4-(2-Benzhydryloxy-ethyl)-1-(4-fluoro-benzyl)-1,2,3,6-tetrahydro-pyridine | 328286-61-9

• 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: 4-(2-Benzhydryloxy-ethyl)-1-(4-fluoro-benzyl)-1,2,3,6-tetrahydro-pyridine
• 英文别名: 4-(2-benzhydryloxyethyl)-1-[(4-fluorophenyl)methyl]-3,6-dihydro-2H-pyridine
• CAS: 328286-61-9
• 化学式: C₂₇H₂₈FNO
• 分子量: 401.524
• InChiKey: VKSQKCXBMWPAJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-Benzhydryloxy-ethyl)-1-(4-fluoro-benzyl)-1,2,3,6-tetrahydro-pyridine 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 三氟化硼乙醚 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 (1S)-4,7,7-trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carboxylic acid (S,S)-4-(2-benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidin-3-yl ester
  参考文献：
  名称：

  High Affinity Hydroxypiperidine Analogues of 4-(2-Benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidine for the Dopamine Transporter:  Stereospecific Interactions in Vitro and in Vivo

  摘要：

  In our effort to develop high-affinity ligands for the dopamine transporter which might find potential use as cocaine medication, a polar hydroxy substituent was introduced into the piperidine ring of one of our disubstituted lead analogues derived from 1-[2-(diphenylmethoxy)ethyl] -4-(3-phenylpropyl)piperazine (GBR 12935). Both cis- and trans-3-hydroxy derivatives were synthesized and the racemic trans isomer, (+/-)-5, was further resolved into two enantiomers. Newly synthesized compounds were characterized for their binding affinity at the dopamine, serotonin, and norepinephrine transporter systems in rat brain. The two enantiomers (+)-5 and (-)-5 exhibited marked differential affinities at the dopamine transporter with (+)-5 being 122-fold more potent than (-)-5 in inhibiting radiolabeled cocaine analogue binding (IC50; 0.46 vs 56.7 nM) and 9-fold more active for inhibiting dopamine uptake (IC50; 4.05 vs 38.0 nM). Furthermore, the most active (+)-5 was 22-fold more potent at the dopamine transporter compared to the standard GBR 12909. Absolute configuration of one of the enantiomers was determined unambiguously by X-ray structural analysis. In in vivo locomotor activity studies, the enantiomer (+)-5 and the racemic ()-5, but not (-)-5, exhibited stimulant activity with a long duration of effect. All three compounds, (+)-5, (-)-5, and ()-5, within the dose range tested, partially (50%) but incompletely (80%) produced cocaine-like responses in mice trained to discriminate 10 mg/kg ip cocaine from vehicle. Compound (-)-5 was distinctive in this regard in that, unlike (+)-5 and (+/-)-5, it did not affect locomotor activity yet, but similar to them, was able to engender (albeit incompletely) cocaine-like responses.

  DOI：

  10.1021/jm020275k
• 作为产物：
  描述：

  4-(2-羟乙基)吡啶 在 sodium tetrahydroborate 、 对甲苯磺酸 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 27.0h， 生成 4-(2-Benzhydryloxy-ethyl)-1-(4-fluoro-benzyl)-1,2,3,6-tetrahydro-pyridine
  参考文献：
  名称：

  High Affinity Hydroxypiperidine Analogues of 4-(2-Benzhydryloxyethyl)-1-(4-fluorobenzyl)piperidine for the Dopamine Transporter:  Stereospecific Interactions in Vitro and in Vivo

  摘要：

  In our effort to develop high-affinity ligands for the dopamine transporter which might find potential use as cocaine medication, a polar hydroxy substituent was introduced into the piperidine ring of one of our disubstituted lead analogues derived from 1-[2-(diphenylmethoxy)ethyl] -4-(3-phenylpropyl)piperazine (GBR 12935). Both cis- and trans-3-hydroxy derivatives were synthesized and the racemic trans isomer, (+/-)-5, was further resolved into two enantiomers. Newly synthesized compounds were characterized for their binding affinity at the dopamine, serotonin, and norepinephrine transporter systems in rat brain. The two enantiomers (+)-5 and (-)-5 exhibited marked differential affinities at the dopamine transporter with (+)-5 being 122-fold more potent than (-)-5 in inhibiting radiolabeled cocaine analogue binding (IC50; 0.46 vs 56.7 nM) and 9-fold more active for inhibiting dopamine uptake (IC50; 4.05 vs 38.0 nM). Furthermore, the most active (+)-5 was 22-fold more potent at the dopamine transporter compared to the standard GBR 12909. Absolute configuration of one of the enantiomers was determined unambiguously by X-ray structural analysis. In in vivo locomotor activity studies, the enantiomer (+)-5 and the racemic ()-5, but not (-)-5, exhibited stimulant activity with a long duration of effect. All three compounds, (+)-5, (-)-5, and ()-5, within the dose range tested, partially (50%) but incompletely (80%) produced cocaine-like responses in mice trained to discriminate 10 mg/kg ip cocaine from vehicle. Compound (-)-5 was distinctive in this regard in that, unlike (+)-5 and (+/-)-5, it did not affect locomotor activity yet, but similar to them, was able to engender (albeit incompletely) cocaine-like responses.

