...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Open Medicinal Chemistry Journal >Hexacyclododecylamines with Sigma-1 Receptor Affinity and Calcium Channel Modulating Ability
【24h】

Hexacyclododecylamines with Sigma-1 Receptor Affinity and Calcium Channel Modulating Ability

机译：具有Sigma-1受体亲和力和钙通道调节能力的六环十二胺

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Introduction: Recent research points to the Sigma Receptor (σR) as a possible neuromodulatory system with multi-functional action and σ1Rs have been suggested as a drug target for a number of CNS conditions. Hexacyclododecylamines have shown σ1R activity and provide an advantageous scaffold for drug design that can improve the blood-brain barrier permeability of privileged structures. Methods and Materials: A series of oxa- and aza- hexaxcyclododecylamines were synthesised and evaluated for sigma-1 receptor activity and voltage-gated calcium channel blocking ability to determine the effect of inclusion of amine containing heterocycles. Results Discussion: The compounds had promising σ1R activities (Ki = 0.067 – 11.86 μM) with the aza-hexacyclododecylamines 12, 24 and 27 showing some of the highest affinities (Ki = 0.067 μM, 0.215 μM and 0.496 μM respectively). This confirms, as observed in previous studies, that the aza compounds are more favourable for σ1R binding than their oxa counterparts. The addition of the amine heterocycle showed affinities similar to that of related structures with only two lipophilic binding regions. This indicates that the inclusion of an amine heterocycle into these structures is a viable option in the design of new σ1R ligands. Significant voltage-gated calcium channel blocking ability was also observed for 12, 24 and 27, suggesting a link between σ1R activity and intracellular calcium levels. Conclusion: The σ1R activity and potential effect on other receptor classes and calcium channels could prove beneficial in pharmacological application.
机译：简介：最近的研究表明，西格玛受体（σR）是一种可能具有多功能作用的神经调节系统，而σ1Rs已被建议作为许多中枢神经系统疾病的药物靶标。六环十二烷基胺具有σ1R活性，为药物设计提供了有利的支架，可以改善特权结构的血脑屏障通透性。方法和材料：合成了一系列的oxa-和aza-hexaxcyclododecylamines，并评估其sigma-1受体活性和电压门控钙通道阻断能力，以确定包含胺类杂环的作用。结果讨论：化合物具有良好的σ1R活性（Ki = 0.067 – 11.86μM），氮杂六环十二烷基胺12、24和27的亲和力最高（Ki = 0.067μM，0.215μM和0.496μM）。如先前研究中所观察到的，这证实了氮杂化合物比oxa对应物更适合σ1R结合。胺杂环的加入显示出与仅具有两个亲脂性结合区的相关结构相似的亲和力。这表明在设计新的σ1R配体时，在这些结构中包含胺杂环是可行的选择。还观察到了对12、24和27的明显的电压门控钙通道阻断能力，表明σ1R活性与细胞内钙水平之间存在联系。结论：σ1R活性以及对其他受体类别和钙通道的潜在作用可能在药理学应用中证明是有益的。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号