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Pyroglutamide-Based P2X7 Receptor Antagonists Targeting Inflammatory Bowel Disease

Abstract : This report deals with the design, the synthesis, and the pharmacological evaluation of pyroglutamide-based P2X7 antagonists. A dozen were shown to possess improved properties, among which inhibition of YO-PRO-1/TO-PRO-3 uptake and IL1β release upon BzATP activation of the receptor and dampening signs of DSS-induced colitis on mice, in comparison with reference antagonist GSK1370319A. Docking study and biological evaluation of synthesized compounds has highlighted new SAR, and low toxicity profiles of pyroglutamides herein described are clues for the finding of a usable h-P2X7 antagonist drug. Such a drug would raise the hope for a cure to many P2X7-dependent pathologies, including inflammatory, neurological, and immune diseases.
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https://hal-normandie-univ.archives-ouvertes.fr/hal-02376260
Contributor : Sahil Adriouch <>
Submitted on : Friday, November 22, 2019 - 2:46:02 PM
Last modification on : Monday, October 12, 2020 - 10:50:03 AM

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Germain Homerin, Samir Jawhara, Xavier Dezitter, Davy Baudelet, Pierrick Dufrénoy, et al.. Pyroglutamide-Based P2X7 Receptor Antagonists Targeting Inflammatory Bowel Disease. Journal of Medicinal Chemistry, American Chemical Society, 2019, Women in Medicinal Chemistry, Epub ahead of print, ⟨10.1021/acs.jmedchem.9b00584⟩. ⟨hal-02376260⟩

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