3-hydroxy-nor-β-lapachone | 778637-91-5

• 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: 3-hydroxy-nor-β-lapachone
• 英文别名: 3-hydroxy-2,2-dimethyl-3H-benzo[g][1]benzofuran-4,5-dione
• CAS: 778637-91-5
• 化学式: C₁₄H₁₂O₄
• 分子量: 244.247
• InChiKey: VDCLTZXJJLMWQH-UHFFFAOYSA-N

物化性质

• 沸点：
  427.2±45.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-hydroxy-nor-β-lapachone 、 甲基-2,3-O-异亚丙基-beta-D-呋喃核糖苷 在 甲烷磺酸 作用下， 以 氯仿 为溶剂， 以62%的产率得到3-[[(3aR,4R,6R,6aR)-4-methoxy-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy]-2,2-dimethyl-3H-benzo[g][1]benzofuran-4,5-dione
  参考文献：
  名称：

  A new approach for the synthesis of 3-substituted cytotoxic nor-β-lapachones

  摘要：

  Several studies have demonstrated the cytotoxic potential of nor-beta-lapachone derivative against cancer cells. Considering nor-beta-lapachone as an important prototype, a set of new 3-substituted nor-beta-lapachones was synthesized by a new synthetic route that involves the use of synthetic intermediate generated for coupling with several nucleophiles containing the carbohydrate and 2H-pyrazole substituent moieties. All the compounds were screened against four tumor cell lines. Two of the compounds showed moderate cytotoxicity, while the other compounds strongly inhibit all tested cancer cell lines.

  DOI：

  10.1590/s0103-50532013000100003
• 作为产物：
  描述：

  黄钟花醌 在 双氧水 、 溴 、 sodium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 3-hydroxy-nor-β-lapachone
  参考文献：
  名称：

  [EN] 5-LIPOXYGENASE ANTAGONISTS
  [FR] ANTAGONISTES DE 5-LIPOXYGÉNASE

  摘要：

  本发明涉及使用β-落花松醌化合物治疗与5-脂氧合酶（5-LO）表达相关的疾病，如癌症，这些化合物抑制5-脂氧合酶（5-LO），如β-落花松醌及其衍生物。提供了治疗与5-脂氧合酶（5-LO）表达相关的疾病的方法以及β-落花松醌化合物在这种方法中的医疗用途，以及选取或预测癌症患者的方法。

  公开号：

  WO2019050422A1

文献信息

• Design of hybrid molecules as antimycobacterial compounds: Synthesis of isoniazid-naphthoquinone derivatives and their activity against susceptible and resistant strains of Mycobacterium tuberculosis
  作者：Wallace J. Reis、Ícaro A.O. Bozzi、Matheus F. Ribeiro、Priscila C.B. Halicki、Laís A. Ferreira、Pedro E. Almeida da Silva、Daniela F. Ramos、Carlos A. de Simone、Eufrânio N. da Silva Júnior

  DOI：10.1016/j.bmc.2019.07.045

  日期：2019.9

  C(−5)T) strains. Compounds 1a, 2a, and 8a were effective against the INHR1 strain, and compounds 1a, 1b, 2a, 3a, 5a, 5b and 8a were effective against the INHR2 strain, with MICs in the range of 3.12–6.25 µg/mL. Compounds 1b and 5b were the most active against H37Rv, with MIC of 0.78 µg/mL. Based on the selectivity index, 1b and 5b can be considered safe as a drug candidate compounds. These results demonstrate

  合成异烟肼-萘醌杂种并针对结核分枝杆菌的易感性菌株（H 37 Rv）和两个耐异烟肼菌株（INH R1和INH R2）进行评估。根据刃天青微量滴定法及其在粘附的小鼠单核巨噬细胞J774.A1细胞（ATCC TIB-67）中的细胞毒性，确定了衍生物的抗分枝杆菌活性。在针对三种结核分枝杆菌的评估的22种化合物中，有21种对H 37 Rv和INH R1（katG S315T）或INH R2（inhA C（-5）T）菌株具有一定的活性。化合物1a，2a和8a对INH R1菌株有效，化合物1a，1b，2a，3a，5a，5b和8a对INH R2菌株有效，MIC范围为3.12–6.25 µg / mL。化合物1b和5b对H 37 Rv的活性最高，MIC为0.78 µg / mL。基于选择性指数1b和5b可以被认为是安全的候选药物化合物。这些结果表明，喹诺酮类化合物可用作开发新的抗结核病药物和对结核分枝杆菌
• Naphthoquinone-based chalcone hybrids and derivatives: synthesis and potent activity against cancer cell lines
  作者：Guilherme A. M. Jardim、Tiago T. Guimarães、Maria do Carmo F. R. Pinto、Bruno C. Cavalcanti、Kaio M. de Farias、Claudia Pessoa、Claudia C. Gatto、Divya K. Nair、Irishi N. N. Namboothiri、Eufrânio N. da Silva Júnior

  DOI：10.1039/c4md00371c

  日期：——

  Naphthoquinone-based chalcone hybrids were synthesized and evaluated for their cytotoxic activity against four cancer cell lines and PBMC. Some of the hybrids exhibited promising anticancer activity with IC₅₀ values < 1 μM.

