4-(2-[4-(4,9-dioxo-4,9-dihydro-1-oxa-2,6-diazacyclopenta[b]naphthalen-3-yl)phenoxy]ethyl)morpholine hydrochloride | 1383471-21-3

• 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: 4-(2-[4-(4,9-dioxo-4,9-dihydro-1-oxa-2,6-diazacyclopenta[b]naphthalen-3-yl)phenoxy]ethyl)morpholine hydrochloride
• 英文别名: 3-[4-(2-Morpholin-4-ylethoxy)phenyl]-[1,2]oxazolo[5,4-g]isoquinoline-4,9-dione;hydrochloride
• CAS: 1383471-21-3
• 化学式: C₂₂H₁₉N₃O₅*ClH
• 分子量: 441.871
• InChiKey: AASLQVRZSFWRDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.64
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  94.8
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  6-bromoisoquinoline-5,8-dione 、 4-(2-Morpholinoethoxy)-benzaldehyde oxime 在 sodium hypochlorite 、 三乙胺 、 盐酸 作用下， 以 二氯甲烷 、 水 、 1,4-二氧六环 为溶剂， 反应 1.75h， 以19%的产率得到4-(2-[4-(4,9-dioxo-4,9-dihydro-1-oxa-2,6-diazacyclopenta[b]naphthalen-3-yl)phenoxy]ethyl)morpholine hydrochloride
  参考文献：
  名称：

  Isoxazolo(aza)naphthoquinones: A new class of cytotoxic Hsp90 inhibitors

  摘要：

  A series of 3-aryl-naphtho[2,3-d]isoxazole-4,9-diones and some of their 6-aza analogues were Synthesized and found to inhibit the heat shock protein 90 (Hsp90). The compounds were tested for their binding to Hsp90 and for their effects on Hsp90 client proteins expression in a series of human tumour cell lines. Representative compounds (7f, 10c) downregulated the Hsp90 client proteins EGFR, Akt, Cdk4, Raf-1, and survivin, and upregulated Hsp70. Most of the compounds, in particular the alkylated 3-pyridyl derivatives, exhibited potent antiproliferative activity, down to two-digit nanomolar range. Preliminary results indicated in vivo activity of 7f against human epithelial carcinoma A431 model growing as tumour xenograft in nude mice, thus supporting the therapeutic potential of this novel series of Hsp90 inhibitors. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.03.036