7-(2-adamantyloxy)-7-oxoheptanoic acid | 1338797-61-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 7-(2-adamantyloxy)-7-oxoheptanoic acid
• CAS: 1338797-61-7
• 化学式: C₁₇H₂₆O₄
• 分子量: 294.391
• InChiKey: MSZBNRIPAPWOBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-(2-adamantyloxy)-7-oxoheptanoic acid 在 4-二甲氨基吡啶 、 5%-palladium/activated carbon 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 32.0h， 生成 2-adamantyl 3-hydroxy-2-methoxyestra-1,3,5(10)-trien-17β-yl pimelate
  参考文献：
  名称：

  Synthesis and biological testing of tubuloclustin analogs containing alicyclic groups and 2-methoxyestradiol moiety

  摘要：

  获得了许多管状簇菌素类似物，即N-[7-(2-金刚烷氧基)-7-氧代庚酰基]-N-去乙酰秋水仙碱。在这些类似物中，秋水仙碱部分被环己烷、金刚烷和2-甲氧基雌二醇部分（甾体通过C(17)原子的羟基连接）正式取代。MTT检测显示，与先导化合物相比，所获得的结合物对A549肺癌细胞的细胞毒性要低得多。

  DOI：

  10.1007/s11172-014-0559-x
• 作为产物：
  描述：

  2-金刚烷醇 、 alkaline earth salt of/the/ methylsulfuric acid 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 以72%的产率得到7-(2-adamantyloxy)-7-oxoheptanoic acid
  参考文献：
  名称：

  Synthesis and SAR requirements of adamantane–colchicine conjugates with both microtubule depolymerizing and tubulin clustering activities

  摘要：

  A series of analogues of conjugate 1, combining an adamantane-based paclitaxel (taxol) mimetic with colchicine was synthesized and tested for cytotoxicity in a cell-based assay with the human lung carcinoma cell line A549. The most active compounds (10 EC50 2 +/- 1.0 nM, 23 EC50 6 +/- 1.4 nM, 26 EC50 5 +/- 1.8 nM, 28 EC50 11 +/- 1.7 nM, 30 EC50 4.8 +/- 0.5 nM) were found to interfere with the microtubule dynamics in an interesting manner. Treatment of the cells with these compounds promoted disassembly of microtubules followed by the formation of stable tubulin clusters. Structure-activity relationships for the analogues of 23 revealed the sensitivity of both cytotoxicity and tubulin clustering ability to the linker length. The presence of adamantane (or another bulky hydrophobic and non-aromatic moiety) in 23 was found to play an important role in the formation of tubulin clusters. Structural requirements for optimal activity have been partially explained by molecular modeling. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.07.040

文献信息

• Synthesis of steroid analogs of tubuloclustin, their cytotoxicity and effect on microtubules of A549 carcinoma cells
  作者：E. V. Nurieva、N. A. Zefirov、A. V. Mamaeva、B. Wobith、S. A. Kuznetsov、O. N. Zefirova

  DOI：10.1007/s11172-018-2123-6

  日期：2018.4

  Synthesis of analogs of tubuloclustin (N-(7-adamant-2-yloxy-7-oxoheptanoyl)-N-deacetylcolchicine (1)) with the colchicine fragment replaced with 2-methoxyestradiol scaffold attached via phenolic hydroxy group was described. Esters 3a–c exhibit moderate cytotoxicity (EC50 = 5–6 μmol L–1) and exert a weak effect on the microtubule network in A549 human lung carcinoma cells similar to the clustering effect

  描述了用通过酚羟基连接的 2-甲氧基雌二醇支架代替秋水仙碱片段的微管粘连蛋白（N-（7-金刚烷-2-基氧基-7-氧代庚酰基）-N-脱乙酰秋水仙碱 (1)) 类似物的合成。酯 3a-c 表现出中等的细胞毒性（EC50 = 5-6 μmol L-1）并且对 A549 人肺癌细胞中的微管网络产生微弱的影响，类似于微管凝集素及其衍生物的聚集效应。具有酚酸酯键的偶联物 6a-c 和 7a-c 稳定性低，化合物 7a-c 对 A549 细胞的微管无活性，而化合物 6a-c 会引起微管卷曲的异常效应。
• Synthesis and antiproliferative activity of combretastatin derivatives with adamantane fragment
  作者：E. V. Nurieva、N. A. Zefirov、N. S. Zefirov、S. A. Kuznetsov、O. N. Zefirova

  DOI：10.1007/s11172-015-1146-5

  日期：2015.9

  The work describes the synthesis of 2-adamantyl 7-[(2-[(2E)-3-(3-hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)prop-2-enoyl]amino}ethyl)amino]-7-oxoheptanoate and 7-[(2-[(2E)-2-(3,4-dimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-enoyl]amino}ethyl)amino]-7-oxoheptanoate. The latter compound exhibits moderate cytotoxicity (EC50 = 4.8 μmol L–1) against the human epithelial lung carcinoma

