异利舍平 | 482-85-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 育亨宾生物碱
• 中文名称: 异利舍平
• 中文别名: (-)-异利血平；(-)-异利舍平
• 英文名称: Isoreserpin
• 英文别名: Isoreserpine；(-)-3-isoreserpine；3-epireserpine；3-isoreserpine；reserpine；methyl (1S,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyl)oxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate
• CAS: 482-85-9
• 化学式: C₃₃H₄₀N₂O₉
• 分子量: 608.689
• InChiKey: QEVHRUUCFGRFIF-VPHNHGCZSA-N

物化性质

• 熔点：
  148-155 °C(lit.)
• 沸点：
  700.1±60.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  118
• 氢给体数：
  1
• 氢受体数：
  10

安全信息

• 危险等级：
  6.1(b)
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险品运输编号：
  UN 1544 6.1/PG 3

反应信息

• 作为反应物：
  描述：

  异利舍平 在 sodium cyanoborohydride 作用下， 以 三氟乙酸 为溶剂， 反应 0.5h， 以87%的产率得到
  参考文献：
  名称：

  某些氧化的吲哚生物碱（如利血平）的2,7-二氢衍生物的还原甲基化

  摘要：

  NaBH 3 CN在酸性介质中将吲哚生物碱四氢茶碱（1a），3-表利血平（2a）和利血平（3a）转化为相应的2,7-二氢化合物（c）。取决于条件，可以通过H 2 CO / NaBH 3 CN在1位（化合物e）处进一步单甲基化（化合物e）或在1位和10位（化合物g处）进行二甲基化。在详细的NMR研究的基础上确定了构型。

  DOI：

  10.1016/0040-4020(96)00449-8
• 作为产物：
  描述：

  利血平 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以18 g的产率得到异利舍平
  参考文献：
  名称：

  Reinvestigation of the mechanism of the acid-catalyzed epimerization of reserpine to isoreserpine

  摘要：

  DOI：

  10.1021/jo00280a052

文献信息

• [EN] ISOTOPE ENHANCED AMBROXOL FOR LONG LASTING AUTOPHAGY INDUCTION<br/>[FR] AMBROXOL À ISOTOPE AMÉLIORÉ POUR INDUCTION D'AUTOPHAGIE DURABLE
  申请人：STC UNM

  公开号：WO2018148113A1

  公开（公告）日：2018-08-16

  The present invention is directed to 13C and/or 2H isotope enhanced ambroxol ("isotope enhanced ambroxol") and its use in the treatment of autophagy infections, especially mycobacterial and other infections, disease states and/or conditions of the lung, such as tuberculosis, especially including drug resistant and multiple drag resistant tuberculosis. Pharmaceutical compositions comprising isotope enhanced amhroxol, alone or in combination with an additional bioactive agent, especially rifamycin antibiotics, including an additional autophagy modulator (an agent which is active to promote or inhibit autophagy), thus being useful against, an autophagy mediated disease state and/or condition), especially an antophagy mediated disease state and/or condition which occurs in the lungs, for example, a Mycobacterium infection. Chronic Obstructive Pulmonary Disease (COPD), asthma, pulmonary fibrosis, cystic fibrosis, Sjogren's disease and lung cancer (small cell and non-small cell lung cancer, among other disease states and/or conditions, especially of the lung. Methods of treating autophagy disease states and/or conditions, especially including autophagy disease states or conditions which occur principally in the lungs of a patient represent a further embodiment of the present invention. An additional embodiment includes methods of synthesizing compounds according to the present invention as otherwise disclosed herein.

  本发明涉及13C和/或2H同位素增强的氨溴索（“同位素增强的氨溴索”）及其在治疗自噬感染，特别是结核分枝杆菌和其他感染、疾病状态和/或肺部疾病条件中的用途，如肺结核，特别是包括耐药和多重耐药结核病。包括同位素增强的氨溴索的药物组合物，单独或与额外的生物活性剂（特别是利福霉素类抗生素，包括额外的自噬调节剂（一种能够促进或抑制自噬的剂），因此对抗自噬介导的疾病状态和/或条件有用），特别是在肺部发生的自噬介导的疾病状态和/或条件，例如分枝杆菌感染。慢性阻塞性肺病（COPD）、哮喘、肺纤维化、囊性纤维化、干燥综合征和肺癌（小细胞和非小细胞肺癌等其他肺部疾病状态和/或条件，特别是肺部疾病状态和/或条件。治疗自噬疾病状态和/或条件的方法，特别包括治疗主要发生在患者肺部的自噬疾病状态或条件的方法，代表本发明的另一实施例。另一实施例包括根据本发明在此披露的其他方法合成化合物的方法。
• Visible‐Light Catalytic Photooxygenation of Monoterpene Indole Alkaloids: Access to Spirooxindole‐1,3‐oxazines
  作者：Thorsten von Drathen、Frank Hoffmann、Malte Brasholz

  DOI：10.1002/chem.201801882

  日期：2018.7.17

  Few natural oxindole alkaloids possess an exceptional spiro‐[(1,3)oxazinan‐3,6′‐oxindole] core structure, which results from an unusual oxidative indole rearrangement. The Rauvolfia alkaloid reserpine can be converted into the spirooxindole‐1,3‐oxazines dioxyreserpine and trioxyreserpine through efficient visible‐light catalytic photooxygenation with anthraquinone photocatalysts. A mechanistic investigation

  很少有天然羟吲哚生物碱具有特殊的螺-[(1,3)oxazinan-3,6'-oxindole]核心结构，这是由不寻常的氧化吲哚重排引起的。通过蒽醌光催化剂的高效可见光催化光氧化作用，萝芙木生物碱利血平可转化为螺氧吲哚-1,3-恶嗪二氧利血平和三氧利血平。一项机理研究为利血平和相关单萜吲哚生物碱的光氧化重排提供了新的思路，螺氧吲哚-1,3-恶嗪产物可以通过还原开环进行稳定化，以获得顺式-十氢异喹啉作为新的对映体纯合成结构单元，如图所示对于双氧利血平。
• Protein stabilized pharmacologically active agents, methods for the preparation thereof and methods for the use thereof
  申请人：Abraxis BioScience, Inc.

