5-(4-chlorophenyl)-2-(3-chloropropyl)-2H-tetrazole

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-(4-chlorophenyl)-2-(3-chloropropyl)-2H-tetrazole
• 英文别名: 5-(4-Chlorophenyl)-2-(3-chloropropyl)tetrazole；5-(4-chlorophenyl)-2-(3-chloropropyl)tetrazole
• 化学式: C₁₀H₁₀Cl₂N₄
• 分子量: 257.122
• InChiKey: LKJMRXMFFINIAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-苯基吡咯烷 、 5-(4-chlorophenyl)-2-(3-chloropropyl)-2H-tetrazole 在 potassium carbonate 、 potassium iodide 作用下， 以 正丁醇 为溶剂， 反应 48.0h， 以59%的产率得到5-(4-chlorophenyl)-2-[3-(2-phenylpyrrolidin-1-yl)propyl]-2H-tetrazole
  参考文献：
  名称：

  带有吡咯烷骨架的四唑衍生物的合成及其对白色念珠菌的抗真菌活性评估

  摘要：

  机会性真菌感染的增加增加了对新的抗真菌剂的设计和合成的需求。考虑到四唑衍生物具有抗真菌活性，并且其中一些处于临床试验阶段，因此合成了带有吡咯烷部分的新的四唑衍生物，以显示其对白色念珠菌的作用方式。通过将各种2-芳基吡咯烷与若干个1-（3-氯丙基）-5-芳基-2 H-四唑进行N-烷基化，获得目标化合物。不管四唑或吡咯烷环上的取代基是什么，反应都在48小时内发生，收率令人满意，在53％至70％之间。我们对合成的化合物进行了筛选，以鉴定这些无毒的抑制作用。白色念珠菌的浮游和无柄细胞，并进行了一系列的后续研究，以检查最有效的抗真菌药的体外和体内活性。领先的抗真菌抑制剂：2- {3- [2-（3-甲基苯基）吡咯烷-1-基]丙基} -5-苯基-2 H-四唑（3aC）和随机选择的抑制剂：5-苯基-2- [3-（2-苯基吡咯烷-1-基）丙基] -2 H-四唑（3aA），5-（4-氯苯基）-2- {3- [

  DOI：

  10.1016/j.ejmech.2018.12.044

文献信息

• Tetrazole derivatives bearing benzodiazepine moiety—synthesis and action mode against virulence of Candida albicans
  作者：M. Staniszewska、T. Zdrojewski、M. Gizińska、M. Rogalska、Ł. Kuryk、A. Kowalkowska、E. Łukowska-Chojnacka

  DOI：10.1016/j.ejmech.2021.114060

  日期：2022.2
• New 1,5 and 2,5-disubstituted tetrazoles-dependent activity towards surface barrier of Candida albicans
  作者：Monika Staniszewska、Małgorzata Gizińska、Ewa Mikulak、Klaudia Adamus、Mirosława Koronkiewicz、Edyta Łukowska-Chojnacka

  DOI：10.1016/j.ejmech.2017.11.089

  日期：2018.2

  A series of novel tetrazole derivatives was synthetized using N-alkylation or Michael-type addition reactions, and screened for their fungistatic potential against Candida albicans (the lack of endpoint = 100%). Among them, the selected compounds 2d, 4b, and 6a differing in substituents at the tetrazole ring were non-toxic to Galleria mellonella larvae in vivo and exerted slight toxicity against Caco-2 in vitro (CC50 at 256 mu g/mL). An antagonistic effect of tetrazole derivatives 2d, 4b, and 6a respectively in combination with Fluconazole was shown using the checker board and colorimetric methods (fractional inhibitory concentration indexes FICIs >1). The most active 2d and 6a displayed an inverse relation between MICs in the presence of exogenous ergosterol, the effect was opposite to Itraconazole and Amphotericin B. The differences between 6a's and 2d's action mode were noted. Combining both flow cytometry and fluorescence image analyses respectively showed the complexity of planktonic and biofilm cell demise mode under the tetrazole derivatives tested. The following evidences for 6a's interaction with fungal membrane were noted: necrosis-like programmed cell death (97.03 +/- 0.88), DNA denaturation (no laddering), mitochondrial damage (KIT assay), reduced adhesion to human epithelium (>50% at 0.0313 mu g/mL, p <= .05), irregular deposit of chitin, and attenuated morphogenesis in mature biofilm. The treatment with 6a reduced pathogenicity of C albicans during infection in G. mellonella. Contrariwise, 2d enhancing fungal adhesion displayed mechanism targeted to the cell wall (due to the presence of 3-chloropropyl clubbed with aryltetrazole) in the presence of osmotic protector. Under 2d, the accidental cell death (88.60% +/- 4.81) was observed.In conclusion, all tetrazole derivatives were obtained in satisfactory yields (60-95%) using efficient, simple and not expensive methods. Fungistatic and slightly anticancer tetrazole derivatives with the novel action mode can circumvent an appearance of antifungal-resistant strains. These results indicate that they are worthy of further studies. (C) 2017 Elsevier Masson SAS. All rights reserved.
• Synthesis of tetrazole derivatives bearing pyrrolidine scaffold and evaluation of their antifungal activity against Candida albicans
  作者：Edyta Łukowska-Chojnacka、Anna Kowalkowska、Małgorzata Gizińska、Mirosława Koronkiewicz、Monika Staniszewska

  DOI：10.1016/j.ejmech.2018.12.044

  日期：2019.2

  in vitro and in vivo activity of the most potent antifungals. The leading antifungal inhibitor: 2-3-[2-(3-Methylphenyl)pyrrolidin-1-yl]propyl}-5-phenyl-2H-tetrazole (3aC) and the randomly selected ones: 5-phenyl-2-[3-(2-phenylpyrrolidin-1-yl)propyl]-2H-tetrazole (3aA), 5-(4-chlorophenyl)-2-3-[2-(4-fluorophenyl)pyrrolidin-1-yl]propyl}-2H-tetrazole (3cD), and 5-(4-chlorophenyl)-2-3-[2-(4-chlorophenyl

  机会性真菌感染的增加增加了对新的抗真菌剂的设计和合成的需求。考虑到四唑衍生物具有抗真菌活性，并且其中一些处于临床试验阶段，因此合成了带有吡咯烷部分的新的四唑衍生物，以显示其对白色念珠菌的作用方式。通过将各种2-芳基吡咯烷与若干个1-（3-氯丙基）-5-芳基-2 H-四唑进行N-烷基化，获得目标化合物。不管四唑或吡咯烷环上的取代基是什么，反应都在48小时内发生，收率令人满意，在53％至70％之间。我们对合成的化合物进行了筛选，以鉴定这些无毒的抑制作用。白色念珠菌的浮游和无柄细胞，并进行了一系列的后续研究，以检查最有效的抗真菌药的体外和体内活性。领先的抗真菌抑制剂：2- 3- [2-（3-甲基苯基）吡咯烷-1-基]丙基} -5-苯基-2 H-四唑（3aC）和随机选择的抑制剂：5-苯基-2- [3-（2-苯基吡咯烷-1-基）丙基] -2 H-四唑（3aA），5-（4-氯苯基）-2- 3- [