(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-(3-morpholin-4-yl-2-oxopropyl)-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 | 1299470-61-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡喃类
• 英文名称: (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-(3-morpholin-4-yl-2-oxopropyl)-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
• CAS: 1299470-61-3
• 化学式: C₄₄H₆₃NO₁₂
• 分子量: 797.984
• InChiKey: HTRUFXDWMJJEAF-OCOUNWRJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  57
• 可旋转键数：
  5
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  130
• 氢给体数：
  0
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  艾瑞布林中间体 在 4-二甲氨基吡啶 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (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-(3-morpholin-4-yl-2-oxopropyl)-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 II: Orally available and active against resistant tumors in vivo

  摘要：

  Eribulin mesylate is a newly approved treatment for locally advanced and metastatic breast cancer. We targeted oral bioavailability and efficacy against multidrug resistant (MDR) tumors for further work. The design, synthesis and evaluation of novel amine-containing analogs of eribulin mesylate are described in this part. Attenuation of basicity of the amino group(s) in the C32 side-chain region led to compounds with low susceptibility to PgP-mediated drug efflux. These compounds were active against MDR tumor cell lines in vitro and in xenograft models in vivo, in addition to being orally bioavailable. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.097

文献信息

• Novel second generation analogs of eribulin. Part II: Orally available and active against resistant tumors in vivo
  作者：Sridhar Narayan、Eric M. Carlson、Hongsheng Cheng、Krista Condon、Hong Du、Sean Eckley、Yongbo Hu、Yimin Jiang、Vipul Kumar、Bryan M. Lewis、Philip Saxton、Edgar Schuck、Boris M. Seletsky、Karen Tendyke、Huiming Zhang、Wanjun Zheng、Bruce A. Littlefield、Murray J. Towle、Melvin J. Yu

  DOI：10.1016/j.bmcl.2011.01.097

  日期：2011.3

  Eribulin mesylate is a newly approved treatment for locally advanced and metastatic breast cancer. We targeted oral bioavailability and efficacy against multidrug resistant (MDR) tumors for further work. The design, synthesis and evaluation of novel amine-containing analogs of eribulin mesylate are described in this part. Attenuation of basicity of the amino group(s) in the C32 side-chain region led to compounds with low susceptibility to PgP-mediated drug efflux. These compounds were active against MDR tumor cell lines in vitro and in xenograft models in vivo, in addition to being orally bioavailable. (C) 2011 Elsevier Ltd. All rights reserved.