发现并优化了一系列强效、高选择性的 IRAK4 抑制剂吲哚胺类化合物。
Discovery and optimization of a potent and selective indazolamine series of IRAK4 inhibitors.
机构信息
Zhejiang Hisun Pharmaceutical Co. Ltd., China, 46 Waisha Rd., Taizhou 318099, China.
Zhejiang Hisun Pharmaceutical Co. Ltd., China, 46 Waisha Rd., Taizhou 318099, China.
出版信息
Bioorg Med Chem Lett. 2021 Jan 1;31:127686. doi: 10.1016/j.bmcl.2020.127686. Epub 2020 Nov 24.
IRAK4 is a key mediator of innate immunity. There is a high interest in identifying novel IRAK4 inhibitors for the treatment of inflammatory autoimmune diseases. We describe here a highly potent and selective IRAK4 inhibitor (HS271) that exhibited superior enzymatic and cellular activities, as well as excellent pharmacokinetic properties. HS271 displayed robust in vivo anti-inflammatory efficacy as evaluated in rat models of LPS induced TNFα production and collagen-induced arthritis.
IRAK4 是先天免疫的关键介质。人们对鉴定新型 IRAK4 抑制剂以治疗炎症性自身免疫性疾病非常感兴趣。我们在这里描述了一种高效且选择性的 IRAK4 抑制剂（HS271），它表现出优异的酶和细胞活性以及良好的药代动力学特性。HS271 在 LPS 诱导的 TNFα 产生和胶原诱导的关节炎大鼠模型中显示出强大的体内抗炎疗效。
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