2-(2,3,4,6-tetra-O-acetyl-1-deoxy-β-D-glucopyranosyl)-1,2-benzisoselenazol-3-(2H)-one | 1356995-80-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(2,3,4,6-tetra-O-acetyl-1-deoxy-β-D-glucopyranosyl)-1,2-benzisoselenazol-3-(2H)-one
• 英文别名: 2-(2,3,4,6-tetra-O-acetyl-1-deoxy-β-D-glucopyranosyl)-benzo[d][1,2]selenazol-3(2H)-one；[(2R,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(3-oxo-1,2-benzoselenazol-2-yl)oxan-2-yl]methyl acetate
• CAS: 1356995-80-6
• 化学式: C₂₁H₂₃NO₁₀Se
• 分子量: 528.374
• InChiKey: IJXCDBAYWUTTKO-PEVLUNPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.31
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  135
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2-(2,3,4,6-tetra-O-acetyl-1-deoxy-β-D-glucopyranosyl)-1,2-benzisoselenazol-3-(2H)-one 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以96%的产率得到2-(1-deoxy-β-D-glucopyranosyl)-benzo[d][1,2]selenazol-3(2H)-one
  参考文献：
  名称：

  [EN] COMPOUNDS TARGETING THE CELL INVASION PROTEIN COMPLEX, THEIR PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE THEREOF
  [FR] COMPOSÉS CIBLANT LE COMPLEXE PROTÉIQUE D'INVASION CELLULAIRE, LEURS COMPOSITIONS PHARMACEUTIQUES ET LEURS PROCÉDÉS D'UTILISATION

  摘要：

  本申请涉及到I式化合物（I）以及它们在抑制AKT-1、FAK和PKCα中至少一种方面的使用，以及在治疗和/或预防转移性疾病方面的使用。

  公开号：

  WO2013059927A1
• 作为产物：
  描述：

  双（2-羧基苯基）二硒化物 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 2-(2,3,4,6-tetra-O-acetyl-1-deoxy-β-D-glucopyranosyl)-1,2-benzisoselenazol-3-(2H)-one
  参考文献：
  名称：

  Aglycone Ebselen and β-d-Xyloside Primed Glycosaminoglycans Co-contribute to Ebselen β-d-Xyloside-Induced Cytotoxicity

  摘要：

  Most beta-D-xylosides with hydrophobic aglycones are nontoxic primers for glycosaminoglycan assembly in animal cells. However, when Ebselen was conjugated to D-xylose, D-glucose, D-galactose, and D-lactose (8A-D), only Ebselen beta-D-xyloside (8A) showed significant cytotoxicity in human cancer cells. The following facts indicated that the aglycone Ebselen and beta-D-xyloside primed glycosaminoglycans co-contributed to the observed cytotoxicity: 1. Ebselen induced S phase cell cycle arrest, whereas 8A induced G2/M cell cycle arrest; 2. 8A augmented early and late phase cancer cell apoptosis significantly compared to that of Ebselen and 8B-D; 3. Both 8A and phenyl-beta-D-xyloside primed glycosaminoglycans with similar disaccharide compositions in CHO-pgsA745 cells; 4. Glycosaminoglycans could be detected inside of cells only when treated with 8A, indicating Ebselen contributed to the unique property of intracellular localization of the primed glycosaminoglycans. Thus, 8A represents a lead compound for the development of novel antitumor strategy by targeting glycosaminoglycans.

  DOI：

  10.1021/acs.jmedchem.7b01835

文献信息

• Synthesis and biological activity of novel organoselenium derivatives targeting multiple kinases and capable of inhibiting cancer progression to metastases
  作者：Krikor Bijian、Zhongwei Zhang、Bin Xu、Su Jie、Bo Chen、Shengbiao Wan、JianHui Wu、Tao Jiang、Moulay A. Alaoui-Jamali

  DOI：10.1016/j.ejmech.2011.12.006

  日期：2012.2

  The present study reports synthesis and biological activity of novel benzoisoselenazolone compounds derived from ebselen and conjugated to a sugar molecule. Cell proliferation assay using cancer cells combined with in vitro biochemical assays revealed that benzoisoselenazolone 2d, 5a, and 6a exerted anti-proliferative activity, which correlated with selective in vitro inhibition of focal adhesion kinase, AKT-1, and protein kinase C-alpha. Active molecules were able to significantly inhibit cell migration and invasion in vitro compared to cells treated with the vehicle alone or ebselen. Moreover, in vivo anticancer activity focusing on lead compound 2d and using an invasive human breast cancer orthotopic mouse model revealed a potent anti-metastatic activity at well-tolerated doses. In summary, these novel benzoisoselenazolones we report herein target multiple kinases with established roles in cancer progression and possess anti-invasive and anti-metastatic activity in preclinical models supporting a potential for therapeutic application for human disease. Crown Copyright (C) 2011 Published by Elsevier Masson SAS. All rights reserved.