2-bromo-5-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-5,6-dihydro-4H-thieno[3,2-c]pyrrol-4-one

• 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: 2-bromo-5-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-5,6-dihydro-4H-thieno[3,2-c]pyrrol-4-one
• 英文别名: 2-bromo-5-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butan-2-yl]-4H-thieno[2,3-c]pyrrol-6-one
• 化学式: C₁₈H₁₅BrF₂N₄O₂S
• 分子量: 469.31
• InChiKey: KPYJZANJFUEYIQ-MLCYQJTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  99.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-bromo-5-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-5,6-dihydro-4H-thieno[3,2-c]pyrrol-4-one 、 吡啶-4-硼酸 在 四(三苯基膦)钯 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 10.0h， 以65.5%的产率得到5-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-2-(pyridin-4-yl)-5,6-dihydro-4H-thieno[3,2-c]pyrrol-4-one
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates

  摘要：

  In order to further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (I), two series of novel azoles featuring thieno[2,3-c]pyrrolidone and thieno[3,2-clpyrroli-done nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SARs of antifungal triazoles. Most of target compounds exhibited excellent activity against Candida and Cryptococcus spp., with MIC values in the range of 0.0625 mu g/ml to 0.0156 mu g/ml. The thieno[3,2-c]pyrrolidone unit was more suited for improving activity against Aspergillus spp. The most potent compound, 18a, was selected for further development due to its significant in vitro activity against Aspergillus spp. (MIC = 0.25 mu g/ml), as well as its high metabolic stability in human liver microsomes. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.023
• 作为产物：
  描述：

  5-溴-3-甲基噻吩-2-甲酸 在 N-溴代丁二酰亚胺(NBS) 、 硫酸 、 水 、 potassium carbonate 、 1-羟基苯并三唑 、 三乙胺 、 sodium hydroxide 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 乙腈 为溶剂， 反应 24.5h， 生成 2-bromo-5-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1H-1,2,4-triazol-1-yl)butan-2-yl]-5,6-dihydro-4H-thieno[3,2-c]pyrrol-4-one
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates

  摘要：

  In order to further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (I), two series of novel azoles featuring thieno[2,3-c]pyrrolidone and thieno[3,2-clpyrroli-done nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SARs of antifungal triazoles. Most of target compounds exhibited excellent activity against Candida and Cryptococcus spp., with MIC values in the range of 0.0625 mu g/ml to 0.0156 mu g/ml. The thieno[3,2-c]pyrrolidone unit was more suited for improving activity against Aspergillus spp. The most potent compound, 18a, was selected for further development due to its significant in vitro activity against Aspergillus spp. (MIC = 0.25 mu g/ml), as well as its high metabolic stability in human liver microsomes. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.023

文献信息

• Design, synthesis, and structure–activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates
  作者：Xufeng Cao、Yuanyuan Xu、Yongbing Cao、Ruilian Wang、Ran Zhou、Wenjing Chu、Yushe Yang

  DOI：10.1016/j.ejmech.2015.08.023

  日期：2015.9

  In order to further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (I), two series of novel azoles featuring thieno[2,3-c]pyrrolidone and thieno[3,2-clpyrroli-done nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SARs of antifungal triazoles. Most of target compounds exhibited excellent activity against Candida and Cryptococcus spp., with MIC values in the range of 0.0625 mu g/ml to 0.0156 mu g/ml. The thieno[3,2-c]pyrrolidone unit was more suited for improving activity against Aspergillus spp. The most potent compound, 18a, was selected for further development due to its significant in vitro activity against Aspergillus spp. (MIC = 0.25 mu g/ml), as well as its high metabolic stability in human liver microsomes. (C) 2015 Elsevier Masson SAS. All rights reserved.