2-chloro-3-hydroxybenzo[b]naphtho[2,3-d]furan-6,11-dione | 151775-45-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: 2-chloro-3-hydroxybenzo[b]naphtho[2,3-d]furan-6,11-dione
• 英文别名: 2-Chloro-3-hydroxy-naphtho[3,2-b]benzofuran-6,11-dione；2-chloro-3-hydroxynaphtho[3,2-b][1]benzofuran-6,11-dione
• CAS: 151775-45-0
• 化学式: C₁₆H₇ClO₄
• 分子量: 298.682
• InChiKey: MELMDXKYKAAXAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-二乙氨基氯乙烷盐酸盐 、 2-chloro-3-hydroxybenzo[b]naphtho[2,3-d]furan-6,11-dione 在 苄基三乙基氯化铵 、 potassium carbonate 作用下， 以 氯仿 、 水 为溶剂， 以14.2%的产率得到2-chloro-3-[2-(diethylamino)ethoxy]benzo[b]naphtho[2,3-d]furan-6,11-dione
  参考文献：
  名称：

  Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones

  摘要：

  Benzofuroquinolinediones (7c and 7d) were synthesized by base-catalyzed condensation of dichloroquinolinediones with phenolic derivatives. Their dialkylaminoalkoxy derivatives (8i-8p) were prepared by reaction with various dialkylaminoalkyl chlorides. The cytotoxicity of the synthesized compounds was evaluated against eight types of human cancer cell lines, and their topoisomerase II inhibition was assessed. In general, the cytotoxicity of benzofuroquinolinediones (8i-8p) was similar or superior to that of doxorubicin and showed more potent inhibitory activity than naphthofurandiones (8a-8h). Also, most of the compounds exhibited excellent topoisomerase II inhibitory activity at a concentration of 5 mu M and two compounds, 8d and 8i, showed IC50 values of inhibitory activity at a concentration of 5 mu M and two compounds, 8d and 8i, showed IC50 values of 1.19 and 0.68 mu M, respectively, and were much more potent than etoposide (IC50 = 78.4 mu M), but similar to doxorubicin (IC50 = 2.67 mu M). However their inhibitory activity on topoisomerase I was lower, and 8d and 8i showed IC50 values of 42.0 and 64.3 mu M, respectively. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.12.012
• 作为产物：
  描述：

  2,3-二氯-1,4-萘醌 、 4-氯间苯二酚 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 以65%的产率得到2-chloro-3-hydroxybenzo[b]naphtho[2,3-d]furan-6,11-dione
  参考文献：
  名称：

  根据“ 2-苯基萘型”结构模式设计抗肿瘤药。2.苯并[b]萘[2,3-d]呋喃-6,11-二酮衍生物的合成及生物活性研究。

  摘要：

  根据我们实验室提出的“ 2-苯基萘型”结构模式假说，设计，合成和评估了许多苯并[b]萘甲[2,3-d]呋喃-6,11-二酮，并在体外进行了评估。它们对人早幼粒细胞白血病细胞（HL-60），小细胞肺癌（SCLC），对顺铂耐药的SCLC细胞（SCLC / CDDP）生长的抑制作用，美国国家癌症研究所针对疾病的原发性抗肿瘤60细胞系，以及药物刺激的拓扑异构酶II介导的DNA切割。在一项或多项生物学测试中，发现许多设计的化合物均具有有效的活性。通常，在一种被测细胞系中发现的活性通常在其他细胞系中回响，并且许多细胞也表现出对拓扑异构酶II介导的裂解活性的实质性抑制活性。其中一种化合物3- [2-（二甲基氨基）乙氧基] -1-羟基苯并[b]萘酚[2,3-d]呋喃-6,11-二酮（8j）在整个系列的药物中均表现出较强的抑制活性。测试面板。因此，似乎所提出的结构模式假设已通过实验验证得到了实质性的支持。

  DOI：

  10.1021/jm00077a016

文献信息

• Design of antineoplastic agents on the basis of the 2-phenylnaphthalene-type structural pattern. 2. Synthesis and biological activity studies of benzo[b]naphtho[2,3-d]furan-6,11-dione derivatives
  作者：C. C. Cheng、Qing Dong、Dun Fu Liu、Yi Lin Luo、Leroy F. Liu、Allan Y. Chen、Chiang Yu、Niramol Savaraj、Ting Chao Chou

  DOI：10.1021/jm00077a016

  日期：1993.12

  Many compounds designed were found to possess potent activity in one or more of the biological tests. In general, activity found in one of the cell lines tested is often echoed in other cell lines and many also expressed substantial inhibitory activity against topoisomerase II-mediated cleavage activities. One of these compounds, 3-[2-(dimethylamino)ethoxy]-1-hydroxybenzo[b]naphthol[2,3-d]furan- 6,11-dione