  公开号：EP1944019A2

  公开（公告）日：2008-07-16

  In accordance with the present invention, there are provided compositions and methods useful for the in vivo delivery of substantially water-insoluble pharmacologically active agents (such as the anticancer drug paclitaxel) in which the pharmacologically active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, protein and pharmacologically active agent in a biocompatible dispersing medium are subjected to high shear, in the absence of any conventional surfactants, and also in the absence of any polymeric core material for the particles. The procedure yields particles with a diameter of less than about 1 micron. The use of specific composition and preparation conditions (e.g., addition of a polar solvent to the organic phase), and careful selection of the proper organic phase and phase fraction, enables the reproducible production of unusually small nanoparticles of less than 200 nm diameter, which can be sterile-filtered. The particulate system produced according to the invention can be converted into a redispersible dry power comprising nanoparticles of water-insoluble drug coated with a protein, and free protein to which molecules of the pharmacological agent are bound. This results in a unique delivery system, in which part of the pharmacologically active agent is readily bioavailable (in the form of molecules bound to the protein), and part of the agent is present within particles without any polymeric matrix therein.

  根据本发明，提供了用于体内输送基本不溶于水的药理活性剂（如抗癌药物紫杉醇）的组合物和方法，其中药理活性剂以涂覆有蛋白质（作为稳定剂）的悬浮颗粒的形式输送。 特别是，在不使用任何常规表面活性剂，也不使用任何聚合物核心材料的情况下，对生物相容性分散介质中的蛋白质和药理活性剂进行高剪切。该过程可产生直径小于约 1 微米的颗粒。使用特定的成分和制备条件（例如，在有机相中加入极性溶剂），并仔细选择适当的有机相和相组分，可重复生产出直径小于 200 纳米的超小型纳米颗粒，这些颗粒可进行无菌过滤。 根据本发明生产的微粒系统可转化为可再分散的干粉，其中包括包覆有蛋白质的水不溶性药物纳米颗粒，以及与药剂分子结合的游离蛋白质。这就形成了一种独特的给药系统，其中部分药理活性剂易于生物利用（以分子与蛋白质结合的形式），而部分药剂则存在于颗粒中，不含任何聚合物基质。
• Novel formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof
  申请人：Abraxis BioScience, LLC

  公开号：EP2272504A2

  公开（公告）日：2011-01-12

  In accordance with the present invention, there are provided compositions and methods useful for the in vivo delivery of substantially water insoluble pharmacologically active agents (such as the anticancer drug paclitaxel) in which the pharmacologically active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, protein and pharmacologically active agent in a biocompatible dispersing medium are subjected to high shear, in the absence of any conventional surfactants, and also in the absence of any polymeric core material for the particles. The procedure yields particles with a diameter of less than about 1 micron. The use of specific composition and preparation conditions (e.g., addition of a polar solvent to the organic phase), and careful selection of the proper organic phase and phase fraction, enables the reproducible production of unusually small nanoparticles of less than 200 nm diameter, which can be sterile-filtered. The particulate system produced according to the invention can be converted into a redispersible dry powder comprising nanoparticles of water-insoluble drug coated with a protein, and free protein to which molecules of the pharmacological agent are bound. This results in a unique delivery system, in which part of the pharmacologically active agent is readily bioavailable (in the form of molecules bound to the protein), and part of the agent is present within particles without any polymeric matrix therein.

  根据本发明，提供了用于体内输送基本不溶于水的药理活性剂（如抗癌药物紫杉醇）的组合物和方法，其中药理活性剂以涂覆蛋白质（作为稳定剂）的悬浮颗粒的形式输送。特别是，在不使用任何常规表面活性剂，也不使用任何聚合物核心材料的情况下，对生物相容性分散介质中的蛋白质和药理活性剂进行高剪切。该过程可产生直径小于约 1 微米的颗粒。使用特定的成分和制备条件（例如，在有机相中加入极性溶剂），并仔细选择适当的有机相和相组分，可重复生产出直径小于 200 纳米的超小型纳米颗粒，这些颗粒可进行无菌过滤。根据本发明生产的微粒系统可转化为可再分散的干粉，其中包括包覆有蛋白质的水不溶性药物纳米颗粒，以及与药剂分子结合的游离蛋白质。这就形成了一种独特的给药系统，其中部分药理活性剂易于生物利用（以分子与蛋白质结合的形式），而部分药剂则存在于颗粒中，不含任何聚合物基质。
• Theranostics platform and methods of use
  申请人：Sanford Burnham Prebys Medical Discovery Institute

  公开号：US10161929B2

  公开（公告）日：2018-12-25

  Theranostics platforms for identifying drugs and nutraceuticals for treatment of rare disease are described. The platforms comprise (a) a cell-phenotype image-enhancing instrument; (b) a drug/nutraceutical library; and (c) a computer-implemented system for analyzing a response of an optically-visible rare-disease cell phenotype to a drug or nutraceutical from the drug/nutraceutical library.

  本文描述了用于识别治疗罕见病的药物和营养保健品的血清学平台。这些平台包括：(a) 细胞表型图像增强仪器；(b) 药物/营养保健品库；(c) 计算机实施系统，用于分析光学可视罕见疾病细胞表型对药物/营养保健品库中药物或营养保健品的反应。

表征谱图