- 1,2,4-triazolo[4,3-a] pyridine derivative as well as preparation method and application thereof
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The invention discloses a 1,2,4-triazolo[4,3-a] pyridine derivative as well as a preparation method and application thereof, and belongs to the field of chemical medicines. The invention provides a compound shown as a formula I or pharmaceutically acceptable salt thereof. The invention also provides a preparation method and application of the compound. Biological experiments show that the compoundhas an obvious inhibition effect on NO releasing of cells, can obviously improve lesions caused by autoimmune hepatitis, and provides a new choice for development and application of anti-liver injury, especially anti-autoimmune disease drugs.
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Paragraph 0085-0087
(2020/12/30)
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- Reactions of 3-R-5-nitropyridines with nucleophiles: Nucleophilic substitution vs conjugate addition
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A number of 3-R-5-nitropyridines were synthesized and their reactions with various types of nucleophiles were investigated. The reaction outcome depends on the nature of a nucleophile: in case of anionic O-, N- and S-nucleophiles the previously unreported substitution of non-activated nitro group occurred while carbon nucleophiles underwent dearomatization of the pyridine ring with the formation of products of 1,2- and 1,4-addition.
- Bastrakov, Maxim A.,Nikol'skiy, Vladislav V.,Starosotnikov, Alexey M.,Fedyanin, Ivan V.,Shevelev, Svyatoslav A.,Knyazev, Daniil A.
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- Synthesis and biological evaluation of (1,2,4)triazole[4,3-a]pyridine derivatives as potential therapeutic agents for concanavalin A-induced hepatitis
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A series of (1,2,4)triazole[4,3-a]pyridine (TZP) derivatives have been designed and synthesized. Compound 8d was identified as having the most potent inhibitory activity on NO release in response to lipopolysaccharide (LPS) stimulation and inhibition of the migration induced by MCP-1 protein on RAW264.7 macrophages. Based on the screening data, an immunofluorescence assay and a real-time qPCR assay were conducted, indicating that compound 8d suppressed NF-κB p65 translocation and expression of inflammatory genes by concanavalin A (Con A)-induced RAW264.7 macrophages. More importantly, 8d also exhibited potent efficacy, alleviating Con A-induced hepatitis by downregulating the levels of plasma alanine transaminase (ALT), aspartate transaminase (AST) and inflammatory infiltration in a mouse autoimmune hepatitis (AIH) model. In addition, the flow cytometry (FCM) data showed that compound 8d inhibited the accumulation of MDSCs in the liver of Con A-induced mice. These findings raise the possibility that compound 8d might serve as a potential agent for the treatment of AIH.
- Shi, Yaojie,Wang, Qianqian,Rong, Juan,Ren, Jing,Song, Xuejiao,Fan, Xiaoli,Shen, Mengyi,Xia, Yong,Wang, Ningyu,Liu, Zhihao,Hu, Quanfang,Ye, Tinghong,Yu, Luoting
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p. 182 - 195
(2019/07/02)
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