1-(3-chloropropyl)-5-phenyl-1H-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: 1-(3-chloropropyl)-5-phenyl-1H-tetrazole
• 英文别名: 1-(3-Chloropropyl)-5-phenyltetrazole；1-(3-chloropropyl)-5-phenyltetrazole
• 化学式: C₁₀H₁₁ClN₄
• 分子量: 222.677
• InChiKey: XFPMFEGGRIMKIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 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：

  4-苄基哌啶 、 1-(3-chloropropyl)-5-phenyl-1H-tetrazole 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 以82%的产率得到4-benzyl-1-(3-(5-phenyl-1H-tetrazol-1-yl)propyl)piperidine
  参考文献：
  名称：

  三重再摄取抑制剂：苄基哌啶-四唑的设计，合成与结构-活性关系

  摘要：

  单胺转运蛋白是治疗各种中枢神经疾病的重要靶标。传统再摄取抑制剂的一些局限性，例如起效延迟，失眠和性功能障碍，迫使人们寻求更安全，更有效的化合物。在这项研究中，我们试图确定新型的单胺再摄取抑制剂。根据我们先前报道的化合物的对接研究，对芳香环（A1）进行了修饰，以生成一系列新的苄基哌啶-四唑。合成了三十一种化合物并评估了它们对5-羟色胺，去甲肾上腺素和多巴胺的三重再摄取抑制。三重再摄取抑制剂，尤其是化合物2q，显示出有效的5-羟色胺再摄取抑制作用，从而验证了我们的设计方法。

  DOI：

  10.1016/j.bmc.2017.07.046
• 作为产物：
  描述：

  苯甲腈 在 sodium azide 、 三乙胺盐酸盐 、 potassium carbonate 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 24.0h， 生成 1-(3-chloropropyl)-5-phenyl-1H-tetrazole
  参考文献：
  名称：

  三重再摄取抑制剂：苄基哌啶-四唑的设计，合成与结构-活性关系

  摘要：

  单胺转运蛋白是治疗各种中枢神经疾病的重要靶标。传统再摄取抑制剂的一些局限性，例如起效延迟，失眠和性功能障碍，迫使人们寻求更安全，更有效的化合物。在这项研究中，我们试图确定新型的单胺再摄取抑制剂。根据我们先前报道的化合物的对接研究，对芳香环（A1）进行了修饰，以生成一系列新的苄基哌啶-四唑。合成了三十一种化合物并评估了它们对5-羟色胺，去甲肾上腺素和多巴胺的三重再摄取抑制。三重再摄取抑制剂，尤其是化合物2q，显示出有效的5-羟色胺再摄取抑制作用，从而验证了我们的设计方法。

  DOI：

  10.1016/j.bmc.2017.07.046

文献信息

• 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.
• Triple reuptake inhibitors: Design, synthesis and structure–activity relationship of benzylpiperidine–tetrazoles
  作者：Suresh Paudel、Xiao Min、Srijan Acharya、Daulat Bikram Khadka、Goo Yoon、Kyeong-Man Kim、Seung Hoon Cheon

  DOI：10.1016/j.bmc.2017.07.046

  日期：2017.10

  limitations of traditional reuptake inhibitors, like delayed onset of action, insomnia, and sexual dysfunction, have compelled the search for safer, more effective compounds. In this study, we have sought to identify novel monoamine reuptake inhibitors. Based upon the docking study of compounds that we had reported previously, aromatic rings (A1) were modified to generate a novel series of benzylpiperidine–tetrazoles

  单胺转运蛋白是治疗各种中枢神经疾病的重要靶标。传统再摄取抑制剂的一些局限性，例如起效延迟，失眠和性功能障碍，迫使人们寻求更安全，更有效的化合物。在这项研究中，我们试图确定新型的单胺再摄取抑制剂。根据我们先前报道的化合物的对接研究，对芳香环（A1）进行了修饰，以生成一系列新的苄基哌啶-四唑。合成了三十一种化合物并评估了它们对5-羟色胺，去甲肾上腺素和多巴胺的三重再摄取抑制。三重再摄取抑制剂，尤其是化合物2q，显示出有效的5-羟色胺再摄取抑制作用，从而验证了我们的设计方法。