ethyl 6-sec-butoxy-3-[3-(ethoxycarbonyl)benzyl]-1-[(6-ethylbenzo[d][1,3]dioxol-5-yl)methyl]-4-oxo-1,4-dihydroquinoline-2-carboxylate | 1159608-61-3

• 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: ethyl 6-sec-butoxy-3-[3-(ethoxycarbonyl)benzyl]-1-[(6-ethylbenzo[d][1,3]dioxol-5-yl)methyl]-4-oxo-1,4-dihydroquinoline-2-carboxylate
• 英文别名: Ethyl 6-butan-2-yloxy-3-[(3-ethoxycarbonylphenyl)methyl]-1-[(6-ethyl-1,3-benzodioxol-5-yl)methyl]-4-oxoquinoline-2-carboxylate
• CAS: 1159608-61-3
• 化学式: C₃₆H₃₉NO₈
• 分子量: 613.708
• InChiKey: CXKRZXUPLHFGBS-UHFFFAOYSA-N

物化性质

• 熔点：
  129-131 °C
• 沸点：
  738.1±60.0 °C(predicted)
• 密度：
  1.237±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 6-sec-butoxy-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71.6%的产率得到3-(3-carboxybenzyl)-1-[(6-ethylbenzo[d][1,3]dioxol-5-yl)methyl]-6-sec-butoxy-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
• 作为产物：
  描述：

  2-碘丁烷 、 ethyl-3-(3-(ethoxycarbonyl)benzyl)-1-((6-ethylbenzo[d][1,3]dioxol-5-yl)methyl)-6-hydroxy-4-oxo-1,4-dihydroquinoline-2-carboxylate 在 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以92.5%的产率得到ethyl 6-sec-butoxy-3-[3-(ethoxycarbonyl)benzyl]-1-[(6-ethylbenzo[d][1,3]dioxol-5-yl)methyl]-4-oxo-1,4-dihydroquinoline-2-carboxylate
  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 of 1,3,6-trisubstituted-2-carboxyquinol-4-ones as selective ET A antagonists and their use as medicaments
  申请人：Stephani Ralph Anthony

  公开号：US20090143426A1

  公开（公告）日：2009-06-04

  The invention discloses the composition and preparation of various 1,3,6-trisubstituted-2-carboxy-quinol-4-ones of the formula 1 where R is H, alkyl, haloalkyl or hydroxyalkyl, R′ is alkyl, nitro, halogen or NR 2 ′″ where R′″ is alkyl or cycloalkyl, and R″ is H or alkyl. The composition of the invented compounds as methods of antagonizing the action of endothelin-1 to treat cardiovascular, pulmonary diseases and obstetric disorders and preterm labor and preeclampsia in mammals is disclosed.

  本发明揭示了各种1,3,6-三取代-2-羧基喹啉-4-酮的组成和制备方法，其化学式为1，其中R为氢、烷基、卤代烷基或羟基烷基，R′为烷基、硝基、卤素或NR2′″，其中R′″为烷基或环烷基，而R″为氢或烷基。本发明揭示了所发明化合物的组成和方法，用于拮抗内皮素-1的作用，以治疗哺乳动物的心血管、肺部疾病和产科障碍，以及早产和妊娠高血压综合症。
• 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.