trans-(6-benzhydryl-tetrahydropyran-3-yl)-(4-fluorobenzyl)-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: trans-(6-benzhydryl-tetrahydropyran-3-yl)-(4-fluorobenzyl)-amine
• 英文别名: trans-(6-benzhydryltetrahydropyran-3-yl)(4-fluorobenzyl)amine；(3R,6S)-6-benzhydryl-N-[(4-fluorophenyl)methyl]oxan-3-amine
• 化学式: C₂₅H₂₆FNO
• 分子量: 375.486
• InChiKey: PZUVPFOEYUKFCA-RPWUZVMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  联苯乙醛 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 9-borabicyclo[3.3.1]nonane dimer 、 草酰氯 、 mercury(II) trifluoroacetate 、 sodium cyanoborohydride 、 magnesium 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 1,2-二氯乙烷 、 苯 为溶剂， 生成 trans-(6-benzhydryl-tetrahydropyran-3-yl)-(4-fluorobenzyl)-amine
  参考文献：
  名称：

  Design, synthesis, and activity of novel cis- and trans-3,6-disubstituted pyran biomimetics of 3,6-disubstituted piperidine as potential ligands for the dopamine transporter

  摘要：

  In our effort to develop novel molecules for the dopamine transporter, we converted our previously designed dopamine transporter specific 3,6-disubstituted piperidine template into corresponding pyran derivatives. cis-Pyran derivative 7b, like their piperidine counterparts, exhibited greater activity for the dopamine transporter compared to the trans-isomer. Further molecular modifications of the cis derivative led to the development of potent analogues which indicated successful bioisosteric replacement of the piperidine ring by a pyran moiety in these 3,6-disubstituted derivatives. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00169-0

文献信息

• [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。
• 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
  作者：Shijun Zhang、Juan Zhen、Maarten E.A. Reith、Aloke K. Dutta

  DOI：10.1016/j.bmc.2004.07.069

  日期：2004.12

  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.
• Design, synthesis, and activity of novel cis- and trans-3,6-disubstituted pyran biomimetics of 3,6-disubstituted piperidine as potential ligands for the dopamine transporter
  作者：Shijun Zhang、Maarteen E.A. Reith、Aloke K. Dutta

  DOI：10.1016/s0960-894x(03)00169-0

  日期：2003.5

  In our effort to develop novel molecules for the dopamine transporter, we converted our previously designed dopamine transporter specific 3,6-disubstituted piperidine template into corresponding pyran derivatives. cis-Pyran derivative 7b, like their piperidine counterparts, exhibited greater activity for the dopamine transporter compared to the trans-isomer. Further molecular modifications of the cis derivative led to the development of potent analogues which indicated successful bioisosteric replacement of the piperidine ring by a pyran moiety in these 3,6-disubstituted derivatives. (C) 2003 Elsevier Science Ltd. All rights reserved.