N-<(tert-butyloxy)carbonyl>-5,6-dihydroxyisoindoline | 156422-96-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-<(tert-butyloxy)carbonyl>-5,6-dihydroxyisoindoline
• 英文别名: tert-butyl 5,6-dihydroxy-2,3-dihydro-1H-isoindole-2-carboxylate；tert-butyl 5,6-dihydroxy-1,3-dihydroisoindole-2-carboxylate
• CAS: 156422-96-7
• 化学式: C₁₃H₁₇NO₄
• 分子量: 251.282
• InChiKey: KQWRHBSEVFOOCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-<(tert-butyloxy)carbonyl>-5,6-dihydroxyisoindoline 在 potassium carbonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 20.0h， 生成
  参考文献：
  名称：

  The Discovery of Capsazepine, the First Competitive Antagonist of the Sensory Neuron Excitants Capsaicin and Resiniferatoxin

  摘要：

  Capsaicin and resiniferatoxin are natural products which act specifically on a subset of primary afferent sensory neurons to open a novel cation-selective ion channel in the plasma membrane. These sensory neurons are involved in nociception, and so, these agents are targets for the design of a novel class of analgesics. Although synthetic agonists at the capsaicin receptor have been described previously, competitive antagonists at this receptor would be interesting and novel pharmacological agents. Structure-activity relationships for capsaicin agonists have previously been rationalized, by ourselves and others, by dividing the capsaicin molecule into three regions-the A (aromatic ring)-, B (amide bond)-, and C (hydrophobic side chain)-regions. In this study, the effects on biological activity of conformational constraint of the A-region with respect to the B-region are discussed. Conformational constraint was achieved by the introduction of saturated ring systems of different sizes. The resulting compounds provided agonists of comparable potency to unconstrained analogues as well as a moderately potent antagonist, capsazepine. This compound is the first competitive antagonist of capsaicin and resiniferatoxin to be described and is active in various systems, in vitro and in vivo. It has recently attracted considerable interest as a tool for dissecting the mechanisms by which capsaicin analogues evoke their effects. NMR spectroscopy and X-ray crystallography experiments, as well as molecular modeling techniques, were used to study the conformational behavior of a representative constrained agonist and antagonist. The conformation of the saturated ring contraint in the two cases was found to differ markedly, dramatically affecting the relative disposition of the A-ring and B-region pharmacophores. In agonist structures, the A- and B-regions were virtually coplanar in contrast to those in the antagonist, in which they were approximately orthogonal. A rationale for agonist and antagonist activity at the capsaicin receptor is proposed, based on the consideration of these conformational differences.

  DOI：

  10.1021/jm00039a006
• 作为产物：
  描述：

  N-(tert-butyloxycarbonyl)-5,6-dimethoxyisoindoline 在 三溴化硼 、 二碳酸二叔丁酯 、 三乙胺 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 以94.8 %的产率得到N-<(tert-butyloxy)carbonyl>-5,6-dihydroxyisoindoline
  参考文献：
  名称：

  Deoxyestrone-based lipofection agents with solution- and solid-state emission properties

  摘要：

  据报道，第一类溶液和固态发光体（SSSE）能够介导不同细胞系的基因转染。这些双亲化合物能在 DNA 存在的情况下自组装，形成具有低毒性的发光脂质体。

  DOI：

  10.1039/d3ob00656e

文献信息

• SAR studies of capsazepinoid bronchodilators. Part 2: Chlorination and catechol replacement in the A-ring
  作者：Magnus Berglund、María F. Dalence-Guzmán、Staffan Skogvall、Olov Sterner

  DOI：10.1016/j.bmc.2007.11.061

  日期：2008.3

  airways. From a systematic variation of the capsazepine structure, divided into four regions, SARs were established. This paper concerns the chlorination of the A-ring as well as the replacement of the catechol with bioisosteric groups. It is revealed that chlorination of the A-ring has a profound effect on activity. Moreover, di-chlorination of the 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline structure

  辣椒素及其衍生物和类似物是人类小气道收缩的一般抑制剂。从辣椒素结构的系统变化分为四个区域，建立了SAR。本文涉及A环的氯化以及生物等位基团取代邻苯二酚。揭示了A环的氯化对活性有深远的影响。此外，与卡塞平相比，对6,7-二羟基-1,2,3,4-四氢异喹啉结构进行二氯化处理会导致效力增加10倍。
• The Discovery of Capsazepine, the First Competitive Antagonist of the Sensory Neuron Excitants Capsaicin and Resiniferatoxin
  作者：Christopher S. J. Walpole、Stuart Bevan、Guenter Bovermann、Johann J. Boelsterli、Robin Breckenridge、John W. Davies、Glyn A. Hughes、Iain James、Lukas Oberer、Janet Winter、Roger Wrigglesworth

  DOI：10.1021/jm00039a006

  日期：1994.6.1

  Capsaicin and resiniferatoxin are natural products which act specifically on a subset of primary afferent sensory neurons to open a novel cation-selective ion channel in the plasma membrane. These sensory neurons are involved in nociception, and so, these agents are targets for the design of a novel class of analgesics. Although synthetic agonists at the capsaicin receptor have been described previously, competitive antagonists at this receptor would be interesting and novel pharmacological agents. Structure-activity relationships for capsaicin agonists have previously been rationalized, by ourselves and others, by dividing the capsaicin molecule into three regions-the A (aromatic ring)-, B (amide bond)-, and C (hydrophobic side chain)-regions. In this study, the effects on biological activity of conformational constraint of the A-region with respect to the B-region are discussed. Conformational constraint was achieved by the introduction of saturated ring systems of different sizes. The resulting compounds provided agonists of comparable potency to unconstrained analogues as well as a moderately potent antagonist, capsazepine. This compound is the first competitive antagonist of capsaicin and resiniferatoxin to be described and is active in various systems, in vitro and in vivo. It has recently attracted considerable interest as a tool for dissecting the mechanisms by which capsaicin analogues evoke their effects. NMR spectroscopy and X-ray crystallography experiments, as well as molecular modeling techniques, were used to study the conformational behavior of a representative constrained agonist and antagonist. The conformation of the saturated ring contraint in the two cases was found to differ markedly, dramatically affecting the relative disposition of the A-ring and B-region pharmacophores. In agonist structures, the A- and B-regions were virtually coplanar in contrast to those in the antagonist, in which they were approximately orthogonal. A rationale for agonist and antagonist activity at the capsaicin receptor is proposed, based on the consideration of these conformational differences.
• Deoxyestrone-based lipofection agents with solution- and solid-state emission properties
  作者：Alexander Huber、Johannes Koch、Kevin Rudolph、Alexander Höing、Fabio Rizzo、Shirley K. Knauer、Jens Voskuhl

  DOI：10.1039/d3ob00656e

  日期：——

  The first class of solution and solid-state emitters (SSSE) capable of mediating gene transfection of different cell lines is reported. These amphiphiles can self-assemble in presence of DNA, forming luminescent lipoplexes that feature low toxicity.

  据报道，第一类溶液和固态发光体（SSSE）能够介导不同细胞系的基因转染。这些双亲化合物能在 DNA 存在的情况下自组装，形成具有低毒性的发光脂质体。