N-(3-((2-(5-(2,4-dichlorophenyl)-4,5-dihydroisoxazol-3-yl)phenoxy)methyl)-5-mercapto-4H-1,2,4-triazol-4-yl)benzamide

• 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: N-(3-((2-(5-(2,4-dichlorophenyl)-4,5-dihydroisoxazol-3-yl)phenoxy)methyl)-5-mercapto-4H-1,2,4-triazol-4-yl)benzamide
• 英文别名: N-[3-[[2-[5-(2,4-dichlorophenyl)-4,5-dihydroisoxazol-3-yl]phenoxy]methyl]-5-sulfanyl-1,2,4-triazol-4-yl]benzamide；N-[3-[[2-[5-(2,4-dichlorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]phenoxy]methyl]-5-sulfanylidene-1H-1,2,4-triazol-4-yl]benzamide
• 化学式: C₂₅H₁₉Cl₂N₅O₃S
• 分子量: 540.43
• InChiKey: RFERHTQVOVNVPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  溴甲烷 、 N-(3-((2-(5-(2,4-dichlorophenyl)-4,5-dihydroisoxazol-3-yl)phenoxy)methyl)-5-mercapto-4H-1,2,4-triazol-4-yl)benzamide 在 potassium carbonate 作用下， 反应 4.0h， 以55%的产率得到N-(3-((2-(5-(2,4-dichlorophenyl)-4,5-dihydroisoxazol-3-yl)phenoxy)methyl)-5-(methylthio)-4H-1,2,4-triazol-4-yl)benzamide
  参考文献：
  名称：

  Hybrid triazoles: Design and synthesis as potential dual inhibitor of growth and efflux inhibition in tuberculosis

  摘要：

  Efflux inhibition is proven bacterial machinery responsible for removal of bacterial wastage including antibiotics. Recently, efflux inhibitors (El) have been tested with encouraging results as an adjuvant therapy for treatment of tuberculosis (TB). Although, El have emerged as innovative approach of treatment for multi drug resistant (MDR) & extensively drug resistant tuberculosis (XDR-TB), toxicity profile limits their wider use. To address this issue, we have attempted synthesizing hybrid molecules those results by combining known El and triazole. This synthesis was aimed to arrive at structure that possesses pharmacophore from known El. Synthesized molecules were evaluated as growth inhibitors (GI) and Efflux inhibitor of TB initially against Mycobacterium smegmatis mc(2)155. Pharmacologically active compounds were then tested for their cytotoxicity to further narrow down search. Most active compounds 144, 145, 154 and 163 were then tested for their GEI action against Mycobacterium tuberculosis (Mtb). Synthesized compounds were also tested for their synergistic action with first line and second line anti-TB drugs and ethidium bromide (EtBr). We arrived at compound 135 as most potent dual inhibitor of tuberculosis. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.054
• 作为产物：
  描述：

  2,4-dichloro-2'-hydroxychalcone 在 palladium 10% on activated carbon 、 氢气 、 羟胺 、 sodium carbonate 、 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， -10.0~20.0 ℃ 、551.59 kPa 条件下， 反应 5.34h， 生成 N-(3-((2-(5-(2,4-dichlorophenyl)-4,5-dihydroisoxazol-3-yl)phenoxy)methyl)-5-mercapto-4H-1,2,4-triazol-4-yl)benzamide
  参考文献：
  名称：

  Hybrid triazoles: Design and synthesis as potential dual inhibitor of growth and efflux inhibition in tuberculosis

  摘要：

  Efflux inhibition is proven bacterial machinery responsible for removal of bacterial wastage including antibiotics. Recently, efflux inhibitors (El) have been tested with encouraging results as an adjuvant therapy for treatment of tuberculosis (TB). Although, El have emerged as innovative approach of treatment for multi drug resistant (MDR) & extensively drug resistant tuberculosis (XDR-TB), toxicity profile limits their wider use. To address this issue, we have attempted synthesizing hybrid molecules those results by combining known El and triazole. This synthesis was aimed to arrive at structure that possesses pharmacophore from known El. Synthesized molecules were evaluated as growth inhibitors (GI) and Efflux inhibitor of TB initially against Mycobacterium smegmatis mc(2)155. Pharmacologically active compounds were then tested for their cytotoxicity to further narrow down search. Most active compounds 144, 145, 154 and 163 were then tested for their GEI action against Mycobacterium tuberculosis (Mtb). Synthesized compounds were also tested for their synergistic action with first line and second line anti-TB drugs and ethidium bromide (EtBr). We arrived at compound 135 as most potent dual inhibitor of tuberculosis. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.054