methyl (2R,4S)-4-hydroxy-1-((R)-1-phenylethyl)piperidine-2-carboxylate | 177944-17-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2R,4S)-4-hydroxy-1-((R)-1-phenylethyl)piperidine-2-carboxylate
• 英文别名: Methyl (2R,4S)-4-Hydroxy-1-[(R)-1-phenylethyl]piperidine-2-carboxylate；methyl (2R,4S)-4-hydroxy-1-[(1R)-1-phenylethyl]piperidine-2-carboxylate
• CAS: 177944-17-1
• 化学式: C₁₅H₂₁NO₃
• 分子量: 263.337
• InChiKey: GQVSOZIWEVUIGC-KWCYVHTRSA-N

物化性质

• 沸点：
  378.7±42.0 °C(Predicted)
• 密度：
  1.156±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (2R,4S)-4-hydroxy-1-((R)-1-phenylethyl)piperidine-2-carboxylate 在 platinum on activated charcoal 草酰氯 、 氢气 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Asymmetric synthesis of cis-(−)-(2R4S)-4-(phosphonomethyl)-2-piperidinecarboxylic acid, a potent NMDA receptor antagonist

  摘要：

  The asymmetric synthesis of cis-(-)-(2R4S)-4-(phosphononomethyl)-2-piperidinecarboxylic acid (1), a potent and specific NMDA receptor antagonist, via an olefin-iminium cyclization is described. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00150-3
• 作为产物：
  描述：

  (R)-N-(1-phenylethyl)but-3-en-1-amine 在 氨 作用下， 以 乙腈 为溶剂， 反应 4.0h， 生成 methyl (2R,4S)-4-hydroxy-1-((R)-1-phenylethyl)piperidine-2-carboxylate
  参考文献：
  名称：

  Asymmetric synthesis of cis-(−)-(2R4S)-4-(phosphonomethyl)-2-piperidinecarboxylic acid, a potent NMDA receptor antagonist

  摘要：

  The asymmetric synthesis of cis-(-)-(2R4S)-4-(phosphononomethyl)-2-piperidinecarboxylic acid (1), a potent and specific NMDA receptor antagonist, via an olefin-iminium cyclization is described. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00150-3

文献信息

• [EN] 3-(5-METHOXY-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE 3-(5-MÉTHOXY-1-OXOISOINDOLIN-2-YL)PIPÉRIDINE-2,6-DIONE ET LEURS UTILISATIONS
  申请人：NOVARTIS AG

  公开号：WO2021124172A1

  公开（公告）日：2021-06-24

  The present disclosure relates to compounds of formula (I') and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

  本公开涉及式(I')的化合物、药物组合物及其在降低广泛间隔锌指蛋白结构域（WIZ）表达水平、诱导胎儿血红蛋白（HbF）表达以及治疗遗传性血液疾病（例如，血红蛋白病，例如，β-血红蛋白病）方面的用途，如镰状细胞病和β-地中海贫血。
• 一种格拉斯吉布关键中间体的制备方法
  申请人：苏州莱安医药化学技术有限公司

  公开号：CN113443995B

  公开（公告）日：2022-10-21

  本发明公开了一种格拉斯吉布关键中间体的制备方法，包括以下步骤：S1、向丙烯酸中依次加入4A分子筛、乙腈、结构式1所示化合物，进行狄尔斯‑阿尔德反应，得到中间产物；S2、将中间产物加入至甲醇中，混合均匀后，再缓慢加入甲醇钠，在搅拌条件下进行开环反应，TLC检测原料反应完全后，降温至0～5℃，采用中和试剂调节pH至6～7，浓缩甲醇，萃取，合并有机相，洗涤，干燥，浓缩，即得粗品；S3、将上述粗品经硅胶柱层析进行分离纯化，即得所述格拉斯吉布关键中间体；其中，所述格拉斯吉布关键中间体为结构式3a所示化合物。本发明一种格拉斯吉布关键中间体的制备方法，工艺简单、安全、环保，保证开环反应顺利进行的同时避免了副产物酰胺的生成。
• Validation of high-affinity binding sites for succinic acid through distinguishable binding of gamma-hydroxybutyric acid receptor-specific NCS 382 antipodes
  作者：Tünde Molnár、Júlia Visy、Ágnes Simon、István Moldvai、Eszter Temesvári-Major、Gábor Dörnyei、Erzsébet Kútiné Fekete、Julianna Kardos

  DOI：10.1016/j.bmcl.2008.08.083

  日期：2008.12

  Gamma-hydroxybutyric acid (GHB) binding to multiple sites for the tricarboxylic acid cycle intermediate succinic acid (SUC) has been disclosed recently. In order to better characterize these targets, distinguishable binding of GHB receptor-specific NCS 382 antipodes to [H-3]-SUC or [H-3]-GHB labelled sites in rat brain synaptic membranes was explored. Eutomer binding parameters suggest identity of the high-affinity target for SUC with a synaptic GHB receptor subtype. (C) 2008 Elsevier Ltd. All rights reserved.
• The discovery of CCR3/H1 dual antagonists with reduced hERG risk
  作者：Ash Bahl、Patrick Barton、Keith Bowers、Steven Brough、Richard Evans、Christopher A. Luckhurst、Tobias Mochel、Matthew W.D. Perry、Aaron Rigby、Robert J. Riley、Hitesh Sanganee、Adam Sisson、Brian Springthorpe

  DOI：10.1016/j.bmcl.2012.08.124

  日期：2012.11

  A series of dual CCR3/H-1 antagonists based on a bispiperidine scaffold were discovered. Introduction of an acidic group overcame hERG liability. Bioavailability was optimised by modulation of physico-chemical properties and physical form to deliver a compound suitable for clinical evaluation. (C) 2012 Elsevier Ltd. All rights reserved.
• 3-(5-methoxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione Derivatives and Uses thereof
  申请人：NOVARTIS AG

  公开号：US20220402904A1

  公开（公告）日：2022-12-22

  The present disclosure relates to compounds of formula (I′) and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.