1-methyl-1H-imidazole-4-carboxylic acid (3-trifluoromethyl-4-fluorobenzyl)-(N-benzyloxycarbonyl-octahydro-cyclopenta[c]pyrrol-5-yl)-amide | 1217315-24-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-methyl-1H-imidazole-4-carboxylic acid (3-trifluoromethyl-4-fluorobenzyl)-(N-benzyloxycarbonyl-octahydro-cyclopenta[c]pyrrol-5-yl)-amide
• CAS: 1217315-24-6
• 化学式: C₂₈H₂₈F₄N₄O₃
• 分子量: 544.549
• InChiKey: ZQLGKYNZCYTZDV-KOUNCHBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.27
• 重原子数：
  39.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  67.67
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-methyl-1H-imidazole-4-carboxylic acid (3-trifluoromethyl-4-fluorobenzyl)-(N-benzyloxycarbonyl-octahydro-cyclopenta[c]pyrrol-5-yl)-amide 在 氢溴酸 、 盐酸 作用下， 以 溶剂黄146 、 乙酸乙酯 为溶剂， 反应 0.33h， 以77%的产率得到1-methyl-1H-imidazole-4-carboxylic acid (3-trifluoromethyl-4-fluorobenzyl)-(octahydro-cyclopenta[c]pyrrol-5-yl)-amide dihydrochloride
  参考文献：
  名称：

  An octahydro-cyclopenta[c]pyrrole series of inhibitors of the type 1 glycine transporter

  摘要：

  We describe a novel series of inhibitors of the type 1 glycine transporter (GlyT1) as an approach to relieving the glutamatergic deficit that is thought to underlie schizophrenia. Synthesis and SAR follow-up of a series of octahydro-cyclopenta[c]pyrrole derivatives afforded potent in vitro inhibition of GlyT1 as well as in vivo activity in elevating CSF glycine. We also found that a 3-O(c-pentyl), 4-F substituent may serve as a surrogate for the widely used 3-trifluoromethoxy group, suggesting its application as an isostere for future medicinal chemistry studies. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.071
• 作为产物：
  描述：

  1-methyl-1H-imidazole-4-carbonyl chloride hydrochloride 、 benzyl (3aR,5r,6aS)-5-((4-fluoro-3-(trifluoromethyl)benzyl)amino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以84.5%的产率得到1-methyl-1H-imidazole-4-carboxylic acid (3-trifluoromethyl-4-fluorobenzyl)-(N-benzyloxycarbonyl-octahydro-cyclopenta[c]pyrrol-5-yl)-amide
  参考文献：
  名称：

  An octahydro-cyclopenta[c]pyrrole series of inhibitors of the type 1 glycine transporter

  摘要：

  We describe a novel series of inhibitors of the type 1 glycine transporter (GlyT1) as an approach to relieving the glutamatergic deficit that is thought to underlie schizophrenia. Synthesis and SAR follow-up of a series of octahydro-cyclopenta[c]pyrrole derivatives afforded potent in vitro inhibition of GlyT1 as well as in vivo activity in elevating CSF glycine. We also found that a 3-O(c-pentyl), 4-F substituent may serve as a surrogate for the widely used 3-trifluoromethoxy group, suggesting its application as an isostere for future medicinal chemistry studies. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.071