3-azido-N-methyl-1-propanamine

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 3-azido-N-methyl-1-propanamine
• 英文别名: 3-azidopropan-1-ol；3-azido-N-methylpropan-1-amine；(3-Azidopropyl)methylamine
• 化学式: C₄H₁₀N₄
• 分子量: 114.15
• InChiKey: OARHWZNDORQUQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  8
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  26.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  溶剂红 49 、 3-azido-N-methyl-1-propanamine 在 三氯氧磷 作用下， 生成
  参考文献：
  名称：

  Fixable Molecular Thermometer for Real-Time Visualization and Quantification of Mitochondrial Temperature

  摘要：

  线粒体温度变化可以作为线粒体产生大量热量的重要代谢指标。因此，开发用于检测线粒体温度的荧光探针已成为一个有吸引力的课题。先前的研究已经成功解决了温度敏感性和线粒体靶向性等主要问题。然而，仍存在一个关键障碍阻碍其实际应用。考虑到线粒体的高度动态特性，尤其是内膜电位的变化，将温度探针永久固定在线粒体中以避免随线粒体状态变化而导致的细胞内定位不稳定是十分必要的。本文报道了第一个可固定的荧光分子温度计Mito-TEM。Mito-TEM基于带正电的罗丹明B荧光团，该荧光团倾向于被带负电的线粒体吸引。含有可旋转取代基的该荧光团也有助于温度响应的荧光性质。最重要的是，Mito-TEM引入了苯甲醛作为锚定单元，与蛋白质的氨基缩合从而将探针固定在线粒体中。通过共定位成像明确证明了Mito-TEM在线粒体中的特定固定。使用Mito-TEM建立了一种通过线粒体的灰度成像来可视化和量化温度分布的方法，并进一步应用于监测光热加热和PMA刺激下活细胞的温度变化。

  DOI：

  10.1021/acs.analchem.8b03395
• 作为产物：
  描述：

  3-azidopropyl methanesulfonate 、 甲胺 在 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 20.0h， 生成 3-azido-N-methyl-1-propanamine
  参考文献：
  名称：

  具有反应性基团的极性红光若丹明染料：合成，光物理性质和双色STED纳米技术应用

  摘要：

  具有强红色荧光，两个极性残基（羟基，伯磷酸酯或磺酸基团）的新型若丹明的合成，反应性和光物理性质，并改善了氨基反应位点（NHS酯或混合的N-琥珀酰亚胺基碳酸酯）的水解稳定性）的报告。所有荧光团均包含N烷基1,2,2-二氢，2,2,4-三甲基喹啉片段，其中大多数带有带有仲羧酰胺基团的完全取代的四氟苯环。在水中的吸收和发射最大值分别在635–639和655–659 nm之间。开发了一种极大简化的方法，该方法可以使带有两个磷酸基团的若丹明红光发射，这些罗丹明与各种功能性连接基兼容。例如，制备了具有叠氮化物残基的磷酸化染料，并将其用于与带有N的应变炔烃的点击反应中-羟基琥珀酰亚胺（NHS）酯基。该方法绕过了磷酸基团的不希望有的活化作用，得到了一种两亲性氨基反应性染料，可以通过改变pH值来控制其在水相和有机相之间的溶解度和分布。在染料中具有另一个取代模式的两个羟基和一个带有两个羧基残基的苯环的存在足以提供亲水性。选择性形成单-

  DOI：

  10.1002/chem.201303433

文献信息

• [EN] COMPOUNDS FOR INHIBITING PROTEIN DEGRADATION AND METHODS OF USE THEREOF IN THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS AGISSANT EN TANT QU'INHIBITEUR DE LA DÉGRADATION PROTÉIQUE ET PROCÉDÉS D'UTILISATION ASSOCIÉS POUR LE TRAITEMENT DU CANCER
  申请人：PI THERAPEUTICS LTD

  公开号：WO2019171379A1

  公开（公告）日：2019-09-12

  The present invention relates to compounds for inhibiting protein degradation and/or the ubiquitin-proteasome system and/or for modulating autophagy, pharmaceutical composition and methods of use thereof in the treatment of cancer.

  本发明涉及用于抑制蛋白降解和/或泛素蛋白酶体系统和/或调节自噬的化合物，以及在癌症治疗中使用的药物组合物和方法。
• Purification Strategy for Direct Nucleophilic Procedures
  申请人：Cyr John

  公开号：US20110112293A1

  公开（公告）日：2011-05-12

  The present invention provides novel and advantageous processes for preparing and purifying chemical compounds such as pharmaceuticals. The processes comprise a nucleophilic substitution reaction with a moiety X wherein the leaving group L of a substrate S in the reaction is covalently attached to a purification moiety M. This concept offers a convenient and lime-saving way to purity the desired product S-X from non-reacted precursors S-L-M and by-products L-M.

  本发明提供了一种新颖和有利的制备和纯化化学化合物，如药物的方法。该方法包括使用一个官能团X进行亲核取代反应，其中反应底物S的离去基团L共价地连接到纯化官能团M上。这个概念提供了一种方便和节省时间的方法，以从未反应的前体S-L-M和副产物L-M中纯化所需的产品S-X。
• Structure−Immunosuppressive Activity Relationships of New Analogues of 15-Deoxyspergualin. 2. Structural Modifications of the Spermidine Moiety
  作者：Luc Lebreton、Eric Jost、Bertrand Carboni、Jocelyne Annat、Michel Vaultier、Patrick Dutartre、Patrice Renaut

