3区 · 医学
Article
作者: Blomgren, Peter ; DiPaolo, Julie ; Currie, Kevin S. ; Katewa, Arna ; Barbosa, James ; Wong, Harvey ; Reif, Karin ; Ortwine, Daniel F. ; Zhao, Zhongdong ; Crawford, James J. ; Deng, Wei ; Lee, Seung H. ; Macaluso, Jen ; Maciejewski, Pat ; Wang, Xiaojing ; Zhou, Fusheng ; Liu, Lichuan ; Xu, Jianjun ; Young, Wendy B. ; Mitchell, Scott A. ; Gallion, Steve ; Xiong, Jin-Ming ; Schmitt, Aaron ; Hu, Huiyong ; Dong, Liming ; Kropf, Jeffrey E. ; Lubach, Joseph W. ; Johnson, Adam R. ; Eigenbrot, Charles ; Scheerens, Heleen ; Chen, Jacob ; Hau, Jonathon ; Bremer, Meire C.
In our continued effort to discover and develop best-in-class Bruton's tyrosine kinase (Btk) inhibitors for the treatment of B-cell lymphomas, rheumatoid arthritis, and systemic lupus erythematosus, we devised a series of novel tricyclic compounds that improved upon the druglike properties of our previous chemical matter. Compounds exemplified by G-744 are highly potent, selective for Btk, metabolically stable, well tolerated, and efficacious in an animal model of arthritis.