4-Hydroxymethyl-2,3-dihydro-1H-cyclopenta[a]anthracene-6,11-dione | 161940-95-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 4-Hydroxymethyl-2,3-dihydro-1H-cyclopenta[a]anthracene-6,11-dione
• 英文别名: 2,3-Dihydro-4-hydroxymethyl-1H-cyclopent[a]anthracene-6,11dione；4-(hydroxymethyl)-2,3-dihydro-1H-cyclopenta[a]anthracene-6,11-dione
• CAS: 161940-95-0
• 化学式: C₁₈H₁₄O₃
• 分子量: 278.307
• InChiKey: JNIJUBTWEYPXDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Hydroxymethyl-2,3-dihydro-1H-cyclopenta[a]anthracene-6,11-dione 在 吡啶 、 氨 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 Carbamic acid 6,11-dioxo-2,3,6,11-tetrahydro-1H-cyclopenta[a]anthracen-4-ylmethyl ester
  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
• 作为产物：
  描述：

  4-(4-Methoxy-benzyloxymethyl)-2,3-dihydro-1H-cyclopenta[a]anthracene-6,11-dione 在 水 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以75%的产率得到4-Hydroxymethyl-2,3-dihydro-1H-cyclopenta[a]anthracene-6,11-dione
  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：##STR2## 本发明还提供包含该化合物的制药组合物，合成该化合物的方法，以及抑制肿瘤细胞生长和治疗具有肿瘤细胞增殖特征的疾病的方法。
• US5476952A
  申请人：——

  公开号：US5476952A

  公开（公告）日：1995-12-19