2,3-dihydro-4-hydroxymethyl-1H-cyclopent[a]anthracene-6,11-dione N-methylcarbamate

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 2,3-dihydro-4-hydroxymethyl-1H-cyclopent[a]anthracene-6,11-dione N-methylcarbamate
• 英文别名: (6,11-dioxo-2,3-dihydro-1H-cyclopenta[a]anthracen-4-yl)methyl N-methylcarbamate
• 化学式: C₂₀H₁₇NO₄
• 分子量: 335.359
• InChiKey: SXEURVSJPHDUFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(2-Cyclopent-1-enyl-allyloxymethyl)-4-methoxy-benzene 在 palladium on activated charcoal 辛烯 、 水 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 96.0h， 生成 2,3-dihydro-4-hydroxymethyl-1H-cyclopent[a]anthracene-6,11-dione N-methylcarbamate
  参考文献：
  名称：

  Cyclopent[a]anthraquinones as DNA-Intercalating Agents with Covalent Bond Formation Potential:  Synthesis and Biological Activity

  摘要：

  A series of mitomycin C (MMC) analogues, namely cyclopentanthraquinone derivatives, were synthesized via Diels-Alder cyclization of naphthoquinone with 1-vinylcyclopent-1-enes. These new compounds are planar structures, like MMC, and bear an aziridine ring and a methyl carbamate side chain. After bioreduction, they are anticipated to be capable of intercalating into double-stranded DNA and bind covalently. Structure-activity relationships were studied. Of these compounds, 2,3-aziridino-4-[[(methylamino)carbonyl]methyl]cyclopent[a]anthracene-6,11-dione (4) was shown to have inhibitory activity against several leukemic and solid tumor cell lines. Mice (BDF1) bearing Lewis lung adenocarcinoma were treated with 4 and MMC (ip, QD x 5). At a dose of 30.0 mg/kg, compound 4 was as effective as MMC (0.8 mg/kg). Compound 4 appears to be less toxic than MMC. DNA unwinding assay indicated that 4 is able to intercalate into DNA double strands and is also a topoisomerase II inhibitor.

  DOI：

  10.1021/jm950881y

文献信息

• Antitumor cyclopentnaphthoquinone and cyclopentanthraquinone derivatives
  申请人：Sloan-Kettering Institute for Cancer Research

  公开号：US05476952A1

  公开（公告）日：1995-12-19

  The present invention provides compounds having the structure: ##STR1## or having the structure: ##STR2## The present invention also provides a pharmaceutical compostion containing the compounds, methods of synthesizing the compounds, as well as methods of inhibiting growth of tumor cells and of treating a subject having a disease characterized by the proliferation of tumor cells.

  本发明提供具有以下结构的化合物：##STR1## 或具有以下结构的化合物：##STR2## 本发明还提供含有这些化合物的药物组合物，合成这些化合物的方法，以及抑制肿瘤细胞生长和治疗患有肿瘤细胞增殖性疾病的受试者的方法。
• US5476952A
  申请人：——

  公开号：US5476952A

  公开（公告）日：1995-12-19
• Cyclopent[<i>a</i>]anthraquinones as DNA-Intercalating Agents with Covalent Bond Formation Potential:  Synthesis and Biological Activity
  作者：Joong Young Kim、Tsann-Long Su、Ting-Chao Chou、Bernd Koehler、Alex Scarborough、Ouathek Ouerfelli、Kyoichi A. Watanabe

  DOI：10.1021/jm950881y

  日期：1996.1.1

  A series of mitomycin C (MMC) analogues, namely cyclopentanthraquinone derivatives, were synthesized via Diels-Alder cyclization of naphthoquinone with 1-vinylcyclopent-1-enes. These new compounds are planar structures, like MMC, and bear an aziridine ring and a methyl carbamate side chain. After bioreduction, they are anticipated to be capable of intercalating into double-stranded DNA and bind covalently. Structure-activity relationships were studied. Of these compounds, 2,3-aziridino-4-[[(methylamino)carbonyl]methyl]cyclopent[a]anthracene-6,11-dione (4) was shown to have inhibitory activity against several leukemic and solid tumor cell lines. Mice (BDF1) bearing Lewis lung adenocarcinoma were treated with 4 and MMC (ip, QD x 5). At a dose of 30.0 mg/kg, compound 4 was as effective as MMC (0.8 mg/kg). Compound 4 appears to be less toxic than MMC. DNA unwinding assay indicated that 4 is able to intercalate into DNA double strands and is also a topoisomerase II inhibitor.