N-isopentyl-3-(8-bromo-5-oxo-5H-1,6-naphthyridin-6-yl)propanamide | 1621259-26-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-isopentyl-3-(8-bromo-5-oxo-5H-1,6-naphthyridin-6-yl)propanamide
• 英文别名: 3-(8-bromo-5-oxo-1,6-naphthyridin-6-yl)-N-(3-methylbutyl)propanamide
• CAS: 1621259-26-4
• 化学式: C₁₆H₂₀BrN₃O₂
• 分子量: 366.258
• InChiKey: KBCCCMSXXWIVPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-(8-bromo-5-oxo-5H-1,6-naphthyridin-6-yl)propionic acid methyl ester 在 1-羟基苯并三唑 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 9.33h， 生成 N-isopentyl-3-(8-bromo-5-oxo-5H-1,6-naphthyridin-6-yl)propanamide
  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.