(E)‑4‑((2‑(methylcarbamothioyl)hydrazineylidene)methyl)benzoic acid

• 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: (E)‑4‑((2‑(methylcarbamothioyl)hydrazineylidene)methyl)benzoic acid
• 英文别名: (e)-4-((2-(Methylcarbamothioyl)hydrazineylidene)methyl)benzoic acid；4-[(E)-(methylcarbamothioylhydrazinylidene)methyl]benzoic acid
• 化学式: C₁₀H₁₁N₃O₂S
• 分子量: 237.282
• InChiKey: KZUPPLAKFHNYDV-WUXMJOGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)‑4‑((2‑(methylcarbamothioyl)hydrazineylidene)methyl)benzoic acid 、 1-amino-2-(2,4difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol 在 N-甲基吗啉 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以72%的产率得到(E)‑N‑(2‑(2,4‑difluorophenyl)‑2‑hydroxy‑3‑(1H‑1,2,4‑triazol‑1‑yl)propyl)‑4‑((2‑(methylcarbamothioyl)hydrazineylidene)methyl)benzamide
  参考文献：
  名称：

  Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans

  摘要：

  Azole antifungals are an important class of antifungal drugs due to their low cost, ability to be administered orally, and broad-spectrum activity. However, their widespread and long-term use have given rise to adaptation mechanisms that render these compounds less effective against common fungal pathogens, includingCandida albicans. New antifungals are desperately needed as drug-resistant strains become more prevalent. We recently showed that copper supplementation potentiates the activity of the azole antifungal fluconazole against the opportunistic fungal pathogenC. albicans. Here, we report eight new azole analogues derived from fluconazole in which one triazole group has been replaced with a metal-binding group, a strategy designed to enhance potentiation of azole antifungal activity by copper. The bioactivity of all eight compounds was tested and compared to that of fluconazole. Three of the analogues showed activity againstC. albicansand two had lower levels of trailing growth. One compound, Flu-TSCZ, was found to impact the levels, speciation, and bioavailability of cellular metals.[GRAPHICS].

  DOI：

  10.1007/s00775-020-01796-x
• 作为产物：
  描述：

  肼基二硫代甲酸甲酯 、 对醛基苯甲酸 以 乙醇 为溶剂， 反应 1.5h， 以79%的产率得到(E)‑4‑((2‑(methylcarbamothioyl)hydrazineylidene)methyl)benzoic acid
  参考文献：
  名称：

  Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans

  摘要：

  Azole antifungals are an important class of antifungal drugs due to their low cost, ability to be administered orally, and broad-spectrum activity. However, their widespread and long-term use have given rise to adaptation mechanisms that render these compounds less effective against common fungal pathogens, includingCandida albicans. New antifungals are desperately needed as drug-resistant strains become more prevalent. We recently showed that copper supplementation potentiates the activity of the azole antifungal fluconazole against the opportunistic fungal pathogenC. albicans. Here, we report eight new azole analogues derived from fluconazole in which one triazole group has been replaced with a metal-binding group, a strategy designed to enhance potentiation of azole antifungal activity by copper. The bioactivity of all eight compounds was tested and compared to that of fluconazole. Three of the analogues showed activity againstC. albicansand two had lower levels of trailing growth. One compound, Flu-TSCZ, was found to impact the levels, speciation, and bioavailability of cellular metals.[GRAPHICS].

  DOI：

  10.1007/s00775-020-01796-x

文献信息

• Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans
  作者：Elizabeth W. Hunsaker、Katherine J. McAuliffe、Katherine J. Franz

  DOI：10.1007/s00775-020-01796-x

  日期：2020.8

  Azole antifungals are an important class of antifungal drugs due to their low cost, ability to be administered orally, and broad-spectrum activity. However, their widespread and long-term use have given rise to adaptation mechanisms that render these compounds less effective against common fungal pathogens, includingCandida albicans. New antifungals are desperately needed as drug-resistant strains become more prevalent. We recently showed that copper supplementation potentiates the activity of the azole antifungal fluconazole against the opportunistic fungal pathogenC. albicans. Here, we report eight new azole analogues derived from fluconazole in which one triazole group has been replaced with a metal-binding group, a strategy designed to enhance potentiation of azole antifungal activity by copper. The bioactivity of all eight compounds was tested and compared to that of fluconazole. Three of the analogues showed activity againstC. albicansand two had lower levels of trailing growth. One compound, Flu-TSCZ, was found to impact the levels, speciation, and bioavailability of cellular metals.[GRAPHICS].