3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione | 1376686-97-3

• 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-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione
• 英文别名: 3-[4-(4-fluorophenyl)triazol-1-yl]-2,2-dimethyl-3H-benzo[g][1]benzofuran-4,5-dione
• CAS: 1376686-97-3
• 化学式: C₂₂H₁₆FN₃O₃
• 分子量: 389.386
• InChiKey: SLUUAYIPFKHINA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  74.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione 、 邻苯二胺 在 sodium acetate 、 溶剂黄146 作用下， 以82%的产率得到1-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethyl-1,2-dihydrobenzo[a]furo[2,3-c]phenazine
  参考文献：
  名称：

  苯并[a]吩嗪衍生物：对抗耐药性结核分枝杆菌的有前景的支架

  摘要：

  耐药性结核分枝杆菌的不断出现使结核病 (TB) 治疗选择仍然不足，迫切需要新的治疗选择。考虑到我们研究小组先前报道的吩嗪衍生物的抗分枝杆菌活性，我们旨在探索可能的应用来规避结核分枝杆菌的耐药性。首先，我们评估了七种苯并[ a ]吩嗪衍生物对十一种结核分枝杆菌菌株的抗菌活性：十种耐药菌株和一种敏感菌株 (H 37 Rv)。然后，我们确定了苯并[ a]吩嗪衍生物并研究了最有希望的化合物的可能作用机制。其中，化合物10是唯一一种对所有被评估菌株均有活性的化合物，其最小抑制浓度介于 18.3 和 146.5 µM 之间。对于某些耐药菌株，该化合物显示出高于利福平的抗菌活性，并且对 MDR 菌株也有活性，表明与抗结核药物不存在交叉耐药性。此外，10显示了进一步体内研究的药理学安全性，其作用机制似乎与氧化应激有关。因此，我们的研究结果表明苯并[ a]吩嗪衍生物是开发新型抗结核药物的有前途的支架，主要用于治疗耐药结核病病例。

  DOI：

  10.1111/cbdd.13853
• 作为产物：
  描述：

  黄钟花醌 在 copper(ll) sulfate pentahydrate 、 双氧水 、 溴 、 sodium carbonate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 3-(4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl)-2,2-dimethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-dione
  参考文献：
  名称：

  苯并[a]吩嗪衍生物：对抗耐药性结核分枝杆菌的有前景的支架

  摘要：

  耐药性结核分枝杆菌的不断出现使结核病 (TB) 治疗选择仍然不足，迫切需要新的治疗选择。考虑到我们研究小组先前报道的吩嗪衍生物的抗分枝杆菌活性，我们旨在探索可能的应用来规避结核分枝杆菌的耐药性。首先，我们评估了七种苯并[ a ]吩嗪衍生物对十一种结核分枝杆菌菌株的抗菌活性：十种耐药菌株和一种敏感菌株 (H 37 Rv)。然后，我们确定了苯并[ a]吩嗪衍生物并研究了最有希望的化合物的可能作用机制。其中，化合物10是唯一一种对所有被评估菌株均有活性的化合物，其最小抑制浓度介于 18.3 和 146.5 µM 之间。对于某些耐药菌株，该化合物显示出高于利福平的抗菌活性，并且对 MDR 菌株也有活性，表明与抗结核药物不存在交叉耐药性。此外，10显示了进一步体内研究的药理学安全性，其作用机制似乎与氧化应激有关。因此，我们的研究结果表明苯并[ a]吩嗪衍生物是开发新型抗结核药物的有前途的支架，主要用于治疗耐药结核病病例。

  DOI：

  10.1111/cbdd.13853

文献信息

• 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.
• On the Search for Potential Antimycobacterial Drugs: Synthesis of Naphthoquinoidal, Phenazinic and 1,2,3-Triazolic Compounds and Evaluation Against<i>Mycobacterium tuberculosis</i>
  作者：Guilherme A. M. Jardim、Eduardo H. G. Cruz、Wagner O. Valença、Jarbas M. Resende、Bernardo L. Rodrigues、Daniela F. Ramos、Ronaldo N. Oliveira、Pedro E. A. Silva、Eufrânio N. da Silva Júnior

  DOI：10.5935/0103-5053.20150067

  日期：——

  Fifteen naphthoquinones, sixteen phenazines and fifteen aryl triazoles were synthesized and evaluated against Mycobacterium tuberculosis. Twenty five substances are reported here for the first time and, among all of the compounds evaluated, six presented MIC (minimal inhibitory concentration) values <= 6.25 mu g mL(-1). These substances are promising antimycobacterial prototypes.
• On the search for potential anti-Trypanosoma cruzi drugs: Synthesis and biological evaluation of 2-hydroxy-3-methylamino and 1,2,3-triazolic naphthoquinoidal compounds obtained by click chemistry reactions
  作者：Eufrânio N. da Silva、Isadora M.M. de Melo、Emilay B.T. Diogo、Verenice A. Costa、José D. de Souza Filho、Wagner O. Valença、Celso A. Camara、Ronaldo N. de Oliveira、Alexandre S. de Araujo、Flávio S. Emery、Marcelo R. dos Santos、Carlos A. de Simone、Rubem F.S. Menna-Barreto、Solange L. de Castro