  该工作描述了 2-金刚烷基 7-[(2-[(2E)-3-(3-羟基-4-甲氧基苯基)-2-(3,4,5-三甲氧基苯基)prop-2-enoyl] 的合成)氨基}乙基)氨基]-7-氧代庚酸酯和7-[(2-[(2E)-2-(3,4-二甲氧基苯基)-3-(3-羟基-4-甲氧基苯基)丙-2-烯酰基]氨基}乙基)氨基]-7-氧代庚酸酯。后一种化合物对人上皮肺癌细胞 A549 表现出中等的细胞毒性（EC50 = 4.8 μmol L-1）。
• Novel antimitotic agents related to tubuloclustin: synthesis and biological evaluation
  作者：Olga N. Zefirova、Evgeniya V. Nurieva、Birgit Wobith、Vladimir V. Gogol、Nikolay A. Zefirov、Andrei V. Ogonkov、Dmitrii V. Shishov、Nikolay S. Zefirov、Sergei A. Kuznetsov

  DOI：10.1007/s11030-017-9739-6

  日期：2017.8

  ine], a highly cytotoxic anti-tubulin compound is known for its ability to promote microtubule disassembly followed by the formation of tubulin clusters of unique morphology. Three series of antimitotic agents related to tubuloclustin were designed and synthesized in order to enhance the molecular diversity of “tubuloclustin-like” family of compounds. The series of compounds with modified adamantane

  管状球蛋白[ N-（7-金刚烷-2-基氧基-7-氧庚庚酰基）-N[-去乙酰基秋水仙碱]，一种具有高度细胞毒性的抗微管蛋白化合物，因其具有促进微管分解，继而形成独特形态的微管蛋白簇的能力而闻名。设计和合成了与微管蛋白有关的三系列抗有丝分裂剂，以增强“微管蛋白样”家族化合物的分子多样性。该系列具有修饰的金刚烷部分的化合物对人肺癌A549细胞具有极强的细胞毒性作用（EC50 = 6–400 nM），并且在影响微管阵列和诱导强微管蛋白簇中起着积极作用。在另外两套化合物中，微管蛋白的秋水仙碱部分被鬼臼毒素或康维他汀A-4取代。所有康普他汀A-4衍生物均显示出明显的细胞毒活性（\（\ hbox EC} 50 = 0.8 -} 1.6 \，\ upmu \ hbox M} \）），但是它们对微管的作用取决于连接器附件的位置。鬼臼毒素衍生物也对A549细胞有毒性（\（\ hbox EC} 50 =
• Synthesis, Antiproliferative Activity, and Effect on Carcinoma A549 Cell Microtubules of New Tubuloclustin Analogs
  作者：N. A. Zefirov、Yu. A. Evteeva、A. R. Fatkulin、S. Schulz、S. A. Kuznetsov、O. N. Zefirova

  DOI：10.1007/s11094-019-02014-y

  日期：2019.8

  Combretastatin analogs of the antitumor agent tubuloclustin N-[7-(adamant-2-yloxy)-7-oxoheptanoyl]-Ndeacetylcolchicine} were prepared via esterification of combretastatin by monoesters of pimelic or adipic acid with adamantan-2-ol or (adamantan-1-yl)methanol. These conjugates were stable and cytotoxic to human lung carcinoma A549 cells (EC50 ≈ 50 – 70 nM) and caused depolymerization of microtubules and slight clustering of tubulin. Tubuloclustin analogs with shortened linkers were prepared via amidation by N-deacetylcolchicine of monoesters of adipic or succinic acids with adamantan-1-ol or (adamantan-1-yl)methanol. The conjugate N-[6-(adamantyl)-6-oxohexanoyl]-N-deacetylcolchicine was more active (EC50 ≈ 4 nM) than tubuloclustin and promoted strong tubulin clusterization. All compounds induced apoptosis of A549 cells. Tests in vivo of N-[6-(adamantyl)-6-oxoheaxnoyl]-N-deacetylcolchicine on carcinoma A549 experimental models were concluded to be promising.

  抗肿瘤药物Tubuloclustin的Combretastatin类似物N-[7-(氟烯-2-氧基)-7-氧代庚酰]-N-去乙酸科克铃}是通过将Combretastatin与含有氟烯-2-醇或（氟烯-1-基）甲醇的庚酸单酯或戊酸单酯进行酯化制备的。这些结合物稳定且对人肺癌A549细胞具有细胞毒性（EC50 ≈ 50 – 70 nM），并导致微管去聚合及微管蛋白的轻微聚集。通过将去乙酰科克铃与含有氟烯-1-醇或（氟烯-1-基）甲醇的戊酸或琥珀酸单酯进行酰胺化，制备了短链接头的Tubuloclustin类似物。结合物N-[6-(氟烯基)-6-氧代己酰]-N-去乙酸科克铃的活性比Tubuloclustin更强（EC50 ≈ 4 nM），并促进了显著的微管蛋白聚集。所有化合物均诱导A549细胞的凋亡。在A549癌症实验模型中对N-[6-(氟烯基)-6-氧代己酰]-N-去乙酸科克铃的体内测试结果被认为是有前景的。