —C 1 alkOC(O)C 1-26 alkyl, or C 1 alkOC(O)OC 1-26 alkyl.

18 . The method of claim 17 , comprising administering dantrolene to the host cell.

19 . The method of claim 17 , comprising administering a pharmaceutically acceptable salt of dantrolene to the host cell.

20 . The method of claim 17 , comprising administering dantrolene sodium to the host cell.

21 . The method of claim 1 , wherein the dantrolene prodrug is:

wherein R is —P(O)(OH) 2 .

22 . The method of claim 9 , wherein the dantrolene prodrug is:

wherein R is —P(O)(OH) 2 .

23 . The method of claim 13 , wherein the dantrolene prodrug is:

wherein R is —P(O)(OH) 2 .

24 . The method of claim 17 , wherein the dantrolene prodrug is:

wherein R is —P(O)(OH) 2 .

Assignees

• Eagle Pharmaceuticals Inc

Inventors

• Hepner Adrian

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61K31/4178 Primary

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title