methyl {1-[(4-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)carbonyl]isoquinolin-4-yl}acetate | 1233249-46-1

• 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: methyl {1-[(4-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)carbonyl]isoquinolin-4-yl}acetate
• 英文别名: Methyl 2-[1-[4-[(3,4-dichlorophenyl)sulfonylamino]benzoyl]isoquinolin-4-yl]acetate
• CAS: 1233249-46-1
• 化学式: C₂₅H₁₈Cl₂N₂O₅S
• 分子量: 529.4
• InChiKey: WRKFQRGMKBMCPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl {1-[(4-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)carbonyl]isoquinolin-4-yl}acetate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以12%的产率得到2-[1-[4-[(3,4-dichlorophenyl)sulfonylamino]benzoyl]isoquinolin-4-yl]acetic 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
• 作为产物：
  描述：

  4-tert-butoxycarbonylaminophenylacetonitrile 在 吡啶 、 草酰氯 、 水 、 silver(I) acetate 、 sodium hexamethyldisilazane 、 三氟乙酸 、 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 47.0h， 生成 methyl {1-[(4-{[(3,4-dichlorophenyl)sulfonyl]amino}phenyl)carbonyl]isoquinolin-4-yl}acetate
  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

• EP2377851
  申请人：——

  公开号：——

  公开（公告）日：——