3,4-dibromo-5-methyl-1H-pyrrole-2-carboxylic acid | 1624309-60-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3,4-dibromo-5-methyl-1H-pyrrole-2-carboxylic acid
• CAS: 1624309-60-9
• 化学式: C₆H₅Br₂NO₂
• 分子量: 282.919
• InChiKey: GQQYXVULUXLCND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-dibromo-5-methyl-1H-pyrrole-2-carboxylic acid 、 1-(5-nitrothiazol-2-yl)piperidin-4-amine 在 1-丙基磷酸酐 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 6.0h， 以50.9%的产率得到3,4-dibromo-5-methyl-N-(1-(5-nitrothiazol-2-yl)piperidin-4-yl)-1H-pyrrole-2-carboxamide
  参考文献：
  名称：

  旋转酶ATPase结构域作为抗结核药物的发现平台：硝噻唑基羧酰胺类似物的基于结构的设计和铅优化

  摘要：

  在这项研究中，我们探索了药物开发不足的分枝杆菌促旋酶ATPase（GyrB）域，以此为模板对我们内部（BITS Pilani）化合物进行结构化虚拟筛选，以发现针对结核分枝杆菌（M.tb.）的新抑制剂。通过结合分子对接和药物化学策略，进一步确定鉴定出的命中基因，以获得优化的类似物，该类似物表现出相当高的体外酶功效和针对M.tb的杀菌特性。高37Rv株。通过差示扫描荧光法实验重新确定了配体对GyrB结构域的结合亲和力。进一步评估hERG毒性（先前报道的N-连接的氨基哌啶类似物的主要限制）表明，这些分子完全没有心脏毒性，这是该类别中的一项重大成就。

  DOI：

  10.1002/cmdc.201402035

文献信息

• Clathrodin, hymenidin and oroidin, and their synthetic analogues as inhibitors of the voltage-gated potassium channels
  作者：Nace Zidar、Aleš Žula、Tihomir Tomašič、Marc Rogers、Robert W. Kirby、Jan Tytgat、Steve Peigneur、Danijel Kikelj、Janez Ilaš、Lucija Peterlin Mašič

  DOI：10.1016/j.ejmech.2017.08.015

  日期：2017.10

  We have prepared three alkaloids from the Agelas sponges, clathrodin, hymenidin and oroidin, and a series of their synthetic analogues, and evaluated their inhibitory effect against six isoforms of the KO subfamily of voltage-gated potassium channels, g(v)1.1-K(v)1.6, expressed in Chinese Hamster ovary (CHO) cells using automated patch clamp electrophysiology assay. The most potent inhibitor was the (E)-N-(3(2-amino-1H-imidazol-4-yl)ally1)-4,5-dichloro-1H-pyrrole-2-carboxamide (6g) with IC50 values between 1.4 and 6.1 mu M against K(v)1.3, K(v)1.4, K(v)1.5 and K(v)1.6 channels. All compounds tested displayed selectivity against K(v)1.1 and K(v)1.2 channels. For confirmation of their activity and selectivity, compounds were additionally evaluated in the second independent system against K(v)1.1-K(v)1.6 and K(v)10.1 channels expressed in Xenopus laevis oocytes under voltage clamp conditions where IC50 values against K(v)1.3K(v)1.6 channels for the most active analogues (e.g. 6g) were lower than 1 mu M. Because of the observed low sub-micromolar IC50 values and fairly low molecular weights, the prepared compounds represent good starting points for further optimisation towards more potent and selective voltage-gated potassium channel inhibitors. (C) 2017 Elsevier Masson SAS. All rights reserved.