4-[3-(5-苯基四唑-2-基)丙基]吗啉 | 3169-54-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-[3-(5-苯基四唑-2-基)丙基]吗啉
• 英文名称: 4-[3-(5-phenyl-2H-tetrazol-2-yl)propyl]morpholine
• 英文别名: 4-[3-(5-phenyl-tetrazol-2-yl)-propyl]-morpholine；4-[3-(5-Phenyltetrazol-2-yl)propyl]morpholine
• CAS: 3169-54-8
• 化学式: C₁₄H₁₉N₅O
• 分子量: 273.338
• InChiKey: ZEIIBTHEFRQZQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  56.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-苯基四氮唑 在 potassium carbonate 、 potassium hydroxide 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 4-[3-(5-苯基四唑-2-基)丙基]吗啉
  参考文献：
  名称：

  New 1,5 and 2,5-disubstituted tetrazoles-dependent activity towards surface barrier of Candida albicans

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2017.11.089

文献信息

• Alkylation of 5-substituted tetrazoles
  作者：Leland. Huff、Ronald A. Henry

  DOI：10.1021/jm00298a059

  日期：1970.7.1
• New Antihypertensive Aminoalkyltetrazoles
  作者：Shin. Hayao、Herbert J. Havera、Wallace G. Strycker、T. J. Leipzig、Rodolfo. Rodriguez

  DOI：10.1021/jm00315a025

  日期：1967.5
• 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.