(2R)-2-benzhydryloxirane | 862647-09-4

• 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)-2-benzhydryloxirane
• 英文别名: (R)-2-benzhydryloxirane；(2R)-2-benzhydryl-oxirane
• CAS: 862647-09-4
• 化学式: C₁₅H₁₄O
• 分子量: 210.276
• InChiKey: QEZITUGLJWMLCF-AWEZNQCLSA-N

物化性质

• 沸点：
  319.1±11.0 °C(Predicted)
• 密度：
  1.127±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (2R)-2-benzhydryloxirane 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 copper(l) iodide 、 sodium hydride 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 43.0h， 生成 (1R,4S,6S)-4-benzhydryl-3,7-dioxabicyclo[4.1.0]heptane
  参考文献：
  名称：

  Discovery of Novel Trisubstituted Asymmetric Derivatives of (2S,4R,5R)-2-benzhydryl-5-benzylaminotetrahydropyran-4-ol, Exhibiting High Affinity for Serotonin and Norepinephrine Transporters in a Stereospecific Manner

  摘要：

  In our structure-activity relationship study on 3,6-disubstituted pyran derivatives, we have carried out asymmetric synthesis and biological characterization of trisubstituted (2S,4R,5R)-2-benzhydryl-5-benzylaminotetrahydropyran-4-ol and (3S,4R,6S)-6-benzhydryl-4-benzylaminotetrahydropyran-3-ol derivatives and their enantiomers. All synthesized derivatives were tested for their affinities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) in the brain by measuring their potency in inhibiting the uptake of [H-3]DA, [H-3]-5-HT, and [3H]NE, respectively. Compounds were also tested for their binding affinity at the DAT by their inhibition of [H-3]WIN 35,428. Biological results indicated that regioselectivity and stereoselectivity played important roles in determining activity for monoamine transporters as only (-)-isomers of 2-benzhydryl-5-benzylaminotetrahydropyran-4-ol derivatives exhibited appreciable potency for the monoamine transporters, in particular for the SERT and NET. Among the active analogues, (-)-9d exhibited potent and selective affinity at the NET (K-i, [H-3]NE = 4.92 nM; DAT/NET = 91 and SERT/NET = 140). One of the derivatives with p-methoxybenzyl substitution, (-)-9a, was potent at both SERT and NET (Ki, [3H]-5-HT = 25.9 and [3H]NE = 15.8 nM, respectively). In the active analogue series ((-)-9a-(-)-9e), a cis-relationship between the biphenyl and the amino moiety was maintained for the SERT and NET interactions, as was observed with our earlier 3,6-disubstituted pyran compounds for the DAT interaction. To the best of our knowledge, this current series of compounds represents a novel class of pyran derivatives as blockers for monoamine transporters.

  DOI：

  10.1021/jm049021k
• 作为产物：
  描述：

  1,1-二苯基丙酮 在 甲醇 、 sodium tetrahydroborate 、 (R,R)-(-)-N,N-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexane diaminocobalt(II) 、 溴 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 147.67h， 生成 (2R)-2-benzhydryloxirane
  参考文献：
  名称：

  AZA-PYRIDONE COMPOUNDS AND USES THEREOF

  摘要：

  本文揭示了氮杂吡啶酮化合物，包括一种或多种氮杂吡啶酮化合物的药物组合物，以及合成这些化合物的方法。本文还揭示了使用氮杂吡啶酮化合物改善和/或治疗疾病和/或病况的方法，包括流感病毒感染在内的正黏液病毒感染。

  公开号：

  US20150072982A1

文献信息

• METHOD OF PREPARING AZA-PYRIDONE COMPOUNDS
  申请人：Alios BioPharma, Inc.

  公开号：US20170260189A1

  公开（公告）日：2017-09-14

  Disclosed herein are methods for obtaining aza-pyridone compounds, which can be useful for ameliorating and/or treating a disease and/or a condition, including an orthomyxovirus infection.

