tert-butyl (2S)-2-(1H-indol-3-ylmethyl)pyrrolidine-1-carboxylate | 869095-96-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butyl (2S)-2-(1H-indol-3-ylmethyl)pyrrolidine-1-carboxylate
• CAS: 869095-96-5
• 化学式: C₁₈H₂₄N₂O₂
• 分子量: 300.401
• InChiKey: AWPXDYSMNUUBCD-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S)-2-(1H-indol-3-ylmethyl)pyrrolidine-1-carboxylate 在 盐酸 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 1-(4-Methoxy-benzenesulfonyl)-3-(S)-1-pyrrolidin-2-ylmethyl-1H-indole
  参考文献：
  名称：

  Conformationally constrained N1-arylsulfonyltryptamine derivatives as 5-HT6 receptor antagonists

  摘要：

  Several series of conformationally constrained N-1-arylsulfonyltryptamine derivatives were prepared and tested for 5-HT6 receptor binding affinity and ability to modulate cAMP production in a cyclase assay. The 3-piperidin-3-yl-, 3-(1-methylpyrrolidin-2-ylmethyl)-, and 3-pyrrolidin-3-yl-1H-indole arrays (8-13) appear to be able to adopt a conformation that allows high affinity 5-HT6 receptor binding, while the beta-carboline array 14 binds with a significantly weaker (10- to 100-fold) affinity. N-1-Benzenesulfonyl-3-piperidin-3-yl-1H-indole 9a is a high affinity full agonist with EC50 = 24 nM. Several of the N-1-arylsulfonyl-3-(1-methylpyrrolidin-2-ylmethyl)-1H-indole derivatives behave as very potent antagonists ((S)- 11r, (S)- 11t; IC50 = 0.8, 1.0 nM). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.028
• 作为产物：
  描述：

  benzyl (S)-2-(1H-indole-3-carbonyl)pyrrolidine-1-carboxylate 在 palladium on activated charcoal lithium aluminium tetrahydride 、 甲酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 2.0h， 生成 tert-butyl (2S)-2-(1H-indol-3-ylmethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  Conformationally constrained N1-arylsulfonyltryptamine derivatives as 5-HT6 receptor antagonists

  摘要：

  Several series of conformationally constrained N-1-arylsulfonyltryptamine derivatives were prepared and tested for 5-HT6 receptor binding affinity and ability to modulate cAMP production in a cyclase assay. The 3-piperidin-3-yl-, 3-(1-methylpyrrolidin-2-ylmethyl)-, and 3-pyrrolidin-3-yl-1H-indole arrays (8-13) appear to be able to adopt a conformation that allows high affinity 5-HT6 receptor binding, while the beta-carboline array 14 binds with a significantly weaker (10- to 100-fold) affinity. N-1-Benzenesulfonyl-3-piperidin-3-yl-1H-indole 9a is a high affinity full agonist with EC50 = 24 nM. Several of the N-1-arylsulfonyl-3-(1-methylpyrrolidin-2-ylmethyl)-1H-indole derivatives behave as very potent antagonists ((S)- 11r, (S)- 11t; IC50 = 0.8, 1.0 nM). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.07.028

文献信息

• DIMERIC IAP INHIBITORS
  申请人：CONDON Stephen M.

  公开号：US20100075911A1

  公开（公告）日：2010-03-25

  Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language

  分子模拟Smac能够通过与细胞IAP（抑制凋亡蛋白）的相互作用来调节凋亡。这些类似物基于IAP结合蛋白的N-末端四肽单体或二聚体，如Smac/DIABLO、Hid、Grim和Reaper，它们与IAP的特定表面凹槽相互作用。本发明还揭示了使用这些肽类模拟物进行治疗的方法。在本发明的各种实施例中，将本发明的Smac类似物与化疗药物结合使用，包括但不限于拓扑异构酶抑制剂、激酶抑制剂、NSAIDs、紫杉醇和含铂化合物。
• Dimeric IAP Inhibitors
  申请人：TetraLogic Pharmaceuticals Corporation

  公开号：US20140329823A1

  公开（公告）日：2014-11-06

  Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language

  分子模拟物（Molecular mimics）可以通过与细胞IAPs（抑制凋亡蛋白）的相互作用来调节凋亡。这些类似物基于IAP结合蛋白的N-末端四肽单体或二聚体，如Smac / DIABLO，Hid，Grim和Reaper，它们与IAP的特定表面凹槽相互作用。本发明还公开了使用这些肽类模拟物进行治疗的方法。在本发明的各种实施例中，将发明的Smac模拟物与化疗药物结合使用，包括但不限于拓扑异构酶抑制剂，激酶抑制剂，NSAIDs，紫杉醇和含铂化合物。
• US7517906B2
  申请人：——

  公开号：US7517906B2

  公开（公告）日：2009-04-14
• US8022230B2
  申请人：——

  公开号：US8022230B2

  公开（公告）日：2011-09-20
• US8497297B2
  申请人：——

  公开号：US8497297B2

  公开（公告）日：2013-07-30