N-(3-azidopropyl)-2,3-dicyanoquinoxaline-6-carboxamide | 1217309-34-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(3-azidopropyl)-2,3-dicyanoquinoxaline-6-carboxamide
• CAS: 1217309-34-6
• 化学式: C₁₄H₁₀N₈O
• 分子量: 306.286
• InChiKey: DIHWZWBTSZSEPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4,5-bis(tert-butylsulfanyl)phthalonitrile 、 N-(3-azidopropyl)-2,3-dicyanoquinoxaline-6-carboxamide 在 magnesium di-n-butanolate 作用下， 以 正丁醇 为溶剂， 反应 19.0h， 以33%的产率得到
  参考文献：
  名称：

  A phthalocyanine–mestranol conjugate for photodynamic therapy prepared via click chemistry

  摘要：

  Introduction of an azide group onto the periphery of a photodynamically effective phthalocyanine (Pc) derivative gives a useful building block for the preparation of Pc conjugates via Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition ('click chemistry'). In this way, Pc-mestranol and Pc-hept-1-yne conjugates (for comparison purposes) are synthesized and their absorption, photochemical, and photophysical properties are studied. The conjugate retains the advantageous photophysical and photochemical properties of Pc. Conjugation with mestranol may lead to improved localization in tumors whereas the Pc unit is responsible for the photodynamic effect. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.12.075
• 作为产物：
  描述：

  2,3-Dicyan-6-chinoxalincarbonsaeure 在 氯化亚砜 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.0h， 生成 N-(3-azidopropyl)-2,3-dicyanoquinoxaline-6-carboxamide
  参考文献：
  名称：

  腈双硫醇生物共轭反应

  摘要：

  贫电子芳基腈由于其高亲电性和与硫醇反应的选择性而成为有前景的生物共轭试剂，尽管通常以可逆的方式进行。先前在此类反应中观察到一种瞬态物质，涉及将两个硫醇加成到腈官能团上，形成四面体氨基二硫缩醛（ADTA）。在这项工作中，探索了杂芳基腈与双硫醇的反应，试图生成稳定的 ADTA，这可以促进新的生物共轭方案。通过使用 1,2-二硫醇，或将亲电子陷阱纳入芳基腈设计中，可以形成稳定的产物。然后在蛋白质修饰的背景下探索所产生的“腈双硫醇”（NBT）反应，特别是进行抗体缀合。通过将这些腈添加到抗体片段的还原二硫键上，结果表明，根据试剂设计，可以生成半胱氨酸到赖氨酸的转移或二硫键桥接的NBT产物。两者均代表位点选择性缀合物，并且在生理条件下用谷胱甘肽攻击时以及在血清中孵育时表现出稳定。此外，NBT 反应在更具挑战性的完整抗体环境中进行了测试，并且所有四个二硫键均被这些新的一碳桥接试剂有效地修饰。总体而言，杂

  DOI：

  10.1021/jacs.3c08762

文献信息

• Photodynamically active phthalocyanine building blocks for click chemistry
  作者：Veronika Novakova、Kamil Kopecky、Miroslav Miletin、Jana Ivincova、Petr Zimcik

  DOI：10.1142/s1088424611003987

  日期：2011.9

  Synthesis of symmetrical and unsymmetrical zinc phthalocyanines from two different precursors 4,5-bis(tert-butylsulfanyl)phthalonitrile (A) and N-(3-azidopropyl)-2,3-dicyanoquinoxaline-6-carboxamide (B) is described. Congeners of AAAA, AAAB, ABAB and AABB type were isolated by a chromatographic technique, however, the congener of BBBB type had to be prepared in a separate reaction. The adjacent and opposite isomers were also separated and fully characterized. Isolated phthalocyanines contained different number of azide groups, a substrate for highly efficient Cu(I) -catalyzed azide-alkyne 1,3-dipolar cycloaddition ("click chemistry"). All phthalocyanines absorbed strongly (ε over 150 000 M^-1.cm^-1) over 700 nm. Their singlet oxygen quantum yields were determined in DMF and ranged from 0.63 to 0.79, fluorescence quantum yields in DMF were considerably lower in the range 0.03–0.06. All these properties make them suitable building blocks for a simple modification and a synthesis of phthalocyanines with better tuned properties for photodynamic therapy.

  介绍了从两种不同的前体 4,5-双（叔丁基硫酰）酞腈（A）和 N-（3-叠氮丙基）-2,3-二氰基喹喔啉-6-甲酰胺（B）合成对称和不对称锌酞菁的过程。通过色谱技术分离出了 AAAA、AAAB、ABAB 和 AABB 型同系物，但 BBBB 型同系物必须通过单独的反应制备。相邻和相反的异构体也被分离出来，并进行了全面的表征。分离出的酞菁含有不同数量的叠氮基团，是高效的 Cu(I) 催化叠氮-炔烃 1,3- 二极环加成（"点击化学"）的底物。所有酞菁在 700 纳米波长范围内都有很强的吸收能力（ε 超过 150 000 M-1.cm-1）。它们在 DMF 中的单线态氧量子产率为 0.63 至 0.79，而在 DMF 中的荧光量子产率则低得多，为 0.03 至 0.06。所有这些特性都使它们成为简单改性和合成具有更好的光动力疗法特性的酞菁的合适构件。
• The effect of the number of carbohydrate moieties on the azaphthalocyanine properties
  作者：Veronika Novakova、Rabia Zeynep Uslu Kobak、Radim Kučera、Kamil Kopecky、Miroslav Miletin、Veronika Krepsová、Jana Ivincová、Petr Zimcik

