2β-(2'-(methoxycarbonyl)eth-1'-enyl)-3β-phenyltropane | 159154-16-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 2β-(2'-(methoxycarbonyl)eth-1'-enyl)-3β-phenyltropane
• 英文别名: methyl (E)-3-[(1R,2S,3S,5S)-8-methyl-3-phenyl-8-azabicyclo[3.2.1]octan-2-yl]prop-2-enoate
• CAS: 159154-16-2
• 化学式: C₁₈H₂₃NO₂
• 分子量: 285.386
• InChiKey: OMLSVYSQLRWXNO-TVFOUJOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2β-(2'-(methoxycarbonyl)eth-1'-enyl)-3β-phenyltropane 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 以95%的产率得到2β-(3'-hydroxyprop-1-enyl)-3β-phenyltropane
  参考文献：
  名称：

  Synthesis, Dopamine Transporter Affinity, Dopamine Uptake Inhibition, and Locomotor Stimulant Activity of 2-Substituted 3β-Phenyltropane Derivatives

  摘要：

  A series of 2 beta-substituted 3 beta-phenyltropanes were synthesized as analogs of cocaine and tested in vitro for their ability to displace bound [H-3]WIN 35,428 (2b) and inhibit; dopamine uptake in rat caudate-putamen tissue. The analogs bound with high affinity (K-i = 11-22 nM) to the dopamine transporter. Increased lipophilicity at the beta-C(2)-position was found to lead to increased binding affinity and increased dopamine uptake potency. However, a direct correlation between clogP values and binding affinity and potency of uptake inhibition was not observed. The unsaturated ester 7 was found to possess weak dopamine uptake inhibition relative to the high binding affinity (IC50/K-i = 10.2). In vivo measurement of stimulated locomotor activity and drug discrimination against cocaine (10 mg/kg, ip) with selected analogs (4, 6, and 7) demonstrated that the behavioral effects of these drugs were approximately equipotent with those of cocaine, The structure-activity relationships of this series of cocaine analogs supports a pharmacophore model in which lipophilic interactions between the B-C(2)position of 3 beta-phenyltropanes and the cocaine binding site on the dopamine transporter lead to enhanced potency while electrostatic interactions have a nonspecific effect.

  DOI：

  10.1021/jm960739c
• 作为产物：
  描述：

  (1R,2S,3S,5S)-8-甲基-3-苯基-8-氮杂双环[3.2.1]辛烷-2-羧酸甲酯 在 lithium aluminium tetrahydride 、 草酰氯 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 25.0h， 生成 2β-(2'-(methoxycarbonyl)eth-1'-enyl)-3β-phenyltropane
  参考文献：
  名称：

  Synthesis, Dopamine Transporter Affinity, Dopamine Uptake Inhibition, and Locomotor Stimulant Activity of 2-Substituted 3β-Phenyltropane Derivatives

  摘要：

  A series of 2 beta-substituted 3 beta-phenyltropanes were synthesized as analogs of cocaine and tested in vitro for their ability to displace bound [H-3]WIN 35,428 (2b) and inhibit; dopamine uptake in rat caudate-putamen tissue. The analogs bound with high affinity (K-i = 11-22 nM) to the dopamine transporter. Increased lipophilicity at the beta-C(2)-position was found to lead to increased binding affinity and increased dopamine uptake potency. However, a direct correlation between clogP values and binding affinity and potency of uptake inhibition was not observed. The unsaturated ester 7 was found to possess weak dopamine uptake inhibition relative to the high binding affinity (IC50/K-i = 10.2). In vivo measurement of stimulated locomotor activity and drug discrimination against cocaine (10 mg/kg, ip) with selected analogs (4, 6, and 7) demonstrated that the behavioral effects of these drugs were approximately equipotent with those of cocaine, The structure-activity relationships of this series of cocaine analogs supports a pharmacophore model in which lipophilic interactions between the B-C(2)position of 3 beta-phenyltropanes and the cocaine binding site on the dopamine transporter lead to enhanced potency while electrostatic interactions have a nonspecific effect.

  DOI：

  10.1021/jm960739c

文献信息

• Synthesis, Cocaine Receptor Affinity, and Dopamine Uptake Inhibition of Several New 2.beta.-Substituted 3.beta.-Phenyltropanes
  作者：Shreekrishna V. Kelkar、Sari Izenwasser、Jonathan L. Katz、Cheryl L. Klein、Naijue Zhu、Mark L. Trudell

  DOI：10.1021/jm00049a004

  日期：1994.11
• Synthesis, Dopamine Transporter Affinity, Dopamine Uptake Inhibition, and Locomotor Stimulant Activity of 2-Substituted 3β-Phenyltropane Derivatives
  作者：Lifen Xu、Shreekrishna V. Kelkar、Stacey A. Lomenzo、Sari Izenwasser、Jonathan L. Katz、Richard H. Kline、Mark L. Trudell

  DOI：10.1021/jm960739c

  日期：1997.3.1

  A series of 2 beta-substituted 3 beta-phenyltropanes were synthesized as analogs of cocaine and tested in vitro for their ability to displace bound [H-3]WIN 35,428 (2b) and inhibit; dopamine uptake in rat caudate-putamen tissue. The analogs bound with high affinity (K-i = 11-22 nM) to the dopamine transporter. Increased lipophilicity at the beta-C(2)-position was found to lead to increased binding affinity and increased dopamine uptake potency. However, a direct correlation between clogP values and binding affinity and potency of uptake inhibition was not observed. The unsaturated ester 7 was found to possess weak dopamine uptake inhibition relative to the high binding affinity (IC50/K-i = 10.2). In vivo measurement of stimulated locomotor activity and drug discrimination against cocaine (10 mg/kg, ip) with selected analogs (4, 6, and 7) demonstrated that the behavioral effects of these drugs were approximately equipotent with those of cocaine, The structure-activity relationships of this series of cocaine analogs supports a pharmacophore model in which lipophilic interactions between the B-C(2)position of 3 beta-phenyltropanes and the cocaine binding site on the dopamine transporter lead to enhanced potency while electrostatic interactions have a nonspecific effect.