  DOI：

  10.1021/jm020275k

文献信息

• N- AND O-SUBSTITUED 4-[2-(DIPHENYLMETHOXY)-ETHYL]-1-[(PHENYL)METHYL]PIPERIDINE ANALOGS AND METHODS OF TREATING CNS DISORDERS THEREWITH
  申请人：Dutta Aloke K.

  公开号：US20080182991A1

  公开（公告）日：2008-07-31

  N- and O-substituted 4[2-diaromaticmethoxy and methylamino)alkyl] piperidines exhibit high CNS activity with respect to the dopamine transporter (DAT) and serotonin transporter (SERT). Preferred compounds exhibit highly differential behavior as between the DAT and SERT and between the DAT and the norepinephrine transporter (NET). The compounds have utility in treating CNS disorders, including but not limited to cocaine addiction, depression, and Parkinson's disease.

  N-和O-取代的4-[2-二芳基甲氧基和甲基氨基)烷基]哌啶表现出高中枢神经系统活性，与多巴胺转运体（DAT）和5-羟色胺转运体（SERT）有关。优选化合物在DAT和SERT以及DAT和去甲肾上腺素转运体（NET）之间表现出高度差异行为。这些化合物在治疗中枢神经系统疾病方面具有实用价值，包括但不限于可卡因成瘾、抑郁症和帕金森病。
• N- and O-Substituted 4-[2-(Diphenylmethoxy)-Ethyl]-1-[(Phenyl)Methyl]Piperdine Analogs and Methods of Treating CNS Disorders Therewith
  申请人：Dutta Aloke K.

  公开号：US20100016600A1

  公开（公告）日：2010-01-21

  N- and O-substituted 4[2-diaromaticmethoxy and methylamino)alkyl]piperidines exhibit high CNS activity with respect to the dopamine transporter (DAT) and serotonin transporter (SERT). Preferred compounds exhibit highly differential behavior as between the DAT and SERT and between the DAT and the norepinephrine transporter (NET). The compounds have utility in treating CNS disorders, including but not limited to cocaine addiction, depression, and Parkinson's disease.

  N-和O-取代的4-[2-二芳基甲氧基和甲基氨基)烷基]哌啶具有高中枢神经系统活性，与多巴胺转运体（DAT）和血清素转运体（SERT）有关。优选化合物在DAT和SERT之间以及在DAT和去甲肾上腺素转运体（NET）之间表现出高度差异的行为。这些化合物在治疗中枢神经系统疾病，包括但不限于可卡因成瘾、抑郁症和帕金森病方面具有用途。
• US7595331B2
  申请人：——

  公开号：US7595331B2

  公开（公告）日：2009-09-29
• US8211916B2
  申请人：——

  公开号：US8211916B2

  公开（公告）日：2012-07-03
• [EN] N- AND O-SUBSTITUTED 4-[2-(DIPHENYLMETHOXY)-ETHYL]-1-[(PHENYL)METHYL]PIPERIDINE ANALOGS AND METHODS OF TREATING CNS DISORDERS THEREWITH<br/>[FR] ANALOGUES DE LA 4-[2-(DIPHÉNYLMÉTHOXY)-ÉTHYL]-1-[(PHÉNYL)MÉTHYL]PIPÉRIDINE SUBSTITUÉS SUR N ET O ET PROCÉDÉS DE TRAITEMENT PAR CEUX-CI DE TROUBLES DU SYSTÈME NERVEUX CENTRAL
  申请人：UNIV WAYNE STATE

  公开号：WO2009094428A2

  公开（公告）日：2009-07-30

  N- and O-substituted 4[2-diaromaticmethoxy and methylamino)alkyl] piperidines exhibit high CNS activity with respect to the dopamine transporter (DAT) and serotonin transporter (SERT). Preferred compounds exhibit highly differential behavior as between the DAT and SERT and between the DAT and the norepinephrine transporter (NET). The compounds have utility in treating CNS disorders, including but not limited to cocaine addiction, depression, and Parkinson's disease.