(+)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid | 858131-67-6

• 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: (+)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid
• 英文别名: (2R,3S)-1-(Phenanthrene-2-carbonyl)-piperazine-2,3-dicarboxylic acid；(2R,3S)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid
• CAS: 858131-67-6
• 化学式: C₂₁H₁₈N₂O₅
• 分子量: 378.384
• InChiKey: IWWXIZOMXGOTPP-ZWKOTPCHSA-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

• 作为产物：
  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

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：Monaghan Daniel T.

  公开号：US06916816B2

  公开（公告）日：2005-07-12

  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

  本发明涉及一种公式（I）的化合物，其中：L是（a）通过将苯并环系统上的一个或多个氢原子替换为一个或多个非氢基团而可选择地被取代; 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，芳基和芳烷基; 或其药学上可接受的酸盐或碱加成盐或体内可水解的酯或酰胺。公式（I）的化合物是选择性NMDA受体调节剂，因此可以在神经测定和中枢神经系统疾病治疗中体外和体内优势使用。
• PHENANTHRYL PIPERAZINYL DICARBOXYLIC ACIDS AS SELECTIVE NMDA RECEPTOR MODULATING AGENTS
  申请人：UNIVERSITY OF BRISTOL

  公开号：EP1244638B1

  公开（公告）日：2004-05-12
• US6916816B2
  申请人：——

  公开号：US6916816B2

  公开（公告）日：2005-07-12
• [EN] METHODS AND COMPOSITIONS FOR THE TREATMENT OF ALZHEIMER<br/>[FR] PROCÉDÉS ET COMPOSITIONS POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：UNIV PAIS VASCO

  公开号：WO2011076946A2

  公开（公告）日：2011-06-30

  The invention relates to AMPA receptor inhibitors and NMDA receptor inhibitors for use in the treatment of a disease associated with deposition of amyloid proteins, more precisely, Alzheimer's disease.