rivastigmine hydrogen tartrate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: rivastigmine hydrogen tartrate
• 英文别名: Rivastigmine tartrate；2,3-dihydroxybutanedioic acid;[3-[(1S)-1-(dimethylamino)ethyl]phenyl] N-ethyl-N-methylcarbamate
• 化学式: C₄H₆O₆*C₁₄H₂₂N₂O₂
• 分子量: 400.429
• InChiKey: GWHQHAUAXRMMOT-MERQFXBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.64
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  148
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  rivastigmine hydrogen tartrate 在 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 利凡斯的明
  参考文献：
  名称：

  利伐斯的明负载的甲氧基聚（乙二醇）-共聚（ε-己内酯）纳米粒子的制备，优化和评价。

  摘要：

  这项研究的目的是制定和研究静脉注射利伐斯明（Riv）负载甲氧基聚（乙二醇）-共聚（ε-己内酯）（MPEG-PCL）纳米颗粒（Riv-NPs）的神经药代动力学和药效学行政。MPEG-ε-己内酯通过MPEG的开环聚合反应合成了MPEG-PCL，并通过纳米沉淀法制备了Riv-NP。响应面D最优设计用于优化Riv-NPs药物递送系统。优化的制剂显示出98.5±2.1 nm的粒径（PS），19.2±1.1％的载药量（DL）和药物的缓释性能。此外，通过AFM和DSC分析表征了优化的Riv-NP。开发了一种简单而灵敏的HPLC-DAD生物分析方法，并将其成功地用于药代动力学研究。在大鼠中进行的神经药代动力学研究表明，积分图是线性的，并且以MPEG-PCL NPs负载的药物的脑部摄取清除率明显高于游离药物。此外，使用莫里斯水迷宫测试的药效学研究结果表明，与游离药物溶液相比，Riv-NPs可以更快地恢复记忆

  DOI：

  10.1021/acschemneuro.9b00691
• 作为产物：
  描述：

  [3-[(1R)-1-bromoethyl]phenyl] N-ethyl-N-methylcarbamate 以> 99%ee; 85的产率得到rivastigmine hydrogen tartrate
  参考文献：
  名称：

  Tetrahedron: Asymmetry 2013, 24, 374-379

  摘要：

  DOI：

文献信息

• SYNTHESIS OF NOVEL INTERMEDIATE(S) FOR PREPARING RIVASTIGMINE
  申请人：Cadila Pharmaceuticals Ltd.

  公开号：US20200095195A1

  公开（公告）日：2020-03-26

  The present invention relates to novel intermediate(s), which are useful for the preparation of Rivastigmine compound of formula (I) and its pharmaceutically acceptable salts. The present invention further relates to the processes for the preparation of such novel intermediate(s) and preparation of Rivastigmine using such novel intermediate(s).

  本发明涉及新型中间体，该中间体对于制备化合物Rivastigmine的公式（I）及其药用可接受的盐是有用的。本发明还涉及制备这种新型中间体的方法以及使用这种新型中间体制备Rivastigmine的方法。
• PREPARATION OF RIVASTIGMINE AND ITS SALTS
  申请人：Mandava Venkata Naga Brahmeswara Rao

  公开号：US20080255383A1

  公开（公告）日：2008-10-16

  There are provided processes for making rivastigmine. In one embodiment, the process includes reacting S-(−)-[1-(3-hydroxyphenyl)ethyl]dimethylamine with N-ethyl-N-methyl carbamoyl chloride in the presence of an organic base to obtain a free base of rivastigmine.

  提供了制备利他林的过程。在一个实施例中，该过程包括在有机碱的存在下，将S-(−)-[1-(3-羟基苯基)乙基]二甲基胺与N-乙基-N-甲基氨基甲酰氯反应，以获得利他林的自由碱。
• [EN] ANTICHOLINERGIC NEUROPROTECTIVE COMPOSITION AND METHODS<br/>[FR] COMPOSITION ET PROCÉDÉS NEUROPROTECTEURS ANTICHOLINERGIQUES
  申请人：CHASE PHARMACEUTICALS CORP

  公开号：WO2014039627A1

  公开（公告）日：2014-03-13

  The present invention relates to a pharmaceutical composition comprising propiverine, trospium or glycopyrrolate; and a non-anticholinergic antiemetic agent. It is also related to a pharmaceutical composition comprising a high dose of solifenacin or a pharmaceutically acceptable salts thereof; and a non-anticholinergic antiemetic agent. Pharmaceutical compositions containing high dose of nsPAChA for use for increasing the AChEI blood concentrations and for combating neurodegeneration are also described. The invention also relates to a method for inducing neuroprotection and combating neurodegeneration in a patient suffering from Alzheimer type dementia as well as to a method for increasing the blood levels of an acetyl choline esterase inhibitor (AChEI) in a human subject treated with an AChEI dose.

