(S)-N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-1H-indole-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-1H-indole-2-carboxamide
• 英文别名: N-[(6S)-2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl]-1H-indole-2-carboxamide
• 化学式: C₁₆H₁₆N₄OS
• 分子量: 312.395
• InChiKey: AIMWCYZEKOOAKG-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-1H-indole-2-carboxamide 在 水 、 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 (S)-3-((6-(1H-indole-2-carboxamido)-4,5,6,7-tetrahydrobenzo-[1,2-d]thiazol-2-yl)amino)-3-oxopropanoic acid
  参考文献：
  名称：

  Discovery of 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazoles as Novel DNA Gyrase Inhibitors Targeting the ATP-Binding Site

  摘要：

  Bacterial DNA gyrase and topoisomerase IV are essential enzymes that control the topological state of DNA during replication and validated antibacterial drug targets. Starting from a library of marine alkaloid oroidin analogues, we identified low micromolar inhibitors of Escherichia coil DNA gyrase based on the 5,6,7,8-tetrahydroquinazoline and 4,5,6,7-tetrahydrobenzo [1,2-d]thiazole scaffolds. Structure-based optimization of the initial hits resulted in low nanomolar E. coil DNA gyrase inhibitors, some of which exhibited micromolar inhibition of E. coil topoisomerase IV and of Staphylococcus aureus homologues. Some of the compounds possessed modest antibacterial activity against Gram positive bacterial strains, while their evaluation against wild-type, impA and Delta tolC E. coil strains suggests that they are efflux pump substrates and/or do not possess the physicochemical properties necessary for cell wall penetration. Our study provides a rationale for optimization of this class of compounds toward balanced dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.

  DOI：

  10.1021/acs.jmedchem.5b00489
• 作为产物：
  描述：

  6-乙酰胺基-2-氨基-4,5,6,7-四氢苯并噻唑 在 L-酒石酸 、 氢溴酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.75h， 生成 (S)-N-(2-amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-1H-indole-2-carboxamide
  参考文献：
  名称：

  Discovery of 4,5,6,7-Tetrahydrobenzo[1,2-d]thiazoles as Novel DNA Gyrase Inhibitors Targeting the ATP-Binding Site

  摘要：

  Bacterial DNA gyrase and topoisomerase IV are essential enzymes that control the topological state of DNA during replication and validated antibacterial drug targets. Starting from a library of marine alkaloid oroidin analogues, we identified low micromolar inhibitors of Escherichia coil DNA gyrase based on the 5,6,7,8-tetrahydroquinazoline and 4,5,6,7-tetrahydrobenzo [1,2-d]thiazole scaffolds. Structure-based optimization of the initial hits resulted in low nanomolar E. coil DNA gyrase inhibitors, some of which exhibited micromolar inhibition of E. coil topoisomerase IV and of Staphylococcus aureus homologues. Some of the compounds possessed modest antibacterial activity against Gram positive bacterial strains, while their evaluation against wild-type, impA and Delta tolC E. coil strains suggests that they are efflux pump substrates and/or do not possess the physicochemical properties necessary for cell wall penetration. Our study provides a rationale for optimization of this class of compounds toward balanced dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.

  DOI：

  10.1021/acs.jmedchem.5b00489

文献信息

• Novel state-dependent voltage-gated sodium channel modulators, based on marine alkaloids from Agelas sponges
  作者：Žiga Hodnik、Tihomir Tomašić、Lucija Peterlin Mašič、Fiona Chan、Robert W. Kirby、David J. Madge、Danijel Kikelj

  DOI：10.1016/j.ejmech.2013.07.034

  日期：2013.12

  a voltage-gated sodium channel modulator. Here we describe the design and synthesis of conformationally restricted clathrodin analogues incorporating the 4,5,6,7-tetrahydrobenzo[d]thiazol-2-amine moiety and evaluation of their modulatory activities on human voltage-gated sodium channel isoforms Nav1.3, Nav1.4 and Nav1.7, as well as their selectivity against cardiac isoform Nav1.5. Compounds were shown

  Clathrodin是从Agelas海绵中分离的生物碱，在1995年被报道为电压门控钠通道调节剂。在这里，我们描述了结合4,5,6,7-四氢苯并[ d ]噻唑-2-胺基团的构象受限克拉德林类似物的设计和合成，以及它们对人电压门控钠通道亚型Na v 1.3的调节活性的评估， Na v 1.4和Na v 1.7以及它们对心脏亚型Na v 1.5的选择性。已显示化合物具有IC 50的Na v 1.3，Na v 1.4和Na v 1.7的状态依赖性调节剂对于通道的打开灭活状态，在较低的微摩尔范围内的值。初步的结构-活性关系研究表明，疏水相互作用对于结合所有三种测试的同工型非常重要。具有针对Na v 1.4的IC 50值为8μM的化合物4e代表了一种新型的选择性依赖于状态的Na v 1.4通道调节剂。