(2S)-2-benzhydryl-3,6-dihydro-2H-pyran | 862647-16-3

• 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)-2-benzhydryl-3,6-dihydro-2H-pyran
• 英文别名: (S)-2-benzhydryl-3,6-dihydro-2H-pyran
• CAS: 862647-16-3
• 化学式: C₁₈H₁₈O
• 分子量: 250.34
• InChiKey: IYBKTVXJHKBXJF-KRWDZBQOSA-N

物化性质

• 熔点：
  74-76 °C
• 沸点：
  369.1±31.0 °C(Predicted)
• 密度：
  1.074±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (2S)-2-benzhydryl-3,6-dihydro-2H-pyran 在 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 (2S,4R,5R)-2-benzhydryl-5-[2-(4-fluoro-phenyl)-ethylamino]-tetrahydropyran-4-ol
  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-diphenyl-2,3-epoxy-propan 在 咪唑 、 Grubbs catalyst first generation 、 copper(l) iodide 、 (R,R)-Jacobsen catalyst 、 四丁基氟化铵 、 水 、 sodium hydride 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 、 苯 为溶剂， 反应 84.0h， 生成 (2S)-2-benzhydryl-3,6-dihydro-2H-pyran
  参考文献：
  名称：

  一种新型三重摄取抑制剂抗抑郁药 (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol (D-142) 的改进不对称合成路线。

  摘要：

  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。

  DOI：

  10.1016/j.tetasy.2011.05.012
• 作为试剂：
  描述：

  (S)-(2-(allyloxy)pent-4-ene-1,1-diyl)dibenzene 在 catalyst 氮 、 hexane-diethyl ether 、 (2S)-2-benzhydryl-3,6-dihydro-2H-pyran 作用下， 以 苯 为溶剂， 反应 20.0h， 以to give 0.15 g (2S)-2-benzhydryl-3,6-dihydro-2H-pyran, 27a (88%, [α]D=(−)79.3, c=1, MeOH)的产率得到(2S)-2-benzhydryl-3,6-dihydro-2H-pyran
  参考文献：
  名称：

  Tri-substituted 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

  摘要：

  小说3,6-二取代吡喃，可选在4位进一步取代，是单胺再摄取抑制剂，具有抗抑郁活性。

  公开号：

  US08937189B2

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。
• Tri-substituted 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
  申请人：Dutta K. Aloke

  公开号：US20060122263A1

  公开（公告）日：2006-06-08

  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，可在4位进一步取代，是单胺再摄取抑制剂，具有抗抑郁药的活性特征。
• 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
  申请人：Dutta K. Aloke

  公开号：US20070276005A1

  公开（公告）日：2007-11-29

  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，可以在4-位置进一步取代，是单胺再摄取抑制剂，具有抗抑郁药的活性特征。
• Tri-Substituted 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
  申请人：Dutta Aloke K.

  公开号：US20080167478A1

  公开（公告）日：2008-07-10

  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，可在4位进一步取代，是单胺再摄取抑制剂，具有抗抑郁药的活性特征。
• TRI-SUBSTITUTED 2-BENZHYDRYL-5-BENZYLAMINO-TETRAHYDRO-PYRAN-4-OL AND 6-BENZHYDRYL-4-BENZYLAMINO-TETRAHYDRO-PYRAN-3-OL ANALOGUES, AND NOVEL 3,6-DISBUSTITUTED PYRAN DERIVATIVES
  申请人：Dutta Aloke K.

  公开号：US20100280091A1

  公开（公告）日：2010-11-04

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

  Novel 3,6-二取代吡喃，其在4-位置可能具有进一步取代基团，是单胺再摄取抑制剂，具有抗抑郁药的活性特征。