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

ChemMedChem
Lingfeng ChenGuang Liang

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.

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Citations

Jan 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ebtesam A BasionyWael A El-Sayed
Jun 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohamed Y MahgoubM Matilde Marques
Nov 8, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gamze TokgözZafer Asım Kaplancıklı

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