threo-N-(o-azido-benzyl)-3-iodomethylphenidate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: threo-N-(o-azido-benzyl)-3-iodomethylphenidate
• 英文别名: (+/-)-threo-N-(o-Azido-benzyl)-3-iodomethylphenidate；methyl (2R)-2-[(2R)-1-[(2-azidophenyl)methyl]piperidin-2-yl]-2-(3-iodophenyl)acetate
• 化学式: C₂₁H₂₃IN₄O₂
• 分子量: 490.344
• InChiKey: KZDQUVCATILJRB-WOJBJXKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  threo-3-iodo-methylphenidate hydrochloride 、 1-叠氮基-2-(溴甲基)苯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 30.17h， 以51%的产率得到threo-N-(o-azido-benzyl)-3-iodomethylphenidate
  参考文献：
  名称：

  Azido-iodo-N-benzyl derivatives of threo-methylphenidate (Ritalin, Concerta): Rational design, synthesis, pharmacological evaluation, and dopamine transporter photoaffinity labeling

  摘要：

  In contrast to tropane-based compounds such as benztropine and cocaine, non-tropane-based photo-affinity ligands for the dopamine transporter (DAT) are relatively unexplored. Towards addressing this knowledge gap, ligands were synthesized in which the piperidine nitrogen of 3- and 4-iodomethylphenidate was substituted with a benzyl group bearing a photoreactive azide. Analog (+/-)-3a demonstrated modest DAT affinity and a radioiodinated version was shown to bind covalently to rat striatal DAT and hDAT expressed in cultured cells. Co-incubation of (+/-)-3a with nonradioactive D-(+)-methylphenidate or (-)-2-beta-carbomethoxy-3-beta-(4-fluorophenyl) tropane (beta-CFT, WIN-35,428, a cocaine analog) blocked DAT labeling. Compound (+/-)-3a represents the first successful example of a DAT photoaffinity ligand based on the methylphenidate scaffold. Such ligands are expected to assist in mapping non-tropane ligand-binding pockets within plasma membrane monoamine transporters. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.11.002

文献信息

• Azido-iodo-N-benzyl derivatives of threo-methylphenidate (Ritalin, Concerta): Rational design, synthesis, pharmacological evaluation, and dopamine transporter photoaffinity labeling
  作者：David J. Lapinsky、Ranganadh Velagaleti、Nageswari Yarravarapu、Yi Liu、Yurong Huang、Christopher K. Surratt、John R. Lever、James D. Foster、Rejwi Acharya、Roxanne A. Vaughan、Howard M. Deutsch

  DOI：10.1016/j.bmc.2010.11.002

  日期：2011.1

  In contrast to tropane-based compounds such as benztropine and cocaine, non-tropane-based photo-affinity ligands for the dopamine transporter (DAT) are relatively unexplored. Towards addressing this knowledge gap, ligands were synthesized in which the piperidine nitrogen of 3- and 4-iodomethylphenidate was substituted with a benzyl group bearing a photoreactive azide. Analog (+/-)-3a demonstrated modest DAT affinity and a radioiodinated version was shown to bind covalently to rat striatal DAT and hDAT expressed in cultured cells. Co-incubation of (+/-)-3a with nonradioactive D-(+)-methylphenidate or (-)-2-beta-carbomethoxy-3-beta-(4-fluorophenyl) tropane (beta-CFT, WIN-35,428, a cocaine analog) blocked DAT labeling. Compound (+/-)-3a represents the first successful example of a DAT photoaffinity ligand based on the methylphenidate scaffold. Such ligands are expected to assist in mapping non-tropane ligand-binding pockets within plasma membrane monoamine transporters. (C) 2010 Elsevier Ltd. All rights reserved.