Remdesivir and remdesivir analogs, solutions, and nanoparticle, liposomal, and microparticle compositions for treating viral infections

Patent metadata

Field	Value
Publication number	US-12516080-B2
Application number	US-202117995254-A
Country	US
Kind code	B2
Filing date	Apr 1, 2021
Priority date	Apr 2, 2020
Publication date	Jan 6, 2026
Grant date	Jan 6, 2026

Abstract

The present invention relates to methods, compounds, and compositions for treating viral infections, including COVID-19 viral infections. In certain embodiments, the compositions comprise: i) a remdesivir analog, ii) remdesivir or a remdesivir analog, and a surfactant, a cyclodextrin, or a combination thereof, iii) nanoparticles comprising albumin and remdesivir or remdesivir analog, iv) liposomes comprising lipids and remdesivir or remdesivir analog; and/or v) microparticles comprising PLA and/or PLGA, and remdesivir or remdesivir analog. In certain embodiments, the compositions are aqueous (e.g., for intravenous administration). In other embodiments, the compositions are nebulized or in the form of a dry powder (e.g., for inhalation by an infected subject).

First claim

We claim:

1 . A compound of Formula I,

wherein:
X is or comprises proteinogenic amino acid side chain;
R is a lipid chain comprising 10 to 40 carbons; and
Ar is an unsubstituted aryl or heteroaryl.

2 . The compound of claim 1 , wherein X is an alanine side chain.

3 . The compound of claim 1 , wherein X is a tryptophan side chain or a phenylalanine side chain.

4 . The compound of claim 1 , wherein X is an amino acid side chain selected from the group consisting of: alanine, phenylalanine, valine, leucine, isoleucine, methionine, tryptophan, proline, glycine, cysteine, glutamine, asparagine, serine, tyrosine, and threonine.

5 . The compound of claim 1 , wherein R is a lipid chain comprising 10 to 20 carbons.

6 . The compound of claim 1 , wherein Ar is an unsubstituted phenyl or naphthyl.

7 . The compound of claim 1 , wherein Ar is selected from

8 . The compound of claim 1 , wherein the compound is a compound of Formula Ia:

wherein:
X is or comprises proteinogenic amino acid side chain; and
R is a lipid chain comprising 10 to 40 carbons.

9 . The compound of claim 8 , wherein X is an amino acid side chain selected from the group consisting of: alanine, phenylalanine, valine, leucine, isoleucine, methionine, tryptophan, proline, glycine, cysteine, glutamine, asparagine, serine, tyrosine, and threonine.

10 . The compound of claim 8 , wherein X is an alanine side chain.

11 . The compound of claim 8 , wherein R is a lipid chain comprising 10 to 20 carbons.

12 . A compound of Formula II:

wherein:
X is or comprises proteinogenic amino acid side chain;
Y is C 2 -C 20 alkylene or C 2 -C 20 alkenylene; and
Z is C 4 -C 40 alkyl, C 4 -C 40 alkenyl, or C 2 -C 20 alkynyl.

13 . The compound of claim 12 , wherein X is an amino acid side chain selected from the group consisting of: alanine, phenylalanine, valine, leucine, isoleucine, methionine, tryptophan, proline, glycine, cysteine, glutamine, asparagine, serine, tyrosine, and threonine.

14 . The compound of claim 12 , wherein Y is C 4 -C 20 alkylene.

15 . The compound of claim 12 , wherein Z is C 4 -C 20 alkyl or C 4 -C 20 alkenyl.

16 . A compound of claim 1 selected from the group consisting of:

17 . A composition comprising an effective amount of a compound of claim 1 , and a pharmaceutically acceptable carrier.

18 . A method of treating a subject comprising:
administering or providing a composition to a subject infected with a virus, wherein the composition comprises: a) a remdesivir analog, b) a remdesivir analog, and a surfactant, a cyclodextrin, or a combination thereof, c) a plurality of nanoparticles each comprising albumin and a remdesivir analog, and/or d) a plurality of liposomes each comprising lipids forming a bilayer and a remdesivir analog, and/or e) a plurality of microparticles each comprising: i) poly(lactic acid) (PLA) and/or poly(lactic-co-glycolic acid) (PLGA), and ii) a remdesivir analog, wherein each remdesivir analog is independently a compound of claim 1 .

Assignees

• Univ Michigan Regents

Inventors

• Sun Duxin
• Gao Wei
• Hu Hongxiang
• Traore Mohamed Dit Mady
• Song Yudong
• Wen Bo
• He Miao
• Yuan Hebao
• Li Ruiting

Classifications

• A61K9/5169

  Proteins, e.g. albumin, gelatin · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61P31/12

  Antivirals · CPC title

• A61K47/40

  Cyclodextrins; Derivatives thereof · CPC title

• A61K9/0078

  for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions · CPC title