期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 11, 期 11, 页码 2195-2203出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.0c00335
关键词
BTK; atropisomer; CD69; autoimmune disease
Bruton's tyrosine kinase (BTK) has been shown to play a key role in the pathogenesis of autoimmunity. Therefor; the inhibition of the kinase activity of BTK with a small molecule inhibitor could offer a breakthrough in the clinical treatment of many autoimmune diseases. This Letter describes the discovery of BMS-986143 through systematic structure-activity relationship (SAR) development. This compound benefits from defined chirality derived from two rotationally stable atropisomeric axes, providing a potent and selective single atropisomer with desirable efficacy and tolerability profiles.
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