  DOI：10.1021/jm991043x

  日期：1999.11.1

  A series of new analogues of 15-deoxyspergualin (DSG), an immunosuppressive agent commercialized in Japan, was synthesized and tested in a graft-versus-host disease (GVHD) model in mice. Various substitutions of the spermidine "D" region were made in order to determine its optimum structure in terms of in vivo immunosuppressive activity. Various positions of methylation were first investigated leading to the discovery of the monomethylated malonic derivative 56h in which the pro-R hydrogen of the methylene a to the primary amine of the spermidine moiety has been replaced by a methyl group. Synthesis of the similarly methylated analogue of the previously reported glycolic derivative LF 08-0299 afforded 60e which demonstrated a powerful activity at a dose as low as 0.3 mg/kg in the GVHD model and was much more potent than DSG in the demanding heart allotransplantation model in rats. The improvement of in vivo activity was supposed to be related to an increase of the metabolic stability of the methylated analogues compared to the parent molecules. Due to its very low active dose, compatible with a subcutaneous administration in humans, and its favorable pharmacological and toxicological profile, 60e was selected as a candidate for clinical evaluation.
• Fixable Molecular Thermometer for Real-Time Visualization and Quantification of Mitochondrial Temperature
  作者：Zhenlong Huang、Ning Li、Xinfu Zhang、Chao Wang、Yi Xiao

  DOI：10.1021/acs.analchem.8b03395

  日期：2018.12.4

  A change of mitochondrial temperature can be an important indicator of mitochondrial metabolism that generates considerable heat. For this reason, development of fluorescent probes to detect mitochondrial temperature has become an attractive topic. Previous efforts have successfully addressed the major issues, such as temperature sensitivity and mitochondrial targetability. However, there remains a key obstacle to practical applications. Considering the highly dynamic features of mitochondria, especially the variation of the inner-membrane potential, it is quite necessary to permanently immobilize a temperature probe in mitochondria in order to avoid unstable intracellular localization along with the changes of mitochondrial status. Herein, we report Mito-TEM, the first fixable, fluorescent molecular thermometer. Mito-TEM is based on a positively charged rhodamine B fluorophore that has the tendency of being attracted to mitochondria, which have negative potential. This fluorophore containing rotatable substituents also contributes to the temperature-responsive fluorescence property. Most importantly, a benzaldehyde is introduced in Mito-TEM as an anchoring unit that condenses with aminos of the protein and thus immobilizes the probe in mitochondria. The specific immobilization of Mito-TEM in mitochondria is unambiguously demonstrated in colocalization imaging. By using Mito-TEM, a method of visualizing and quantifying a temperature distribution through grayscale imaging of mitochondria is established and further applied to monitor the temperature changes of live cells under light heating and PMA stimulation.

  线粒体温度变化可以作为线粒体产生大量热量的重要代谢指标。因此，开发用于检测线粒体温度的荧光探针已成为一个有吸引力的课题。先前的研究已经成功解决了温度敏感性和线粒体靶向性等主要问题。然而，仍存在一个关键障碍阻碍其实际应用。考虑到线粒体的高度动态特性，尤其是内膜电位的变化，将温度探针永久固定在线粒体中以避免随线粒体状态变化而导致的细胞内定位不稳定是十分必要的。本文报道了第一个可固定的荧光分子温度计Mito-TEM。Mito-TEM基于带正电的罗丹明B荧光团，该荧光团倾向于被带负电的线粒体吸引。含有可旋转取代基的该荧光团也有助于温度响应的荧光性质。最重要的是，Mito-TEM引入了苯甲醛作为锚定单元，与蛋白质的氨基缩合从而将探针固定在线粒体中。通过共定位成像明确证明了Mito-TEM在线粒体中的特定固定。使用Mito-TEM建立了一种通过线粒体的灰度成像来可视化和量化温度分布的方法，并进一步应用于监测光热加热和PMA刺激下活细胞的温度变化。
• Polar Red-Emitting Rhodamine Dyes with Reactive Groups: Synthesis, Photophysical Properties, and Two-Color STED Nanoscopy Applications
  作者：Kirill Kolmakov、Christian A. Wurm、Dirk N. H. Meineke、Fabian Göttfert、Vadim P. Boyarskiy、Vladimir N. Belov、Stefan W. Hell

  DOI：10.1002/chem.201303433

  日期：2014.1.3

  of them bear a fully substituted tetrafluoro phenyl ring with a secondary carboxamide group. The absorption and emission maxima in water are in the range of 635–639 and 655–659 nm, respectively. A vastly simplified approach to red‐emitting rhodamines with two phosphate groups that are compatible with diverse functional linkers was developed. As an example, a phosphorylated dye with an azide residue was

  具有强红色荧光，两个极性残基（羟基，伯磷酸酯或磺酸基团）的新型若丹明的合成，反应性和光物理性质，并改善了氨基反应位点（NHS酯或混合的N-琥珀酰亚胺基碳酸酯）的水解稳定性）的报告。所有荧光团均包含N烷基1,2,2-二氢，2,2,4-三甲基喹啉片段，其中大多数带有带有仲羧酰胺基团的完全取代的四氟苯环。在水中的吸收和发射最大值分别在635–639和655–659 nm之间。开发了一种极大简化的方法，该方法可以使带有两个磷酸基团的若丹明红光发射，这些罗丹明与各种功能性连接基兼容。例如，制备了具有叠氮化物残基的磷酸化染料，并将其用于与带有N的应变炔烃的点击反应中-羟基琥珀酰亚胺（NHS）酯基。该方法绕过了磷酸基团的不希望有的活化作用，得到了一种两亲性氨基反应性染料，可以通过改变pH值来控制其在水相和有机相之间的溶解度和分布。在染料中具有另一个取代模式的两个羟基和一个带有两个羧基残基的苯环的存在足以提供亲水性。选择性形成单-