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J Enzyme Inhib Med Chem. 2019 Dec;34(1):1121-1130. doi: 10.1080/14756366.2019.1618291.

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

Author information

1
a School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Institute of Innovative Drugs , Anhui Medical University , Hefei , People's Republic of China.

Abstract

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.

KEYWORDS:

Pyrazolo[4,3-]pyrimidine; acute lung injury; anti-inflammatory activity; synthesis

PMID:
31117832
PMCID:
PMC6534230
DOI:
10.1080/14756366.2019.1618291
[Indexed for MEDLINE]
Free PMC Article

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