Identification of quinazoline based inhibitors of IRAK4 for the treatment of inflammation

Bioorganic & Medicinal Chemistry Letters
Graham F SmithAlan Northrup

Abstract

Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R and TLR based signaling. Therefore selective inhibition of the kinase activity of this protein represents an attractive target for the treatment of inflammatory diseases. Medicinal chemistry optimization of high throughput screening (HTS) hits with the help of structure based drug design led to the identification of orally-bioavailable quinazoline based IRAK4 inhibitors with excellent pharmacokinetic profile and kinase selectivity. These highly selective IRAK4 compounds show activity in vivo via oral dosing in a TLR7 driven model of inflammation.

Citations

Dec 7, 2017·Proceedings of the National Academy of Sciences of the United States of America·Li WangHao Wu
Mar 28, 2019·Expert Opinion on Therapeutic Patents·William T McElroy
Nov 27, 2020·Bioorganic & Medicinal Chemistry Letters·Wenqiang ZhaiLei Chen
Mar 19, 2020·ACS Medicinal Chemistry Letters·Naomi S RajapaksaMarian C Bryan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here