  基于萘醌的查尔酮杂合物被合成并对其对四种癌细胞系和PBMC的细胞毒活性进行了评估。其中一些杂合物表现出有前景的抗癌活性，IC₅₀值小于1μM。
• Natural product-inspired profluorophores for imaging NQO1 activity in tumour tissues
  作者：Zhiming Cheng、Wagner O. Valença、Gleiston G. Dias、Jamie Scott、Nicole D. Barth、Fabio de Moliner、Gabriela B.P. Souza、Richard J. Mellanby、Marc Vendrell、Eufrânio N. da Silva Júnior

  DOI：10.1016/j.bmc.2019.07.017

  日期：2019.9

  trimethyl-lock quinone profluorophores as activity-based probes for imaging NAD(P)H:quinone oxidoreductase (NQO1) in cancer cells and tumour tissues. Profluorophores were prepared via synthetic routes from naturally-occurring quinones and characterised in vitro using recombinant enzymes, to be further validated in cells and fresh frozen canine tumour tissues as potential new tools for cancer detection and imaging

  在这里，我们设计了一组三甲基锁醌原荧光团作为基于活性的探针，用于对癌细胞和肿瘤组织中的NAD（P）H：醌氧化还原酶（NQO1）进行成像。原发荧光团是通过合成途径从天然存在的醌中制备的，并在体外使用重组酶进行表征，待在细胞和新鲜的冷冻犬肿瘤组织中进一步验证，作为潜在的新的癌症检测和成像工具。
• 3-Arylamino and 3-Alkoxy-nor-β-lapachone Derivatives: Synthesis and Cytotoxicity against Cancer Cell Lines
  作者：Eufrânio N. da Silva Júnior、Clara F. de Deus、Bruno C. Cavalcanti、Cláudia Pessoa、Letícia V. Costa-Lotufo、Raquel C. Montenegro、Manoel O. de Moraes、Maria do Carmo F. R. Pinto、Carlos A. de Simone、Vitor F. Ferreira、Marilia O. F. Goulart、Carlos Kleber Z. Andrade、Antônio V. Pinto

  DOI：10.1021/jm900865m

  日期：2010.1.14

  Several 3-arylamino and 3-alkoxy-nor-β-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC50 below 2 μM. The arylamino para-nitro and the 2,4-dimethoxy substituted naphthoquinones showed the best cytoxicity profile, while the ortho-nitro and

  以中等至高产率合成了几种 3-芳基氨基和 3-烷氧基-去甲-β-拉帕酮衍生物，发现对癌细胞 SF295（中枢神经系统）、HCT8（结肠）、MDA-MB435（黑色素瘤）、和 HL60（白血病），IC 50低于 2 μM。芳氨基对硝基和 2,4-二甲氧基取代的萘醌表现出最好的细胞毒性，而邻硝基和 2,4-二甲氧基取代的萘醌比多柔比星更具选择性，并且与前体拉帕酮相似，因此很有前景。抗癌药物开发中的新先导化合物。
• Synthesis and anti-Trypanosoma cruzi activity of derivatives from nor-lapachones and lapachones
  作者：Eufrânio N. da Silva Júnior、Maria Cecília B.V. de Souza、Michelle C. Fernandes、Rubem F.S. Menna-Barreto、Maria do Carmo F.R. Pinto、Francisco de Assis Lopes、Carlos Alberto de Simone、Carlos Kleber Z. Andrade、Antônio V. Pinto、Vitor F. Ferreira、Solange L. de Castro

  DOI：10.1016/j.bmc.2008.03.032

  日期：2008.5

  New naphthoquinone derivatives were synthesized and assayed against bloodstream trypomastigote forms of Trypanosoma cruzi, the etiological agent of Chagas' disease. The compounds were rationalized based on hybrid drugs and appear as important compounds against this parasite. From nor-lapachol were prepared five substituted ortho-naphthofuranquinones, a non-substituted para-naphthofuranquinone, a new oxyrane and an azide and from alpha-lapachone a new non-substituted para-naphthofuranquinone. Other five substituted ortho-naphthofuranquinones recently designed as cytotoxic, were also evaluated. The most active compounds were the ortho naphthofuranquinones 3-(4-methoxyphenylamino)-2,3-dihydro-2,2-dimethylnaphtho[1,2-b]furan-4,5-dione and 3-(3-nitrophenylamino)-2,3-dihydro-2,2-dimethylnaphtho[1,2-b]furan-4,5-dione with trypanocidal activity higher than that of benznidazole, the standard drug. The compounds were rationalized based on hybrid drugs and appear as important compounds against T. cruzi. The trypanocidal activity of these substances endowed with redox properties representing a good starting point for a medicinal chemistry program aiming the chemotherapy of Chagas' disease. (c) 2008 Elsevier Ltd. All rights reserved.