NLRP3 inflammasome inhibitors

Patent metadata

Field	Value
Publication number	US-12378222-B2
Application number	US-202418917653-A
Country	US
Kind code	B2
Filing date	Oct 16, 2024
Priority date	Aug 3, 2022
Publication date	Aug 5, 2025
Grant date	Aug 5, 2025

Abstract

The present invention relates to novel pyridazin-3-yl phenol compounds of formula (I):

wherein R 1 , R 2 , R 3 , R 4 and R 5 are defined herein, which inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activity. The invention further relates to the processes for their preparation, pharmaceutical compositions and medicaments containing them, and their use in the treatment of diseases and disorders mediated by NLRP3.

First claim

What is claimed is:

1. A compound, or a pharmaceutically acceptable salt thereof, having the following structure:

2. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

3. The compound of claim 1 , wherein the compound is in a crystalline form.

4. The compound according to claim 3 , wherein the crystalline form is selected from a hydrate, form A, form B, a hippurate salt and a hydrochloride salt.

5. The compound according to claim 3 , wherein the crystalline form has an X-ray powder diffraction pattern as shown in any one of FIG. 1 , FIG. 4 , FIG. 7 , FIG. 10 , or FIG. 13 , or FIG. 13 , when measured using CuKα radiation.

6. The compound according to claim 3 , wherein the crystalline form is a hydrate.

7. The compound according to claim 6 , wherein the ratio of compound to water molecule is 1:1.

8. The compound according to claim 3 , wherein the compound is a hydrochloride salt.

9. The compound according to claim 3 , wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one peak having an angle of refraction 2θ values (CuKα λ=1.5418 Å) selected from 20.2°, 20.5°, 21.1° and 23.2°, measured at a temperature of about 25° C. and an x-ray wavelength, λ, of 1.5418 Å.

10. The compound according to claim 3 , wherein the crystalline form has an X-ray powder diffraction pattern comprising at least two peaks having an angle of refraction 2θ values (CuKα λ=1.5418 Å) selected from 20.2°, 20.5°, 21.1° and 23.2°, measured at a temperature of about 25° C. and an x-ray wavelength, λ, of 1.5418 Å.

11. The compound according to claim 3 , wherein the crystalline form has an X-ray powder diffraction pattern comprising at least three peaks having an angle of refraction 2θ values (CuKα λ=1.5418 Å) selected from 20.2°, 20.5°, 21.1° and 23.2°, measured at a temperature of about 25° C. and an x-ray wavelength, λ, of 1.5418 Å.

12. The compound according to claim 3 , wherein the crystalline form has an X-ray powder diffraction pattern comprising at least four peaks having an angle of refraction 2θ values (CuKα 2=1.5418 Å) selected from 20.2°, 20.5°, 21.1° and 23.2°, measured at a temperature of about 25° C. and an x-ray wavelength, λ, of 1.5418 Å.

13. The compound according to claim 9 , wherein the X-ray powder diffraction pattern further comprises at least one peak having an angle of refraction 2θ values (CuKα λ=1.5418 Å) selected from 16.2°, 16.6°, 18.0, 24.0° and 28.1°, measured at a temperature of about 25° C. and an x-ray wavelength, λ, of 1.5418 Å.

14. The compound according to claim 9 , wherein the X-ray powder diffraction pattern further comprises at least two peaks having an angle of refraction 2θ values (CuKα λ=1.5418 Å) selected from 16.2°, 16.6°, 18.0, 24.0° and 28.1°, measured at a temperature of about 25° C. and an x-ray wavelength, λ, of 1.5418 Å.

15. The compound according to claim 9 , wherein the X-ray powder diffraction pattern further comprises at least three peaks having an angle of refraction 2θ values (CuKα λ=1.5418 Å) selected from 16.2°, 16.6°, 18.0, 24.0° and 28.1°, measured at a temperature of about 25° C. and an x-ray wavelength, λ, of 1.5418 Å.

16. The compound according to claim 9 , wherein the X-ray powder diffraction pattern further comprises at least four peaks having an angle of refraction 2θ values (CuKα λ=1.5418 Å) selected from 16.2°, 16.6°, 18.0, 24.0° and 28.1°, measured at a temperature of about 25° C. and an x-ray wavelength, λ, of 1.5418 Å.

17. The compound according to claim 9 , wherein the X-ray powder diffraction pattern further comprises five peaks having an angle of refraction 2θ values (CuKα λ=1.5418 Å) selected from 16.2°, 16.6°, 18.0, 24.0° and 28.1°, measured at a temperature of about 25° C. and an x-ray wavelength, λ, of 1.5418 Å.

18. The compound according to claim 3 , which has an X-ray powder diffraction pattern as shown in FIG. 1 when measured using CuKα radiation.

Assignees

• Novartis Ag

Inventors

• Ge Xiaobin
• Mattes Henri
• Shi Zhicong
• Xia Mei
• Ye Ning

Classifications

• C07D491/048

  the oxygen-containing ring being five-membered · CPC title

• A61K45/06

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

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61K31/501

  not condensed and containing further heterocyclic rings · CPC title