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Design, synthesis and anti-inflammatory evaluation of 3-amide benzoic acid derivatives as novel P2Y receptor antagonists. | LitMetric
The P2Y receptor (P2YR) 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 P2YR antagonists. The most potent antagonist, 16c, showed comparable activity (IC = 1.77 nM) to PPTN, the most potent P2YR 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.
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China Pharmaceutical University , 639 Longmian Avenue, Nanjing, 211198, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University , 24 Tongjiaxiang, Nanjing, 210009, PR China. Electronic address:
P2Y nucleotide receptor plays important roles in series of physiological and pathologic events especially associated with immune and inflammation. Based on the 3-amide benzoic acid scaffold reported by our group previously, a series of 5-aryl-3-amide benzoic acid derivatives were designed as novel P2Y antagonists with improved pharmacokinetic properties. Among which compound 11m showed most potent P2Y antagonizing activity with an IC value of 2.
China Pharmaceutical University , Tongjiaxiang 24, Nanjing, 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University , Tongjiaxiang 24, Nanjing, 210009, China. Electronic address:
The P2Y receptor (P2YR) 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 P2YR antagonists. The most potent antagonist, 16c, showed comparable activity (IC = 1.
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