(+/-)-threo-Ritalinol

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (+/-)-threo-Ritalinol
• 英文别名: (RS)-2-phenyl-2-(RS)-piperidin-2-yl-ethanol；Threo-ritalinol hydrochloride；(2R)-2-phenyl-2-[(2R)-piperidin-2-yl]ethanol
• 化学式: C₁₃H₁₉NO
• 分子量: 205.3
• InChiKey: IKNCLLOBJQVKNP-CHWSQXEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-threo-Ritalinol 在 ruthenium trichloride 、 sodium periodate 、 三乙胺 作用下， 以 四氢呋喃 、 四氯化碳 、 水 、 乙腈 为溶剂， 反应 21.0h， 生成 1-(tert-butyloxycarbonyl)-α-(R)-phenyl-2-(R)-piperidineacetic acid
  参考文献：
  名称：

  The First Enantioselective Synthesis of (2R,2‘R)-threo-(+)-Methylphenidate Hydrochloride

  摘要：

  DOI：

  10.1021/jo9821473
• 作为产物：
  描述：

  盐酸右哌甲酯 在 lithium aluminium tetrahydride 作用下， 生成 (+/-)-threo-Ritalinol
  参考文献：
  名称：

  Deutsch, Howard M., Medicinal Chemistry Research, 1998, vol. 8, # 1-2, p. 91 - 99

  摘要：

  DOI：

文献信息

• Synthesis and Pharmacology of Site-Specific Cocaine Abuse Treatment Agents:  Restricted Rotation Analogues of Methylphenidate
  作者：Deog-Il Kim、Howard M. Deutsch、Xiaocong Ye、Margaret M. Schweri

  DOI：10.1021/jm061354p

  日期：2007.5.1

  [4.4.0]decanes (quinolizidines), which were envisioned as restricted rotational analogues (RRAs) of methylphenidate (MP), was synthesized and tested for inhibitory potency against [(3)H]WIN35,428, [3H]citalopram, and [3H]nisoxetine binding to the dopamine, serotonin, and norepinephrine transporters, respectively. Two different synthetic schemes were used; a Wittig reaction or acylation (followed by

  合成了一系列的threo-1-aza-3或4-取代的5-苯基[4.4.0]癸烷（喹喔啉），它们被设想为哌醋甲酯（MP）的限制性旋转类似物（RRA），并进行了抑制性测试对[（3H）] WIN35,428，[3H]西酞普兰和[3H]尼西西汀分别与多巴胺，5-羟色胺和去甲肾上腺素转运蛋白结合的效力。使用了两种不同的合成方案。Wittig反应或酰化反应（随后是分子内缩合反应）是每种方案的关键特征。未取代的RRA，苏式（反式）-1-氮杂-5-苯基[4.4.0]癸烷（12a），与不受约束的苏式-MP等效于[（3）H] WIN35,428结合。这些RRA中的额外环（降低构象自由度）以及该额外环上4位取代基的方向和极性对于生物活性至关重要。通常，RRA在与三个转运蛋白的结合亲和力上与相应的不受约束的MP衍生物平行。结果表明，其中甲酯的羰基H键合到哌啶基NH的MP的构象可能是分子的生物活性形式。
• Stereospezifische Cyclisierungen α – ω-disubstituierter Aminoäthanole. 1. Mitt.: 1-Aryl-3-imino-3H-oxazolo-[3,4-a]perhydro-pyridine und Verwandte
  作者：H. Wollweber、R. Hiltmann

  DOI：10.1002/ardp.19733060408

  日期：——

  möglichen diastereomeren 1,2‐Aminoalkohole ausgehend das jeweils gewünschte cis‐ oder trans‐Iminooxazolidin synthetisieren. Die alkalische Hydrolyse dieser Stoffe erfolgt ohne merkliche Racemisierung. Durch Anwendung der ”︁Carbamoyl‐Thionylchloridmethode„ und nachfolgende Hydrolyse läßt sich sein sterisch einheitlicher 1,2‐disubstituierter Aminoalkohol in seine entgegengesetzt konfigurierte Form überführen

