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EP-4735463-A1 - COMPOUNDS AND USES THEREFOR

EP4735463A1EP 4735463 A1EP4735463 A1EP 4735463A1EP-4735463-A1

Abstract

Disclosed are glycanic compounds and their use for treating or inhibiting the development of an inflammatory condition or a condition associated with an activity of a cytokine, such as asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and dermatitis.

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: ( ) (VI) or a pharmaceutically acceptable salt, solvate or prodrug thereof, 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 L 19 L 20 L 21 L 22 L 23 L 24 L 25 , L 26 , L 28 , L 29 , L 30 , L 31 and L 32 are independently selected from optionally substituted C 1 -C 5 alkylene, optionally substituted C 2 -C 5 alkenylene and optionally substituted C 2 -C 5 alkynylene; L 2 , L 5 , L 14 and L 27 are independently selected from optionally substituted C 2 -C 8 alkylene, optionally substituted C 2 -C 8 alkenylene and optionally substituted C 2 -C 8 alkynylene; X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , X 9 , X 10 , X 11 , X 12 , X 13 , X 14 , X 15 , X 16 , X 17 and X 18 are independently selected from CH and N; and R 1 is selected from optionally substituted C1-C12 alkyl, optionally substituted C 2 -C 12 alkenyl and optionally substituted C 2 -C 12 alkynyl.
  2. 2. The compound according to claim 1, wherein X 1 -X 18 are CH.
  3. 3. The compound according to claim 1 or claim 2, wherein L 1 , L 3 , L 4 , L 6 , L 7 , |_8 |_9 |_10 |_U |_12 |_13 |_15 |_16 |_17 |_18 |_19 L20 |_21 L22 L23 |_24 |_25 L26 L28 L29 L30 and L 32 are optionally substituted C 1 -C 3 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 , L 19 , L 20 , L 21 , L 22 , L 23 , L 24 , L 25 , L 26 , L 28 , L 29 , L 30 and L 32 are methylene.
  5. 5. The compound according to any one of claims 1-4, wherein L 2 and L 31 are each independently optionally substituted C 2 -C 5 alkylene.
  6. 6. The compound according to claim 5, wherein L 2 and L 31 are propylene.
  7. 7. The compound according to any one of claims 1-6, wherein L 5 is optionally substituted C 3 -C 6 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 C 2 -C 4 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 L 27 is optionally substituted C 2 -C 4 alkylene.
  12. 12. The compound according to claim 11, wherein L 27 is ethylene.
  13. 13. The compound according to any one of claims 1-12, wherein R 1 is optionally substituted C 6 -C 10 alkyl.
  14. 14. The compound according to claim 13, wherein R 1 is octyl.
  15. 15. The compound according to any one of claims 1-12, wherein R 1 is methyl.
  16. 16. The compound according to any one of claims 1-15, wherein the compound is a compound of Formula VII, VIII, IX, X, XI, XII or XIII, or a pharmaceutically acceptable salt, solvate or prodrug thereof: (VII), (XIII).
  17. 17. The compound according to any one of claims 1-16, wherein the compound is in the form of a salt and the salt is the sodium salt.
  18. 18. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-17 and a pharmaceutically acceptable carrier or diluent.
  19. 19. A compound or a pharmaceutically acceptable salt, solvate or prodrug thereof according to any one of claims 1-17 for use in therapy.
  20. 20. A method of treating or inhibiting the development of an inflammatory condition iinn 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 1-17 to the subject.

Description

TITLE OF THE INVENTION "COMPOUNDS AND USES THEREFOR" RELATED APPLICATIONS [0001] This application claims priority to Australian Provisional Patent Application No. 2023902115 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 an inflammatory condition or a condition associated with an activity of a cytokine, such as asthma, chronic obstructive pulmonary disease (CORD), acute respiratory distress syndrome (ARDS) and dermatitis. 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] Asthma is a chronic lung disease with increasing incidence worldwide. The World Health Organization estimates that asthma affected about 262 million people worldwide in 2019 and caused about 455,000 deaths. Asthma is characterized by inflammation and muscle tightening around the airways, mucus hypersecretion and subepithelial fibrosis. Common symptoms include wheezing, coughing, shortness of breath and chest tightness. While asthma is unable to be cured, many asthma sufferers are able to manage their symptoms using the currently available therapies, including bronchodilators and steroids. However, some asthma sufferers, particularly moderate to severe asthmatic patients, have persistent disease despite the use of such therapies. [0005] Cytokines, including chemokines, interferons, interleukins, lymphokines and tumor necrosis factors, are important intracellular signaling molecules. While these molecules are essential for normal cellular processes including cellular growth and maturation and play an essential role in the immune response, they also play a role in the development and/or progression of a number of immune-mediated conditions or diseases and cancer cell proliferation. Cytokines are particularly known to be associated with inflammatory conditions, such as asthma. In this regard, antibodies targeting IL-5 and IL-13 have been shown to provide benefit for severe asthma patients. However, an effective non-corticosteroid therapy for general use is yet to be developed. It is evident that more effective therapies for asthma and other inflammatory conditions are required. [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] The present invention is predicated in part on the discovery of particular compounds that interact wit