3α-(3-fluoro-4-methylphenyl)nortropane-2β-carboxylic acid methyl ester | 855834-83-2

• 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: 3α-(3-fluoro-4-methylphenyl)nortropane-2β-carboxylic acid methyl ester
• 英文别名: RTI 539；3α-(4-fluoro-3-methylphenyl)-2β-carboxylic acid methyl ester；methyl (1R,2S,3R,5S)-3-(3-fluoro-4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 855834-83-2
• 化学式: C₁₆H₂₀FNO₂
• 分子量: 277.339
• InChiKey: QDZIBQWKRRRXAL-VIRABCJISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 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：
  38.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3α-(3-fluoro-4-methylphenyl)nortropane-2β-carboxylic acid methyl ester 在 水 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 (1R,2S,3R,5S)-8-(tert-butoxycarbonyl)-3-(3-fluoro-4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of 2β,3α-(substituted phenyl)nortropanes as potential norepinephrine transporter imaging agents

  摘要：

  A series of 2 beta,3 alpha-(substituted phenyl)nortropanes was synthesized and evaluated in vitro for human monoamine transporters. All compounds studied in this series exhibited nanomolar potency for the norepinephrine transporter (NET). Radiolabeling and nonhuman primate microPET brain imaging studies were performed with the most promising compound, [C-11]1, to determine its utility as a NET imaging agent. Despite high in vitro affinity for the human NET, the high uptake of [C-11]1 in the caudate and putamen excludes its use as an in vivo PET imaging agent for the NET. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.056
• 作为产物：
  描述：

  4-溴-2-氟甲苯 在 sodium tetrahydroborate 、 正丁基锂 、 1-氯乙基氯甲酸酯 、 nickel diacetate 作用下， 以 甲醇 、 乙醚 、 正己烷 、 1,2-二氯乙烷 为溶剂， 反应 24.5h， 生成 3α-(3-fluoro-4-methylphenyl)nortropane-2β-carboxylic acid methyl ester
  参考文献：
  名称：

  3α-（取代的苯基）降冰片烷2β-羧酸甲酯的合成及其单胺转运蛋白的结合性能。去甲肾上腺素转运蛋白选择性化合物。

  摘要：

  3α-（取代的苯基）降冰片烷2β-羧酸甲酯（8a-h）对去甲肾上腺素转运蛋白（NET）有很高的亲和力。最有效和选择性最大的化合物是3alpha-（3-氟-4-甲基苯基）降冰片烷2β-羧酸甲酯（8d），在NET处的Ki值为0.43 nM，相对于结合的选择性为21倍和55倍多巴胺和5-羟色胺转运蛋白。8d的发展使具有相同结构类别的所有三种转运蛋白具有选择性的可用化合物。

  DOI：

  10.1021/jm058164j

文献信息

• Synthesis and biological evaluation of 2β,3α-(substituted phenyl)nortropanes as potential norepinephrine transporter imaging agents
  作者：Fanxing Zeng、Jeffrey S. Stehouwer、Nachwa Jarkas、Ronald J. Voll、Larry Williams、Vernon M. Camp、John R. Votaw、Michael J. Owens、Clinton D. Kilts、Charles B. Nemeroff、Mark M. Goodman

  DOI：10.1016/j.bmcl.2007.03.056

  日期：2007.6

  A series of 2 beta,3 alpha-(substituted phenyl)nortropanes was synthesized and evaluated in vitro for human monoamine transporters. All compounds studied in this series exhibited nanomolar potency for the norepinephrine transporter (NET). Radiolabeling and nonhuman primate microPET brain imaging studies were performed with the most promising compound, [C-11]1, to determine its utility as a NET imaging agent. Despite high in vitro affinity for the human NET, the high uptake of [C-11]1 in the caudate and putamen excludes its use as an in vivo PET imaging agent for the NET. (C) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and Monoamine Transporter Binding Properties of 3α-(Substituted phenyl)nortropane-2β-carboxylic Acid Methyl Esters. Norepinephrine Transporter Selective Compounds
  作者：F. Ivy Carroll、Sameer Tyagi、Bruce E. Blough、Michael J. Kuhar、Hernn A. Navarro

  DOI：10.1021/jm058164j

  日期：2005.6.1

  3alpha-(substituted phenyl)nortropane-2beta-carboxylic acid methyl esters (8a-h) showed high affinity for the norepinephrine transporter (NET). The most potent and selective compound was 3alpha-(3-fluoro-4-methylphenyl)nortropane-2beta-carboxylic acid methyl ester (8d), with a Ki of 0.43 nM at the NET and 21- and 55-fold selectivity relative to binding at the dopamine and serotonin transporters. The development

  3α-（取代的苯基）降冰片烷2β-羧酸甲酯（8a-h）对去甲肾上腺素转运蛋白（NET）有很高的亲和力。最有效和选择性最大的化合物是3alpha-（3-氟-4-甲基苯基）降冰片烷2β-羧酸甲酯（8d），在NET处的Ki值为0.43 nM，相对于结合的选择性为21倍和55倍多巴胺和5-羟色胺转运蛋白。8d的发展使具有相同结构类别的所有三种转运蛋白具有选择性的可用化合物。