methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[(cyclopropanecarbonylamino)methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate | 1043910-78-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 长春花生物碱
• 英文名称: methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[(cyclopropanecarbonylamino)methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate
• CAS: 1043910-78-6
• 化学式: C₄₉H₆₁N₅O₇
• 分子量: 832.053
• InChiKey: CHQKWZSZYCOZFU-COANAFCUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  61
• 可旋转键数：
  11
• 环数：
  10.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[(cyclopropanecarbonylamino)methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate 在 N-溴代丁二酰亚胺(NBS) 、 二乙胺 、 三氟乙酸 、 silver tetrafluoroborate 作用下， 以 二氯甲烷 、 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 3-demethoxycarbonyl-3-(cyclopropanecarbonylamino)methylvinorelbine
  参考文献：
  名称：

  Synthesis and structure–activity relationship studies of cytotoxic vinorelbine amide analogues

  摘要：

  A series of 3-demethoxycarbonyl-3-acylamide methyl vinorelbine derivatives (compounds 7a-7z) were designed, synthesized, and evaluated for their inhibition activities against human non-small cell lung cancer cell line (A549). Most of the amide derivatives exhibited potent cytotoxicity, with the size of the introduced substituents being the foremost factor in determining the resultant cytotoxic activity. Test results in vivo against nude mice bearing A549 xenografts indicated that 7y showed comparable activities compared to the parent NVB. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.024
• 作为产物：
  描述：

  3-demethoxycarbonyl-3-aminomethyl-4-deacetylvindoline 在 吡啶 、 盐酸 、 iron(III) chloride 、 sodium hydride 作用下， 以 四氢呋喃 、 水 、 mineral oil 为溶剂， 反应 8.25h， 生成 methyl (13S,15R)-13-[(1R,9R,10S,11R,12R,19R)-11-acetyloxy-10-[(cyclopropanecarbonylamino)methyl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2,4,6,13-tetraen-4-yl]-17-ethyl-1,11-diazatetracyclo[13.3.1.04,12.05,10]nonadeca-4(12),5,7,9,16-pentaene-13-carboxylate
  参考文献：
  名称：

  细胞毒性脱水长春碱酰胺衍生物的合成及其构效关系研究

  摘要：

  设计，合成了一系列3-脱甲氧基羰基-3-酰胺甲基脱水长春碱衍生物（5b - 24b），并评估了它们对两种肿瘤细胞系（A549和HeLa）的增殖抑制活性。大多数酰胺脱水长春碱衍生物表现出强的细胞毒性，所引入的取代基的大小是确定所得细胞毒性活性的最主要因素。针对三种有效化合物（6b，12b和24b）对肉瘤180的体内测试结果表明，在脱水长春碱（1e）的22位引入酰胺基可以提高效力和毒性。

  DOI：

  10.1021/np900157t

文献信息

• Synthesis and Structure−Activity Relationship Studies of Cytotoxic Anhydrovinblastine Amide Derivatives
  作者：Yong Shao、Han-Kun Zhang、Hong Ding、Hai-Tian Quan、Li-Guang Lou、Li-Hong Hu

  DOI：10.1021/np900157t

  日期：2009.6.26

  A series of 3-demethoxycarbonyl-3-amide methyl anhydrovinblastine derivatives (5b−24b) was designed, synthesized, and evaluated for their proliferation inhibition activities against two tumor cell lines (A549 and HeLa). Most of the amide anhydrovinblastine derivatives exhibited potent cytotoxicity, with the size of the introduced substituents being the foremost factor in determining the resultant cytotoxic

  设计，合成了一系列3-脱甲氧基羰基-3-酰胺甲基脱水长春碱衍生物（5b - 24b），并评估了它们对两种肿瘤细胞系（A549和HeLa）的增殖抑制活性。大多数酰胺脱水长春碱衍生物表现出强的细胞毒性，所引入的取代基的大小是确定所得细胞毒性活性的最主要因素。针对三种有效化合物（6b，12b和24b）对肉瘤180的体内测试结果表明，在脱水长春碱（1e）的22位引入酰胺基可以提高效力和毒性。
• Synthesis and structure–activity relationship studies of cytotoxic vinorelbine amide analogues
  作者：Lingjun Hu、Weibin Song、Yuhui Meng、Dean Guo、Xuan Liu、Lihong Hu

  DOI：10.1016/j.bmcl.2012.10.024

  日期：2012.12

  A series of 3-demethoxycarbonyl-3-acylamide methyl vinorelbine derivatives (compounds 7a-7z) were designed, synthesized, and evaluated for their inhibition activities against human non-small cell lung cancer cell line (A549). Most of the amide derivatives exhibited potent cytotoxicity, with the size of the introduced substituents being the foremost factor in determining the resultant cytotoxic activity. Test results in vivo against nude mice bearing A549 xenografts indicated that 7y showed comparable activities compared to the parent NVB. (C) 2012 Elsevier Ltd. All rights reserved.