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EP-4735462-A1 - COMPOUNDS AND USES THEREFOR

EP4735462A1EP 4735462 A1EP4735462 A1EP 4735462A1EP-4735462-A1

Abstract

Disclosed are glycanic compounds and their use for treating or inhibiting the development of a viral infection in a subject, especially a coronavirus infection, such as a SARS-CoV-2 infection, or for treating conditions associated with viral infections, such as an acute inflammatory condition, cytokine release syndrome (CRS) or a cytokine storm, severe acute respiratory syndrome (SARS) or acute respiratory distress syndrome (ARDS).

Inventors

  • PAYNE, Alan David
  • COOMBE, DEIRDRE ROMA
  • MOHAMED, Shifaza

Assignees

  • GLYCOSYNNOVATIONS PTY LTD

Dates

Publication Date
20260506
Application Date
20240701

Claims (20)

  1. THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS: 1. A compound of Formula I, II or III: wherein: L 1 , L 3 , L 4 , L 6 , L 7 , L 8 , L 9 , L 10 , L 11 , L 12 , L 13 , L 15 , L 16 , L 17 , L 18 and L 19 are independently selected from optionally substituted C1-C5 alkylene, optionally substituted C2-C5 alkenylene and optionally substituted C2-C5 alkynylene; L 2 , L 5 and L 14 are independently selected from optionally substituted C2-C8 alkylene, optionally substituted C2-C8 alkenylene and optionally substituted C2-C8 alkynylene; X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 and X 11 are independently selected from CH and N; and R 1 is selected from optionally substituted C2-C12 alkyl, optionally substituted C2-C12 alkenyl and optionally substituted C2-C12 alkynyl.
  2. 2. The compound according to claim 1, wherein X 1 -X 11 are CH.
  3. 3. The compound according to claim 1 or claim 2, wherein L 1 , L 3 , L 4 , L 6 , L 7 , L 8 , L 9 , L 10 , L 11 , L 12 , L 13 , L 15 , L 16 , L 17 , L 18 and L 19 are optionally substituted C1-C3 alkylene.
  4. 4. The compound according to claim 3, wherein L 1 , L 3 , L 4 , L 6 , L 7 , L 8 , L 9 , L 10 , L 11 , L 12 , L 13 , L 15 , L 16 , L 17 , L 18 and L 19 are methylene.
  5. 5. The compound according to any one of claims 1-4, wherein L 2 is optionally substituted C2-C5 alkylene.
  6. 6. The compound according to claim 5, wherein L 2 is propylene.
  7. 7. The compound according to any one of claims 1-6, wherein L 5 is optionally substituted C3-C6 alkylene.
  8. 8. The compound according to claim 7, wherein L 5 is butylene.
  9. 9. The compound according to any one of claims 1-8, wherein L 14 is optionally substituted C2-C4 alkylene.
  10. 10. The compound according to claim 9, wherein L 14 is ethylene.
  11. 11. The compound according to any one of claims 1-10, wherein R 1 is optionally substituted C6-C10 alkyl.
  12. 12. The compound according to claim 11, wherein R 1 is octyl.
  13. 13. The compound according to any one of claims 1-12, wherein the compound is a compound of Formula IV, V or VI or a pharmaceutically acceptable salt, solvate or prodrug thereof:
  14. 14. The compound according to any one of claims 1-13, wherein the compound is in the form of a salt and the salt is the sodium salt.
  15. 15. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 and a pharmaceutically acceptable carrier or diluent.
  16. 16. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 for use in therapy.
  17. 17. A method of treating or inhibiting the development of a viral infection in a subject comprising, consisting or consisting essentially of administering a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-14 or a compound of Formula VII or a pharmaceutically acceptable salt, solvate or prodrug thereof to the subject:
  18. 18. The method according to claim 17, wherein the infection is caused by a virus expressing a viral fusion protein.
  19. 19. The method according to claim 17 or claim 18, wherein the infection is caused by an enveloped virus.
  20. 20. The method according to any one of claims 17-19, wherein the infection is caused by a virus that interacts with an ACE2 polypeptide-expressing cell.

