(+/-)-1'-{[2-(trimethylsilyl)ethoxy]methyl}-3H-spiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridine]-2',3(1'H)-dione | 957122-45-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: (+/-)-1'-{[2-(trimethylsilyl)ethoxy]methyl}-3H-spiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridine]-2',3(1'H)-dione
• 英文别名: (+/-)-1'-{[2-(trimethylsilyl)ethoxy]methyl}-3H-spiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridin]-2',3(1'H)-dione；1'-{[2-(trimethylsilyl)ethoxy]methyl}-3H-spiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridine]-2',3'(1'H)-dione；1'-(2-Trimethylsilylethoxymethyl)spiro[cyclopentane-3,3'-pyrrolo[2,3-b]pyridine]-1,2'-dione
• CAS: 957122-45-1
• 化学式: C₁₇H₂₄N₂O₃Si
• 分子量: 332.475
• InChiKey: ADWNBIBXHQBLEH-UHFFFAOYSA-N

物化性质

• 沸点：
  516.9±50.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.73
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  59.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-1'-{[2-(trimethylsilyl)ethoxy]methyl}-3H-spiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridine]-2',3(1'H)-dione 在 palladium 10% on activated carbon 盐酸 、 氨 、 氢气 、 potassium iodide 、 sodium nitrite 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 为溶剂， 反应 24.25h， 生成 (6S)-3-iodo-5,7-dihydrospiro[cyclopenta[b]pyridine-6,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one
  参考文献：
  名称：

  [EN] MONOCYCLIC CGRP RECEPTOR ANTAGONISTS
  [FR] ANTAGONISTES DES RÉCEPTEURS CGRP MONOCYCLIQUES

  摘要：

  公开号：

  WO2009120652A3
• 作为产物：
  描述：

  7-氮杂吲哚 在 pyridinium hydrobromide perbromide 、 氯化铵 、 caesium carbonate 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 (+/-)-1'-{[2-(trimethylsilyl)ethoxy]methyl}-3H-spiro[cyclopentane-1,3'-pyrrolo[2,3-b]pyridine]-2',3(1'H)-dione
  参考文献：
  名称：

  Ubrogepant. Calcitonin gene-related peptide (CGRP) receptor antagonist, Treatment of migraine

  摘要：

  Migraineis ranked as the sixth cause of years lost due to disability, with around 1.04 billion migraine sufferers globally. Triptans are considered the standard for acute migraine treatment, but an important number of migraineurs do not respond to them and these drugs are contraindicated in patients with cardiovascular disease. Migraine therapy is currently undergoing tremendous development, i.e., 5-HT1F receptor agonists (ditans), anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies, and small-molecule CGRP receptor antagonists (gepants). Ubrogepant (MK-1620) is a small-molecule, potent and selective CGRP receptor antagonist. In two phase III clinical trials (ACHIEVE I and II), ubrogepant showed, at 2 hours, significant percentages of pain freedom, and absence of the most bothersome symptoms in migraine patients. In a phase III study to assess the long-term (52-week) safety and tolerability, ubrogepant displayed good tolerability, and no signs of hepatic toxicity. In March 2019, the U.S. Food and Drug Administration accepted the new drug application (NDA) for ubrogepant for the acute treatment of migraine.

  DOI：

  10.1358/dof.2019.44.11.3035581

文献信息

• [EN] IMIDAZOLINONE DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'IMIDAZOLINONE EN TANT QU'ANTAGONISTES DE RÉCEPTEURS CGRP
  申请人：MERCK SHARP & DOHME

  公开号：WO2010077752A1

  公开（公告）日：2010-07-08

  The present invention is directed to imidazolinone derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及嘧啶啉酮衍生物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• Substituted monocyclic CGRP receptor antagonists
  申请人：Wood Michael R.

  公开号：US20070265225A1

  公开（公告）日：2007-11-15

  Compounds of formula I: (wherein variables A 1 , A 2 , A 3 , A 4 , m, n, J, Q, R 4 , E a , E b , E c , R 6 , R 7 , R e , R f , R PG and Y are as described herein) which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  式I的化合物：(其中变量A1、A2、A3、A4、m、n、J、Q、R4、Ea、Eb、Ec、R6、R7、Re、Rf、RPG和Y如本文所述)是CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗涉及CGRP的疾病中使用这些化合物和组合物。
• 哌啶酮羧酰胺氮杂茚满CGRP受体拮抗剂
  申请人：默沙东公司

  公开号：CN103328478A

  公开（公告）日：2013-09-25

  本发明涉及式I的哌啶酮羧酰胺氮杂茚满衍生物，其是CGRP受体的拮抗剂，并可用于治疗或预防其中涉及CGRP的疾病，诸如偏头痛。本发明还涉及含有这些化合物的药物组合物和这些化合物与组合物在预防或治疗其中涉及CGRP的这样的疾病中的用途。
• WO2008/130512
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2008/153852
  申请人：——

  公开号：——

  公开（公告）日：——