Channel modulators

Patent metadata

Field	Value
Publication number	US-11401516-B2
Application number	US-201916673729-A
Country	US
Kind code	B2
Filing date	Nov 4, 2019
Priority date	Aug 22, 2014
Publication date	Aug 2, 2022
Grant date	Aug 2, 2022

Abstract

The inventions relate to compositions and articles of manufacture comprising connexin modulators, pannexin modulators, gap junction modulators, hemichannel modulators, and pannexin channel modulators and their use, alone or in combination, in treating ocular and other disorders.

First claim

We claim:

1. A method for inhibiting inflammasome activity in a subject, comprising administering to said subject a connexin 43 hemichannel modulator according to Formula I or Formula II in an amount effective to modulate inflammasome activity.

2. The method according to claim 1 , wherein the modulator is a compound according to Formula I.

3. The method according to claim 1 , wherein the modulator is a compound according to Formula II.

4. The method according to claim 2 , wherein the modulator is tonabersat.

5. A method according to claim 1 , wherein said inflammasome is the NLRP3 inflammasome.

6. A method according to claim 1 , wherein said inhibition of inflammasome activity comprises inhibition of inflammasome activation .

7. The method according to claim 1 , wherein said inhibition of inflammasome activity comprises inhibition of activation of an inflammatory cascade by an inflammasome.

8. The method according to claim 6 , wherein the inflammasome is the NLRP3 inflammasome.

9. The method according to claim 7 , wherein the inflammasome is the NLRP3 inflammasome.

10. The method according to claim 1 , wherein the subject has lung inflammation, an inflammatory cardiac insult, acute respiratory distress syndrome, acute lung injury, pericardial effusion, pericarditis, or systemic inflammatory response syndrome.

11. The method according to claim 10 , wherein the subject is human, the connexin 43 hemichannel modulator is tonabersat or a prodrug of tonabersat, and the connexin 43 hemichannel modulator is administered during or before lung inflammation.

12. A method according to any of claim 1 , 2 , 4 - 9 , 10 or 11 , wherein said connexin 43 hemichannel modulator is administered by oral, systemic, intranasal, parenteral, transdermal or ocular administration, or by implantation or infusion.

13. The method according to any of claim 1 , 2 , 4 - 9 , 10 or 11 , wherein the compound according to Formula I is tonabersat.

14. The method according to any of claim 1 - 9 , 10 or 11 , wherein the subject is human.

15. The method according to claim 10 , wherein the prodrug of tonabersat is a compound according to Formula II.

16. The method according to any of claim 1 , 2 , 4 - 9 , 10 or 11 , wherein the subject is human, the compound according to Formula I is tonabersat, and the tonabersat is administered orally.

17. A method for inhibiting inflammasome activity in a human subject, comprising administering a tonabersat compound to said human subject in an amount effective to modulate inflammasome activity.

18. A method according to claim 16 , wherein NLRP3 inflammasome activity is inhibited.

19. A method according to claim 17 , wherein the inhibition of NLRP3 inflammasome activity comprises inhibition of NLRP3 inflammasome activation.

20. The method according to claim 17 , wherein the inhibition of NLRP3 inflammasome activity comprises inhibition of the activation of an inflammatory cascade by the NLRP3 inflammasome.

21. A method according to any of claim 17 - 19 or 20 , wherein tonabersat compound is tonabersat.

22. A method according to any of claim 17 - 19 or 20 , wherein tonabersat compound is a tonabersat prodrug.

23. A method according to claim 21 , wherein the tonabersat prodrug is a compound according to Formula II.

24. A method according to claim 21 , wherein the tonabersat is administered orally.

25. A method according to claim 21 , wherein the tonabersat is administered by systemic, intranasal, parenteral, transdermal or ocular administration, or by implantation or infusion.

Assignees

• Auckland Uniservices Ltd
• Ocunexus Therapeutics Inc

Inventors

• Green Colin Richard
• Kim Yeri
• Phillips Anthony
• Duft Bradford James

Classifications

• A61K38/08 Primary

  Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K31/575

  substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K31/195

  having an amino group · CPC title

• A61K31/498

  Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine · CPC title