Discovery of Selective Irreversible Inhibitors for Bruton’s Tyrosine Kinase

A series of highly selective irreversible inhibitors for Bruton's tyrosine kinase (Btk) was developed using a structural bioinformatics approach. Their capabilities to modulate Btk's activity were characterized both in vitro and in vivo. Oral treatment with once-a-day dosing of compound 4 greatly inhibited disease development in a rodent rheumatoid arthritis (RA) model. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2452/2007/z600221_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to…