2β-(2-phenylethyl)-3β-(4-chlorophenyl)tropane

• 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-phenylethyl)-3β-(4-chlorophenyl)tropane
• 英文别名: (1R,2S,3S,5S)-3-(4-chlorophenyl)-8-methyl-2-(2-phenylethyl)-8-azabicyclo[3.2.1]octane
• 化学式: C₂₂H₂₆ClN
• 分子量: 339.908
• InChiKey: KCICRXGLELYHLS-FNAHDJPLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  脱水芽子碱甲基酯甲磺酸盐 在 platinum on activated charcoal 正丁基锂 、 草酰氯 、 氢气 、 二异丁基氢化铝 、 二甲基亚砜 作用下， 以 乙醚 、 正己烷 、 二氯甲烷 、 环己烷 、 甲苯 为溶剂， -40.0~25.0 ℃ 、275.79 kPa 条件下， 反应 20.0h， 生成 2β-(2-phenylethyl)-3β-(4-chlorophenyl)tropane
  参考文献：
  名称：

  Chemistry and Biology of the 2.beta.-Alkyl-3.beta.-phenyl Analogs of Cocaine: Subnanomolar Affinity Ligands That Suggest a New Pharmacophore Model at the C-2 Position

  摘要：

  A series of 2 beta-alkyl-3 beta-phenyltropanes (i.e., the 2 beta-alkyl analogues of the WIN series) were prepared as analogues of cocaine and tested for their ability to displace [H-3]mazindol binding and to inhibit high-affinity dopamine uptake into striatal nerve endings (synaptosomes). These 2 beta-alkyl analogues were readily prepared in optically pure form starting from cocaine by proceeding through the 2 beta-phenyl-bearing aldehyde 6 as a key intermediate. Wittig reaction of 6 with the appropriate phosphorane and hydrogenation delivered the final products. Ah new compounds with the exception of 8e were found to exhibit nanomolar or subnanomolar affinity for the cocaine binding site in the rat striatum. These results are in apparent opposition to the binding model previously proposed which suggests a hydrogen bond donor-acceptor interaction to be present in the vicinity of the C-2 substituent. Taken together with our previous reports and recent findings from other laboratories, we suggest a new pharmacophore model in which 2 beta-substituents lacking H-bond accepters enhance affinity to the binding site through hydrophobic interactions. The new SAR data contained herein may be relevant to the design of possible cocaine antagonists.

  DOI：

  10.1021/jm00016a012

文献信息

• Chemistry and Biology of the 2.beta.-Alkyl-3.beta.-phenyl Analogs of Cocaine: Subnanomolar Affinity Ligands That Suggest a New Pharmacophore Model at the C-2 Position
  作者：Alan P. Kozikowski、M. K. Eddine Saiah、Kenneth M. Johnson、John S. Bergmann

  DOI：10.1021/jm00016a012

  日期：1995.8

  A series of 2 beta-alkyl-3 beta-phenyltropanes (i.e., the 2 beta-alkyl analogues of the WIN series) were prepared as analogues of cocaine and tested for their ability to displace [H-3]mazindol binding and to inhibit high-affinity dopamine uptake into striatal nerve endings (synaptosomes). These 2 beta-alkyl analogues were readily prepared in optically pure form starting from cocaine by proceeding through the 2 beta-phenyl-bearing aldehyde 6 as a key intermediate. Wittig reaction of 6 with the appropriate phosphorane and hydrogenation delivered the final products. Ah new compounds with the exception of 8e were found to exhibit nanomolar or subnanomolar affinity for the cocaine binding site in the rat striatum. These results are in apparent opposition to the binding model previously proposed which suggests a hydrogen bond donor-acceptor interaction to be present in the vicinity of the C-2 substituent. Taken together with our previous reports and recent findings from other laboratories, we suggest a new pharmacophore model in which 2 beta-substituents lacking H-bond accepters enhance affinity to the binding site through hydrophobic interactions. The new SAR data contained herein may be relevant to the design of possible cocaine antagonists.