Discovery and Optimization of A Potent and Selective Indazolamine Series of IRAK4 Inhibitors,Bioorganic & Medicinal Chemistry Letters

当前位置： X-MOL 学术 › Bioorg. Med. Chem. Lett. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Discovery and Optimization of A Potent and Selective Indazolamine Series of IRAK4 Inhibitors
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2020-11-24 , DOI: 10.1016/j.bmcl.2020.127686
Wenqiang Zhai ₁ , Yongping Lu ₁ , Yabo Zhu ₁ , Mengguang Zhou ₁ , Cheng Ye ₁ , Zheng-Zheng Shi ₁ , Wenjian Qian ₁ , Taishan Hu ₁ , Lei Chen ₁

Affiliation

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 collagen-induced arthritis.

中文翻译：

发现和优化的IRAK4抑制剂的有效和选择性吲唑胺系列。

IRAK4是先天免疫的关键介体。鉴定用于治疗炎性自身免疫疾病的新型IRAK4抑制剂引起了高度兴趣。我们在这里描述了一种高效的，选择性的IRAK4抑制剂（HS271），它表现出卓越的酶和细胞活性，以及出色的药代动力学特性。如在LPS诱导的TNFα产生胶原诱导的关节炎的大鼠模型中所评估的，HS271显示出强大的体内抗炎功效。

更新日期：2020-11-25

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南