Discovery of triazolo [1,5-a ] pyridine derivatives as novel JAK1/2 inhibitors

被引：1

作者：

Lu, Kuan ^{[1
,2
]}

Wu, Weibin ^{[2
,3
]}

Zhang, Cunlong ^{[2
,3
]}

Liu, Zijian ^{[2
]}

Xiao, Boren ^{[6
]}

Yuan, Zigao ^{[2
]}

Li, Anqi ^{[6
]}

Chen, Dawei ^{[2
]}

Zhai, Xin ^{[1
]}

Jiang, Yuyang ^{[1
,4
,5
]}

机构：

[1] Shenyang Pharmaceut Univ, Dept Pharmaceut Engn, Shenyang 110016, Liaoning, Peoples R China

[2] Shenzhen Kivita Innovat Drug Discovery Inst, Shenzhen 518057, Peoples R China

[3] Tsinghua Univ, Grad Sch Shenzhen, Natl & Local United Engn Lab Personalized Antitum, Shenzhen 518055, Peoples R China

[4] Tsinghua Univ, Tsinghua Shenzhen Int Grad Sch, Joint Key State Lab Tumor Chemogen, Shenzhen 518055, Peoples R China

[5] Tsinghua Univ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China

[6] Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 14期

关键词：

PLACEBO; PATHWAY;

D O I：

10.1016/j.bmcl.2020.127225

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Small molecule JAK inhibitors have been demonstrated efficacy in rheumatoid arthritis, inflammatory bowel disease, and psoriasis with the approval of several drugs. Aiming to develop potent JAK1/2 inhibitors, two series of triazolo [1,5-a] pyridine derivatives were designed and synthesized by various strategies. The pharmacological results identified the optimized compounds J-4 and J-6, which exerted high potency against JAK1/2, and selectivity over JAK3 in enzyme assays. Furthermore, J-4 and J-6 effectively suppressed proliferation of JAK1/2 high-expression BaF3 cells accompanied with acceptable metabolic stability in liver microsomes. Therefore, J-4 and J-6 might serve as promising JAK1/2 inhibitors for further investigation. © 2020

引用

页数：5

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