cis-(6-benzhydryltetrahydropyran-3-yl)(1H-indol-5-ylmethyl)amine

• 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: cis-(6-benzhydryltetrahydropyran-3-yl)(1H-indol-5-ylmethyl)amine
• 英文别名: cis-(3S-6S)-(6-Benzhydryl-tetrahydropyran-3-yl)-(1H-indol-5-ylmethyl)amine；(3S,6S)-6-benzhydryl-N-(1H-indol-5-ylmethyl)oxan-3-amine
• 化学式: C₂₇H₂₈N₂O
• 分子量: 396.532
• InChiKey: UJBRKEMHKNOCKI-AHWVRZQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  37
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1,1-diphenylhex-5-en-2-ol 在 palladium on activated charcoal 、 Grubbs catalyst first generation sodium azide 、 9-BBN-THF 、 氢气 、 mercury(II) trifluoroacetate 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 100.0 ℃ 、413.68 kPa 条件下， 反应 38.0h， 生成 cis-(6-benzhydryltetrahydropyran-3-yl)(1H-indol-5-ylmethyl)amine
  参考文献：
  名称：

  Structural requirements for 2,4- and 3,6-disubstituted pyran biomimetics of cis-(6-benzhydryl-piperidin-3-yl)-benzylamine compounds to interact with monoamine transporters

  摘要：

  In our effort to delineate novel pharmacophoric configuration of bioisosteric pyran versions of cis-(6-benzhydryl-piperidin-3-yl)-benzylamine derivatives in interacting with the monoamine transporter, further structure-activity relationship study was carried out. Both cis and trans 2,4- and 3,6-disubstituted derivatives were synthesized to determine the positional importance of N-substitution on affinity for monoamine transporters, that is the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET) in rat brain. For that purpose, the potency of compounds was determined in competing for the binding of [H-3]WIN 35,428, [H-3]citalopram, and [H-3]nisoxetine, respectively. Selected compounds were also evaluated for their activity in inhibiting the uptake of [H-3]DA by DAT. Our binding results demonstrated potency in 3,6-di substituted derivatives while 2,4-disubstituted derivatives failed to exhibit any appreciable binding affinity. Further structural exploration of the exocyclic N-atom in 3,6-disubstituted derivatives produced compounds potent at both DAT and NET. Compounds 16h and 16o with hydroxyl and amino groups in the phenyl moiety of the benzyl group produced the highest activity for the NET. In this regard, compound 16e with a methoxy substituent produced weak affinity at NET, which upon conversion into a hydroxyl functionality as in 16h produced potent affinity for the NET. Various indole derivatives displayed different interactions; the 5-substituted indole derivative 16n exerted potent affinity for NET, confirming the bioisosteric equivalence between this indole moiety and the phenyl-4-hydroxy group in 16h. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.07.069

文献信息

• Further Structural Exploration of Trisubstituted Asymmetric Pyran Derivatives (2<i>S</i>,4<i>R</i>,5<i>R</i>)-2-Benzhydryl-5-benzylamino-tetrahydropyran-4-ol and Their Corresponding Disubstituted (3<i>S</i>,6<i>S</i>) Pyran Derivatives:  A Proposed Pharmacophore Model for High-Affinity Interaction with the Dopamine, Serotonin, and Norepinephrine Transporters
  作者：Shijun Zhang、Fernando Fernandez、Stuart Hazeldine、Jeffrey Deschamps、Juan Zhen、Maarten E. A. Reith、Aloke K. Dutta

  DOI：10.1021/jm0601699

  日期：2006.7.1

  reported. 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 [(3)H]DA, [(3)H]5-HT, and [(3)H]NE, respectively. The compounds were also tested for their binding potency at the DAT by their ability to inhibit binding of [(3)H]WIN

  在我们以前的报告中，我们描述了一系列新颖的不对称吡喃衍生物（2S，4R，5R）-2-苯甲基-5-苄基氨基-四氢吡喃-4-醇及其对映体，它们在大脑中可作为单胺转运蛋白的阻滞剂。在本报告中，我们通过在分子模板中引入官能团来描述对该系列分子的进一步探索，这应促进与转运蛋白形成H键。此外，报道了一种新的合成方案，用于不对称合成双取代的顺式（6-苯甲酰基-四氢-吡喃-3-基）-苄基胺类似物及其生物学特性。测试了所有合成的衍生物对多巴胺转运蛋白（DAT），血清素转运蛋白（SERT），和去甲肾上腺素转运蛋白（NET）在大脑中的作用，分别通过测量它们抑制[[3] H] DA，[（3）H] 5-HT和[（3）H] NE的吸收的能力来实现。还通过抑制[[3] H] WIN 35，428的结合能力测试了化合物在DAT的结合力。结果表明存在官能团，例如-OH，-NH（2） ，以及二取代和三取代化合物中的生物等位5
• TRI-SUBSTITUED 2-BENZHYDRYL-5-BENZYLAMINO-TETRAHYDRO-PYRAN-4-OL AND 6-BENZHYDRYL-4-BENZYLAMINO-TETRAHYDRO-PYRAN-3-OL ANALOGUES, AND NOVEL 3,6-DISUBSTITUTED PYRAN DERIVATIVES
  申请人：WAYNE STATE UNIVERSITY

  公开号：EP1734948B1

  公开（公告）日：2014-06-11