((2R,4S)-1-benzylazetidine-2,4-diyl)dimethanol | 127310-66-1

• 物质功能分类: 有机原料 - 醇、酚、酚醇类化合物及衍生物
• 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: ((2R,4S)-1-benzylazetidine-2,4-diyl)dimethanol
• 英文别名: cis-(1-Benzylazetidine-2,4-diyl)dimethanol；[(2S,4R)-1-benzyl-4-(hydroxymethyl)azetidin-2-yl]methanol
• CAS: 127310-66-1
• 化学式: C₁₂H₁₇NO₂
• 分子量: 207.272
• InChiKey: STVDKEPRJUNWSZ-TXEJJXNPSA-N

物化性质

• 熔点：
  72-74 °C
• 沸点：
  342.9±12.0 °C(Predicted)
• 密度：
  1.167±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  43.7
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  ((2R,4S)-1-benzylazetidine-2,4-diyl)dimethanol 在 氢气 、 palladium(II) hydroxide 作用下， 20.0 ℃ 、101.33 kPa 条件下， 生成 (2R,4S)-2,4-Azetidinedimethanol
  参考文献：
  名称：

  Synthesis and evaluation of novel azetidine analogs as potent inhibitors of vesicular [3H]dopamine uptake

  摘要：

  Lobelane analogs that incorporate a central piperidine or pyrrolidine moiety have previously been reported by our group as potent inhibitors of VMAT2 function. Further central ring size reduction of the piperidine moiety in lobelane to a four-membered heterocyclic ring has been carried out in the current study to afford novel cis-and trans-azetidine analogs. These azetidine analogs (15a-15c and 22a-22c) potently inhibited [H-3]dopamine (DA) uptake into isolated synaptic vesicles (K-i <= 66 nM). The cis-4-methoxy analog 22b was the most potent inhibitor (K-i = 24 nM), and was twofold more potent that either lobelane (2a, K-i = 45 nM) or norlobelane (2b, K-i = 43 nM). The trans-methylenedioxy analog, 15c (K-i = 31 nM), was equipotent with the cis-analog, 22b, in this assay. Thus, cis-and trans-azetidine analogs 22b and 15c represent potential leads in the discovery of new clinical candidates for the treatment of methamphetamine abuse. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.001
• 作为产物：
  描述：

  苄胺 在 sodium tetrahydroborate 、 sodium hydride 、 苯甲醇 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 、 叔丁醇 为溶剂， 反应 20.75h， 生成 ((2R,4S)-1-benzylazetidine-2,4-diyl)dimethanol
  参考文献：
  名称：

  Synthesis and bioactivity of a new class of rigid glutamate analogs. Modulators of the N-methyl-D-aspartate receptor

  摘要：

  A variety of derivatives of azetidine-2,4-dicarboxylic acid were synthesized and examined for their ability to stimulate 45Ca2+ uptake in cultures of cerebellar granule cells. Of the compounds tested, the cis-azetidine-2,4-dicarboxylic acid (10f) was found to be the most potent agent in potentiating glutamate, aspartate, or N-methyl-D-aspartate (NMDA) stimulated 45Ca2+ uptake at the NMDA receptor. The mechanism of action of 10f was further investigated in [3H]MK-801 binding assays and [3H]GABA release from cultured embryonic rat forebrain neurons. All of the results from the functional studies of azetidine 10f are consistent with a selectivity of action at the NMDA receptor. Moreover, azetidine 10f appears to exhibit a dual type of action, behaving as a glutamate-like agonist at higher concentrations and as a positive modulator at concentrations below 50 microM.

  DOI：

  10.1021/jm00168a007

文献信息

• Azetidine Based Transition State Analogue Inhibitors of <i>N</i>-Ribosyl Hydrolases and Phosphorylases
  作者：Gary B. Evans、Richard H. Furneaux、Ben Greatrex、Andrew S. Murkin、Vern L. Schramm、Peter C. Tyler

  DOI：10.1021/jm701265n

  日期：2008.2.1

  ribooxacarbenium carbon from the fixed purine to phosphate and water nucleophiles, respectively. As the lysis reaction progresses along the reaction coordinate, the distance between the purine and carbocation increases and the distance between carbocation and nucleophile decreases. Immucillin-H and DADMe-immucillin-H have been shown previously to be potent inhibitors of purine nucleoside phosphorylases and lie more

