(+)-(1R*,2R*)-2-[(1S*)-1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-1-fluorocyclopropanecarboxylic acid heptyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (+)-(1R*,2R*)-2-[(1S*)-1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-1-fluorocyclopropanecarboxylic acid heptyl ester
• 英文别名: (2S)-2-amino-2-[(1R,2R)-2-fluoro-2-heptoxycarbonylcyclopropyl]-3-(9H-xanthen-9-yl)propanoic acid
• 化学式: C₂₇H₃₂FNO₅
• 分子量: 469.553
• InChiKey: KODSEJACNKIQDH-RNJDCESWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (+)-(1R*,2R*)-2-[(1S*)-1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-1-fluorocyclopropancarboxylic acid 、 正庚醇 在 氯化亚砜 作用下， 反应 4.0h， 以78%的产率得到(+)-(1R*,2R*)-2-[(1S*)-1-amino-1-carboxy-2-(9H-xanthen-9-yl)ethyl]-1-fluorocyclopropanecarboxylic acid heptyl ester
  参考文献：
  名称：

  Synthesis, in vitro pharmacology, and pharmacokinetic profiles of 2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)-ethyl]-1-fluorocyclopropanecarboxylic acid and its 6-heptyl ester, a potent mGluR2 antagonist

  摘要：

  In this paper, we describe the synthesis of (+)-(1R*,2R*)-2-[(1S*)-1-amino-1-carboxy- 2-(9H-xanthen-9-yl)-ethyl]-1-fluoro-cyclopropanecarboxylic acid (+)-16a, a compound, that is, fluorinated at the alpha position of the carboxylic acid in the cyclopropane ring of a group II mGluRs antagonist, 1 (LY341495), using a previously reported stereoselective cyclopropanation reaction. The fluorinated compound (+)-16a exhibited almost the same affinity (IC50 = 3.49 nM) for mGluR2 as 1 but had a superior pharmacokinetic pro. le. Furthermore, a marked elevation of the plasma levels of (+)-16a was observed following the administration of a prodrug, (+)-17. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.02.066

文献信息

• Synthesis, in vitro pharmacology, and pharmacokinetic profiles of 2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)-ethyl]-1-fluorocyclopropanecarboxylic acid and its 6-heptyl ester, a potent mGluR2 antagonist
  作者：Kazunari Sakagami、Akito Yasuhara、Shigeyuki Chaki、Ryoko Yoshikawa、Yasunori Kawakita、Akio Saito、Takeo Taguchi、Atsuro Nakazato

  DOI：10.1016/j.bmc.2008.02.066

  日期：2008.4

  In this paper, we describe the synthesis of (+)-(1R*,2R*)-2-[(1S*)-1-amino-1-carboxy- 2-(9H-xanthen-9-yl)-ethyl]-1-fluoro-cyclopropanecarboxylic acid (+)-16a, a compound, that is, fluorinated at the alpha position of the carboxylic acid in the cyclopropane ring of a group II mGluRs antagonist, 1 (LY341495), using a previously reported stereoselective cyclopropanation reaction. The fluorinated compound (+)-16a exhibited almost the same affinity (IC50 = 3.49 nM) for mGluR2 as 1 but had a superior pharmacokinetic pro. le. Furthermore, a marked elevation of the plasma levels of (+)-16a was observed following the administration of a prodrug, (+)-17. (C) 2008 Elsevier Ltd. All rights reserved.