4-azido-α-lapachone | 1443743-41-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: 4-azido-α-lapachone
• 英文别名: 4-Azido-2,2-dimethyl-3,4-dihydrobenzo[g]chromene-5,10-dione；4-azido-2,2-dimethyl-3,4-dihydrobenzo[g]chromene-5,10-dione
• CAS: 1443743-41-6
• 化学式: C₁₅H₁₃N₃O₃
• 分子量: 283.287
• InChiKey: HKJNKCAALJABOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-戊炔 、 4-azido-α-lapachone 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 为溶剂， 以50%的产率得到2,2-dimethyl-4-(4-propyl-1H-1,2,3-triazol-1-yl)-3,4-dihydro-2H-benzo[g]chromene-5,10-dione
  参考文献：
  名称：

  Potent naphthoquinones against antimony-sensitive and -resistant Leishmania parasites: Synthesis of novel α- and nor-α-lapachone-based 1,2,3-triazoles by copper-catalyzed azide–alkyne cycloaddition

  摘要：

  Continuing our screening program for novel anti-parasite compounds, we synthesized seven 1,4-naphthoquinones coupled to 1,2,3-triazoles, five nor-beta-lapachone-based 1,2,3-triazoles and ten alpha-lapachone-based 1,2,3-triazoles. These and other naphthoquinonoid compounds were evaluated for their activity against promastigote forms of antimony-sensitive and -resistant strains of Leishmania infantum (syn. Leishmania chagasi) and Leishmania amazonensis. The toxicity of these compounds to mammalian cells was also examined. The substances were more potent than an antimonial drug, with IC50 values ranging from 1.0 to 50.7 mu M. Nor-alpha-lapachone derivatives showed the highest antileishmanial activity, with selectivity indices in the range of 10-15. These compounds emerged as important leads for further investigation as antileishmanial agents. Additionally, one of these compounds exhibited cross-resistance in Sb-resistant Leishmania and could provide a molecular tool for investigating the multidrug resistance mechanisms in Leishmania parasites. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.02.038
• 作为产物：
  描述：

  ALPHA-拉杷醌 在 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 二氯甲烷 为溶剂， 生成 4-azido-α-lapachone
  参考文献：
  名称：

  Molecular hybridization as a powerful tool towards multitarget quinoidal systems: synthesis, trypanocidal and antitumor activities of naphthoquinone-based 5-iodo-1,4-disubstituted-, 1,4- and 1,5-disubstituted-1,2,3-triazoles

  摘要：

  一些混合化合物展示出有希望的钩端螺旋体杀灭和抗癌活性。

  DOI：

  10.1039/c6md00216a

文献信息

• Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights
  作者：Eduardo H.G. da Cruz、Molly A. Silvers、Guilherme A.M. Jardim、Jarbas M. Resende、Bruno C. Cavalcanti、Igor S. Bomfim、Claudia Pessoa、Carlos A. de Simone、Giancarlo V. Botteselle、Antonio L. Braga、Divya K. Nair、Irishi N.N. Namboothiri、David A. Boothman、Eufrânio N. da Silva Júnior

  DOI：10.1016/j.ejmech.2016.06.019

  日期：2016.10

  Selenium-containing quinone-based 1,2,3-triazoles were synthesized using click chemistry, the copper catalyzed azide-alkyne 1,3-dipolar cycloaddition, and evaluated against six types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), PC3 (human prostate cells), SF295 (human glioblastoma cells), MDA-MB-435 (melanoma cells) and OVCAR-8 (human ovarian

  使用点击化学（铜催化叠氮化物-炔烃 1,3-偶极环加成）合成含硒醌基 1,2,3-三唑，并针对六种类型的癌细胞系进行评估：HL-60（人早幼粒细胞白血病细胞） ）、HCT-116（人结肠癌细胞）、PC3（人前列腺细胞）、SF295（人胶质母细胞瘤细胞）、MDA-MB-435（黑色素瘤细胞）和OVCAR-8（人卵巢癌细胞）。一些化合物显示 IC 50值 < 0.3 μM。还使用非肿瘤细胞（例如外周血单核（PBMC）、V79 和 L929 细胞）测定了所评估的醌的细胞毒性潜力。NAD(P)H:醌氧化还原酶 1 (NQO1) 的机制作用也得到了阐明。这些化合物可以为更有效的抗癌药物开发和递送提供有前途的新先导衍生物，并且代表了报道的最活跃的拉帕酮类之一。
• [EN] LAPACHONE DERIVATIVES CONTAINING TWO REDOX CENTERS AND METHODS OF USE THEREOF<br/>[FR] DÉRIVÉS DE LAPACHONE CONTENANT DEUX CENTRES REDOX ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：UNIV TEXAS

  公开号：WO2017070012A1

  公开（公告）日：2017-04-27

  Provided herein are compounds containing two redox centers including a chalcogen redox center of the formula: wherein: R1, R2, X1, X2, Y1, and m are as defined herein. Also provided herein are pharmaceutical composition of the present compounds and methods of treatment using the compounds including their use in the treatment of cancer.

