3-(piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine hydrochloride | 1211595-41-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 3-(piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine hydrochloride
• 英文别名: 3-Piperidin-4-yl-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine;hydrochloride
• CAS: 1211595-41-3
• 化学式: C₁₂H₁₉N₃*ClH
• 分子量: 241.764
• InChiKey: VKUJECBNFWJRBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.11
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  29.8
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine hydrochloride 、 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 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 3.25h， 生成 3-(1-{3-[(6-chloronaphthalen-2-yl)sulfonyl]propanoyl}piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine
  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-butyl 4-(imidazo[1,2-a]pyridin-3-yl)piperidine-1-carboxylate 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 1,4-二氧六环 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 反应 22.75h， 生成 3-(piperidin-4-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine hydrochloride
  参考文献：
  名称：

  [EN] METALLO-BETA-LACTAMASE INHIBITORS
  [FR] INHIBITEURS DE MÉTALLO-BÊTA-LACTAMASES

  摘要：

  本发明涉及式(I)的化合物，这些化合物是金属β-内酰胺酶抑制剂，以及这些化合物的合成和与β-内酰胺类抗生素一起用于克服耐药性的用途。

  公开号：

  WO2015112441A1

文献信息

• [EN] METALLO-BETA-LACTAMASE INHIBITORS<br/>[FR] INHIBITEURS DE MÉTALLO-BÊTA-LACTAMASES
  申请人：MERCK SHARP & DOHME

  公开号：WO2015112441A1

  公开（公告）日：2015-07-30

  The present invention relates to compounds of formula (I) that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

  本发明涉及式(I)的化合物，这些化合物是金属β-内酰胺酶抑制剂，以及这些化合物的合成和与β-内酰胺类抗生素一起用于克服耐药性的用途。
• EP1564213
  申请人：——

  公开号：——

  公开（公告）日：——
• US9708336B2
  申请人：——

  公开号：US9708336B2

  公开（公告）日：2017-07-18
• METALLO-BETA-LACTAMASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20160333021A1

  公开（公告）日：2016-11-17

  The present invention relates to compounds of formula (I) that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

  本发明涉及式(I)的化合物，这些化合物是金属β-内酰胺酶抑制剂，以及这些化合物的合成和与β-内酰胺类抗生素一起用于克服耐药性的用途。
• 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.