多种取代吡啶-2(1)-酮的合成及其对皮肤炎性机械性异常性疼痛的抗痛觉过敏作用评估。
Synthesis of diversely substituted pyridin-2(1)-ones and evaluation of their anti-allodynic effect on cutaneous inflammatory mechanical allodynia.
作者信息
Frazier Théo, Murail Pauline, Boulangé Arthur, Chalane Nazim, Giraud Francis, Artola Alain, Dallel Radhouane, Anizon Fabrice, Moreau Pascale
机构信息
Université Clermont Auvergne, CNRS, Clermont Auvergne INP, ICCF F-63000 Clermont-Ferrand France
Université Clermont Auvergne, CHU Clermont-Ferrand, Inserm, Neuro-Dol F-63000 Clermont-Ferrand France
出版信息
RSC Med Chem. 2024 Jul 3;15(8):2900-2921. doi: 10.1039/d4md00375f. eCollection 2024 Aug 14.
Abstract
A series of 3,5-disubtituted pyridin-2(1)-ones was synthesized. As part of a structure-activity relationship study performed in this series, structural modifications were based on 3-(indol-4-yl)-5-(pyridin-4-ylamino)pyridin-2(1)-one B, which exhibited a potent anti-allodynic effect in a rat model of inflammatory pain. In this study, new compounds were assessed for their ability to inhibit cutaneous mechanical allodynia in rats by using the capsaicin pain model. Compound 36, a 2-methoxypyridine derivative, yielded the most promising outcome, demonstrating an enhanced analgesic effect.
摘要
合成了一系列3,5-二取代吡啶-2(1)-酮。作为对该系列进行的构效关系研究的一部分，结构修饰基于3-(吲哚-4-基)-5-(吡啶-4-基氨基)吡啶-2(1)-酮B，其在炎性疼痛大鼠模型中表现出强效的抗痛觉过敏作用。在本研究中，通过使用辣椒素疼痛模型评估了新化合物抑制大鼠皮肤机械性痛觉过敏的能力。化合物36，一种2-甲氧基吡啶衍生物，产生了最有前景的结果，显示出增强的镇痛效果。
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