7-O-(6-aminohexanoyl)paclitaxel | 220167-86-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 7-O-(6-aminohexanoyl)paclitaxel
• 英文别名: 7-(aminocaproyl)paclitoxel；[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-diacetyloxy-9-(6-aminohexanoyloxy)-15-[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
• CAS: 220167-86-2
• 化学式: C₅₃H₆₂N₂O₁₅
• 分子量: 967.08
• InChiKey: YVTONJXJPAZIDV-OFSAWIQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.81
• 重原子数：
  70.0
• 可旋转键数：
  16.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  253.38
• 氢给体数：
  4.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  (S)-11-formy-4-乙基-4-羟基-1,12-二氢-4H-2-噁-6,12a-二氮杂-二苯并b,h芴-3,13-二酮 、 7-O-(6-aminohexanoyl)paclitaxel 在 4 A molecular sieve 作用下， 以 苯 为溶剂， 以69.3%的产率得到
  参考文献：
  名称：

  Antitumor agents 216. Synthesis and evaluation of paclitaxel–camptothecin conjugates as novel cytotoxic agents1

  摘要：

  Five conjugates (16-20) composed of a paclitaxel and a camptothecin derivative joined by an imine linkage were synthesized and evaluated as cytotoxic agents and as inhibitors of DNA topoisomerase I. All of the conjugates were potent inhibitors of tumor cell replication with improved activity relative to camptothecin. Significantly, compounds 16-18 were more active than paclitaxel and camptothecin against HCT-8 (colon adenocarcinoma) cell replication, and the spectrum of activity was different from a simple mixture of paclitaxel and camptothecin. All of the conjugates were significantly less potent than camptothecin as inhibitors of human topoisomerase I in vitro with 16, 18, and 19 showing only marginal activity at 50 M Based on activity against drug-resistant cell line replication, one could conclude that the conjugates are simply acting as 'weak taxanes', but the spectrum of activity, particularly against MCF-7 and HCT-8, strongly suggests that a novel mechanism of action has been achieved through conjugation. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00040-3
• 作为产物：
  描述：

  N-苄氧羰基--6-氨基己酸 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 7.0h， 生成 7-O-(6-aminohexanoyl)paclitaxel
  参考文献：
  名称：

  Antitumor agents 216. Synthesis and evaluation of paclitaxel–camptothecin conjugates as novel cytotoxic agents1

  摘要：

  Five conjugates (16-20) composed of a paclitaxel and a camptothecin derivative joined by an imine linkage were synthesized and evaluated as cytotoxic agents and as inhibitors of DNA topoisomerase I. All of the conjugates were potent inhibitors of tumor cell replication with improved activity relative to camptothecin. Significantly, compounds 16-18 were more active than paclitaxel and camptothecin against HCT-8 (colon adenocarcinoma) cell replication, and the spectrum of activity was different from a simple mixture of paclitaxel and camptothecin. All of the conjugates were significantly less potent than camptothecin as inhibitors of human topoisomerase I in vitro with 16, 18, and 19 showing only marginal activity at 50 M Based on activity against drug-resistant cell line replication, one could conclude that the conjugates are simply acting as 'weak taxanes', but the spectrum of activity, particularly against MCF-7 and HCT-8, strongly suggests that a novel mechanism of action has been achieved through conjugation. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00040-3

文献信息

• Synthesis and evaluation of [14C]-Labelled and fluorescent-Tagged paclitaxel derivatives as new biological probes
  作者：Ch.Srinivasa Rao、Jao-Jia Chu、Rai-Shung Liu、Yiu-Kay Lai

  DOI：10.1016/s0968-0896(98)00158-8

  日期：1998.11

  results in this report demonstrate that (a) the new paclitaxel derivatives 4, 9, 11 could be prepared with good yields starting from paclitaxel; (b) the [14C]acetylation step was found to be better by using [14C]acetic anhydride rather than [14C]sodium acetate; (c) the radiochemical purity of 4 was 96% and its specific activity was 48 mCi/mmol; (d) the cytotoxicity of 4 was close to that of paclitaxel

  我们的本报告涉及迄今未报道的7-（[[羰基-14C]-乙酰基]紫杉醇4和两种新的生物活性7取代的荧光紫杉烷类化合物（FITC 9和若丹明11）的制备，以及对其作为生物探针的应用的评价。本报告中的结果表明：（a）从紫杉醇开始可以制备高收率的新紫杉醇衍生物4、9、11；（b）发现通过使用[14C]乙酸酐而不是[14C]乙酸钠，[14C]乙酰化步骤更好。（c）4的放射化学纯度为96％，比活为48 mCi / mmol；（d）4的细胞毒性接近紫杉醇，而9，11的活性远低于紫杉醇，但这些细胞毒性水平足以满足其生物学应用；（e）事实证明，使用9和11进行的流式细胞术定量分析药物与使用4进行的基于放射性的测定具有同等效率；（f）在两种情况下，通过9和11进行的细胞内荧光定位都是有效的，并且微管网络模式可见。（g）11时总体荧光成像效率更好，而9时荧光强度更高；（h）在9和11的荧光研究中均观察到了核仁染