3β-(3'-iodo-4'-aminophenyl)tropane-2β-carboxylic acid methyl ester | 140695-31-4

• 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: 3β-(3'-iodo-4'-aminophenyl)tropane-2β-carboxylic acid methyl ester
• 英文别名: 3β-(4'-amino-3'-iodophenyl)tropane-2β-carboxylic acid methyl ester；RTI 88；methyl (1R,2S,3S,5S)-3-(4-amino-3-iodophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 140695-31-4
• 化学式: C₁₆H₂₁IN₂O₂
• 分子量: 400.259
• InChiKey: MVPPCIDUAFXDAL-DRABBMOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3β-(3'-iodo-4'-aminophenyl)tropane-2β-carboxylic acid methyl ester 在 亚硝酸丁酯 、 copper dichloride 作用下， 以 乙腈 为溶剂， 反应 0.17h， 以71%的产率得到3β-(4'-chloro-3'-iodophenyl)tropane-2β-carboxylic acid methyl ester
  参考文献：
  名称：

  3β-（3'，4'-二取代的苯基）托烷-2β-羧酸甲酯的合成及其单胺转运蛋白的结合性能。

  摘要：

  3β-（3'-甲基-4'-氯苯基）肌烷-2-羧酸甲酯（3b，RTI-112）是对多巴胺和5-羟色胺转运蛋白（DAT和5-羟色胺都具有高亲和力的3-苯基环烷类似物分别为HTT）。化合物3b在恒河猴中显示出可卡因自我给药的显着减少，但仍不能维持强大的药物自我给药。PET研究表明，与更多DAT选择性类似物（例如GBR 12909和3-（4-氯苯基）托烷-2-羧酸苯基酯（RTI-113））不同，当3b以其ED剂量给药时，DAT占有率未检测到（50）用于减少可卡因的自我管理。相反，在该剂量下它高度占据5-HTT。在这项研究中，我们报告了几种新的3-（3'，4' -二取代的苯基）托烷-2-羧酸甲酯（3c-k），其结合性质与3b非常相似。除3'，4'-二甲基类似物3k外，所有化合物在DAT和5-HTT处分别具有亚纳摩尔的IC（50）和K（i）值。3'-氯-4'-溴类似物3e（IC（50）= 0.12 n

  DOI：

  10.1021/jm040185a
• 作为产物：
  描述：

  3β-(4-aminophenyl)-2β-tropane-2β-carboxylic acid methyl ester 在 一氯化碘 、 溶剂黄146 作用下， 生成 3β-(3'-iodo-4'-aminophenyl)tropane-2β-carboxylic acid methyl ester
  参考文献：
  名称：

  Probes for the cocaine receptor. Potentially irreversible ligands for the dopamine transporter

  摘要：

  Several potentially irreversible ligands (i.e., wash-resistant binding inhibitors) for the cocaine receptor site on the dopamine transporter, derived from (-)-cocaine or 3-beta-phenyltropan-2-beta-carboxylic acid methyl ester (WIN 35,065-2), were prepared and shown to produce wash-resistant inhibition of [H-3]-3-beta-(p-fluorophenyl)tropan-2-beta-carboxylic acid methyl ester ([H-3]WIN 35,428) binding. All the compounds prepared had the same absolute configuration as cocaine; they include analogues possessing chemically reactive groups such as the isothiocyanato and bromoacetamido as well as photoactive azido groups. The potentially irreversible ligands, as well as all the intermediates prepared in this study, were evaluated for their ability to inhibit the binding of [H-3]WIN 35,428 in coincubation experiments. Of the potentially irreversible ligands, 3-beta-(p-chlorophenyl)tropan-2-beta-carboxylic acid 2-[p-(bromoacetamido)phenyl]ethyl ester (6c) had the highest apparent potency. The potentially irreversible ligands were also preincubated, and inhibition of [H-3]WIN 35,428 binding was determined both before and after washing the ligand-exposed tissues. The most effective ligands in this regard were 3-beta-(3-iodo-4-azidophenyl)tropan-2-beta-carboxylic acid methyl ester (5) and 3-beta-(p-chlorophenyl)tropan-2-beta-carboxylic acid 2-(3-iodo-4-azidophenyl)ethyl ester (6d). The structure-activity relationships of these data are discussed.

  DOI：

  10.1021/jm00088a017