2-[1-[4-[2-(3,4-dichlorophenyl)ethylcarbamoyl]benzoyl]isoquinolin-4-yl]acetic acid | 1233248-13-9

• 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-(3,4-dichlorophenyl)ethylcarbamoyl]benzoyl]isoquinolin-4-yl]acetic acid
• 英文别名: 2-[1-[4-[2-(3,4-Dichlorophenyl)ethylcarbamoyl]benzoyl]isoquinolin-4-yl]acetic acid
• CAS: 1233248-13-9
• 化学式: C₂₇H₂₀Cl₂N₂O₄
• 分子量: 507.373
• InChiKey: DEKAJKZBTSPPSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  96.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl 4-{[4-(2-methoxy-2-oxoethyl)isoquinolin-1-yl]carbonyl}benzoate 在 吡啶 、 草酰氯 、 水 、 N,N-二甲基甲酰胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 反应 17.0h， 生成 2-[1-[4-[2-(3,4-dichlorophenyl)ethylcarbamoyl]benzoyl]isoquinolin-4-yl]acetic acid
  参考文献：
  名称：

  Isoquinoline derivatives as potent CRTH2 antagonists: Design, synthesis and SAR

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2013.10.025

文献信息

• 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.