N-(4-甲酰基-1,2,3,10-四甲氧基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基)乙酰胺 | 2730-82-7

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 中文名称: N-(4-甲酰基-1,2,3,10-四甲氧基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基)乙酰胺
• 英文名称: 4-Formylcolchicine
• 英文别名: 1-Formyl-colchicin；N-[(7S)-4-formyl-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
• CAS: 2730-82-7
• 化学式: C₂₃H₂₅NO₇
• 分子量: 427.454
• InChiKey: JUWAUXATKRGHCK-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  7

制备方法与用途

4-甲酰基秋水仙碱是一种有效的抗癌剂，对A549、HT-29和HCT116细胞表现出显著的细胞毒性活性，其IC50值分别为1.007、0.128和0.054µM。

反应信息

• 作为反应物：
  描述：

  N-(4-甲酰基-1,2,3,10-四甲氧基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基)乙酰胺 在 sodium chlorite 、 sodium dihydrogenphosphate 、 2-甲基-2-丁烯 、 叠氮磷酸二苯酯 、 水 、 三乙胺 作用下， 以 四氢呋喃 、 叔丁醇 为溶剂， 生成 4-Aminocolchicine
  参考文献：
  名称：

  Design, Synthesis, and Antitumor Activity of 4-Halocolchicines and Their Pro-drugs Activated by Cathepsin B

  摘要：

  Novel colchicine derivatives possessing various substituents at the C4 position were prepared. Among them, 4-halo derivatives 3-6 were found to exhibit higher activity against cancer cell lines (A549, HT29, HCT116) as well as on mice transplanted with the HCT116 human colorectal carcinoma cell line than colchicine (1). Further, utilizing the 4-substituted colchicines, we prepared pro-drugs having a dipeptide side chain and demonstrated that these pro-drugs were activated by cathepsin B, an enzyme overexpressed in tumor cells, and exhibited selective toxicity to the tumor cells.

  DOI：

  10.1021/ml100287y
• 作为产物：
  描述：

  1,1-二氯甲醚 、 秋水仙碱 在 四氯化锡 作用下， 以 二氯甲烷 为溶剂， 生成 N-(4-甲酰基-1,2,3,10-四甲氧基-9-氧代-6,7-二氢-5H-苯并[d]庚搭烯-7-基)乙酰胺
  参考文献：
  名称：

  4-Chlorocolchicine derivatives bearing a thiourea side chain at the C-7 position as potent anticancer agents

  摘要：

  合成了一系列4-取代的秋水仙碱衍生物，并对其进行了评估，旨在开发新型抗癌药物。结果发现，在C-7位带有硫脲侧链的4-氯秋水仙碱衍生物对三种人癌细胞系（A549、HT-29和HCT116）显示出显著的细胞毒性。特别是，在C-7位带有乙基硫脲的化合物26在体内具有高抗肿瘤活性，并且有效剂量范围广泛。此外，在C-7位侧链带有(5-甲基吡唑-3-基)硫脲的化合物58，在体外表现出强烈的细胞毒性和良好的代谢稳定性。

  DOI：

  10.1039/c3md00287j

文献信息

• From Colchicine and Some of Its Derivatives to 1,2,3,9,10-Pentamethoxybenzo[a]heptalenes
  作者：Pavlos Kouroupis、Hans-J�rgen Hansen

  DOI：10.1002/hlca.19950780517

  日期：1995.8.9

  into the benzo[a]heptalene derivatives 9, 18, and 34, respectively, by Hofmann degradation of the corresponding deacetylcolchiceine 3, 19, and 29, respectively, followed by methylation of the two O-functions first with diazomethane and then with trimethoxonium tetrafluoroborate (Scheme 2 and 6). The thus formed tropylium salts gave, on deprotonation with Me3N in CHCl3, the expected pentamethoxybenzo[a]heptalenes

  从秋水仙碱（2）开始，分两步合成4-甲基秋水仙碱（13）（方案5）。在三个步骤中，还可以从2（方案8）中获得4-乙基秋水仙碱（28）。秋水仙素（2）及其衍生物13和28已被转化为苯并[一个]庚搭烯衍生物9，18，和34，分别由霍夫曼相应deacetylcolchiceine的降解3,19，和29分别用重氮甲烷，然后用四氟硼酸三甲氧肟酸甲酯将两个O-官能团甲基化（方案2和6）。由此形成的盐鎓了，去质子化上与我3 N的氯仿3，预期pentamethoxybenzo [一个] heptalenes 9,18，和34，分别。9（图3）和18（图7）的X射线晶体结构分析，庚烯骨架上H原子的邻位偶合常数的测定以及新苯并的外消旋化率的测量[一个]庚烷显示C（4）上的取代基对庚烯骨架扭曲程度的显着影响。解析的庚烯的绝对构型是由它们在350 nm附近的长波CD最大值推导出来的。在该范围内具有负最大值的庚烷具有（7a
• JP5829520
  申请人：——

  公开号：——

  公开（公告）日：——
• Design, Synthesis, and Antitumor Activity of 4-Halocolchicines and Their Pro-drugs Activated by Cathepsin B
  作者：Naoko Yasobu、Mariko Kitajima、Noriyuki Kogure、Yoshiyuki Shishido、Takeshi Matsuzaki、Masato Nagaoka、Hiromitsu Takayama

  DOI：10.1021/ml100287y

  日期：2011.5.12

  Novel colchicine derivatives possessing various substituents at the C4 position were prepared. Among them, 4-halo derivatives 3-6 were found to exhibit higher activity against cancer cell lines (A549, HT29, HCT116) as well as on mice transplanted with the HCT116 human colorectal carcinoma cell line than colchicine (1). Further, utilizing the 4-substituted colchicines, we prepared pro-drugs having a dipeptide side chain and demonstrated that these pro-drugs were activated by cathepsin B, an enzyme overexpressed in tumor cells, and exhibited selective toxicity to the tumor cells.
• 4-Chlorocolchicine derivatives bearing a thiourea side chain at the C-7 position as potent anticancer agents
  作者：Hiroyuki Nishiyama、Masahiro Ono、Takuya Sugimoto、Toshio Sasai、Naoyuki Asakawa、Satoshi Ueno、Yoshitaka Tominaga、Takashi Yaegashi、Masato Nagaoka、Takeshi Matsuzaki、Noriyuki Kogure、Mariko Kitajima、Hiromitsu Takayama

  DOI：10.1039/c3md00287j

  日期：——

  A series of 4-substituted colchicine derivatives were synthesized and evaluated with an eye toward developing new anticancer agents. As a result, 4-chlorocolchicine derivatives bearing a thioureide side chain at the C-7 position were found to exhibit significant cytotoxicities to three human cancer cell lines (A549, HT-29, and HCT116). In particular, compound 26 having an ethylthioureide group at the C-7 had high antitumor activity in vivo and a broad effective dosage range. Furthermore, compound 58, which has a (5-methylpyrazol-3-yl)thioureide group at the C-7 side chain, exhibited strong cytotoxicity and desirable metabolic stability in vitro.

  合成了一系列4-取代的秋水仙碱衍生物，并对其进行了评估，旨在开发新型抗癌药物。结果发现，在C-7位带有硫脲侧链的4-氯秋水仙碱衍生物对三种人癌细胞系（A549、HT-29和HCT116）显示出显著的细胞毒性。特别是，在C-7位带有乙基硫脲的化合物26在体内具有高抗肿瘤活性，并且有效剂量范围广泛。此外，在C-7位侧链带有(5-甲基吡唑-3-基)硫脲的化合物58，在体外表现出强烈的细胞毒性和良好的代谢稳定性。