1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-((4-isopropyl-4H-1,2,4-triazol-3-yl)thio)ethan-1-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-((4-isopropyl-4H-1,2,4-triazol-3-yl)thio)ethan-1-one
• 英文别名: Cathepsin X inhibitor Z9；1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-[(4-propan-2-yl-1,2,4-triazol-3-yl)sulfanyl]ethanone
• 化学式: C₁₅H₁₇N₃O₃S
• 分子量: 319.384
• InChiKey: MAPGFLOHGFHEOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  91.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-((4-isopropyl-4H-1,2,4-triazol-3-yl)thio)ethan-1-one 在 ammonium acetate 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 反应 40.17h， 以50%的产率得到1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-((4-isopropyl-4H-1,2,4-triazol-3-yl)thio)ethan-1-amine
  参考文献：
  名称：

  Structure-activity relationships of triazole-benzodioxine inhibitors of cathepsin X

  摘要：

  Cathepsin X is a cysteine carboxypeptidase that is involved in various physiological and pathological processes. In particular, highly elevated expression and activity of cathepsin X has been observed in cancers and neurodegenerative diseases. Previously, we identified compound Z9 (1-(2,3-dihydrobenzo [b][1,4]dioxin-6-yl)-2-((4-isopropyl-4H-1,2,4-triazol-3-yl)thio)ethan-1-one) as a potent and specific reversible cathepsin X inhibitor. Here, we have explored the effects of chemical variations to Z9 of either benzodioxine or triazol moieties, and the importance of the central ketomethylenethio linker. The ketomethylenethio linker was crucial for cathepsin X inhibition, whereas changes of the triazole heterocycle did not alter the inhibitory potencies to a greater extent. Replacement of benzodioxine moiety with substituted benzenes reduced cathepsin X inhibition. Overall, several synthesized compounds showed similar or improved inhibitory potencies against cathepsin X compared to Z9, with IC50 values of 7.1 mu M-13.6 mu M. Additionally, 25 inhibited prostate cancer cell migration by 21%, which is under the control of cathepsin X. (c) 2020 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2020.112218
• 作为产物：
  描述：

  6-乙酰基-1,4-苯并二氧杂环 在 copper(ll) bromide 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 20.0h， 生成 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2-((4-isopropyl-4H-1,2,4-triazol-3-yl)thio)ethan-1-one
  参考文献：
  名称：

  Structure-activity relationships of triazole-benzodioxine inhibitors of cathepsin X

  摘要：

  Cathepsin X is a cysteine carboxypeptidase that is involved in various physiological and pathological processes. In particular, highly elevated expression and activity of cathepsin X has been observed in cancers and neurodegenerative diseases. Previously, we identified compound Z9 (1-(2,3-dihydrobenzo [b][1,4]dioxin-6-yl)-2-((4-isopropyl-4H-1,2,4-triazol-3-yl)thio)ethan-1-one) as a potent and specific reversible cathepsin X inhibitor. Here, we have explored the effects of chemical variations to Z9 of either benzodioxine or triazol moieties, and the importance of the central ketomethylenethio linker. The ketomethylenethio linker was crucial for cathepsin X inhibition, whereas changes of the triazole heterocycle did not alter the inhibitory potencies to a greater extent. Replacement of benzodioxine moiety with substituted benzenes reduced cathepsin X inhibition. Overall, several synthesized compounds showed similar or improved inhibitory potencies against cathepsin X compared to Z9, with IC50 values of 7.1 mu M-13.6 mu M. Additionally, 25 inhibited prostate cancer cell migration by 21%, which is under the control of cathepsin X. (c) 2020 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2020.112218

文献信息

• Structure-activity relationships of triazole-benzodioxine inhibitors of cathepsin X
  作者：Urša Pečar Fonović、Damijan Knez、Martina Hrast、Nace Zidar、Matic Proj、Stanislav Gobec、Janko Kos

  DOI：10.1016/j.ejmech.2020.112218

  日期：2020.5

  Cathepsin X is a cysteine carboxypeptidase that is involved in various physiological and pathological processes. In particular, highly elevated expression and activity of cathepsin X has been observed in cancers and neurodegenerative diseases. Previously, we identified compound Z9 (1-(2,3-dihydrobenzo [b][1,4]dioxin-6-yl)-2-((4-isopropyl-4H-1,2,4-triazol-3-yl)thio)ethan-1-one) as a potent and specific reversible cathepsin X inhibitor. Here, we have explored the effects of chemical variations to Z9 of either benzodioxine or triazol moieties, and the importance of the central ketomethylenethio linker. The ketomethylenethio linker was crucial for cathepsin X inhibition, whereas changes of the triazole heterocycle did not alter the inhibitory potencies to a greater extent. Replacement of benzodioxine moiety with substituted benzenes reduced cathepsin X inhibition. Overall, several synthesized compounds showed similar or improved inhibitory potencies against cathepsin X compared to Z9, with IC50 values of 7.1 mu M-13.6 mu M. Additionally, 25 inhibited prostate cancer cell migration by 21%, which is under the control of cathepsin X. (c) 2020 Published by Elsevier Masson SAS.