(2R,4S)-1-methyl-4-(phosphonomethyl)piperidine-2-carboxylic acid | 113229-64-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,4S)-1-methyl-4-(phosphonomethyl)piperidine-2-carboxylic acid
• CAS: 113229-64-4
• 化学式: C₈H₁₆NO₅P
• 分子量: 237.192
• InChiKey: WUAIWOKLDATGLK-NKWVEPMBSA-N

物化性质

• 熔点：
  256-260 °C
• 沸点：
  474.6±55.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  98.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯甲基吡啶 在 platinum(IV) oxide 、 palladium on activated charcoal 盐酸 、 硫酸 、 氢气 、 sodium hydride 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 25.0~80.0 ℃ 、275.79 kPa 条件下， 反应 16.17h， 生成 (2R,4S)-1-methyl-4-(phosphonomethyl)piperidine-2-carboxylic acid
  参考文献：
  名称：

  4-(Phosphonoalkyl)- and 4-(phosphonoalkenyl)-2-piperidinecarboxylic acids: synthesis, activity at N-methyl-D-aspartic acid receptors and anticonvulsant activity

  摘要：

  A series of 4-(phosphonoalkyl)- and 4-(phosphonoalkenyl)-2-piperidinecarboxylic acids were synthesized, and their biological activity was assessed as competitive ligands for the NMDA receptor, both in vitro by using a receptor binding assay ([3H]CGS 19755 binding) and in vivo by using an NMDA seizure model in mice. The analogues were also evaluated in [3H]AMPA and [3H]kainate binding to assess their affinity for non-NMDA excitatory amino acid receptor subtypes. A number of these analogues show potent and selective NMDA antagonistic activity both in vitro and in vivo. Most notable are 4-(phosphonomethyl)-2-piperidinecarboxylic acid (1a) (CGS 19755) and the phosphonopropenyl analogue 1i, both of which show anticonvulsant activity in the 1-2 mg/kg ip range. With the aid of computer-assisted modeling, a putative bioactive conformation for AP-5 is hypothesized from the SAR data presented and a preliminary model for the antagonist-preferring state of the NMDA receptor is presented.

  DOI：

  10.1021/jm00129a025

文献信息

• Certain phosphonic acids and derivatives
  申请人：CIBA-GEIGY AG

  公开号：EP0203891B1

  公开（公告）日：1991-05-15
• HUTCHISON, ALAN J.;SHAW, KENNETH R.;SCHNEIDER, JOSEF A.
  作者：HUTCHISON, ALAN J.、SHAW, KENNETH R.、SCHNEIDER, JOSEF A.

  DOI：——

  日期：——
• 4-(Phosphonoalkyl)- and 4-(phosphonoalkenyl)-2-piperidinecarboxylic acids: synthesis, activity at N-methyl-D-aspartic acid receptors and anticonvulsant activity
  作者：Alan J. Hutchison、Michael Williams、Christoff Angst、Reynalda De Jesus、Louis Blanchard、Robert H. Jackson、E. Jay Wilusz、Deborah E. Murphy、Patrick S. Bernard

  DOI：10.1021/jm00129a025

  日期：1989.9

  A series of 4-(phosphonoalkyl)- and 4-(phosphonoalkenyl)-2-piperidinecarboxylic acids were synthesized, and their biological activity was assessed as competitive ligands for the NMDA receptor, both in vitro by using a receptor binding assay ([3H]CGS 19755 binding) and in vivo by using an NMDA seizure model in mice. The analogues were also evaluated in [3H]AMPA and [3H]kainate binding to assess their affinity for non-NMDA excitatory amino acid receptor subtypes. A number of these analogues show potent and selective NMDA antagonistic activity both in vitro and in vivo. Most notable are 4-(phosphonomethyl)-2-piperidinecarboxylic acid (1a) (CGS 19755) and the phosphonopropenyl analogue 1i, both of which show anticonvulsant activity in the 1-2 mg/kg ip range. With the aid of computer-assisted modeling, a putative bioactive conformation for AP-5 is hypothesized from the SAR data presented and a preliminary model for the antagonist-preferring state of the NMDA receptor is presented.