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Design, Synthesis, and Structure–Activity Relationship Analysis of Thiazolo[3,2‐ a ]pyrimidine Derivatives with Anti‐inflammatory Activity in Acute Lung Injury
Author(s) -
Chen Lingfeng,
Jin Yiyi,
Fu Weitao,
Xiao Siyang,
Feng Chen,
Fang Bo,
Gu Yugui,
Li Chenglong,
Zhao Yunjie,
Liu Zhiguo,
Liang Guang
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700175
Subject(s) - pyrimidine , in vivo , tumor necrosis factor alpha , lipopolysaccharide , pharmacology , lung , in vitro , chemistry , structure–activity relationship , medicine , stereochemistry , immunology , biochemistry , biology , microbiology and biotechnology
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.