(1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33R,35R,36S)-20-[(2S)-3-hydroxy-2-methoxypropyl]-21-methoxy-14-methyl-8,15-dimethylidene-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 | 1297302-26-1

• 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)-20-[(2S)-3-hydroxy-2-methoxypropyl]-21-methoxy-14-methyl-8,15-dimethylidene-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: 1297302-26-1
• 化学式: C₄₁H₆₀O₁₂
• 分子量: 744.92
• InChiKey: RUYJOQDPUIVGCB-MZLQLVDZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  53
• 可旋转键数：
  5
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33R,35R,36S)-20-[(2S)-3-hydroxy-2-methoxypropyl]-21-methoxy-14-methyl-8,15-dimethylidene-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 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 生成
  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
• 作为产物：
  描述：

  艾瑞布林中间体 在 咪唑 、 四丁基氟化铵 、 咪唑盐酸盐 、 silver(l) oxide 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1S,3S,6S,9S,12S,14R,16R,18S,20R,21R,22S,26R,29S,31R,32S,33R,35R,36S)-20-[(2S)-3-hydroxy-2-methoxypropyl]-21-methoxy-14-methyl-8,15-dimethylidene-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：

  新型的第二代eribulin类似物。第一部分：含有亲脂性C32侧链的化合物克服了P-糖蛋白敏感性

  摘要：

  甲磺酸依里布林（Halaven™）是海洋聚醚大环内酯类盐菌素B的全合成类似物，最近在美国被批准用于治疗乳腺癌。日本和欧盟目前也正在对其进行监管审查。我们在该支架上继续进行的药物化学研究集中在通过降低这些化合物对P糖蛋白（P-gp）介导的药物外排的敏感性，从而提高了口服生物利用度，脑部渗透性和抗多药耐药性（MDR）肿瘤的功效。用生理pH值中性的片段替换eribulin的1,2-氨基醇C32侧链导致鉴定出具有明显更低的P-gp敏感性的类似物。这些类似物在体外对敏感和MDR细胞系均保持低至亚nM的效力。在这个系列中，亲脂性的提高通常会导致P-gp敏感性降低。除了在细胞培养中的效力外，这些化合物在小鼠异种移植模型中还显示出体内活性。

  DOI：

  10.1016/j.bmcl.2011.01.111

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.
• Novel second generation analogs of eribulin. Part I: Compounds containing a lipophilic C32 side chain overcome P-glycoprotein susceptibility
  作者：Sridhar Narayan、Eric M. Carlson、Hongsheng Cheng、Hong Du、Yongbo Hu、Yimin Jiang、Bryan M. Lewis、Boris M. Seletsky、Karen Tendyke、Huiming Zhang、Wanjun Zheng、Bruce A. Littlefield、Murray J. Towle、Melvin J. Yu

  DOI：10.1016/j.bmcl.2011.01.111

  日期：2011.3

  medicinal chemistry efforts on this scaffold have focused on oral bioavailability, brain penetration and efficacy against multidrug resistant (MDR) tumors by lowering the susceptibility of these compounds to P-glycoprotein (P-gp)-mediated drug efflux. Replacement of the 1,2-amino alcohol C32 side chain of eribulin with fragments neutral at physiologic pH led to the identification of analogs with significantly

  甲磺酸依里布林（Halaven™）是海洋聚醚大环内酯类盐菌素B的全合成类似物，最近在美国被批准用于治疗乳腺癌。日本和欧盟目前也正在对其进行监管审查。我们在该支架上继续进行的药物化学研究集中在通过降低这些化合物对P糖蛋白（P-gp）介导的药物外排的敏感性，从而提高了口服生物利用度，脑部渗透性和抗多药耐药性（MDR）肿瘤的功效。用生理pH值中性的片段替换eribulin的1,2-氨基醇C32侧链导致鉴定出具有明显更低的P-gp敏感性的类似物。这些类似物在体外对敏感和MDR细胞系均保持低至亚nM的效力。在这个系列中，亲脂性的提高通常会导致P-gp敏感性降低。除了在细胞培养中的效力外，这些化合物在小鼠异种移植模型中还显示出体内活性。