(2S,4R,5R)-2-benzhydryl-5-((3-hydroxy-4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol

• 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: (2S,4R,5R)-2-benzhydryl-5-((3-hydroxy-4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol
• 英文别名: (2S,4R,5R)-2-benzhydryl-5-[(3-hydroxy-4-methoxyphenyl)methylamino]oxan-4-ol
• 化学式: C₂₆H₂₉NO₄
• 分子量: 419.521
• InChiKey: DCNGWBRYVSTJTB-RQTOMXEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  71
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2S,4R,5R)-5-amino-2-benzhydryltetrahydro-2H-pyran-4-ol 、 异香兰素 在 溶剂黄146 、 sodium cyanoborohydride 作用下， 以 1,2-二氯乙烷 、 MeOH 为溶剂， 反应 0.5h， 以73%的产率得到(2S,4R,5R)-2-benzhydryl-5-((3-hydroxy-4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol
  参考文献：
  名称：

  Development of potent dopamine–norepinephrine uptake inhibitors (DNRIs) based on a (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol molecular template

  摘要：

  Current therapy of depression is less than ideal with remission rates of only 25-35% and response rates of 45-60%. It has been hypothesized that a dysfunctional dopaminergic system in the mesocorticolimbic pathway in depressive disorder may lead to development of anhedonia associated with loss of pleasure and interest along with loss of motivation. The current antidepressants do not address dopamine dysfunction which might explain their low efficacy. In this report, we have described an SAR study on our pyran-based triple reuptake inhibitors (TRIs) which are being investigated as the next-generation antidepressants. In the present work we demonstrate that our lead TRIs can be modified with appropriate aromatic substitutions to display a highly potent SSRI profile for compounds 2a and 4a (K-i (SERT); 0.71 and 2.68 nM, respectively) or a potent DNRI profile for compounds 6b and 6h (K-i (DAT/NET); 8.94/4.76 and 13/7.37 nM, respectively). Compounds 4g-4i exhibited potencies at all three monoamine transporters. The results provide insights into the structural requirements for developing selective dual- and triple-uptake inhibitors from a unique pyran molecular template for an effective management of depression and related disorders. (c) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.040

文献信息

• Substituted Pyran Derivatives
  申请人：Wayne State University

  公开号：US20140309427A1

  公开（公告）日：2014-10-16

  Certain 3,6-disubstituted and 2, 4, 5-trisubstituted pyran derivatives that exhibit potent activity on monoamine transport systems are provided. The 3, 6 and 2, 4, 5 pyrans are useful in probing the effects of their binding to monoamine transporter systems and the corresponding relationships to various afflictions affecting the CNS, or as a treatment for various CNS-related disorders in which the monoamine transport and related systems are implicated.

  提供了在单胺转运系统上表现出强效活性的某些3,6-二取代和2,4,5-三取代吡喃衍生物。这些3,6和2,4,5吡喃物在探究它们与单胺转运体系的结合效应以及与影响中枢神经系统的各种疾病之间的关系，或作为治疗涉及单胺转运和相关系统的各种中枢神经系统相关疾病的方法中是有用的。
• SUBSTITUTED PYRAN DERIVATIVES
  申请人：WAYNE STATE UNIVERSITY

  公开号：US20170015645A1

  公开（公告）日：2017-01-19

  Certain 3,6-disubstituted and 2, 4, 5-trisubstituted pyran derivatives that exhibit potent activity on monoamine transport systems are provided. The 3, 6 and 2, 4, 5 pyrans are useful in probing the effects of their binding to monoamine transporter systems and the corresponding relationships to various afflictions affecting the CNS, or as a treatment for various CNS-related disorders in which the monoamine transport and related systems are implicated.
• US9458124B2
  申请人：——

  公开号：US9458124B2

  公开（公告）日：2016-10-04
• Development of potent dopamine–norepinephrine uptake inhibitors (DNRIs) based on a (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol molecular template
  作者：Soumava Santra、Horrick Sharma、Seenuvasan Vedachalam、Tamara Antonio、Maarten Reith、Aloke Dutta

  DOI：10.1016/j.bmc.2014.12.040

  日期：2015.2

  Current therapy of depression is less than ideal with remission rates of only 25-35% and response rates of 45-60%. It has been hypothesized that a dysfunctional dopaminergic system in the mesocorticolimbic pathway in depressive disorder may lead to development of anhedonia associated with loss of pleasure and interest along with loss of motivation. The current antidepressants do not address dopamine dysfunction which might explain their low efficacy. In this report, we have described an SAR study on our pyran-based triple reuptake inhibitors (TRIs) which are being investigated as the next-generation antidepressants. In the present work we demonstrate that our lead TRIs can be modified with appropriate aromatic substitutions to display a highly potent SSRI profile for compounds 2a and 4a (K-i (SERT); 0.71 and 2.68 nM, respectively) or a potent DNRI profile for compounds 6b and 6h (K-i (DAT/NET); 8.94/4.76 and 13/7.37 nM, respectively). Compounds 4g-4i exhibited potencies at all three monoamine transporters. The results provide insights into the structural requirements for developing selective dual- and triple-uptake inhibitors from a unique pyran molecular template for an effective management of depression and related disorders. (c) 2014 Elsevier Ltd. All rights reserved.