  DOI：10.1016/j.ejmech.2012.03.039

  日期：2012.6

  Five 2-hydroxy-3-substituted-aminomethyl naphthoquinones, nine 1,2,3-triazolic para-naphthoquinones, five nor-beta-lapachone-based 1,2,3-triazoles, and several other naphthoquinonoid compounds were synthesized and evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease, continuing our screening program for new trypanocidal compounds. Among all the substances, 16-18, 23, 25-29 and 30-33 were herein described for the first time and fifteen substances were identified as more potent than the standard drug benznidazole, with IC50/24 h values in the range of 10.9-101.5 mu M. Compounds 14 and 19 with Selectivity Index of 18.9 and 6.1 are important structures for further studies. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Potent antileukemic action of naphthoquinoidal compounds: evidence for an intrinsic death mechanism based on oxidative stress and inhibition of DNA repair
  作者：Bruno C. Cavalcanti、Igor O. Cabral、Felipe A. R. Rodrigues、Francisco W. A. Barros、Danilo D. Rocha、Hemerson I. F. Magalhães、Dinara J. Moura、Jenifer Saffi、João A. P. Henriques、Tatiane S. C. Carvalho、Manoel O. Moraes、Cláudia Pessoa、Isadora M. M. de Melo、Eufrânio N. da Silva Júnior

  DOI：10.1590/s0103-50532013000100019

  日期：——

  The current study describes that nor-beta-lapachone and its arylamino derivatives, iodinated and methylated naphthoquinones and nor-beta-lapachone-based 1,2,3-triazoles exhibited pronounced cytotoxic effects against four human leukemia cell lines (HL-60, K562, Molt-4 and Jurkat). Nor-beta-lapachones arylamino substituted with potent activity were identified, revealing themselves as potential prototypes against tumor cell lines. Moreover, cells treated with these compounds showed DNA damage according to the standard comet assay, a finding that was, at least in part, due to increased intracellular levels of ROS. HL-60 cells were chosen to study the underlying molecular mechanisms of cytotoxicity. Drug-induced apoptosis in HL-60 cells was observed by flow cytometry analyses. Strains of Saccharomyces cerevisiae were used for a preliminary investigation into the mechanism of drug action on DNA topoisomerases. These results suggested that the cytotoxicity of these compounds apparently does not involve topoisomerase inhibition, but that treatment impairs DNA repair activity, thus triggering cell death. Considering their pro-oxidant properties, we investigated the ability of these compounds to induce apoptosis and chromosomal aberrations as micronuclei in Chinese hamster lung fibroblasts (V79 cells). Morphological apoptotic nuclei and micronuclei induction following drug treatment were observed, suggesting a correlation between DNA damage and apoptosis.
• Benzo[ <i>a</i> ]phenazine derivatives: promising scaffolds to combat resistant <i>Mycobacterium tuberculosis</i>
  作者：Priscila Cristina Bartolomeu Halicki、Eufrânio Nunes da Silva Júnior、Guilherme Augusto de Melo Jardim、Renata Gomes de Almeida、Juliano Rosa de Menezes Vicenti、Bruna Lisboa Gonçalves、Pedro Eduardo Almeida da Silva、Daniela Fernandes Ramos

  DOI：10.1111/cbdd.13853

  日期：——

  activity of phenazine derivatives previously reported by our research group, we aimed to explore possible applications to circumvent the resistance in M. tuberculosis. Firstly, we evaluated the antimicrobial activity of seven benzo[a]phenazine derivatives against eleven M. tuberculosis strains: ten resistant and one susceptible (H37Rv). Then, we determined the cytotoxicity of benzo[a]phenazine derivatives

  耐药性结核分枝杆菌的不断出现使结核病 (TB) 治疗选择仍然不足，迫切需要新的治疗选择。考虑到我们研究小组先前报道的吩嗪衍生物的抗分枝杆菌活性，我们旨在探索可能的应用来规避结核分枝杆菌的耐药性。首先，我们评估了七种苯并[ a ]吩嗪衍生物对十一种结核分枝杆菌菌株的抗菌活性：十种耐药菌株和一种敏感菌株 (H 37 Rv)。然后，我们确定了苯并[ a]吩嗪衍生物并研究了最有希望的化合物的可能作用机制。其中，化合物10是唯一一种对所有被评估菌株均有活性的化合物，其最小抑制浓度介于 18.3 和 146.5 µM 之间。对于某些耐药菌株，该化合物显示出高于利福平的抗菌活性，并且对 MDR 菌株也有活性，表明与抗结核药物不存在交叉耐药性。此外，10显示了进一步体内研究的药理学安全性，其作用机制似乎与氧化应激有关。因此，我们的研究结果表明苯并[ a]吩嗪衍生物是开发新型抗结核药物的有前途的支架，主要用于治疗耐药结核病病例。