N-[3-(benzyloxy)phenyl]piperidine-4-carboxamide hydrochloride | 1124219-45-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[3-(benzyloxy)phenyl]piperidine-4-carboxamide hydrochloride
• 英文别名: N-(3-phenylmethoxyphenyl)piperidine-4-carboxamide;hydrochloride
• CAS: 1124219-45-9
• 化学式: C₁₉H₂₂N₂O₂*ClH
• 分子量: 346.857
• InChiKey: VRIMNMXWGQDXEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.63
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  50.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  tert-butyl 4-{[3-(benzyloxy)phenyl]-carbamoyl}piperidine-1-carboxylate 在 盐酸 作用下， 以 氯仿 为溶剂， 生成 N-[3-(benzyloxy)phenyl]piperidine-4-carboxamide hydrochloride
  参考文献：
  名称：

  Fluorinated Benzyloxyphenyl Piperidine-4-carboxamides with Dual Function against Thrombosis: Inhibitors of Factor Xa and Platelet Aggregation

  摘要：

  A series of benzyloxy anilides of nipecotic (5, 6) and isonipecotic (7, 8) acids were synthesized and assayed in vitro as inhibitors of ADP-induced platelet aggregation and the blood coagulation enzymes factor Xa (FXa) and thrombin (FIIa). An exploration of effects of the amidine group attached at the piperidine nitrogen,position and substitution (F, phenyl) of the benzyloxy group, and addition of fluorine/s on the second (distal) phenyl ring, led us to single out some promising isonipecotamide derivatives 7. Addition of meta-F and para-CF3 on the distal phenyl ring resulted in a 6-to-18-fold enhancement of the FXa potency and in 2-to-4-fold increase of the antiplatelet potency, the last depending to a large extent upon lipophilicity. Two congeners of N-{[3-(1,1'-biphenyl-4-yl)methoxy]phenyl}piperidine-4-carboxamide (7m and 7p) proved to be potent FXa-selective inhibitors (K-i = 130 and 57 nM, respectively) and antiplatelet agents and were identified as leads for developing new dual function antithrombotic drugs.

  DOI：

  10.1021/jm801141f

文献信息

• Fluorinated Benzyloxyphenyl Piperidine-4-carboxamides with Dual Function against Thrombosis: Inhibitors of Factor Xa and Platelet Aggregation
  作者：Modesto de Candia、Francesco Liantonio、Andrea Carotti、Raimondo De Cristofaro、Cosimo Altomare

  DOI：10.1021/jm801141f

  日期：2009.2.26

  A series of benzyloxy anilides of nipecotic (5, 6) and isonipecotic (7, 8) acids were synthesized and assayed in vitro as inhibitors of ADP-induced platelet aggregation and the blood coagulation enzymes factor Xa (FXa) and thrombin (FIIa). An exploration of effects of the amidine group attached at the piperidine nitrogen,position and substitution (F, phenyl) of the benzyloxy group, and addition of fluorine/s on the second (distal) phenyl ring, led us to single out some promising isonipecotamide derivatives 7. Addition of meta-F and para-CF3 on the distal phenyl ring resulted in a 6-to-18-fold enhancement of the FXa potency and in 2-to-4-fold increase of the antiplatelet potency, the last depending to a large extent upon lipophilicity. Two congeners of N-[3-(1,1'-biphenyl-4-yl)methoxy]phenyl}piperidine-4-carboxamide (7m and 7p) proved to be potent FXa-selective inhibitors (K-i = 130 and 57 nM, respectively) and antiplatelet agents and were identified as leads for developing new dual function antithrombotic drugs.