2-[1-[4-[(2-methylpropan-2-yl)oxycarbonylamino]benzoyl]isoquinolin-4-yl]acetic acid | 1233249-38-1

• 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-methylpropan-2-yl)oxycarbonylamino]benzoyl]isoquinolin-4-yl]acetic acid
• 英文别名: methyl[1-({4-[(tert-butoxycarbonyl)amino]phenyl}carbonyl)isoquinolin-4-yl]acetate；Methyl 2-[1-[4-[(2-methylpropan-2-yl)oxycarbonylamino]benzoyl]isoquinolin-4-yl]acetate
• CAS: 1233249-38-1
• 化学式: C₂₄H₂₄N₂O₅
• 分子量: 420.465
• InChiKey: GWAMMYJIPVQUTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  94.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[1-[4-[(2-methylpropan-2-yl)oxycarbonylamino]benzoyl]isoquinolin-4-yl]acetic acid 在 吡啶 、 三氟乙酸 作用下， 以 氯仿 为溶剂， 反应 3.5h， 生成 methyl {1-[(4-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)carbonyl]isoquinolin-4-yl}acetate
  参考文献：
  名称：

  EP2377851

  摘要：

  公开号：
• 作为产物：
  描述：

  4-tert-butoxycarbonylaminophenylacetonitrile 在 草酰氯 、 水 、 silver(I) acetate 、 sodium hexamethyldisilazane 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 44.5h， 生成 2-[1-[4-[(2-methylpropan-2-yl)oxycarbonylamino]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 receptor antagonists: Synthesis and SAR
  作者：Rie Nishikawa-Shimono、Yoshinori Sekiguchi、Takeshi Koami、Madoka Kawamura、Daisuke Wakasugi、Kazuhito Watanabe、Shunichi Wakahara、Kayo Matsumoto、Tetsuo Takayama

  DOI：10.1016/j.bmcl.2012.03.009

  日期：2012.5

  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.