三位置换的1,3,5-Triazines作为组胺H4受体对手,在体内有着有前途的活动
Agnieszka Olejarz-Maciej1, Szczepan Mogilski2, Tadeusz Karcz1
1Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College in Kraków, Medyczna 9, 30-688 Kraków, Poland.
Molecules (Basel, Switzerland)
|May 27, 2023
概括
研究人员发现了一种新化合物,化合物6,向组胺H4受体 (H4R) 缓解疼痛. 这种H4R对手在临床前模型中表现出显著的抗炎和止痛作用.
科学领域:
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
- 神经科学是一个神经科学.
背景情况:
- 组胺H4受体 (H4R) 是治疗炎症和疼痛的关键标.
- 现有的H4R配体显示出潜在的止痛作用,特别是在炎症性疼痛模型中.
研究的目的:
- 合成和评估新型的1,3,5-triazine衍生物作为潜在的H4R配体.
- 为了确定强效和安全的H4R抗剂来治疗疼痛和.
主要方法:
- 合成了19种新的非循环和非循环的1,3,5-三衍生物.
- 在体外对受体亲和力,对抗性活性 (β-arrestin,cAMP测定) 的药理学评估.
- 在体外评估化合物6的血脑屏障透性 (PAMPA) 和细胞毒性 (HepG2,SH-5YSY细胞).
- 在卡拉基南诱导的炎症性疼痛和基因组胺/氨酸诱导的的模型中对化合物6的体内测试.
主要成果:
- 化合物6对H4R表现出中度的亲和力 (Ki = 63nM) 和强大的对抗活性.
- 化合物6显示出良好的血脑屏障透性 (Pe = 12.26 × 10-6 cm/s) 并且没有显著的毒性.
- 活体研究表明,化合物6具有抗炎和止痛特性,并减少模型中的行为.
结论:
- 化合物6是一种新的1,3,5-triazine衍生物,是一种有前途的H4R抗剂.
- 在临床前模型中证明的疗效需要进一步研究治疗疼痛和的治疗应用.
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