- Design and Synthesis of Novel Amino-triazine Analogues as Selective Bruton's Tyrosine Kinase Inhibitors for Treatment of Rheumatoid Arthritis
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Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of multiple diseases, such as B-cell malignances, asthma, and rheumatoid arthritis. A series of novel aminotriazines were identified as highly selective inhibitors of BTK by a scaffold-hopping approach. Subsequent SAR studies of this series using two conformationally different BTK proteins, an activated form of BTK and an unactivated form of BTK, led to the discovery of a highly selective BTK inhibitor, 4b. With significant efficacy in models in vivo and good ADME and safety profiles, 4b was advanced into preclinical studies.
- Kawahata, Wataru,Asami, Tokiko,Kiyoi, Takao,Irie, Takayuki,Taniguchi, Haruka,Asamitsu, Yuko,Inoue, Tomoko,Miyake, Takahiro,Sawa, Masaaki
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supporting information
p. 8917 - 8933
(2018/10/09)
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