  本发明涉及一种包含丙烯胺、托斯匹铵或格隆溴铵的药物组合物；以及一种非抗胆碱能的抗恶心药物。它还涉及一种包含高剂量索利那非或其药用盐的药物组合物；以及一种非抗胆碱能的抗恶心药物。还描述了含有高剂量nsPAChA的药物组合物，用于增加AChEI血浓度并对抗神经退行性疾病。该发明还涉及一种诱导神经保护和对抗神经退行性疾病的方法，适用于患有阿尔茨海默型痴呆症的患者，以及一种用于增加接受AChEI剂量治疗的人体受试者的乙酰胆碱酯酶抑制剂（AChEI）血液水平的方法。
• Novel inhibitors of glutaminyl cyclase
  申请人：Schilling Stephan

  公开号：US20050215573A1

  公开（公告）日：2005-09-29

  The present invention relates to novel inhibitors of glutaminyl cyclase and combinations thereof for the treatment of neuronal disorders, especially Alzheimer's disease, Down Syndrome, Parkinson disease, Chorea Huntington, pathogenic psychotic conditions, schizophrenia, impaired food intake, sleep-wakefulness, impaired homeostatic regulation of energy metabolism, impaired autonomic function, impaired hormonal balance, impaired regulation, body fluids, hypertension, fever, sleep dysregulation, anorexia, anxiety related disorders including depression, seizures including epilepsy, drug withdrawal and alcoholism, neurodegenerative disorders including cognitive dysfunction and dementia.

  本发明涉及新型谷氨酰环化酶抑制剂及其组合物，用于治疗神经系统疾病，特别是阿尔茨海默病、唐氏综合征、帕金森病、亨廷顿舞蹈症、致病性精神病症、精神分裂症、食欲受损、睡眠-觉醒、体内能量代谢的失衡、自主神经功能受损、激素平衡受损、调节失调、体液平衡、高血压、发热、睡眠失调、厌食症、焦虑相关疾病包括抑郁症、癫痫发作包括癫痫、药物戒断和酗酒、神经退行性疾病包括认知功能障碍和痴呆症。
• Novel process for the preparation of phenylcarbamates
  申请人：Raheem Mohammed Abdul

  公开号：US20080306280A1

  公开（公告）日：2008-12-11

  This invention relates to a process for the preparation of an aminoalkyl phenyl carbamate compound of formula 1, wherein R 1 and R 2 independently are hydrogen or C 1-6 alkyl; R 3 and R 4 are the same or different and each is a lower alkyl; or R 3 and R 4 together with the nitrogen to which they are attached form a cyclic moiety of a three to eight-member ring, with or without a hetero atom like nitrogen or oxygen; R 5 and R 6 independently are hydrogen, linear, branched or cyclic C 1-6 alkyl, allyl, propargyl or benzyl; or R 5 and R 6 together with the nitrogen to which they are attached form a cyclic moiety of three to eight member ring, with or without a hetero atom like nitrogen or oxygen; the carbon center marked with “*” is racemic or enantiomerically enriched (R)- or (S)-configuration; and pharmaceutically acceptable addition salts, and crystalline and amorphous forms thereof comprising the steps of: i) converting an amine R 5 R 6 NH to a carbamoylimidazolium salt of formula 3 wherein R 5 and R 6 are as defined above; X − is a counterion and R 7 is an alkyl or aryl group; ii) reacting in a solvent at a controlled reaction temperature the compound of formula 3 with a compound of formula 4, wherein R 1 , R 2 , R 3 , R 4 and “*” are as defined above to give the compound of formula 1; and iii) isolating the compound of formula 1.

  本发明涉及一种制备式为1的氨基烷基苯基氨酯化合物的方法，其中R1和R2独立地是氢或C1-6烷基；R3和R4相同或不同，每个是较低的烷基；或者R3和R4与它们连接的氮一起形成一个三至八元环的环状结构，带有或不带有类似氮或氧的杂原子；R5和R6独立地是氢、线性、支链或环状的C1-6烷基、烯丙基、丙炔基或苄基；或者R5和R6与它们连接的氮一起形成一个三至八元环的环状结构，带有或不带有类似氮或氧的杂原子；标有“*”的碳中心是外消旋的或对映富集的(R)-或(S)-构型；以及药学上可接受的加合盐，以及包括以下步骤的晶体和非晶态形式：i)将胺R5R6NH转化为式3的羧酰咪唑盐，其中R5和R6如上定义；X^-是一个对离子，R7是一个烷基或芳基；ii)在溶剂中在受控反应温度下，将式3的化合物与式4的化合物反应，其中R1、R2、R3、R4和“*”如上定义，以得到式1的化合物；和iii)分离出式1的化合物。