1-{4-(methoxycarbonyl)phenylcarbonyl}-4-(3,3,5,5,-tetramethyl-2,5-dioxaborolidin-1-y1)isoquinoline | 1374249-67-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-{4-(methoxycarbonyl)phenylcarbonyl}-4-(3,3,5,5,-tetramethyl-2,5-dioxaborolidin-1-y1)isoquinoline
• 英文别名: Methyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)isoquinoline-1-carbonyl)benzoate；methyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinoline-1-carbonyl]benzoate
• CAS: 1374249-67-8
• 化学式: C₂₄H₂₄BNO₅
• 分子量: 417.269
• InChiKey: BMUZSFJFRLGJDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.55
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  74.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-{4-(methoxycarbonyl)phenylcarbonyl}-4-(3,3,5,5,-tetramethyl-2,5-dioxaborolidin-1-y1)isoquinoline 在 碳酸氢钠 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 生成 tert-butyl 1-[4-(methoxycarbonyl)phenylcarbonyl]isoquinolin-4-yloxyacetate
  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：

  对氰基甲基苯甲酸甲酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 1-{4-(methoxycarbonyl)phenylcarbonyl}-4-(3,3,5,5,-tetramethyl-2,5-dioxaborolidin-1-y1)isoquinoline
  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