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

The identification and lead optimization of a series of pyrazolo[3,4- d ]pyridazinone derivatives are described as a novel class of potent irreversible BTK inhibitors, resulting in the discovery of compound 8 . Compound 8 exhibited high potency against BTK kinase and acceptable PK profile. Furthermore, compound 8 demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model.
Competing Interests: The authors declare no competing financial interest.