(+/-)-cis-PPDA | 858131-66-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (+/-)-cis-PPDA
• 英文别名: (-)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid；cis-1-(phenanthrene-2-ylcarbonyl)piperazine-2,3-dicarboxylic acid；(2s,3r)-1-(Phenanthren-2-Ylcarbonyl)piperazine-2,3-Dicarboxylic Acid；(2S,3R)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid
• CAS: 858131-66-5
• 化学式: C₂₁H₁₈N₂O₅
• 分子量: 378.384
• InChiKey: IWWXIZOMXGOTPP-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-cis-PPDA 在 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 0.08h， 生成 (+)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid
  参考文献：
  名称：

  Piperazine-2,3-dicarboxylic Acid Derivatives as Dual Antagonists of NMDA and GluK1-Containing Kainate Receptors

  摘要：

  Competitive N-methyl-D-aspartate receptor (NMDAR) antagonists bind to the GluN2 subunit, of which there are four types (GluN2A-D). We report that some N-1-substituted derivatives of cis-piperazine-2,3-dicarboxylic acid display improved relative affinity for GluN2C and GluN2D versus GluN2A and GluN2B. These derivatives also display subtype selectivity among the more distantly related kainate receptor family. Compounds 18i and (-)-4 were the most potent kainate receptor antagonists, and 18i was selective for GluK1 versus GluK2, GluK3 and AMPA receptors. Modeling studies revealed structural features required for activity at GluK1 subunits and suggested that S674 was vital for antagonist activity. Consistent with this hypothesis, replacing the equivalent residue in GluK3 (alanine) with a serine imparts 18i antagonist activity. Antagonists with dual GluN2D and GluK1 antagonist activity may have beneficial effects in various neurological disorders. Consistent with this idea, antagonist 18i (30 mg/kg ip) showed antinociceptive effects in an animal model of mild nerve injury.

  DOI：

  10.1021/jm201230z
• 作为产物：
  描述：

  2-菲甲酸 在 sodium hydroxide 、 氯化亚砜 作用下， 以 1,4-二氧六环 、 水 、 苯 为溶剂， 反应 12.0h， 生成 (+/-)-cis-PPDA
  参考文献：
  名称：

  N1-取代的哌嗪-2,3-二羧酸衍生物作为NMDA受体拮抗剂的合成与药理作用。

  摘要：

  竞争性NMDA受体拮抗剂的结合位点位于NR2亚基上，其中有四种类型（NR2A-D）。典型的拮抗剂，例如（R）-AP5，具有亚单位选择性为NR2A> NR2B> NR2C> NR2D。竞争性NMDA受体拮抗剂（2R，3S）-（1-联苯基-4-羰基）哌嗪-2,3-二羧酸（PBPD，16b）与NR2A和NR2B相比，对NR2C和NR2D的相对亲和力增强，显示出非同寻常的选择性。合成了16b的带有芳基或芳基取代基的哌啶-2,3-二羧酸的N（1）连接基团的类似物，以探讨NR2C / NR2D选择性的结构要求。菲-2-羰基类似物16e对NR2C和NR2D的亲和力高> 60倍，对NR2C / NR2D的选择性是NR2A / NR2B的3-5倍。菲-3-羰基类似物（16f）的效力较低，但选择性更高，分别对NR2D的选择性是NR2A和NR2B的5倍和7倍。因此，带有大量疏水残基的拮抗剂具有与典型拮抗剂不同的NR2亚基选择性。

  DOI：

  10.1021/jm0492498

文献信息

• Phenanthryl piperazinyl dicarboxylic acids as selective nmda receptor modulating agents
  申请人：——

  公开号：US20030078237A1

  公开（公告）日：2003-04-24

  Disclosed are compounds of formula (I) wherein: L is (a) optionally substituted by replacement of one or more of the hydrogen atoms on the phenanthrene ring system by one or more groups other than hydrogen; A is CH 2 , SO 2 or C═O; X is CO 2 H, PO 3 H 2 , PO 2 H 2 , PO 2 HR 5 , PO 2 HOR 5 , SO 3 H, SO 2 H, or tetrazole; and R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from H, alkyl, alkenyl, alkynyl, aryl and aralkyl; or a pharmaceutically acceptable acid salt or base addition salt or an in vivo hydrolysable ester or amide thereof. Compounds of formula (I) are selective NMDA receptor modulating agents and, therefore, may be used to advantage in vitro in neuroassays and in vivo in the treatment of disorders of the CNS.

  公开了化合物的结构式(I)，其中：L是(a)通过将菲环上的一个或多个氢原子替换为一个或多个非氢基团而选择性地取代的；A是CH2，SO2或C═O；X是CO2H，PO3H2，PO2H2，PO2HR5，PO2HOR5，SO3H，SO2H或四唑；R1、R2、R3、R4和R5独立地选择自H、烷基、烯基、炔基、芳基和芳基烷基；或其药学上可接受的酸盐或碱加合盐或体内可水解的酯或酰胺。结构式(I)的化合物是选择性NMDA受体调节剂，因此，在神经分析中和中枢神经系统疾病的治疗中可以得到优势应用。
• PHENANTHRYL PIPERAZINYL DICARBOXYLIC ACIDS AS SELECTIVE NMDA RECEPTOR MODULATING AGENTS
  申请人：UNIVERSITY OF NEBRASKA BOARD OF REGENTS

  公开号：EP1244638A2

  公开（公告）日：2002-10-02
• A DRUG SCREENING PLATFORM FOR RETT SYNDROME
  申请人：The Regents of the University of California

  公开号：EP2841067A2

  公开（公告）日：2015-03-04
• DRUG SCREENING PLATFORM FOR RETT SYNDROME
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20150119327A1

  公开（公告）日：2015-04-30

  The invention provides a method for restoring a neural cell having a deficiency or alteration in glutamatergic pathway affecting neuron and/or glial function comprising contacting the cell with a NMDA receptor antagonist(s) and/or modulator(s) of a glutamatergic pathway, thereby restoring the neural cell having a deficiency or alteration in glutamatergic pathways affecting neuron and/or glial function.
• US6916816B2
  申请人：——

  公开号：US6916816B2

  公开（公告）日：2005-07-12