Description

TITLE OF THE INVENTION “COMPOUNDS AND USES THEREFOR” [0001] This application claims priority to Australian Provisional Patent Application No. 2023902113 entitled "Compounds and uses therefor" filed 30 June 2023, the contents of which are incorporated herein by reference in their entirety. FIELD OF THE INVENTION [0002] This invention relates generally to glycanic compounds and their use for treating or inhibiting the development of a viral infection in a subject, especially a coronavirus infection, such as a SARS-CoV-2 infection, or for treating conditions associated with viral infections, such as an acute inflammatory condition, cytokine release syndrome (CRS) or a cytokine storm, severe acute respiratory syndrome (SARS) or acute respiratory distress syndrome (ARDS). BACKGROUND OF THE INVENTION [0003] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavor to which this specification relates. [0004] Viral infections cause a significant economic and social burden to be placed on society, which has been particularly demonstrated by the recent pandemic caused by the coronavirus, SARS-CoV-2. SARS-CoV-2, is a recently emerged virus that causes an often-fatal respiratory disease, COVID-19. The current pandemic caused by SARS-CoV-2 is a health emergency that requires the development of new vaccines and therapeutics to prevent or treat infections caused by this virus. [0005] SARS-CoV-2 is closely related to severe acute respiratory syndrome coronavirus (SARS-CoV) (Lu et al., Lancet 2020, 395 (10224), 565-574) and recent studies have demonstrated that SARS-CoV-2 spike protein, like SARS-CoV, uses the angiotensin converting enzyme 2 (ACE2) as a cellular receptor to initiate membrane fusion and infection (Hoffmann et al., Cell 2020181(2): 271–280). SARS-CoV-2 engages the ACE2 receptor with higher affinity binding than SARS-CoV (Wrapp et al., Science 2020, 367 (6483), 1260-1263). A number of other viruses use glycoproteins on their surfaces as fusion proteins to interact with and gain entry into host cells to effect infection, including enveloped viruses such as influenza and human immunodeficiency virus (HIV). Accordingly, the interaction between the viral fusion protein and the host cell ligand is an attractive therapeutic target for a number of important viral infections. [0006] Glycosaminoglycans (GAGs) are linear polysaccharides of very diverse structures. They occur naturally as the glycan moiety of proteoglycans and play pivotal roles in many biological processes within the human body, including the binding and presentation of certain cytokines/growth factors to their cell surface receptors, thereby enhancing receptor signaling. Glycosaminoglycans within extracellular matrices also sequester certain cytokines, growth factors, chemokines and enzymes in specific locations within tissues. However, GAG interactions with particular cytokines, growth factors, chemokines and enzymes can contribute to physiologically adverse processes such as excessive inflammation, cancer growth and metastasis and various immunological reactions with counterproductive outcomes. Currently, some of the best known GAGs belong to the heparin/heparan sulfate family of sulfated polysaccharides. Heparin is best known for its anticoagulant activity, but more recent data indicates that heparin can also have anti-inflammatory activity. Mechanistically these activities are the result of some of the structures in heparin/heparan sulfates binding to three-dimensional motifs on proteins. Given their ability to bind to and modulate the activity of biological regulators, GAGs have been proposed as potential therapeutic agents. [0007] However, natural GAGs are not ideal therapeutic agents due to their extreme structural heterogeneity, particularly in their complex sulfation patterns, and the difficulties in isolating specific GAG structural entities. This means, generally the natural GAG structural motifs that best bind particular cytokines, growth factors, chemokines or enzymes are unknown. The synthesis of GAG structures is also extremely complex and the synthesis of even small GAG structures requires many synthetic steps. As the complex sulfation patterns of GAGs contributes to their protein binding characteristics, the multiple synthetic steps cannot be avoided when synthesizing GAGs for therapeutic purposes. Accordingly, GAGs or analogues or mimetics thereof which have more suitable therapeutic properties are desired. SUMMARY OF THE INVENTION [0008] WO 2018/068090 A1 discloses a number of compounds which have improved synthetic routes compared to GAGs and, therefore, more suitable therapeutic properties. The present invention is predicated i