  N-核糖基磷酸化酶和水解酶通过将阳离子核糖氧碳carb碳分别从固定的嘌呤迁移到磷酸和水亲核试剂来催化亲核取代反应。随着裂解反应沿着反应坐标进行，嘌呤和碳正离子之间的距离增加，而碳正离子和亲核试剂之间的距离减小。以前已显示Immucillin-H和DADMe-immucillin-H是嘌呤核苷磷酸化酶的有效抑制剂，分别位于该反应坐标的反应物和产物侧。目前正在人类临床试验中针对不同适应症的这两种酶抑制剂都是手性的且制造昂贵。现在，我们报告DADMe-immucillins的氮杂环丁烷类似物的合成，
• Passerini Reactions on Biocatalytically Derived Chiral Azetidines
  作者：Lisa Moni、Luca Banfi、Andrea Basso、Andrea Bozzano、Martina Spallarossa、Ludger Wessjohann、Renata Riva

  DOI：10.3390/molecules21091153

  日期：——

  The purpose of this study was to explore a series of Passerini reactions on a biocatalytically derived enantiopure azetidine-2-carboxyaldehyde in order to obtain, in a diastereoselective manner, polyfunctionalised derivatives having the potential to be cyclized to chiral bridged bicyclic nitrogen heterocycles. While diastereoselectivity was poor under classical Passerini conditions, a significant increase

  这项研究的目的是探索对生物催化衍生的对映体纯的氮杂环丁烷-2-羧醛进行的一系列Passerini反应，以便以非对映选择性的方式获得具有被环化为手性桥联双环氮杂环的潜力的多官能衍生物。尽管在经典Passerini条件下非对映选择性差，但通过使用溴化锌作为促进剂，非对映选择性显着增加（高达76:24）。该方法学范围广，收率始终良好。
• [EN] SUBSTITUTED PHENYLOXAZOLIDINONES FOR ANTIMICROBIAL THERAPY<br/>[FR] PHENYL-OXAZOLIDINONES SUBSTITUÉES POUR LA THÉRAPIE ANTIMICROBIENNE
  申请人：THE GLOBAL ALLIANCE FOR TB DRUG DEV INC

  公开号：WO2017015106A1

  公开（公告）日：2017-01-26

  The present invention relates to novel oxazolidinones (Formula I): or a pharmaceutically acceptable salt having ring A characterized by N-containing monocyclic, bicyclic or spirocyclic substituents, to their preparation, and to their use as drugs for treating Mycobacterium tuberculosis and other microbial infections, either alone or in combination with other anti-infective treatments.

  本发明涉及新型噁唑烷酮（化学式I）：或具有由含氮的单环、双环或螺环取代基特征的环A的药用盐，以及其制备方法，以及作为用于治疗结核分枝杆菌和其他微生物感染的药物的用途，可以单独使用或与其他抗感染治疗结合使用。
• [EN] METHOD OF TREATMENT WITH 3-CYCLOPROPYLCARBONYL-3,6-DIAZABICYCLO[3.1.1]HEPTANE<br/>[FR] MÉTHODE DE TRAITEMENT PAR 3-CYCLOPROPYLCARBONYL-3,6-DIAZABICYCLO[3,1.1]HEPTANE
  申请人：TARGACEPT INC

  公开号：WO2014011863A1

  公开（公告）日：2014-01-16

  The present invention relates to 3-cyclopropylcarbonyl-3,6-diazabicyclo[3.1.1]heptane, its salt forms, pharmaceutical compositions, and methods of treatment thereof.

  本发明涉及3-环丙基甲酰基-3,6-二氮杂双环[3.1.1]庚烷，其盐形式，药物组合物和治疗方法。
• 一种二氮杂桥化合物的合成方法
  申请人：上海凌富药物研究有限公司

  公开号：CN113999239B

  公开（公告）日：2022-11-11

  本发明提供了一种二氮杂桥化合物的合成方法，属于有机合成领域。本发明涉及的反应方程式如下：反应步骤如下：步骤1，将化合物2与NH3或NH3溶液接触，得到反应混合物；步骤2，对反应混合物进行后处理，即得化合物1，式中，R为芳基、取代芳基、烷基或卤代烷基，n＝1或2。本发明以化合物2和NH3为原料，因此不仅能够有效缩短工艺流程，节约工艺成本，还能够在一定程度上提高反应收率。