  非对映异构 1,2-二取代氨基乙醇立体定向环化为 4,5-二取代 2-亚氨基恶唑烷 a) 用卤化氰同时保持构型，b) 用“︁氨基甲酰亚硫酰氯法”和 Waldenscher 反演。通过结合这两个过程，一种可能的非对映异构 1,2-氨基醇可用于合成所需的顺式或反式亚氨基恶唑烷。这些物质的碱性水解发生时没有明显的外消旋化。通过应用“︁氨基甲酰亚硫酰氯法”和随后的水解，其空间均匀的1,2-二取代氨基醇可以转化为其相反构型的形式。
• Efficient Synthesis of a New Series of Piperidine Ring–Modified Alcohol and Methyl Ether Analogs of (±)-<i>threo</i>-Methyl Phenyl(piperidin-2-yl)acetate
  作者：Babatunde Ojo

  DOI：10.1080/00397911.2011.569681

  日期：2012.10

  Abstract A series of novel piperidine ring–modified alcohol and methyl ether analogs of (±)-threo-methyl phenyl(piperidin-2-yl)acetate was synthesized. This series of methyl phenyl(piperidin-2-yl)acetate analogs was developed by piperidine ring alkylation and/or acylation followed by lithium aluminum hydride reduction to give alcohol derivatives. Methylation of the alcohol analogs by extension of standard

  摘要 合成了一系列新型哌啶环改性醇和(±)-苏-甲基苯基(哌啶-2-基)乙酸酯的甲基醚类似物。该系列甲基苯基(哌啶-2-基)乙酸酯类似物是通过哌啶环烷基化和/或酰化，然后氢化铝锂还原得到醇衍生物而开发的。通过扩展标准文献程序对醇类似物进行甲基化得到相应的甲基醚衍生物。这些化合物的化学结构是根据质量和 1H NMR 光谱数据以及 CHN 元素分析数据确定的。对文献方法的一些重大修改使反应更有效，并且通常获得了良好的产率。图形概要
• Quantitative structure–activity relationship studies of threo-methylphenidate analogs
  作者：Milind Misra、Qing Shi、Xiaocong Ye、Ewa Gruszecka-Kowalik、Wei Bu、Zhanzhu Liu、Margaret M. Schweri、Howard M. Deutsch、Carol A. Venanzi

  DOI：10.1016/j.bmc.2010.08.034

  日期：2010.10.15

  Complementary two-dimensional (2D) and three-dimensional (3D) Quantitative Structure-Activity Relationship (QSAR) techniques were used to derive a preliminary model for the dopamine transporter (DAT) binding affinity of 80 racemic threo-methylphenidate (MP) analogs. A novel approach based on using the atom-level E-state indices of the 14 common scaffold atoms in a sphere exclusion protocol was used to identify a test set for 2D-and 3D-QSAR model validation. Comparative Molecular Field Analysis (CoMFA) contour maps based on the structure-activity data of the training set indicate that the 2' position of the phenyl ring cannot tolerate much steric bulk and that addition of electron-withdrawing groups to the 3' or 40 positions of the phenyl ring leads to improved DAT binding affinity. In particular, the optimal substituents were found to be those whose bulk is mainly in the plane of the phenyl ring. Substituents with significant bulk above or below the plane of the ring led to decreased binding affinity. Suggested alterations to be explored in the design of new compounds are the placement at the 3' and 4' position of the phenyl ring of electron-withdrawing groups that lie chiefly in the plane of the ring, for example, halogen substituents on the 3',4'-benzo analog, 79. A complementary 2D-QSAR approach-partial least squares analysis using a reduced set of Molconn-Z descriptors-supports the CoMFA structure-activity interpretation that phenyl ring substitution is a major determinant of DAT binding affinity. The potential usefulness of the CoMFA models was demonstrated by the prediction of the binding affinity of methyl 2-(naphthalen-1-yl)-2-(piperidin-2-yl) acetate, an analog not in the original data set, to be in good agreement with the experimental value. (C) 2010 Elsevier Ltd. All rights reserved.
• Deutsch, Howard M., Medicinal Chemistry Research, 1998, vol. 8, # 1-2, p. 91 - 99
  作者：Deutsch, Howard M.

  DOI：——

  日期：——