Design and synthesis of novel pyrazolo[4,3-d]pyrimidines as potential therapeutic agents for acute lung injury

Journal of Enzyme Inhibition and Medicinal Chemistry

Ming Ming Liu¹  Jing Bo Shi¹  Liu Zeng Chen¹  Xin Huang¹  Bao Shi Wang¹ 

[1] School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, People's Republic of Chin;

关键词: d;    synthesis;    anti-inflammatory activity;    acute lung injury;   

DOI  :  10.1080/14756366.2019.1618291

来源: publisher

【 摘 要 】

Four series of total 35 new pyrazolo[4,3-d]pyrimidine compounds were designed, synthesized and evaluated for their inhibitory activity against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 4e was found to be the most potent inhibitor, which decreased the production of cytokines in vitro, such as NO, IL-6 and TNF-α, with IC50 values of 2.64, 4.38 and 5.63 μM, respectively. Further studies showed that compound 4e inhibited cytokines secretion of macrophages through suppressing TLR4/p38 signaling pathway. Additionally, compound 4e showed in vivo anti-inflammatory activity in LPS-induced model of acute lung injury. These data suggested that compound 4e may be a promising lead structure for the treatment of ALI.

【 授权许可】

CC BY