3-(3-carboxybenzyl)-6-(carboxymethoxy)-1-[(6-ethylbenzo[d][1,3]dioxol-5-yl)methyl]-4-oxo-1,4-dihydroquinoline-2-carboxylic acid | 1257974-52-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-(3-carboxybenzyl)-6-(carboxymethoxy)-1-[(6-ethylbenzo[d][1,3]dioxol-5-yl)methyl]-4-oxo-1,4-dihydroquinoline-2-carboxylic acid
• 英文别名: 6-(carboxymethoxy)-3-[(3-carboxyphenyl)methyl]-1-[(6-ethyl-1,3-benzodioxol-5-yl)methyl]-4-oxoquinoline-2-carboxylic acid
• CAS: 1257974-52-9
• 化学式: C₃₀H₂₅NO₁₀
• 分子量: 559.529
• InChiKey: PCEPXCZCOCDRRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  41
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  160
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  ethyl 6-(2-ethoxy-2-oxoethoxy)-3-[3-(ethoxycarbonyl)benzyl]-1-[(6-ethylbenzo[d][1,3]dioxol-5-yl)methyl]-4-oxo-1,4-dihydroquinoline-2-carboxylate 在 水 、 potassium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以81%的产率得到3-(3-carboxybenzyl)-6-(carboxymethoxy)-1-[(6-ethylbenzo[d][1,3]dioxol-5-yl)methyl]-4-oxo-1,4-dihydroquinoline-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and pharmacological activity of 1,3,6-trisubstituted-4-oxo-1,4-dihydroquinoline-2-carboxylic acids as selective ETA antagonists

  摘要：

  A series of 1,3,6-trisubsituted-4-oxo-1,4-dihyroquinoline-2-carboxylic acid analogs (2a-m) were designed and synthesized and their pharmacological activity determined, with the objective to better understand their SAR as potential ETA selective inhibitors. Most of the compounds displayed significant ETA antagonist activity having IC50 for inhibition of binding of the [I-125] ET-1 to ETA receptor < 10 nM, with good selectivity for ETA antagonism over ETB receptor. Based on the in vitro results, SAR of this series of compounds requires an alkoxy substituent at the 6-position to be a straight and saturated chain up to three carbons long, since substitution of unsaturated and branched alkyloxy groups results in decrease in ETA antagonist activity. In this series, compound 2c (6-O-n-propyl analog) was found to be most potent (IC50 = 0.11 nM) with ETB/ETA selectivity of 8303. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.074

文献信息

• Synthesis and pharmacological activity of 1,3,6-trisubstituted-4-oxo-1,4-dihydroquinoline-2-carboxylic acids as selective ETA antagonists
  作者：Hardik J. Patel、Nicole Olgun、István Lengyel、Sandra Reznik、Ralph A. Stephani

  DOI：10.1016/j.bmcl.2010.08.074

  日期：2010.11

  A series of 1,3,6-trisubsituted-4-oxo-1,4-dihyroquinoline-2-carboxylic acid analogs (2a-m) were designed and synthesized and their pharmacological activity determined, with the objective to better understand their SAR as potential ETA selective inhibitors. Most of the compounds displayed significant ETA antagonist activity having IC50 for inhibition of binding of the [I-125] ET-1 to ETA receptor < 10 nM, with good selectivity for ETA antagonism over ETB receptor. Based on the in vitro results, SAR of this series of compounds requires an alkoxy substituent at the 6-position to be a straight and saturated chain up to three carbons long, since substitution of unsaturated and branched alkyloxy groups results in decrease in ETA antagonist activity. In this series, compound 2c (6-O-n-propyl analog) was found to be most potent (IC50 = 0.11 nM) with ETB/ETA selectivity of 8303. (C) 2010 Elsevier Ltd. All rights reserved.