101. Design, synthesis and anti-inflammatory evaluation of 3-amide benzoic acid derivatives as novel P2Y14 receptor antagonists.
- Author
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Zhang, Zhenguo, Hao, Kun, Li, Hanwen, Lu, Ran, Liu, Chunxiao, Zhou, Mengze, Li, Baiyang, Meng, Zibo, Hu, Qinghua, and Jiang, Cheng
- Subjects
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ACID derivatives , *BENZOIC acid , *G protein coupled receptors - Abstract
The P2Y 14 receptor (P2Y 14 R) 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 P2Y 14 R antagonists. The most potent antagonist, 16c , showed comparable activity (IC 50 = 1.77 nM) to PPTN, the most potent P2Y 14 R antagonist reported. Compound 16c demonstrated dramatically improved aqueous solubility and excellent metabolic stability in rat and human microsomes. Investigation of the anti-inflammatory effect of 16c was performed in MSU treated THP-1 cells by flow cytometry, Western Blot and immunofluorescence labeling technology, which exhibited that 16c might be a promising candidate for further research. Image 1 • A series of 3-amide benzoic acids was identified as novel P2Y 14 R antagonists. • Compound 16c showed potent anti-inflammatory effect. • Compound 16c demonstrated dramatically improved aqueous solubility and excellent metabolic stability. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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