3-(1-oxo-1H-isoquinolin-2-yl)propionic acid methyl ester

• 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: 3-(1-oxo-1H-isoquinolin-2-yl)propionic acid methyl ester
• 英文别名: Methyl 3-(1-oxoisoquinolin-2-yl)propanoate；methyl 3-(1-oxoisoquinolin-2-yl)propanoate
• 化学式: C₁₃H₁₃NO₃
• 分子量: 231.251
• InChiKey: ZLYKQTUDMQWOSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(1-oxo-1H-isoquinolin-2-yl)propionic acid methyl ester 在 盐酸 、 氯化亚砜 、 sodium hydride 、 对甲苯磺酸 作用下， 以 乙醚 、 水 、 苯 为溶剂， 反应 50.5h， 生成 2-(3,5-dioxo-1-hexyl)isoquinolin-1(2H)-one
  参考文献：
  名称：

  Galanthan环系统的光化学方法

  摘要：

  已经开发了五步法，原子高效的Galanthan四环骨架合成方法。关键步骤是不寻常的分子内de Mayo反应，该反应使用异卡西替利底物和在氮上官能化的系链。靶分子由异卡西替利生产的总产率为35％。

  DOI：

  10.1021/jo0356560
• 作为产物：
  描述：

  3-溴丙酸甲酯 、 1-羟基异喹啉 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 以64%的产率得到3-(1-oxo-1H-isoquinolin-2-yl)propionic acid methyl ester
  参考文献：
  名称：

  Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as proteasome inhibitors

  摘要：

  A new series of pseudopeptide boronate proteasome inhibitors (2-3) was developed, through optimization of our previously described analogs of bortezomib, bearing a bicyclic 1,6-naphthyridin-5(6H)-one scaffold as P3 fragment (1). The biological evaluation on human 20S proteasome displayed a promising inhibition profile, especially for compounds bearing a P2 ethylene fragment, which exhibited Ki values in the nanomolar range for the ChT-L activity (e.g. 2a, Ki = 0.057 μM) and considerable selectivity for proteasome over bovine pancreatic α-chymotrypsin. Docking experiments into the yeast 20S proteasome revealed that the ligands are accommodated predominantly into the ChT-L site and that they covalently bind to the active site threonine residue via boron atom. Within the cellular assays performed against a 60 cancer cell line panel, compounds 3e and 3f demonstrated also good antiproliferative activity and compound 3f emerged as promising lead compound for the development of anticancer agents targeting melanoma and non-small cell lung cancer.

  DOI：

  10.1016/j.ejmech.2014.06.017

文献信息

• Optimization of peptidomimetic boronates bearing a P3 bicyclic scaffold as proteasome inhibitors
  作者：Valeria Troiano、Kety Scarbaci、Roberta Ettari、Nicola Micale、Carmen Cerchia、Andrea Pinto、Tanja Schirmeister、Ettore Novellino、Silvana Grasso、Antonio Lavecchia、Maria Zappalà

  DOI：10.1016/j.ejmech.2014.06.017

  日期：2014.8

  A new series of pseudopeptide boronate proteasome inhibitors (2-3) was developed, through optimization of our previously described analogs of bortezomib, bearing a bicyclic 1,6-naphthyridin-5(6H)-one scaffold as P3 fragment (1). The biological evaluation on human 20S proteasome displayed a promising inhibition profile, especially for compounds bearing a P2 ethylene fragment, which exhibited Ki values in the nanomolar range for the ChT-L activity (e.g. 2a, Ki = 0.057 μM) and considerable selectivity for proteasome over bovine pancreatic α-chymotrypsin. Docking experiments into the yeast 20S proteasome revealed that the ligands are accommodated predominantly into the ChT-L site and that they covalently bind to the active site threonine residue via boron atom. Within the cellular assays performed against a 60 cancer cell line panel, compounds 3e and 3f demonstrated also good antiproliferative activity and compound 3f emerged as promising lead compound for the development of anticancer agents targeting melanoma and non-small cell lung cancer.
• A Photochemical Approach to the Galanthan Ring System
  作者：David E. Minter、Christopher D. Winslow

  DOI：10.1021/jo0356560

  日期：2004.3.1

  A five-step, atom-efficient synthesis of the Galanthan tetracyclic skeleton has been developed. The key step is an unusual intramolecular de Mayo reaction using an isocarbostyril substrate with a functionalized tether on nitrogen. The target molecule is produced in 35% overall yield from isocarbostyril.

  已经开发了五步法，原子高效的Galanthan四环骨架合成方法。关键步骤是不寻常的分子内de Mayo反应，该反应使用异卡西替利底物和在氮上官能化的系链。靶分子由异卡西替利生产的总产率为35％。