Polyamine transport inhibitors as antivirals

Patent metadata

Field	Value
Publication number	US-11752113-B2
Application number	US-202117469827-A
Country	US
Kind code	B2
Filing date	Sep 8, 2021
Priority date	Sep 9, 2020
Publication date	Sep 12, 2023
Grant date	Sep 12, 2023

Abstract

Disclosed herein are polyamine transport inhibitors (PTI) and methods of use as antivirals. Disclosed PTI compounds are useful as treatments for viral infections or can be used as prophylactic agents that protect high risk individuals from becoming infected by the virus. The disclosed PTI compounds can be used alone or in combination with other agents (or other antivirals) to improve patient outcomes such as DFMO (or Remdesivir).

First claim

What is claimed is:

1. A method of treating an infection by a Ebola virus, SARS-CoV1 or Sars-CoV-2 virus in a subject in need comprising administering a composition comprising at least at least one of compounds (i)-(xix):

wherein R1 is Me or H;

wherein R is H and x and y are both 4, or R is (CH 2 ) 4 NH 2 and x and y are both 4, or R is (CH 2 ) 3 NH 2 , x is 3, and y is 4;

wherein x is 1 or 2;

wherein x is 1 or 2;

wherein x is 2;

wherein X is CH or N;

wherein X is OH or H;

wherein R in compounds iii-xix is NH(CH 2 ) 4 NH(CH 2 ) 4 NHMe; or a pharmaceutically acceptable salt of any of compounds i-xix, and, optionally

or a pharmaceutically acceptable salt thereof, and optionally a pharmaceutically acceptable carrier.

2. The method of claim 1 , further comprising co-administering at least one other active agent, wherein the at least one other active agent is AMXT1501, GW5074, DFMO, methylcyclohexylamine and N 1 Cyclohexyl-1,3-diaminopropane or CGP-48664 or a combination thereof.

3. The method of claim 1 , further comprising co-administering at least one agent comprising remdesivir, chloroquine, hydroxychloroquine, entecavir, cabotegravir, rilpivirine, stavudine, valganciclovir, or cidofovir.

4. The method of claim 1 , wherein the composition is formulated for oral administration.

5. The method of claim 4 , wherein the composition is in the form of a dispersible tablet, orally disintegrating tablet, effervescent tablet, chewable tablet, sprinkle granules, dry suspension or dry syrup for reconstitution, quick melt wafers, lozenge, or chewing gum.

6. The method of claim 1 , wherein the composition is formulated for parenteral administration.

7. The method of claim 6 , wherein the composition is in the form of a liquid suspension or solution.

8. A composition comprising at least one of compounds (i)-(xix):

wherein R1 is Me or H;

wherein R is H and x and y are both 4, or R is (CH 2 ) 4 NH 2 and x and y are both 4, or R is (CH 2 ) 3 NH 2 , x is 3, and y is 4;

wherein x is 1 or 2;

wherein x is 1 or 2;

wherein x is 2;

wherein X is CH or N;

wherein X is OH or H;

wherein R in compounds iii-xix is NH(CH 2 ) 4 NH(CH 2 ) 4 NHMe; or a pharmaceutically acceptable salt of any of compounds i-xix, and further comprising

or a pharmaceutically acceptable salt thereof.

9. The composition of claim 8 further comprising at least one of remdesivir, chloroquine, hydroxychloroquine, entecavir, cabotegravir, rilpivirine, stavudine, valganciclovir, or cidofovir.

10. The composition of claim 8 , formulated for oral administration.

11. The composition of claim 10 , wherein the composition is in the form of a dispersible tablet, orally disintegrating tablet, effervescent tablet, chewable tablet, sprinkle granules, dry suspension or dry syrup for reconstitution, quick melt wafers, lozenge, or chewing gum.

12. The composition of claim 8 , formulated for parenteral administration.

Assignees

• Univ Central Florida Res Found Inc
• Univ Boston
• Univ Boston

Inventors

• Phanstiel Iv Otto
• Connor John

Classifications

• A61K31/4706 Primary

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

• A61K31/132 Primary

  having two or more amino groups, e.g. spermidine, putrescine · CPC title

• A61K31/13

  Amines {(A61K31/04 takes precedence)} · CPC title

• A61K31/513

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title

• A61K31/198

  Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00) · CPC title