Ethanesulfonic acid biphenyl-2-ylmethyl-(S)-pyrrolidin-3-yl-amide | 1049777-53-8

• 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: Ethanesulfonic acid biphenyl-2-ylmethyl-(S)-pyrrolidin-3-yl-amide
• 英文别名: N-[(2-phenylphenyl)methyl]-N-[(3S)-pyrrolidin-3-yl]ethanesulfonamide
• CAS: 1049777-53-8
• 化学式: C₁₉H₂₄N₂O₂S
• 分子量: 344.478
• InChiKey: JTFGLXWULCGHRY-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  57.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 Ethanesulfonic acid biphenyl-2-ylmethyl-(S)-pyrrolidin-3-yl-amide 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 Ethanesulfonic acid biphenyl-2-ylmethyl-((S)-1-methyl-pyrrolidin-3-yl)-amide
  参考文献：
  名称：

  Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine as selective noradrenaline reuptake inhibitors: Reducing P-gp mediated efflux by modulation of H-bond acceptor capacity

  摘要：

  Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine are disclosed as a new series of noradrenaline reuptake inhibitors (NRI). Carboxamide 9e, carbamate 11b and sulfonamide 13a were identified as potent NRIs with excellent selectivity over SRI and DRI, good in vitro metabolic stability and weak CYP inhibition. Carbamate 11b demonstrated superior transit performance in MDCK-mdr1 cell lines with minimal P-gp efflux which was attributed to reduced HBA capacity of the carbamate group. Evaluation in vivo, in rat microdialysis experiments, showed 11b increased noradrenaline levels by 400% confirming good CNS penetration. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.06.071
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 Ethanesulfonic acid biphenyl-2-ylmethyl-(S)-pyrrolidin-3-yl-amide
  参考文献：
  名称：

  Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine as selective noradrenaline reuptake inhibitors: Reducing P-gp mediated efflux by modulation of H-bond acceptor capacity

  摘要：

  Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine are disclosed as a new series of noradrenaline reuptake inhibitors (NRI). Carboxamide 9e, carbamate 11b and sulfonamide 13a were identified as potent NRIs with excellent selectivity over SRI and DRI, good in vitro metabolic stability and weak CYP inhibition. Carbamate 11b demonstrated superior transit performance in MDCK-mdr1 cell lines with minimal P-gp efflux which was attributed to reduced HBA capacity of the carbamate group. Evaluation in vivo, in rat microdialysis experiments, showed 11b increased noradrenaline levels by 400% confirming good CNS penetration. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.06.071

文献信息

• Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine as selective noradrenaline reuptake inhibitors: Reducing P-gp mediated efflux by modulation of H-bond acceptor capacity
  作者：Paul V. Fish、Nancy S. Barta、David L.F. Gray、Thomas Ryckmans、Alan Stobie、Florian Wakenhut、Gavin A. Whitlock

  DOI：10.1016/j.bmcl.2008.06.071

  日期：2008.8

  Derivatives of (3S)-N-(biphenyl-2-ylmethyl)pyrrolidin-3-amine are disclosed as a new series of noradrenaline reuptake inhibitors (NRI). Carboxamide 9e, carbamate 11b and sulfonamide 13a were identified as potent NRIs with excellent selectivity over SRI and DRI, good in vitro metabolic stability and weak CYP inhibition. Carbamate 11b demonstrated superior transit performance in MDCK-mdr1 cell lines with minimal P-gp efflux which was attributed to reduced HBA capacity of the carbamate group. Evaluation in vivo, in rat microdialysis experiments, showed 11b increased noradrenaline levels by 400% confirming good CNS penetration. (c) 2008 Elsevier Ltd. All rights reserved.