Controlled-delivery cromakalim prodrugs

Patent metadata

Field	Value
Publication number	US-12454539-B2
Application number	US-202217836871-A
Country	US
Kind code	B2
Filing date	Jun 9, 2022
Priority date	Dec 12, 2019
Publication date	Oct 28, 2025
Grant date	Oct 28, 2025

Abstract

The present invention provides cromakalim phosphate prodrugs, compositions, and their use for the modulation of ATP-sensitive potassium (KATP) channels for therapeutic purposes.

First claim

We claim:

1. A compound of the formula:

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 of the formula

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 of the formula

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 of the formula

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 of the formula

or a pharmaceutically acceptable salt thereof.

6. A compound of Formula I:

wherein X + is a counterbalancing, pharmaceutically acceptable cation, which is selected from the group consisting of an alkali metal cation and an ammonium ion.

7. The compound of claim 6 wherein X + is Na + , K + , Li + or Cs + .

8. The compound of claim 6 wherein X + is selected from the group consisting of:

9. The compound of claim 6 of the structure:

10. The compound of claim 6 of the structure:

11. The compound of claim 6 of the structure:

12. The compound of claim 6 of the structure:

13. A compound of Formula II:

wherein M 2+ is a divalent pharmaceutically acceptable cation selected from the group consisting of an alkaline earth metal cation, a metal cation with an oxidation state of +2, and an ammonium ion with a net positive charge of two.

14. The compound of claim 13 wherein M 2+ is Mg 2+ , Ca 2+ , Sr 2+ , Zn 2+ , or Fe 2+ .

15. The compound of claim 13 wherein M 2+ is selected from the group consisting of

16. The compound of claim 13 of the structure:

17. The compound of claim 13 of the structure:

18. The compound of claim 13 of the structure:

19. The compound of claim 13 of the structure:

Assignees

• Qlaris Bio Inc
• Mayo Found Medical Education & Res

Inventors

• Htoo Thurein M
• Wirostko Barbara M
• Fautsch Michael P
• Garnett Ian
• Massarenti Chiara

Classifications

• C07F9/65586 Primary

  at least one of the hetero rings does not contain nitrogen as ring hetero atom · CPC title

• C07C211/26

  of an unsaturated carbon skeleton containing at least one six-membered aromatic ring · CPC title

• C07C211/10

  Diaminoethanes · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title