| 1299470-52-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡喃类
• CAS: 1299470-52-2
• 化学式: C₄₆H₆₉NO₁₁
• 分子量: 812.054
• InChiKey: FVLWOHXXDLAFGL-TUPJWKPMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.19
• 重原子数：
  58.0
• 可旋转键数：
  5.0
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  115.77
• 氢给体数：
  1.0
• 氢受体数：
  12.0

反应信息

• 作为反应物：
  描述：

  在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 以48%的产率得到(1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33R,35R,36S)-21-methoxy-14-methyl-8,15-dimethylidene-20-[[(2S)-4-(2-methylprop-2-enyl)morpholin-2-yl]methyl]-2,19,30,34,37,39,40,41-octaoxanonacyclo[24.9.2.13,32.13,33.16,9.112,16.018,22.029,36.031,35]hentetracontan-24-one
  参考文献：
  名称：

  Novel second generation analogs of eribulin. Part III: Blood–brain barrier permeability and in vivo activity in a brain tumor model

  摘要：

  Novel second generation analogs of eribulin mesylate, a tubulin agent recently approved for the treatment of breast cancer, are reported. Our recent efforts have focused on expanding the target indications for this class of compounds to other tumor types. Herein, we describe the design, synthesis and evaluation of eribulin analogs active against brain tumor cell lines in vitro and corresponding brain tumor models in mice. Attenuation of basicity of the amino group(s) in the C32 side-chain region led to compounds with lower susceptibility to P-gp mediated drug efflux, allowing these compounds to permeate through the blood-brain barrier. In preclinical in vivo studies, these compounds showed significantly higher levels in the brain and cerebrospinal fluid as compared to eribulin. In addition, analogs within this series showed antitumor activity in an orthotopic murine model of human glioblastoma. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.096
• 作为产物：
  描述：

  在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以97%的产率得到
  参考文献：
  名称：

  Novel second generation analogs of eribulin. Part III: Blood–brain barrier permeability and in vivo activity in a brain tumor model

  摘要：

  Novel second generation analogs of eribulin mesylate, a tubulin agent recently approved for the treatment of breast cancer, are reported. Our recent efforts have focused on expanding the target indications for this class of compounds to other tumor types. Herein, we describe the design, synthesis and evaluation of eribulin analogs active against brain tumor cell lines in vitro and corresponding brain tumor models in mice. Attenuation of basicity of the amino group(s) in the C32 side-chain region led to compounds with lower susceptibility to P-gp mediated drug efflux, allowing these compounds to permeate through the blood-brain barrier. In preclinical in vivo studies, these compounds showed significantly higher levels in the brain and cerebrospinal fluid as compared to eribulin. In addition, analogs within this series showed antitumor activity in an orthotopic murine model of human glioblastoma. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.096