2-[1-[4-[2-(4-chlorophenyl)ethylcarbamoyl]benzoyl]isoquinolin-4-yl]oxyacetic acid | 1353487-23-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 2-[1-[4-[2-(4-chlorophenyl)ethylcarbamoyl]benzoyl]isoquinolin-4-yl]oxyacetic acid
• CAS: 1353487-23-6
• 化学式: C₂₇H₂₁ClN₂O₅
• 分子量: 488.927
• InChiKey: AXMIILQUXGEXAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-溴-1-氯异喹啉 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 水 、 potassium acetate 、 sodium hexamethyldisilazane 、 碳酸氢钠 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 2-[1-[4-[2-(4-chlorophenyl)ethylcarbamoyl]benzoyl]isoquinolin-4-yl]oxyacetic acid
  参考文献：
  名称：

  Isoquinoline derivatives as potent CRTH2 receptor antagonists: Synthesis and SAR

  摘要：

  Synthesis and structure-activity relationship of a novel series of isoquinoline CRTH2 receptor antagonists are described. One of the most potent compounds, TASP0376377 (6m), showed not only potent binding affinity (IC50 = 19 nM) but also excellent functional antagonist activity (IC50 = 13 nM). TASP0376377 was tested for its ability of a chemotaxis assay to show the effectiveness (IC50 = 23 nM), which was in good agreement with the CRTH2 antagonist potency. Furthermore, TASP0376377 showed sufficient selectivity for binding to CRTH2 over the DP1 prostanoid receptor (IC50 > 1 mu M) and COX-1 and COX-2 enzymes (IC50 > 10 mu M). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.03.009

文献信息

• ISOQUINOLINE DERIVATIVE
  申请人：Takayama Tetsuo

  公开号：US20130096310A1

  公开（公告）日：2013-04-18

  A compound represented by formula (I) or a pharmaceutically acceptable salt thereof has an effect of inhibiting CRTH2 and, therefore, is useful as a pharmaceutical.

  由化学式(I)表示的化合物或其药用盐具有抑制CRTH2的作用，因此可用作药物。
• Isoquinoline derivatives as potent CRTH2 antagonists: Design, synthesis and SAR
  作者：Rie Nishikawa-Shimono、Yoshinori Sekiguchi、Takeshi Koami、Madoka Kawamura、Daisuke Wakasugi、Kazuhito Watanabe、Shunichi Wakahara、Kayo Kimura、Susumu Yamanobe、Tetsuo Takayama

  DOI：10.1016/j.bmc.2013.10.025

  日期：2013.12

  In this study, we describe the synthesis and structure-activity relationship (SAR) of a series of isoquinoline chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists. TASP0376377 (15-20), one of the most potent compounds, showed a potent binding affinity (IC50 = 19 nM) in addition to the excellent functional antagonist activity (IC50 = 13 nM). Moreover, the efficacy of this compound in a chemotaxis assay (IC50 = 23 nM) was in good agreement with its potency as a CRTH2 antagonist. In addition, 15-20 exhibited greater selectivity in binding to CRTH2 than to the DP1 prostanoid receptor (IC50 > 1 mu M) or the enzymes COX-1 and COX-2 (IC50 > 10 mu M). (C) 2013 Elsevier Ltd. All rights reserved.