2-(4-{3-[(6-chloronaphthalen-2-yl)sulfonyl]propanoyl}piperazin-1-yl)-5-methyl-1,2-dihydro-3H-imidazo[1,5-c]imidazol-3-one | 873088-62-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(4-{3-[(6-chloronaphthalen-2-yl)sulfonyl]propanoyl}piperazin-1-yl)-5-methyl-1,2-dihydro-3H-imidazo[1,5-c]imidazol-3-one
• 英文别名: 6-[4-[3-(6-chloronaphthalen-2-yl)sulfonylpropanoyl]piperazin-1-yl]-3-methyl-7H-imidazo[1,5-c]imidazol-5-one
• CAS: 873088-62-1
• 化学式: C₂₃H₂₄ClN₅O₄S
• 分子量: 501.994
• InChiKey: IOPAWTDJMUKCAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-methyl-2-(piperazin-1-yl)-1,2-dihydro-3H-imidazo[1,5-c]imidazol-3-one 、 3-[(6-chloronaphthalen-2-yl)sulfonyl]propanoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以76%的产率得到2-(4-{3-[(6-chloronaphthalen-2-yl)sulfonyl]propanoyl}piperazin-1-yl)-5-methyl-1,2-dihydro-3H-imidazo[1,5-c]imidazol-3-one
  参考文献：
  名称：

  Discovery of Imidazo[1,5-c]imidazol-3-ones: Weakly Basic, Orally Active Factor Xa Inhibitors

  摘要：

  The coagulation enzyme factor Xa (FXa) has been recognized as a promising target for the development of new antithrombotic agents. We previously found compound I to be an orally bioavailable FXa inhibitor in fasted monkeys; however, I showed poor bioavailability in rats and fed monkeys. To work out the pharmacokinetic problems, we focused our synthetic efforts on the chemical conversion of the 4-(imidazo[1,2-a]pyridin-5-yl)piperazine moiety of 1 to imidazolylpiperidine derivatives (fused and nonfused), which resulted in the discovery of the weakly basic imidazo[1,5-c]imidazol-3-one 3q as a potent and selective FXa inhibitor. Compound 3q showed favorable oral bioavailability in rats and monkeys under both fasted and fed conditions and antithrombotic efficacy in a rat model of venous thrombosis after oral administration, without a significant increase in bleeding time (unlike warfarin). On the basis of these promising properties, compound 3q was selected for further evaluation.

  DOI：

  10.1021/jm701548u

文献信息

• Discovery of Imidazo[1,5-<i>c</i>]imidazol-3-ones: Weakly Basic, Orally Active Factor Xa Inhibitors
  作者：Yasuhiro Imaeda、Takanobu Kuroita、Hiroki Sakamoto、Tetsuji Kawamoto、Mamoru Tobisu、Noriko Konishi、Katsuhiko Hiroe、Masaki Kawamura、Toshimasa Tanaka、Keiji Kubo

  DOI：10.1021/jm701548u

  日期：2008.6.1

  The coagulation enzyme factor Xa (FXa) has been recognized as a promising target for the development of new antithrombotic agents. We previously found compound I to be an orally bioavailable FXa inhibitor in fasted monkeys; however, I showed poor bioavailability in rats and fed monkeys. To work out the pharmacokinetic problems, we focused our synthetic efforts on the chemical conversion of the 4-(imidazo[1,2-a]pyridin-5-yl)piperazine moiety of 1 to imidazolylpiperidine derivatives (fused and nonfused), which resulted in the discovery of the weakly basic imidazo[1,5-c]imidazol-3-one 3q as a potent and selective FXa inhibitor. Compound 3q showed favorable oral bioavailability in rats and monkeys under both fasted and fed conditions and antithrombotic efficacy in a rat model of venous thrombosis after oral administration, without a significant increase in bleeding time (unlike warfarin). On the basis of these promising properties, compound 3q was selected for further evaluation.