Design, Synthesis, and Structure–Activity Relationship Analysis of Thiazolo[3,2‐a]pyrimidine Derivatives with Anti‐inflammatory Activity in Acute Lung Injury

ChemMedChem - Tập 12 Số 13 - Trang 1022-1032 - 2017
Lingfeng Chen1,2,3, Yiyi Jin1,3, Weitao Fu1, Siyang Xiao1, Chen Feng1, Bo Fang1, Yugui Gu4, Chenglong Li1, Yunjie Zhao1, Zhiguo Liu1, Guang Liang1,2
1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
2School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, China
3these authors contributed equally to this work
4School of Chemical Engineering and Materials, Wenzhou University, Wenzhou, Zhejiang, 325035 China

Tóm tắt

Abstract

Acute lung injury (ALI) has a high lethality rate, and interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) contribute most to tissue deterioration in cases of ALI. In this study, we designed and synthesized a new series of thiazolo[3,2‐a]pyrimidine derivatives based on a previously identified lead compound, and we evaluated their anti‐inflammatory activities. Structure–activity relationship studies led to the discovery of two highly potent inhibitors. The two promising compounds were found to inhibit lipopolysaccharide (LPS)‐induced IL‐6 and TNF‐α release in a dose‐dependent manner in mouse primary peritoneal macrophages (MPMs). Furthermore, administration of these compounds resulted in lung histopathological improvements and attenuated LPS‐induced ALI in vivo. Taken together, these data indicate that these novel thiazolo[3,2‐a]pyrimidine derivatives could be developed as candidate drugs for the treatment of ALI.

Từ khóa


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ChemMedChem

Tập 12 Số 13

1022-1032

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