4-Chlorodeacetylcolchicine | 1267986-38-8

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 英文名称: 4-Chlorodeacetylcolchicine
• 英文别名: (7S)-7-amino-4-chloro-1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one
• CAS: 1267986-38-8
• 化学式: C₂₀H₂₂ClNO₅
• 分子量: 391.851
• InChiKey: DSHKSQLFKDTXKT-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  80
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-Chlorodeacetylcolchicine 在 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 4-chloro-N-((1-methyl-1H-1,2,4-triazol-5-yl)carbamothioyl)deacetylcolchicine
  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
• 作为产物：
  描述：

  秋水仙碱 在 4-二甲氨基吡啶 、 N-氯代丁二酰亚胺 、 sodium methylate 、 溶剂黄146 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 19.83h， 生成 4-Chlorodeacetylcolchicine
  参考文献：
  名称：

  JP5829520

  摘要：

  公开号：

文献信息

• 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.
• Design and Synthesis of 4-Chlorocolchicine-Derived Prodrug Capable of Forming Nanoparticles by Self-Assembly
  作者：Hiromitsu Takayama、Mariko Kitajima、Akihiro Morita、Shimpei Endo、Noriyuki Kogure、Kenjirou Higashi、Kunikazu Moribe

  DOI：10.3987/com-16-s(s)51

  日期：——

  We have designed and synthesized colchicine-derived prodrug 7, which is composed of a 4-chlorocolchicine derivative, a dipeptide side chain cleavable by cathepsin B, a spacer containing a disulfide bond, and hydrophobic vitamin E. Prodrug 7 was capable of forming nanoparticles by self-assembly. Mean particle diameter evaluated by dynamic light scattering measurement was ca. 205 nm.
• JP5829520
  申请人：——

  公开号：——

  公开（公告）日：——
• 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。