Design, synthesis and anti-inflammatory evaluation of 3-amide benzoic acid derivatives as novel P2Y(14) receptor antagonists
Design, synthesis and anti-inflammatory evaluation of 3-amide benzoic acid derivatives as novel P2Y(14) receptor antagonists
复制标题
新型P2Y(14)受体拮抗剂3-酰胺苯甲酸衍生物的设计、合成及抗炎评价
DOI：
10.1016/j.ejmech.2019.111564
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发表时间：
2019
影响因子：
6.7
通讯作者：
Jiang Cheng
中科院分区：
文献类型：
--
作者：
Zhang Zhenguo;Hao Kun;Li Hanwen;Lu Ran;Liu Chunxiao;Zhou Mengze;Li Baiyang;Meng Zibo;Hu Qinghua;Jiang Cheng
p2y14受体（P2Y14R）在炎症过程的调节中起着关键作用，但很少有拮抗剂被报道。一系列3-酰胺苯甲酸衍生物被鉴定为新型有效的P2Y14R拮抗剂。最有效的拮抗剂16c显示出与最有效的P2Y14R拮抗剂PPTN相当的活性（IC50= 1.77 nM）。化合物16c在大鼠和人微粒体中表现出显著改善的水溶性和良好的代谢稳定性。通过流式细胞术、Western Blot和免疫荧光标记技术对MSU处理的THP-1 细胞进行了抗炎作用的研究，表明16c可能是一个有前景的研究对象。
The P2Y14receptor (P2Y14R) plays a key role in the modulation of inflammatory process, but very few classes of antagonists have been reported. A series of 3-amide benzoic acid derivatives were identified as novel and potent P2Y14R antagonists. The most potent antagonist,16c, showed comparable activity (IC50= 1.77 nM) to PPTN, the most potent P2Y14R antagonist reported. Compound16cdemonstrated dramatically improved aqueous solubility and excellent metabolic stability in rat and human microsomes. Investigation of the anti-inflammatory effect of16cwas performed in MSU treated THP-1 cells by flow cytometry, Western Blot and immunofluorescence labeling technology, which exhibited that16cmight be a promising candidate for further research.