Z-3-benzylidene-2-[3-(dimethylamino)propyl]-2,3-dihydro-1H-isoindol-1-one | 284685-13-8

• 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: Z-3-benzylidene-2-[3-(dimethylamino)propyl]-2,3-dihydro-1H-isoindol-1-one
• 英文别名: 3-benzylidene-2-[3-(dimethylamino)propyl]-2,3-dihydro-1H-isoindol-1-one；3-(Z)-benzylidene-N-[3-(N,N-dimethylamino)propyl]-1-isoindolinone；(3Z)-3-benzylidene-2-[3-(dimethylamino)propyl]isoindol-1-one
• CAS: 284685-13-8
• 化学式: C₂₀H₂₂N₂O
• 分子量: 306.407
• InChiKey: XSBYHWZEXSJGMU-CYVLTUHYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,6-二溴己烷 、 Z-3-benzylidene-2-[3-(dimethylamino)propyl]-2,3-dihydro-1H-isoindol-1-one 以 乙腈 为溶剂， 反应 5.0h， 以57%的产率得到3-(Z)-benzylidene-2-{3-[1-(6-{1,1-dimethyl-1-[3-(3-(Z)-benzylidene-1-oxo-2,3-dihydro-1H-2-isoindolyl)propyl]ammonio}hexyl)-1,1-dimethylammonio]propyl}-1-isoindolinone dibromide
  参考文献：
  名称：

  Structure−Activity Relationships in a Series of Bisquaternary Bisphthalimidine Derivatives Modulating the Muscarinic M₂-Receptor Allosterically

  摘要：

  Hexane-bisammonium-type compounds containing lateral phthalimide moieties are well-established ligands of the common allosteric binding site of muscarinic M-2 receptors. Previous structure-activity relationships (SAR) revealed two positively charged centers and two lateral phthalimide moieties in a defined arrangement to be essential of a high allosteric potency. The purpose of this study was to replace one carbonyl group of the phthalimides with hydrogens, hydroxy, alkoxy, phenyl, benzyl, and benzylidene groups in order to check the influence of these substituents on the allosteric activity in antagonist-linked receptors. The analysis of the quantitative SAR indicated that a high allosteric potency is related to a certain amount of rigidity as well as polarizibility and the ability to form hydrophobic interactions.

  DOI：

  10.1021/jm991136e
• 作为产物：
  描述：

  (Z)-3-benzylidenephthalide 在 甲酸 作用下， 以 乙醇 为溶剂， 反应 4.5h， 生成 Z-3-benzylidene-2-[3-(dimethylamino)propyl]-2,3-dihydro-1H-isoindol-1-one
  参考文献：
  名称：

  Structure−Activity Relationships in a Series of Bisquaternary Bisphthalimidine Derivatives Modulating the Muscarinic M₂-Receptor Allosterically

  摘要：

  Hexane-bisammonium-type compounds containing lateral phthalimide moieties are well-established ligands of the common allosteric binding site of muscarinic M-2 receptors. Previous structure-activity relationships (SAR) revealed two positively charged centers and two lateral phthalimide moieties in a defined arrangement to be essential of a high allosteric potency. The purpose of this study was to replace one carbonyl group of the phthalimides with hydrogens, hydroxy, alkoxy, phenyl, benzyl, and benzylidene groups in order to check the influence of these substituents on the allosteric activity in antagonist-linked receptors. The analysis of the quantitative SAR indicated that a high allosteric potency is related to a certain amount of rigidity as well as polarizibility and the ability to form hydrophobic interactions.

  DOI：

  10.1021/jm991136e

文献信息

• The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1<i>H</i>-isoindolin-1-ones
  作者：Ommid Anamimoghadam、Saira Mumtaz、Anke Nietsch、Gaetano Saya、Cherie A Motti、Jun Wang、Peter C Junk、Ashfaq Mahmood Qureshi、Michael Oelgemöller

  DOI：10.3762/bjoc.13.275

  日期：——

  The synthesis of various 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones was realized following a simple three-step process. The protocol utilized the photodecarboxylative addition of readily available carboxylates to N-(bromoalkyl)phthalimides as a versatile and efficient key step. The initially obtained hydroxyphthalimidines were readily converted to the desired N-diaminoalkylated 3-arylmethylene-2

  通过简单的三步过程即可实现各种3-芳基亚甲基-2,3-二氢-1H-异吲哚-1-酮的合成。该协议利用了容易获得的羧酸酯的光脱羧加成到N-（溴代烷基）邻苯二甲酰亚胺的通用有效步骤。最初获得的羟基邻苯二甲酰亚胺通过酸催化的脱水作用随后被相应的仲胺亲核取代，可以很容易地转化为所需的N-二氨基烷基化的3-芳基亚甲基-2，3-二氢-1H-异吲哚-1-酮。该程序已成功应用于中性形式的已知局部麻醉药（AL-12，AL-12B和AL-5）的合成。
• Continuous Flow Photochemical and Thermal Multi-Step Synthesis of Bioactive 3-Arylmethylene-2,3-Dihydro-1H-Isoindolin-1-Ones
  作者：Saira Mumtaz、Mark J. Robertson、Michael Oelgemöller

  DOI：10.3390/molecules24244527

  日期：——

  An effective multi-step continuous flow approach towards N-diaminoalkylated 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones, including the local anesthetic compound AL-12, has been realized. Compared to the traditional decoupled batch processes, the combined photochemical–thermal–thermal flow setup rapidly provides the desired target compounds in superior yields and significantly shorter reaction

  一种针对 N-二氨基烷基化 3-芳基亚甲基-2,3-dihydro-1H-isoindolin-1-ones 的有效多步连续流动方法，包括局部麻醉化合物 AL-12，已经实现。与传统的分批分离工艺相比，组合的光化学-热-热流动设置以优异的产率和显着更短的反应时间快速提供所需的目标化合物。
• Structure−Activity Relationships in a Series of Bisquaternary Bisphthalimidine Derivatives Modulating the Muscarinic M₂-Receptor Allosterically
  作者：Hector M. Botero Cid、Christian Tränkle、Knut Baumann、Rainer Pick、Elisabeth Mies-Klomfass、Evi Kostenis、Klaus Mohr、Ulrike Holzgrabe

  DOI：10.1021/jm991136e

  日期：2000.6.1

  Hexane-bisammonium-type compounds containing lateral phthalimide moieties are well-established ligands of the common allosteric binding site of muscarinic M-2 receptors. Previous structure-activity relationships (SAR) revealed two positively charged centers and two lateral phthalimide moieties in a defined arrangement to be essential of a high allosteric potency. The purpose of this study was to replace one carbonyl group of the phthalimides with hydrogens, hydroxy, alkoxy, phenyl, benzyl, and benzylidene groups in order to check the influence of these substituents on the allosteric activity in antagonist-linked receptors. The analysis of the quantitative SAR indicated that a high allosteric potency is related to a certain amount of rigidity as well as polarizibility and the ability to form hydrophobic interactions.