Protein kinase inhibitors and uses thereof for the treatment of diseases and conditions

Patent metadata

Field	Value
Publication number	US-12516055-B2
Application number	US-202017595406-A
Country	US
Kind code	B2
Filing date	May 14, 2020
Priority date	May 16, 2019
Publication date	Jan 6, 2026
Grant date	Jan 6, 2026

Abstract

Identified compounds demonstrate protein kinase inhibitory activity. More specifically, the compounds are demonstrated to inhibit receptor interacting kinase 2 (RIPK2) and/or Activin-like kinase 2 (ALK2) and/or receptor interacting kinase 3 (RIPK3). Compounds that are either dual RIPK2/ALK2 inhibitors or that preferentially inhibit RIPK2 or ALK2 or RIPK3 could provide therapeutic benefit. Compounds that function as RIPK3 inhibitors provide therapeutic benefit in the treatment of inflammatory and degenerative conditions.

First claim

What is claimed is:

1 . A compound having a structure of:

or pharmacologically acceptable salt thereof.

2 . The compound according to claim 1 .

3 . A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 1 , or a pharmacologically acceptable salt thereof, and a pharmaceutically acceptable excipient, adjuvant, carrier, buffer, stabilizer, or mixture thereof.

4 . The pharmaceutical composition of claim 3 comprising the therapeutically effective amount of

5 . A method of treating an inflammatory disease or condition involving receptor interacting kinase 3 (RIPK3) inhibitory activity comprising administering the pharmaceutical composition according to claim 3 , wherein the inflammatory disease or condition involving RIPK3 inhibitory activity is Influenza A virus (IAV) infection.

6 . The method of claim 5 , wherein the pharmaceutical composition comprises the therapeutically effective amount of

7 . The method of claim 5 , wherein the inflammatory or degenerative disease or condition involving RIPK3 activity is Influenza A virus (IAV) infection.

8 . A method of treating a protein kinase related disease or condition comprising administering the pharmaceutical composition according to claim 3 , wherein the protein kinase related disease or condition is Influenza A virus (IAV) infection.

9 . The method of claim 8 , wherein the pharmaceutical composition comprises the therapeutically effective amount of

10 . The method of claim 5 , wherein the inflammatory disease or condition involving RIPK3 activity is IAV-induced respiratory distress syndrome (ARDS).

11 . The method of claim 5 , wherein the inflammatory disease or condition involving RIPK3 activity is IAV-induced viral pneumonia or bacterial pneumonia.

12 . The method of claim 5 , wherein the inflammatory disease or condition involving RIPK3 activity is IAV-induced necrotic lung injury.

13 . The method of claim 5 , wherein the inflammatory disease or condition involving RIPK3 activity is IAV-induced necroptosis.

Assignees

• Univ Houston System
• Tufts College
• Institute For Cancer Res

Inventors

• Cuny Gregory
• Degterev Alexei
• Nikhar Sameer
• Balachandran Siddharth

Classifications

• A61K31/541

  Non-condensed thiazines containing further heterocyclic rings · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P29/00

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

• A61P31/16

  for influenza or rhinoviruses · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title