  根据我们实验室提出的“ 2-苯基萘型”结构模式假说，设计，合成和评估了许多苯并[b]萘甲[2,3-d]呋喃-6,11-二酮，并在体外进行了评估。它们对人早幼粒细胞白血病细胞（HL-60），小细胞肺癌（SCLC），对顺铂耐药的SCLC细胞（SCLC / CDDP）生长的抑制作用，美国国家癌症研究所针对疾病的原发性抗肿瘤60细胞系，以及药物刺激的拓扑异构酶II介导的DNA切割。在一项或多项生物学测试中，发现许多设计的化合物均具有有效的活性。通常，在一种被测细胞系中发现的活性通常在其他细胞系中回响，并且许多细胞也表现出对拓扑异构酶II介导的裂解活性的实质性抑制活性。其中一种化合物3- [2-（二甲基氨基）乙氧基] -1-羟基苯并[b]萘酚[2,3-d]呋喃-6,11-二酮（8j）在整个系列的药物中均表现出较强的抑制活性。测试面板。因此，似乎所提出的结构模式假设已通过实验验证得到了实质性的支持。
• Synthesis, Cytotoxicity and Topoisomerase II Inhibitory Activity of Benzonaphthofurandiones
  作者：Hee-Kyung Rhee、Young-Joo Kwon、Hwa-Jin Chung、Sang-Kook Lee、Hea-Young ParkChoo

  DOI：10.5012/bkcs.2011.32.7.2391

  日期：2011.7.20

  Benzonaphthofurandiones containing four coplanar fused aromatic rings were synthesized and evaluated for their cytotoxicity against five human cancer cell lines, and their inhibitory activity on topoisomerases. These benzonaphthofurandiones were prepared by condensation of 2,3-dichloronaphthoquinone and three aromatic diols with base catalysts in alcohol. The synthesized compounds were o-alkylated with six dialkylaminoalkyl halides. The hydroxy derivatives (8a-8g) exhibited relatively potent cytotoxicity among the prepared compounds. These compounds were evaluated as excellent inhibitors against topoisomerase II (topo II). Especially, the hydroxy analogue with branched methyl side chain (8e) showed high cytotoxicity against cancer cell lines and good inhibitory activity on topo II.

  合成了四稠并芳环共平面的苯并萘呋喃二酮类化合物， 并评价了其对五种人癌细胞株的细胞毒性及其拓扑异构酶抑制活性。这些苯并萘呋喃二酮类化合物是通过2,3-二氯萘醌与三种芳香二醇在醇中以碱催化缩合制备的。合成的化合物再用六种二烷氨基烷基卤进行对位烷基化。在制备的化合物中， 这些具有羟基的衍生物(8a-8g)表现出相对较强的细胞毒性。这些化合物被评价为拓扑异构酶II (topo II)的优秀抑制剂。尤其是， 具有支链甲基侧链的羟基类似物 (8e) 对癌细胞株显示出高细胞毒性以及良好的拓扑异构酶II抑制活性。
• Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones
  作者：Hee-Kyung Rhee、Hyen Joo Park、Sang Kook Lee、Chong-Ock Lee、Hea-Young Park Choo

  DOI：10.1016/j.bmc.2006.12.012

  日期：2007.2

  Benzofuroquinolinediones (7c and 7d) were synthesized by base-catalyzed condensation of dichloroquinolinediones with phenolic derivatives. Their dialkylaminoalkoxy derivatives (8i-8p) were prepared by reaction with various dialkylaminoalkyl chlorides. The cytotoxicity of the synthesized compounds was evaluated against eight types of human cancer cell lines, and their topoisomerase II inhibition was assessed. In general, the cytotoxicity of benzofuroquinolinediones (8i-8p) was similar or superior to that of doxorubicin and showed more potent inhibitory activity than naphthofurandiones (8a-8h). Also, most of the compounds exhibited excellent topoisomerase II inhibitory activity at a concentration of 5 mu M and two compounds, 8d and 8i, showed IC50 values of inhibitory activity at a concentration of 5 mu M and two compounds, 8d and 8i, showed IC50 values of 1.19 and 0.68 mu M, respectively, and were much more potent than etoposide (IC50 = 78.4 mu M), but similar to doxorubicin (IC50 = 2.67 mu M). However their inhibitory activity on topoisomerase I was lower, and 8d and 8i showed IC50 values of 42.0 and 64.3 mu M, respectively. (c) 2007 Elsevier Ltd. All rights reserved.