N,N-diallyl (1R,2R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1-(2-thienyl)-cyclopropanecarboxamide | 1085180-87-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N,N-diallyl (1R,2R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1-(2-thienyl)-cyclopropanecarboxamide
• 英文别名: (1R,2R)-2-[(1,3-dioxoisoindol-2-yl)methyl]-N,N-bis(prop-2-enyl)-1-thiophen-2-ylcyclopropane-1-carboxamide
• CAS: 1085180-87-5
• 化学式: C₂₃H₂₂N₂O₃S
• 分子量: 406.505
• InChiKey: ZXSUALBJMYBORQ-HJPURHCSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  85.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-diallyl (1R,2R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1-(2-thienyl)-cyclopropanecarboxamide 在 甲基肼 作用下， 以 乙醇 、 甲苯 为溶剂， 以2.34 g的产率得到N,N-diallyl (1R,2R)-2-(aminomethyl)-1-(2-thienyl)-cyclopropanecarboxamide
  参考文献：
  名称：

  Characterization of Thien-2-yl 1S,2R-Milnacipran Analogues as Potent Norepinephrine/Serotonin Transporter Inhibitors for the Treatment of Neuropathic Pain

  摘要：

  Thien-2-yl 1S,2R-milnacipran analogues were synthesized and characterized as norepinephrine/serotonin transporter inhibitors. These compounds possessed higher potencies than IS,2R-milnacipran (2R-1) while maintaining low molecular weight and moderate lipophilicity, which are the important features for the pharmacological and pharmacokinetic characteristics of milnacipran (1). Thus, compound 5c exhibited IC50 values of 2.3 and 32 nM, respectively, at NET and SERT, which were more than 10-fold better than those of 1 (NET IC50 = 77 nM, SERT IC50 = 420 nM). Moreover, 5c achieved the same efficacy as 1, but with much lower doses, in a rodent spinal nerve ligation pain model. In addition, 5c displayed desirable pharmacokinetic properties in several species, including high oral availability and significant brain penetration.

  DOI：

  10.1021/jm8009537
• 作为产物：
  描述：

  (1S,2R)-2-[(1,3-dioxoisoindol-2-yl)methyl]-1-thiophen-2-ylcyclopropane-1-carbonyl chloride 、 二烯丙基胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以6.16 g的产率得到N,N-diallyl (1R,2R)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)-1-(2-thienyl)-cyclopropanecarboxamide
  参考文献：
  名称：

  Characterization of Thien-2-yl 1S,2R-Milnacipran Analogues as Potent Norepinephrine/Serotonin Transporter Inhibitors for the Treatment of Neuropathic Pain

  摘要：

  Thien-2-yl 1S,2R-milnacipran analogues were synthesized and characterized as norepinephrine/serotonin transporter inhibitors. These compounds possessed higher potencies than IS,2R-milnacipran (2R-1) while maintaining low molecular weight and moderate lipophilicity, which are the important features for the pharmacological and pharmacokinetic characteristics of milnacipran (1). Thus, compound 5c exhibited IC50 values of 2.3 and 32 nM, respectively, at NET and SERT, which were more than 10-fold better than those of 1 (NET IC50 = 77 nM, SERT IC50 = 420 nM). Moreover, 5c achieved the same efficacy as 1, but with much lower doses, in a rodent spinal nerve ligation pain model. In addition, 5c displayed desirable pharmacokinetic properties in several species, including high oral availability and significant brain penetration.

  DOI：

  10.1021/jm8009537