(2S)-2-[5-[2-(2-azabicyclo[2.2.2]oct-2-yl)-1,1-dimethyl-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]-N-(2-pyridin-4-ylethyl)propan-1-amine

• 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: (2S)-2-[5-[2-(2-azabicyclo[2.2.2]oct-2-yl)-1,1-dimethyl-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]-N-(2-pyridin-4-ylethyl)propan-1-amine
• 英文别名: In3；(S)-1-(2-aza-bicyclo[2.2.2]octan-2-yl)-2-(2-(3,5-dimethylphenyl)-3-(1-(2-(pyridin-4-yl)ethylamino)propan-2-yl)-1H-indol-5-yl)-2-methylpropan-1-one；1-(2-azabicyclo[2.2.2]octan-2-yl)-2-[2-(3,5-dimethylphenyl)-3-[(2S)-1-(2-pyridin-4-ylethylamino)propan-2-yl]-1H-indol-5-yl]-2-methylpropan-1-one
• 化学式: C₃₇H₄₆N₄O
• 分子量: 562.798
• InChiKey: GGVFLXSCFPVLMS-WPCLDFDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  61
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-吡啶乙酸盐酸盐 在 硼烷 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 生成 (2S)-2-[5-[2-(2-azabicyclo[2.2.2]oct-2-yl)-1,1-dimethyl-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]-N-(2-pyridin-4-ylethyl)propan-1-amine
  参考文献：
  名称：

  Orally bioavailable, indole-based nonpeptide GnRH receptor antagonists with high potency and functional activity

  摘要：

  Stereospecific introduction of a methyl group to the indole-3-side chain enhanced activity in our tryptamine-derived series of GnRH receptor antagonists. Further improvements were achieved by variation of the bicyclic amino moiety of the tertiary amide and by adjustment of the tether length to a pyridine or pyridone terminus. These modifications culminated in analogue 24, which had oral activity in a rat model and acceptable oral bioavailability and half-life in dogs and monkeys. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00512-1

文献信息

• Rescue of gonadotropin releasing hormone receptor mutants
  申请人：——

  公开号：US20040191251A1

  公开（公告）日：2004-09-30

  Herein disclosed is a method of rescuing gonadotropin-releasing hormone receptor (GnRHR) mutants with IN3 or a mimetic thereof. IN3 significantly rescues 11 missense mutations as assessed by radioligand binding and by IP production. Such rescue occurred despite widely disparate loci along the receptor. In addition, many altered GnRH receptors (terminally truncated, internal deletions, or lacking the ability to form bridges to form tertiary structure) were rescued with IN3.

  本文公开了一种用 IN3 或其模拟物挽救促性腺激素释放激素受体（GnRHR）突变体的方法。根据放射性配体结合和 IP 生成的评估， 能明显挽救 11 个错义突变体。尽管受体上的基因位点差异很大，但这种拯救作用还是发生了。此外，许多改变的 GnRH 受体（末端截短、内部缺失或缺乏形成三级结构的桥接能力）也被 挽救。
• Pharmacoperones for correcting disease states involving protein misfolding
  申请人：Conn Michael P.

  公开号：US20050203019A1

  公开（公告）日：2005-09-15

  This application relates to methods of identifying pharmacoperone agents that can restore function to a misfolded protein, such as a misfolded protein that causes disease. Also disclosed are methods of using such pharmacoperone agents to treat a disease or disorder that results from the misfolded protein.

  本申请涉及鉴定可使折叠错误的蛋白质（如导致疾病的折叠错误蛋白质）恢复功能的药效蛋白拮抗剂的方法。此外，还公开了使用这种药效蛋白拮抗剂治疗由折叠错误蛋白质引起的疾病或紊乱的方法。
• RESTORING FUNCTION TO GONADOTROPIN RELEASING HORMONE RECEPTOR MUTANTS
  申请人：Oregon Health and Science University

  公开号：EP1599494A2

  公开（公告）日：2005-11-30
• USE OF LHRH ANTAGONISTS FOR INTERMITTENT TREATMENTS
  申请人：ENGEL Juergen

  公开号：US20090221569A1

  公开（公告）日：2009-09-03

  The invention relates to methods of treatment or prophylaxis of physiological and/or pathological conditions with at least one LHRH antagonist, in particular at least one peptidomimetic LHRH antagonistsuch that the at least one LHRH antagonist is administered in a dose, which does not cause chemical (hormonal) castration.
• RESCUE OF GONADOTROPIN RELEASING HORMONE RECEPTOR MUTANTS
  申请人：Conn P. Michael

  公开号：US20100144605A1

  公开（公告）日：2010-06-10

  Herein disclosed is a method of rescuing gonadotropin-releasing hormone receptor (GnRHR) mutants with IN3 or a mimetic thereof. IN3 significantly rescues 11 missense mutations as assessed by radioligand binding and by IP production. Such rescue occurred despite widely disparate loci along the receptor. In addition, many altered GnRH receptors (terminally truncated, internal deletions, or lacking the ability to form bridges to form tertiary structure) were rescued with IN3.