Discovery of Potent and Selective Tricyclic Inhibitors of Bruton’s Tyrosine Kinase with Improved Druglike Properties

[Image: see text] 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 pr...

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Detalles Bibliográficos
Autores principales: Wang, Xiaojing, Barbosa, James, Blomgren, Peter, Bremer, Meire C., Chen, Jacob, Crawford, James J., Deng, Wei, Dong, Liming, Eigenbrot, Charles, Gallion, Steve, Hau, Jonathon, Hu, Huiyong, Johnson, Adam R., Katewa, Arna, Kropf, Jeffrey E., Lee, Seung H., Liu, Lichuan, Lubach, Joseph W., Macaluso, Jen, Maciejewski, Pat, Mitchell, Scott A., Ortwine, Daniel F., DiPaolo, Julie, Reif, Karin, Scheerens, Heleen, Schmitt, Aaron, Wong, Harvey, Xiong, Jin-Ming, Xu, Jianjun, Zhao, Zhongdong, Zhou, Fusheng, Currie, Kevin S., Young, Wendy B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467183/
https://www.ncbi.nlm.nih.gov/pubmed/28626519
http://dx.doi.org/10.1021/acsmedchemlett.7b00103
Descripción
Sumario:[Image: see text] 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.

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