  本文提供了含有两个氧化还原中心的化合物，其中包括一个硫属氧化还原中心，其化学式如下：其中：R1、R2、X1、X2、Y1和m如本文所定义。本文还提供了所述化合物的药物组合物以及使用这些化合物进行治疗的方法，包括它们在癌症治疗中的应用。
• On the synthesis of quinone-based BODIPY hybrids: New insights on antitumor activity and mechanism of action in cancer cells
  作者：Talita B. Gontijo、Rossimiriam P. de Freitas、Flavio S. Emery、Leandro F. Pedrosa、José B. Vieira Neto、Bruno C. Cavalcanti、Claudia Pessoa、Aaron King、Fabio de Moliner、Marc Vendrell、Eufrânio N. da Silva Júnior

  DOI：10.1016/j.bmcl.2017.08.007

  日期：2017.9

  quinone-based BODIPY hybrids were synthesised and characterised by NMR analysis and mass spectrometry. We measured their cytotoxic activity against cancer and normal cell lines, performed mechanistic studies by lipid peroxidation and determination of reduced (GSH) and oxidized (GSSG) glutathione, and imaged their subcellular localisation by confocal microscopy. Cell imaging experiments indicated that

  合成了基于荧光醌的BODIPY杂化物，并通过NMR分析和质谱表征。我们测量了它们对癌症和正常细胞系的细胞毒性活性，通过脂质过氧化和确定还原型（GSH）和氧化型（GSSG）谷胱甘肽进行了机理研究，并通过共聚焦显微镜对它们的亚细胞定位进行了成像。细胞成像实验表明，基于nor-β-lapachone的BODIPY衍生物可能优先定位于癌细胞的溶酶体中。这些结果证明了杂醌-BODIPY衍生物作为潜在的原型在寻找新的有效拉帕酮抗肿瘤药物方面的潜力。
• Synthesis and anti-Trypanosoma cruzi activity of naphthoquinone-containing triazoles: Electrochemical studies on the effects of the quinoidal moiety
  作者：Emilay B.T. Diogo、Gleiston G. Dias、Bernardo L. Rodrigues、Tiago T. Guimarães、Wagner O. Valença、Celso A. Camara、Ronaldo N. de Oliveira、Mauro G. da Silva、Vitor F. Ferreira、Yen Galdino de Paiva、Marilia O.F. Goulart、Rubem F.S. Menna-Barreto、Solange L. de Castro、Eufrânio N. da Silva Júnior

  DOI：10.1016/j.bmc.2013.08.055

  日期：2013.11

  In our continued search for novel trypanocidal compounds, twenty-six derivatives of para-and orthonaphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17-24, 28-30 and 36-38 are described herein for the first time. Three of these novel compounds (28-30) were found to be more potent than the standard drug benznidazole, with IC50/24 h values between 6.8 and 80.8 mu M. Analysis of the toxicity to heart muscle cells led to LC50/24 h of <125, 63.1 and 281.6 mu M for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent. (C) 2013 Elsevier Ltd. All rights reserved.
• Potent naphthoquinones against antimony-sensitive and -resistant Leishmania parasites: Synthesis of novel α- and nor-α-lapachone-based 1,2,3-triazoles by copper-catalyzed azide–alkyne cycloaddition
  作者：Tiago T. Guimarães、Maria do Carmo F.R. Pinto、Juliane S. Lanza、Maria N. Melo、Rubens L. do Monte-Neto、Isadora M.M. de Melo、Emilay B.T. Diogo、Vitor F. Ferreira、Celso A. Camara、Wagner O. Valença、Ronaldo N. de Oliveira、Frédéric Frézard、Eufrânio N. da Silva Júnior

  DOI：10.1016/j.ejmech.2013.02.038

  日期：2013.5

  Continuing our screening program for novel anti-parasite compounds, we synthesized seven 1,4-naphthoquinones coupled to 1,2,3-triazoles, five nor-beta-lapachone-based 1,2,3-triazoles and ten alpha-lapachone-based 1,2,3-triazoles. These and other naphthoquinonoid compounds were evaluated for their activity against promastigote forms of antimony-sensitive and -resistant strains of Leishmania infantum (syn. Leishmania chagasi) and Leishmania amazonensis. The toxicity of these compounds to mammalian cells was also examined. The substances were more potent than an antimonial drug, with IC50 values ranging from 1.0 to 50.7 mu M. Nor-alpha-lapachone derivatives showed the highest antileishmanial activity, with selectivity indices in the range of 10-15. These compounds emerged as important leads for further investigation as antileishmanial agents. Additionally, one of these compounds exhibited cross-resistance in Sb-resistant Leishmania and could provide a molecular tool for investigating the multidrug resistance mechanisms in Leishmania parasites. (C) 2013 Elsevier Masson SAS. All rights reserved.