N-ethyl-N-(5-(trifluoromethyl)-2-(6-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)benzyl)cyclopropanecarboxamide | 1420070-69-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: N-ethyl-N-(5-(trifluoromethyl)-2-(6-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)benzyl)cyclopropanecarboxamide
• 英文别名: N-ethyl-N-[[5-(trifluoromethyl)-2-[6-(trifluoromethyl)pyrrolo[2,3-b]pyridin-1-yl]phenyl]methyl]cyclopropanecarboxamide
• CAS: 1420070-69-4
• 化学式: C₂₂H₁₉F₆N₃O
• 分子量: 455.403
• InChiKey: NECDYYYEMKQFES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-ethyl-N-(5-(trifluoromethyl)-2-(6-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)benzyl)cyclopropanecarboxamide 在 N-溴代丁二酰亚胺(NBS) 、 1,2,3,4,5-五苯基-1′-(二叔丁基膦)二茂铁 、 三氟乙酸 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 4.5h， 生成 2-[1-[2-[[Cyclopropanecarbonyl(ethyl)amino]methyl]-4-(trifluoromethyl)phenyl]-6-(trifluoromethyl)pyrrolo[2,3-b]pyridin-3-yl]acetic acid
  参考文献：
  名称：

  Structure–activity relationships (SAR) and structure–kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists II: Lead optimization

  摘要：

  Extensive structure-activity relationship (SAR) and structure-kinetic relationship (SKR) studies in the bicyclic heteroaromatic series of CRTh2 antagonists led to the identification of several molecules that possessed both excellent binding and cellular potencies along with long receptor residence times. A small substituent in the bicyclic core provided an order of magnitude jump in dissociation half-lives. Selected optimized compounds demonstrated suitable pharmacokinetic profiles. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.08.029
• 作为产物：
  描述：

  6-氯-吡咯并[2,3-b]吡啶-1-羧酸乙酯 在 trans-N,N'-dimethyl-1,2-cyclohexyldiamine 、 甲醇 、 potassium phosphate 、 copper(l) iodide 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 38.0h， 生成 N-ethyl-N-(5-(trifluoromethyl)-2-(6-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)benzyl)cyclopropanecarboxamide
  参考文献：
  名称：

  Structure–activity relationships (SAR) and structure–kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists II: Lead optimization

  摘要：

  Extensive structure-activity relationship (SAR) and structure-kinetic relationship (SKR) studies in the bicyclic heteroaromatic series of CRTh2 antagonists led to the identification of several molecules that possessed both excellent binding and cellular potencies along with long receptor residence times. A small substituent in the bicyclic core provided an order of magnitude jump in dissociation half-lives. Selected optimized compounds demonstrated suitable pharmacokinetic profiles. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.08.029

文献信息

• New CRTh2 antagonists
  申请人：Almirall, S.A.

  公开号：EP2548876A1

  公开（公告）日：2013-01-23

  The present invention relates to compounds of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by CRTh2 antagonist activity.

  本发明涉及式(I)的化合物，制备这种化合物的方法以及它们在治疗病理状况或疾病中的应用，该病理状况或疾病容易通过CRTh2拮抗活性得到改善。
• [EN] NEW CRTH2 ANTAGONISTS<br/>[FR] NOUVEAUX ANTAGONISTES DE CRTH2
  申请人：ALMIRALL SA

  公开号：WO2013010880A1

  公开（公告）日：2013-01-24

  The present invention relates to compounds of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by CRTh2 antagonist activity.

  本发明涉及式(I)的化合物，以及制备这种化合物的方法，以及它们在治疗病理状况或疾病中的应用，这些病理状况或疾病容易通过CRTh2拮抗活性得到改善。
• Structure–activity relationships (SAR) and structure–kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists II: Lead optimization
  作者：Juan Antonio Alonso、Miriam Andrés、Mónica Bravo、Marta Calbet、Paul R. Eastwood、Peter Eichhorn、Cristina Esteve、Manel Ferrer、Elena Gómez、Jacob González、Marta Mir、Imma Moreno、Silvia Petit、Richard S. Roberts、Sara Sevilla、Bernat Vidal、Laura Vidal、Pere Vilaseca、Miriam Zanuy

  DOI：10.1016/j.bmcl.2014.08.029

  日期：2014.11

  Extensive structure-activity relationship (SAR) and structure-kinetic relationship (SKR) studies in the bicyclic heteroaromatic series of CRTh2 antagonists led to the identification of several molecules that possessed both excellent binding and cellular potencies along with long receptor residence times. A small substituent in the bicyclic core provided an order of magnitude jump in dissociation half-lives. Selected optimized compounds demonstrated suitable pharmacokinetic profiles. (C) 2014 Elsevier Ltd. All rights reserved.