1-(4-methoxyphenyl)-3-(4-(3-morpholinopropyl)-4H-1,2,4-triazol-3-yl)-6-(4-(2-oxopiperidin-1-yl)phenyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(4-methoxyphenyl)-3-(4-(3-morpholinopropyl)-4H-1,2,4-triazol-3-yl)-6-(4-(2-oxopiperidin-1-yl)phenyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one
• 英文别名: 1-(4-methoxyphenyl)-6-[4-(2-oxopiperidin-1-yl)phenyl]-3-[4-(3-(morpholin-4-yl)-propyl)-4H-1,2,4-triazol-3-yl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridin-7-one；1-(4-Methoxyphenyl)-3-[4-(3-morpholin-4-ylpropyl)-1,2,4-triazol-3-yl]-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5-dihydropyrazolo[3,4-c]pyridin-7-one；1-(4-methoxyphenyl)-3-[4-(3-morpholin-4-ylpropyl)-1,2,4-triazol-3-yl]-6-[4-(2-oxopiperidin-1-yl)phenyl]-4,5-dihydropyrazolo[3,4-c]pyridin-7-one
• 化学式: C₃₃H₃₈N₈O₄
• 分子量: 610.716
• InChiKey: IWBMPLCNPFEVOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (2Z)-氯[(4-甲氧基苯基)亚肼基]乙酸乙酯 在 盐酸 、 铁粉 、 sodium hydride 、 氯化铵 、 一水合肼 、 三乙胺 、 三氟乙酸 、 三甲胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 溶剂黄146 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.5h， 生成 1-(4-methoxyphenyl)-3-(4-(3-morpholinopropyl)-4H-1,2,4-triazol-3-yl)-6-(4-(2-oxopiperidin-1-yl)phenyl)-1,4,5,6-tetrahydro-7H-pyrazolo[3,4-c]pyridin-7-one
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationship of novel and effective apixaban derivatives as FXa inhibitors containing 1,2,4-triazole/pyrrole derivatives as P2 binding element

  摘要：

  Four series of novel and potent FXa inhibitors possessing the 1,2,4-triazole moiety and pyrrole moiety as P2 binding element and dihydroimidazoleitetrahydropyrimidine groups as P4 binding element were designed, synthesized, and evaluated for their anticoagulant activity in human and rabbit plasma in vitro. Most compounds showed moderate to excellent activity. Compounds 14a, 16, 18c, 26c, 35a, and 35b were further examined for their inhibition activity against human FXa in vitro and rat venous thrombosis in vivo. The most promising compound 14a, with an IC50 (FXa) value of 0.15 mu M and 99% inhibition rate, was identified for further evaluation as an FXa inhibitor. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.09.024

文献信息

• Design, synthesis, and structure–activity relationship of novel and effective apixaban derivatives as FXa inhibitors containing 1,2,4-triazole/pyrrole derivatives as P2 binding element
  作者：Yong Wang、Xiaoqing Sun、Di Yang、Zhuang Guo、Xuxu Fan、Minhua Nie、Feng Zhang、Yue Liu、Yue Li、Yulin Wang、Ping Gong、Yajing Liu

  DOI：10.1016/j.bmc.2016.09.024

  日期：2016.11

  Four series of novel and potent FXa inhibitors possessing the 1,2,4-triazole moiety and pyrrole moiety as P2 binding element and dihydroimidazoleitetrahydropyrimidine groups as P4 binding element were designed, synthesized, and evaluated for their anticoagulant activity in human and rabbit plasma in vitro. Most compounds showed moderate to excellent activity. Compounds 14a, 16, 18c, 26c, 35a, and 35b were further examined for their inhibition activity against human FXa in vitro and rat venous thrombosis in vivo. The most promising compound 14a, with an IC50 (FXa) value of 0.15 mu M and 99% inhibition rate, was identified for further evaluation as an FXa inhibitor. (C) 2016 Elsevier Ltd. All rights reserved.