7,8-二甲氧基-2,3,4,5-四氢-2-苯并氮杂卓 | 95469-38-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: 7,8-二甲氧基-2,3,4,5-四氢-2-苯并氮杂卓
• 英文名称: 7,8-dimethoxy-2,3,4,5-tetrahydro-1H-benzo[c]azepine
• 英文别名: 7,8-Dimethoxy-2,3,4,5-tetrahydro-2-benzazepine；7,8-dimethoxy-2,3,4,5-tetrahydro-1H-2-benzazepine
• CAS: 95469-38-8
• 化学式: C₁₂H₁₇NO₂
• 分子量: 207.272
• InChiKey: QHNGDKGTMYVCMX-UHFFFAOYSA-N

物化性质

• 熔点：
  42-44°C
• 沸点：
  328.4±42.0 °C(Predicted)
• 密度：
  1.046±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、DMSO、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7,8-二甲氧基-2,3,4,5-四氢-2-苯并氮杂卓 在 potassium carbonate 、 一水合肼 、 sodium iodide 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 4-(7,8-dimethoxy-4,5-dihydro-1H-benzo[c]azepin-2(3H)-yl)butan-1-amine
  参考文献：
  名称：

  Effect of structural modification in the amine portion of substituted aminobutyl-benzamides as ligands for binding σ1 and σ2 receptors

  摘要：

  5-Bromo-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2,3-dimethoxy-benzamide (1) is one of the most potent and selective sigma(2) receptor ligands reported to date. A series of new analogs, where the amine ring fused to the aromatic ring was varied in size (5-7) and the location of the nitrogen in this ring was modified, has been synthesized and assessed for their sigma(1)/sigma(2) binding affinity and selectivity. The binding affinity of an open-chained variant of 1 was also evaluated. Only the five-membered ring congener of 1 displayed a higher sigma(1)/sigma(2) selectivity, derived from a higher sigma(2) affinity and a lower sigma(1) affinity. Positioning the nitrogen adjacent to the aromatic ring in the five-membered and six-membered ring congeners dramatically decreased affinity for both subtypes. Thus, location of the nitrogen within a constrained ring is confirmed to be key to the exceptional sigma(2) receptor binding affinity and selectivity for this active series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.02.006
• 作为产物：
  描述：

  3,4-二甲氧基苯丙酸 在 ammonium hydroxide 、 sodium tetrahydroborate 、 氯化亚砜 、 硫酸 、 三氟化硼乙醚 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 7,8-二甲氧基-2,3,4,5-四氢-2-苯并氮杂卓
  参考文献：
  名称：

  7,8-二甲氧基-2,3,4,5-四氢-1H-苯并[c]氮 杂卓盐酸盐及其制备方法

  摘要：

  本发明公开了7,8‑二甲氧基‑2,3,4,5‑四氢‑1H‑苯并[c]氮杂卓盐酸盐及其制备方法，以3,4‑二甲氧基苯丙酸为起始物，在氯化亚砜催化、然后胺解得到3,4‑二甲氧基苯丙酰胺；三氟化硼乙醚、硼氢化钠还原得到3,4‑二甲氧基苯丙胺；乙酰基保护后在硫酸和多聚甲醛中反应得到N‑乙酰基‑7,8‑二甲氧基‑2,3,4,5‑四氢‑1H‑苯并[c]氮杂卓；脱去乙酰基、Boc保护得到N‑Boc‑7,8‑二甲氧基‑2,3,4,5‑四氢‑1H‑苯并[c]氮杂卓；通入盐酸气体得到7,8‑二甲氧基‑2,3,4,5‑四氢‑1H‑苯并[c]氮杂卓盐酸盐，该制备方法条件相对温和，产物易处理纯化，适合批量制备。

  公开号：

  CN107298655B

文献信息

• Lithiated β-aminoalkyl sulfones as mono and dinucleophiles in the preparation of nitrogen heterocycles: Application to the synthesis of capsazepine
  作者：Diego A. Alonso、Ana Costa、Balbino Mancheño、Carmen Nájera

  DOI：10.1016/s0040-4020(97)00163-4

  日期：1997.3

  lithiation of N-benzyl-β-tosylethanamine (10a) and N-benzyl-α-phenyl-β-tosylethanamine (10b) with n-butyllithium at −78°C leads to monoanions 11a and 11b, respectively. Intermediates 11 react with different monoelectrophiles (D2O, alkyl halides, and carbonyl compounds) at the α-position with respect to the sulfone, and with dielectrophiles (1,3-, 1,4-dihalides, α-bromoacetates, and α-chloroketones) to afford

  在-78℃下用正丁基锂对N-苄基-β-甲苯磺胺（10a）和N-苄基-α-苯基-β-甲苯磺胺（10b）进行锂化分别产生单阴离子11a和11b。中间体11与相对于砜在α位的不同单亲电子试剂（D 2 O，烷基卤化物和羰基化合物）反应，并与二亲电子试剂（1,3-，1,4-二卤化物，α-溴乙酸酯和α （-氯酮），得到相应的6、7和5元氮杂环。苯并ze庚因衍生物13ae通过11a与4，5-双（氯甲基）-1，2-二甲氧基苯反应获得的α ，被转化成辣椒素25的中间前体24，辣椒素25是感觉神经元兴奋剂辣椒素和树脂毒素的拮抗剂。环状β-氨基砜：N-苄基-3-甲苯磺酰基哌啶（13aa）在轴向位置与锂离子亲电试剂反应生成锂27。在将迈克尔加成至巴豆酸甲酯的情况下，将相应的加合物转化成1-氮杂双环[3.3.1]壬南-2-酮衍生物。最后，用一些代表性的衍生物研究了碱诱导的脱氢亚磺酰化，还原性脱磺酰化和朱莉娅的甲基化。
• 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.
• Synthesis of 2,3,4,5-Tetrahydro-1H-2-benzazepines via Pummerer-Type Cyclization of N-Arylmethyl-N-(3-phenylsulfinylpropyl)formamides
  作者：Takehiro Sano、Yoshie Horiguchi、Toshiaki Saitoh、Sachiko Terakado、Konomi Honda、Tomoko Kimura、Jun Toda

  DOI：10.3987/com-00-s(i)97

  日期：——
• [DE] PYRROLOPYRIDIN-DERIVATE UND DEREN VERWENDUNG ZUR NUKLEARMEDIZINISCHEN BILDGEBUNG<br/>[EN] PYRROLOPYRIDINE DERIVATIVES AND THEIR USE FOR NUCLEAR-MEDICAL IMAGING<br/>[FR] DÉRIVÉS DE PYRROLOPYRIDINE ET LEUR UTILISATION POUR L'IMAGERIE MÉDICALE NUCLÉAIRE
  申请人：HELMHOLTZ ZENTRUM DRESDEN

  公开号：WO2020108688A1

  公开（公告）日：2020-06-04

  Die Erfindung betrifft eine Verbindung der allgemeinen Formel (I), worin Ar ein Pyridin-Ring ist. Außerdem ist eine Präkursor-Verbindung zur Herstellung einer Verbindung der Formel (I) vorgesehen, die anstelle einer Gruppe R1 eine Abgangsgruppe aufweist.