Nlrp3 inflammasome inhibitors

Patent metadata

Field	Value
Publication number	US-2025034114-A1
Application number	US-202418917653-A
Country	US
Kind code	A1
Filing date	Oct 16, 2024
Priority date	Aug 3, 2022
Publication date	Jan 30, 2025
Grant date	—

Abstract

The present invention relates to novel pyridazin-3-yl phenol compounds of formula (I):wherein R1, R2, R3, R4 and R5 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 . A combination comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and one or more therapeutic agents.

4 . A method of treating a disease or disorder in which the NLRP3 signaling contributes to the pathology, and/or symptoms, and/or progression, of said disease or disorder, comprising administering a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

5 . The method of treating according to claim 4 , wherein the disease or disorder is selected from inflammasome-related diseases/disorders, immune diseases, inflammatory diseases, auto-immune diseases, or auto-inflammatory diseases, for example, autoinflammatory fever syndromes, cryopyrin-associated periodic syndrome, liver related diseases/disorders, chronic liver disease, viral hepatitis, non-alcoholic steatohepatitis, alcoholic steatohepatitis, and alcoholic liver disease, inflammatory arthritis related disorders, gout, calcium pyrophosphate dihydrate crystal deposition disease, osteoarthritis, rheumatoid arthritis, arthropathy, kidney related diseases, hyperoxaluria, lupus nephritis, Type I/Type II diabetes and related complications, nephropathy, retinopathy, hypertensive nephropathy, hemodialysis related inflammation, neuroinflammation-related diseases, multiple sclerosis, brain infection, acute injury, neurodegenerative diseases, Alzheimer's disease, cardiovascular/metabolic diseases/disorders, cardiovascular risk reduction, hypertension, atherosclerosis, type I and type II diabetes and related complications, peripheral artery disease, acute heart failure, inflammatory skin diseases, hidradenitis suppurativa, acne, wound healing and scar formation, asthma, sarcoidosis, age-related macular degeneration, and cancer related diseases/disorders, colon cancer, lung cancer, myeloproliferative neoplasms, leukemias, myelodysplastic syndromes, myelofibrosis, chronic obstructive pulmonary disorder, chronic myelomonocytic leukaemia, post-Myocardial Infarction Heart Failure.

6 . A method of inhibiting the NLRP3 inflammasome activity in a subject in need thereof, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

Assignees

• Novartis Ag

Inventors

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

Classifications

• 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

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D237/20

  Nitrogen atoms (nitro radicals C07D237/12) · CPC title