2β-(3'-phenyl-3'-oxopropyl)-3β-phenyltropane | 187829-49-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2β-(3'-phenyl-3'-oxopropyl)-3β-phenyltropane
• CAS: 187829-49-8
• 化学式: C₂₃H₂₇NO
• 分子量: 333.473
• InChiKey: BOTUPWAYGYHQRQ-FNAHDJPLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.92
• 重原子数：
  25.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  20.31
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  2β-(3'-phenyl-3'-oxopropyl)-3β-phenyltropane 在 氢氧化钾 、 肼 作用下， 以 二乙二醇 为溶剂， 以68%的产率得到2β-(3'-phenylpropyl)-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,5S)-2β-formyl-3β-phenyltropane 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 甲醇 、 乙醚 、 乙腈 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 126.0h， 生成 2β-(3'-phenyl-3'-oxopropyl)-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