  DOI：10.1039/c2dt30971h

  日期：——

  A series of azaphthalocyanines (AzaPc) bearing one, two, four or eight isopropylidene-protected galactosyl units was prepared by azide–alkyne click reaction or by classical Pc template cyclotetramerization of the corresponding dicyanopyrazine and AzaPc properties important for photodynamic therapy were compared. All compounds absorbed at long wavelengths (above 650 nm) and belonged to strong singlet oxygen producers (ΦΔ = 0.58–0.64) retaining significant fluorescence emission (ΦF = 0.026–0.23). The only exception was the compound with four isopropyliden-protected galactosyl units where partial aggregation was observed. Removal of protecting groups increased the polar character of all AzaPc. However, only AzaPc bearing eight galactoses was found to be water-soluble (105 mg mL−1) but noticeably aggregated in water as well as in organic solvents (DMF, DMSO). Amphiphilic AzaPc bearing one deprotected galactose was incorporated into the lipidic bilayer of liposomes in a nonaggregated form. Liposomes may therefore be a suitable delivery system for this amphiphilic photosensitizer.

  一系列含有一个、两个、四个或八个异丙烯基保护的半乳糖基团的氮杂酞菁（AzaPc）通过叠氮-炔烃点击反应或通过相应的二氰基吡嗪的经典酞菁模板环四聚化法合成。比较了这些AzaPc在光动力治疗中重要的性质。所有化合物均在长波长（超过650 nm）处有吸收，并且是强单线态氧生产者（ΦΔ = 0.58–0.64），保留了显著的荧光发射（ΦF = 0.026–0.23）。唯一的例外是具有四个异丙烯基保护的半乳糖单位的化合物，观察到部分聚集。去除保护基团后，所有AzaPc的极性特性都增强。然而，只有含有八个半乳糖的AzaPc被发现是水溶性的（105 mg mL−1），但在水中以及有机溶剂（DMF、DMSO）中明显聚集。具有一个去保护半乳糖的两亲性AzaPc以非聚集形式被纳入了脂质体的脂双层中。因此，脂质体可能是这种两亲性光敏剂的合适递送系统。
• A phthalocyanine–mestranol conjugate for photodynamic therapy prepared via click chemistry
  作者：Veronika Novakova、Petr Zimcik、Miroslav Miletin、Kamil Kopecky、Jana Ivincová

  DOI：10.1016/j.tetlet.2009.12.075

  日期：2010.2

  Introduction of an azide group onto the periphery of a photodynamically effective phthalocyanine (Pc) derivative gives a useful building block for the preparation of Pc conjugates via Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition ('click chemistry'). In this way, Pc-mestranol and Pc-hept-1-yne conjugates (for comparison purposes) are synthesized and their absorption, photochemical, and photophysical properties are studied. The conjugate retains the advantageous photophysical and photochemical properties of Pc. Conjugation with mestranol may lead to improved localization in tumors whereas the Pc unit is responsible for the photodynamic effect. (C) 2009 Elsevier Ltd. All rights reserved.
• The Nitrile Bis-Thiol Bioconjugation Reaction
  作者：Mikesh Patel、Nafsika Forte、Charlie R. Bishop、Michael J. Porter、Matthew Dagwell、Kersti Karu、Vijay Chudasama、James R. Baker

  DOI：10.1021/jacs.3c08762

  日期：2024.1.10

  nitriles are promising reagents for bioconjugation due to their high electrophilicity and selectivity for reaction with thiols, albeit generally in a reversible manner. A transient species has previously been observed in such reactions, involving the addition of two thiols to the nitrile functional group, forming a tetrahedral amino dithioacetal (ADTA). In this work, the reaction of heteroaryl nitriles

  贫电子芳基腈由于其高亲电性和与硫醇反应的选择性而成为有前景的生物共轭试剂，尽管通常以可逆的方式进行。先前在此类反应中观察到一种瞬态物质，涉及将两个硫醇加成到腈官能团上，形成四面体氨基二硫缩醛（ADTA）。在这项工作中，探索了杂芳基腈与双硫醇的反应，试图生成稳定的 ADTA，这可以促进新的生物共轭方案。通过使用 1,2-二硫醇，或将亲电子陷阱纳入芳基腈设计中，可以形成稳定的产物。然后在蛋白质修饰的背景下探索所产生的“腈双硫醇”（NBT）反应，特别是进行抗体缀合。通过将这些腈添加到抗体片段的还原二硫键上，结果表明，根据试剂设计，可以生成半胱氨酸到赖氨酸的转移或二硫键桥接的NBT产物。两者均代表位点选择性缀合物，并且在生理条件下用谷胱甘肽攻击时以及在血清中孵育时表现出稳定。此外，NBT 反应在更具挑战性的完整抗体环境中进行了测试，并且所有四个二硫键均被这些新的一碳桥接试剂有效地修饰。总体而言，杂