多组分帕塞里尼反应作为一种方法来获得结构,活性和性质的多样性:软硬的化物/大麻素调节器
Angela Lamberti1, Marta Serafini2, Silvio Aprile2
1Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universidad Miguel Hernández, Elche, Spain.
European journal of medicinal chemistry
|September 12, 2024
概括
研究人员探索了内分泌体 (EV) /内分泌体 (EC) 系统,发现了针对炎症和疼痛的新化合物. 化合物41作为TRPV1和CB2受体的平衡激动剂具有良好的代谢稳定性.
科学领域:
- 药理学和药物化学 药理学和药物化学
- 神经科学是一个神经科学.
- 生物化学 生物化学
背景情况:
- 内分泌体 (EV) 和内分泌体 (EC) 系统表现出交叉声,表明一个统一的EV/EC系统.
- 这个系统涉及TRPV1,CB1,CB2受体,内源性配体和代谢酶.
- EV/EC系统的失调与炎症,疼痛,神经退行性疾病和骨/皮肤疾病有关.
研究的目的:
- 使用以多样性为导向的方法开发针对EV/EC系统的新型化合物.
- 为了产生类似于内源性配体的α-acyloxycarboxamides,用于选.
- 确定在炎症和皮肤疾病中具有潜在治疗应用的药物.
主要方法:
- 利用帕塞里尼反应来进行以多样性为导向的α-氧化碳胺的合成.
- 选合成化合物对TRPV1,CB1和CB2受体的活性.
- 在皮肤细胞,肝脏部分和血中评估了代谢稳定性.
主要成果:
- 产生了各种各样的化合物,对TRPV1,CB1和CB2具有不同的活性,并且具有异质的代谢稳定性.
- 已识别出适用于不同给药途径的化合物,从局部 (软药) 到全身 (硬药).
- 化合物41表现出平衡的TRPV1和CB2激动性,高选择性比其他标,以及良好的代谢稳定性.
结论:
- 开发的合成策略有效地产生了具有更好的药物相似性的EV/EC系统调节器.
- 化合物41对涉及EV/EC系统的疾病,特别是炎症和疼痛,是一种有前途的治疗.
- 这些发现支持通过调节EV/EC系统来开发针对皮肤疾病,炎症和疼痛的向疗法.
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