  本文披露了一种获取氮杂吡啶酮化合物的方法，该方法可用于改善和/或治疗疾病和/或病况，包括流感病毒感染。
• Flexible and biomimetic analogs of triple uptake inhibitor 4-((((3S,6S)-6-benzhydryltetrahydro-2H-pyran-3-yl)amino)methyl)phenol: Synthesis, biological characterization, and development of a pharmacophore model
  作者：Horrick Sharma、Soumava Santra、Joy Debnath、Tamara Antonio、Maarten Reith、Aloke Dutta

  DOI：10.1016/j.bmc.2013.11.017

  日期：2014.1

  and the N-benzyl group as well as the orientation of the secondary nitrogen were also important for TUI activity. We have validated our findings by synthesizing and testing novel asymmetric pyran analogs. The present work has also resulted in the discovery of a new series of asymmetric tetrahydrofuran derivatives as novel TUIs. Lead compounds 41 and 42 exhibited moderate TUI activity. Interestingly

  在这项研究中，我们基于新型不对称吡喃衍生物和新开发的不对称呋喃衍生物生成了三重摄取抑制剂化合物的药效团模型。该模型揭示了抑制剂对多巴胺转运蛋白 (DAT)、血清素转运蛋白 (SERT) 和去甲肾上腺素转运蛋白 (NET) 表现出平衡活性的重要特征。特别是，发现训练集中的活性吡喃化合物常见的“折​​叠”构象对三重摄取抑制活性至关重要。此外，二苯甲基部分与N之间的距离-苄基以及二级氮的取向对于TUI活性也很重要。我们通过合成和测试新型不对称吡喃类似物验证了我们的发现。目前的工作还发现了一系列新的不对称四氢呋喃衍生物作为新型 TUI。先导化合物41和42表现出中等的 TUI 活性。有趣的是，四氢呋喃铅化合物（例如41和42）的最高 TUI 活性表现在与吡喃 TUI 类似的立体化学偏好中，例如D - 161。
• [EN] TRI-SUBSTITUED 2-BENZHYDRYL-5-BENZLAMINO-TETRAHYDRO-PYRAN-4-OL AND 6-BENZHYDRYL-4-BENZYLAMINO-TETRAHYDRO-PYRAN-3-OL ANALOGUES, AND NOVEL 3,6-DISUBSTITUTED PYRAN DERIVATIVES<br/>[FR] À TROIS SUBSTITUT 2-BENZHYDRYL-5- BENZLAMINO- TÉTRAHYDROPYRAN-4-OL ET 6-BENZHYDRYL-4-BENZYLAMINO-ANALOGUES TÉTRAHYDROPYRAN-3-OL ET NOUVEAUX DÉRIVÉS PYRANNE DISUBSTITUÉ 3,6
  申请人：UNIV WAYNE STATE

  公开号：WO2005105075A1

  公开（公告）日：2005-11-10

  Novel 3,6-disubstituted pyrans, optionally with a further substituent at the 4-position, are monoamine reuptake inhibitors with activity profiles of anti- depressants.

  小说3,6-二取代吡喃，可选地在4-位置进一步取代，是具有抗抑郁活性剖面的单胺再摄取抑制剂。
• [EN] AZA-PYRIDONE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS D'AZA-PYRIDONE ET LEURS UTILISATIONS
  申请人：ALIOS BIOPHARMA INC

  公开号：WO2016145103A1

  公开（公告）日：2016-09-15

  Disclosed herein are aza-pyridone compounds, pharmaceutical compositions that include one or more aza-pyridone compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an orthomyxovirus infection, with an aza-pyridone compound. Examples of an orthomyxovirus viral infection include an influenza infection.

  本文披露了氮杂吡啶酮化合物、包含一种或多种氮杂吡啶酮化合物的药物组合物，以及合成这些化合物的方法。本文还披露了使用氮杂吡啶酮化合物改善和/或治疗疾病和/或病况的方法，包括对流感病毒感染等病况的治疗。其中，流感病毒感染是一种流感感染的例子。
• An improved asymmetric synthetic route to a novel triple uptake inhibitor antidepressant (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol (D-142)
  作者：Bhaskar Gopishetty、Sanjib Gogoi、Aloke K. Dutta

  DOI：10.1016/j.tetasy.2011.05.012

  日期：2011.5

  Triple monoamine reuptake inhibitors have been implicated in the development of a new generation of antidepressants with higher efficacy than the currently existing therapies. In this paper, we have developed an alternative efficient synthetic route for triple monoamine reuptake inhibitor D-142 in 18.5% overall yield in 11 steps starting from diphenylmethane. D-142 was developed by us recently. The

  三重单胺再摄取抑制剂参与了新一代抗抑郁药的开发，其疗效高于目前现有的疗法。在本文中，我们开发了一种替代的有效合成路线，以二苯甲烷为原料，在 11 个步骤中以 18.5% 的总收率制备三元单胺再摄取抑制剂 D-142。D-142 是我们最近开发的。本合成策略的关键步骤是通过顺式溴中间体从烯烃优先形成溴醇，这在整个合成中引入了显着的效率。此外，我们开发了一种有效的方法来将光学活性中间体二醇回收回所需的手性环氧化物。