1-methyl-1H-imidazole-4-carboxylic acid (3-cyclopentyloxy-4-fluorobenzyl)-(octahydro-cyclopenta[c]pyrrol-5-yl)-amide | 1031332-80-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-methyl-1H-imidazole-4-carboxylic acid (3-cyclopentyloxy-4-fluorobenzyl)-(octahydro-cyclopenta[c]pyrrol-5-yl)-amide
• CAS: 1031332-80-5
• 化学式: C₂₄H₃₁FN₄O₂
• 分子量: 426.534
• InChiKey: CLMVMIDTRWHVDW-REPLKXPHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  59.39
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 1-methyl-1H-imidazole-4-carboxylic acid (3-cyclopentyloxy-4-fluorobenzyl)-(octahydro-cyclopenta[c]pyrrol-5-yl)-amide 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 盐酸 作用下， 以 水 、 1,2-二氯乙烷 、 乙酸乙酯 为溶剂， 反应 16.0h， 生成 1-methyl-1H-imidazole-4-carboxylic acid (3-cyclopentyloxy-4-fluorobenzyl)-(2-methyl-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-carboxylic acid (3-cyclopentyloxy-4-fluorobenzyl)-(N-t-butylcarboxy-octahydro-cyclopenta[c]pyrrol-5-yl)-amide 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 16.0h， 以94%的产率得到1-methyl-1H-imidazole-4-carboxylic acid (3-cyclopentyloxy-4-fluorobenzyl)-(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