Discovery and Evaluation of Pyrazolo[3,4-<i>d</i>]pyridazinone as a Potent and Orally Active Irreversible BTK Inhibitor

Abstract

The identification and lead optimization of a series of pyrazolo[3,4-<i>d</i>]pyridazinone derivatives are described as a novel class of potent irreversible BTK inhibitors, resulting in the discovery of compound <b>8</b>. Compound <b>8</b> exhibited high potency against BTK kinase and acceptable PK profile. Furthermore, compound <b>8</b> demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model.