3-羟基苯并[b]萘[2,3-d]呋喃-6,11-二酮 | 97620-82-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 中文名称: 3-羟基苯并[b]萘[2,3-d]呋喃-6,11-二酮
• 英文名称: 3-hydroxybenzo[b]naphtho[2,3-d]furane-6,11-dione
• 英文别名: 3-hydroxybenzo[b]naphtho[2,3-d]furan-6,11-dione；3-hydroxy-benzo[b]naphtho[2,3-d]furan-6,11-dione；3-hydroxy-benzo[b]naphtho[2,3-d]furan-6,11-quinone；3-Hydroxy-benzo[b]naphtho[2,3-d]furan-6,11-chinon；5'-Hydroxy-benzo<1',2'-5,4>naphtho-<2'.3'-2.3>furan-1,4-dion；3-hydroxynaphtho[3,2-b][1]benzofuran-6,11-dione
• CAS: 97620-82-1
• 化学式: C₁₆H₈O₄
• mdl: MFCD02181130
• 分子量: 264.237
• InChiKey: CRJFVPJRQFLPOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 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

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  3-羟基苯并[b]萘[2,3-d]呋喃-6,11-二酮 在 氨基磺酰氯 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 以69%的产率得到
  参考文献：
  名称：

  Synthesis, in vitro and in vivo activity of benzophenone-based inhibitors of steroid sulfatase

  摘要：

  Steroid sulfatase (STS) is all important new therapeutic target in oncology. Attempts to design nonsteroidal STS inhibitors, because of the oestrogenicity of the original lead oestrone 3-O-sulfamate in rodents, have led to the discovery of benzophenone-4,4'-O,O-bis-sulfamate (BENZOMATE, 3). The nonfused bicyclic BENZOMATE is a highly potent STS inhibitor in vitro, inhibiting STS activity in intact MCF-7 breast cancer cells by >70% at 0.1 muM and in placental microsomes by >98% at 10 mum. When MCF-7 cells were pre-treated with 3 at 1 muM and then washed to remove unbound inhibitor, the initial 94% inhibition was reduced to 89% suggesting that 3, like other sulfamate-based STS inhibitors, inhibits the enzyme irreversibly. This agent also inhibits rat liver STS activity by 84% and 93% respectively 24 h after a single dose of 1 or 10 mg/kg, demonstrating that BENZOMATE possesses similar in Vivo potency to the established potent nonsteroidal inhibitor 667COUMATE. Several modifications were made to BENZOMATE structurally and effects on in vitro activity were examined. These structure-activity relationship studies show that its carbonyl and bis-sulfamate groups are pivotal for activity, although conformational flexibility is not required. Two rigid anthraquinone-based sulfamate derivatives however showed inhibitory activity significantly better than BENZOMATE in the MCF-7 cell assay. BENZOMATE and related analogues therefore represent all important class of non-steroidal STS inhibitor and lead compounds for future drug design. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.040
• 作为产物：
  描述：

  2,3-二氯-1,4-萘醌 、 间苯二酚 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 以97%的产率得到3-羟基苯并[b]萘[2,3-d]呋喃-6,11-二酮
  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

• 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。
• Oestrogen-17-sulphamates as inhibitors of steroid sulphatase
  申请人：Sterix Limited

  公开号：US07119081B2

  公开（公告）日：2006-10-10

  There is provided a compound of Formula I wherein X is a ring system; R1 is any one of a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group; R2 is any one of a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group; wherein when X is a steroidal structure and both of R1 and R2 are sulphamate groups, the steroidal ring system (X) represents an oestrogen; and wherein said compound is capable of inhibiting steroid sulphatase (STS) activity and/or is capable of acting as a modulator of cell cycling and/or as a modulator of apoptosis and/or as a modulator of cell growth. There is also provided a compound of Formula VIII wherein R2 is any one of a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group; and wherein said compound is capable of inhibiting steroid sulphatase (STS) activity and/or is capable of acting as a modulator of cell cycling and/or as a modulator of apoptosis and/or as a modulator of cell growth.

  提供了一种公式I的化合物，其中X是一个环系统；R1是磺酰胺基团、膦酸酯基团、硫代膦酸酯基团、磺酸基团或磺酰胺基团中的任意一种；R2是磺酰胺基团、膦酸酯基团、硫代膦酸酯基团、磺酸基团或磺酰胺基团中的任意一种；其中当X是类固醇结构且R1和R2均为磺酰胺基团时，类固醇环系统（X）代表一种雌激素；所述化合物能够抑制类固醇硫酸酯酶（STS）活性和/或能够作为细胞周期调节剂和/或细胞凋亡调节剂和/或细胞生长调节剂。还提供了一种公式VIII的化合物，其中R2是磺酰胺基团、膦酸酯基团、硫代膦酸酯基团、磺酸基团或磺酰胺基团中的任意一种；所述化合物能够抑制类固醇硫酸酯酶（STS）活性和/或能够作为细胞周期调节剂和/或细胞凋亡调节剂和/或细胞生长调节剂。
• Liebermann, Chemische Berichte, 1899, vol. 32, p. 920
  作者：Liebermann

  DOI：——

  日期：——
• 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.
• US7119081B2
  申请人：——

  公开号：US7119081B2

  公开（公告）日：2006-10-10