tert-butyl 4-(5-methyl-3-oxo-1H-imidazo[1,5-c]imidazol-2(3H)-yl)piperidine-1-carboxylate | 1034411-61-4

• 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: tert-butyl 4-(5-methyl-3-oxo-1H-imidazo[1,5-c]imidazol-2(3H)-yl)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-(3-methyl-5-oxo-7H-imidazo[1,5-c]imidazol-6-yl)piperidine-1-carboxylate
• CAS: 1034411-61-4
• 化学式: C₁₆H₂₄N₄O₃
• 分子量: 320.392
• InChiKey: SCCAMVPYFDQSIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  67.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(5-methyl-3-oxo-1H-imidazo[1,5-c]imidazol-2(3H)-yl)piperidine-1-carboxylate 在 盐酸 作用下， 以 水 为溶剂， 反应 0.5h， 生成 5-methyl-2-(4-piperidinyl)-1,2-dihydro-3H-imidazo[1,5-c]imidazol-3-one dihydrochloride
  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
• 作为产物：
  描述：

  tert-butyl4-{[(2-methyl-1H-imidazol-5-yl)methyl]amino}piperidine-1-carboxylate 、 N,N'-羰基二咪唑 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 15.0h， 以77%的产率得到tert-butyl 4-(5-methyl-3-oxo-1H-imidazo[1,5-c]imidazol-2(3H)-yl)piperidine-1-carboxylate
  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.