Sdz eaa 494 | 132014-88-1

• 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: Sdz eaa 494
• 英文别名: 4-[(E)-3-phosphonoprop-2-enyl]piperazine-2-carboxylic acid
• CAS: 132014-88-1
• 化学式: C₈H₁₅N₂O₅P
• 分子量: 250.19
• InChiKey: VZXMZMJSGLFKQI-ORCRQEGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -7
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  110
• 氢给体数：
  4
• 氢受体数：
  7

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。
• Pharmaceutical combinations for the treatment of stroke and traumatic brain injury
  申请人：——

  公开号：US20020045656A1

  公开（公告）日：2002-04-18

  This invention relates to methods of treating traumatic brain injury (TBI) or hypoxic or ischemic stroke, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with either: (a) a neutrophil inhibitory factor (NIF); (b) a sodium channel antagonist; (c) a nitric oxide synthase (NOS) inhibitor; (d) a glycine site antagonist; (e) a potassium channel opener; (f) an AMPA/kainate receptor antagonist; (g) a calcium channel antagonist; (h) a GABA-A receptor modulator (e.g., a GABA-A receptor agonist); or (i) an antiinflammatory agent.

  本发明涉及治疗创伤性脑损伤（TBI）或缺氧性或缺血性中风的方法，包括向需要此类治疗的患者注射NR2B亚型选择性N-甲基-D-天门冬氨酸（NMDA）受体拮抗剂，与以下任一组合：（a）中性粒细胞抑制因子（NIF）；（b）钠通道拮抗剂；（c）一氧化氮合酶（NOS）抑制剂；（d）甘氨酸位点拮抗剂；（e）钾通道开放剂；（f）AMPA / kainate受体拮抗剂；（g）钙通道拮抗剂；（h）GABA-A受体调节剂（例如，GABA-A受体激动剂）；或（i）抗炎药物。
• Novel-prodrugs for phosphorus-containing compounds
  申请人：Erion D. Mark

  公开号：US20050288240A1

  公开（公告）日：2005-12-29

  Prodrugs of formula I, their uses, their intermediates, and their method of manufacture are described: wherein: V, W, and W′ are independently selected from the group consisting of —H, alkyl, aralkyl, alicyclic, aryl, substituted aryl, heteroaryl, substituted heteroaryl, 1-alkenyl, and 1-alkynyl; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group containing 5-7 atoms, optionally 1 heteroatom, substituted with hydroxy, acyloxy, alkoxycarbonyloxy, or aryloxycarbonyloxy attached to a carbon atom that is three atoms from both O groups attached to the phosphorus; or together V and Z are connected via an additional 3-5 atoms to form a cyclic group, optionally containing 1 heteroatom, that is fused to an aryl group at the beta and gamma position to the O attached to the phosphorus; together V and W are connected via an additional 3 carbon atoms to form an optionally substituted cyclic group containing 6 carbon atoms and substituted with one substituent selected from the group consisting of hydroxy, acyloxy, alkoxycarbonyloxy, alkylthiocarbonyloxy, and aryloxycarbonyloxy, attached to one of said carbon atoms that is three atoms from an O attached to the phosphorus; together Z and W are connected via an additional 3-5 atoms to form a cyclic group, optionally containing one heteroatom, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl; together W and W′ are connected via an additional 2-5 atoms to form a cyclic group, optionally containing 0-2 heteroatoms, and V must be aryl, substituted aryl, heteroaryl, or substituted heteroaryl; Z is selected from the group consisting of —CHR 2 OH, —CHR 2 OC(O)R 3 , —CHR 2 OC(S)R 3 , —CHR 2 OC(S)OR 3 , —CHR 2 OC(O)SR 3 , —CHR 2 OCO 2 R 3 , —OR 2 , —SR 2 , —CHR 2 N 3 , —CH 2 aryl, —CH(aryl)OH, —CH(CH═CR 2 2)OH, —CH(C≡CR 2 )OH, —R 2 , —NR 2 2 , —OCOR 3 , —OCO 2 R 3 , —SCOR 3 , —SCO 2 R 3 , —NHCOR 2 , —NHCO 2 R 3 , —CH 2 NHaryl, —(CH 2 ) p —OR 12 , and —(CH 2 ) p —SR 12 ; p is an integer 2 or 3; with the provisos that: a) V, Z, W, W′ are not all —H; and b) when Z is —R 2 , then at least one of V, W, and W′ is not —H, alkyl, aralkyl, or alicyclic; R 2 is selected from the group consisting of R 3 and —H; R 3 is selected from the group consisting of alkyl, aryl, alicyclic, and aralkyl; R 12 is selected from the group consisting of —H, and lower acyl; M is selected from the group that attached to PO 3 2− , P 2 O 6 3− , or P 3 O 9 4− is a biologically active agent, and is attached to the phosphorus in formula I via a carbon, oxygen, sulfur or nitrogen atom; and pharmaceutically acceptable prodrugs and salts thereof.

  本文描述了公式I的前药、其用途、其中间体以及其制造方法：其中：V、W和W′独立地选自由-H、烷基、芳基烷基、脂环烷基、取代芳基、杂芳基、取代杂芳基、1-烯基和1-炔基组成的群；或者V和Z通过额外的3-5个原子连接形成含有5-7个原子的环状基团，可选地含有1个杂原子，取代羟基、酰氧基、烷氧羰氧基或芳氧羰氧基，连接到离磷的两个O基团都相隔三个原子的碳原子上；或者V和Z通过额外的3-5个原子连接形成一个环状基团，可选地含有1个杂原子，与连接到磷的O的β和γ位的芳基团融合；V和W通过额外的3个碳原子连接形成一个可选地取代的含有6个碳原子的环状基团，取代基选自羟基、酰氧基、烷氧羰氧基、烷基硫酰氧基和芳基羰氧基，连接到离一个连接到磷的O的三个原子的碳原子上；Z和W通过额外的3-5个原子连接形成一个环状基团，可选地含有一个杂原子，V必须是芳基、取代芳基、杂芳基或取代杂芳基；W和W′通过额外的2-5个原子连接形成一个环状基团，可选地含有0-2个杂原子，V必须是芳基、取代芳基、杂芳基或取代杂芳基；Z选自由CHR2OH、CHR2OC(O)R3、CHR2OC(S)R3、CHR2OC(S)OR3、CHR2OC(O)SR3、CHR2OCO2R3、OR2、SR2、CHR2N3、CH2芳基、CH(芳基)OH、CH(CH═CR22)OH、CH(C≡CR2)OH、R2、NR22、OCOR3、OCO2R3、SCOR3、SCO2R3、NHCOR2、NHCO2R3、 NH芳基、( )pOR12和( )pSR12；p是整数2或3；但需要满足以下条件：a）V、Z、W、W′不全为—H；并且b）当Z为—R2时，V、W和W′中至少有一个不是—H、烷基、芳基烷基或脂环烷基；R2选自R3和—H的群；R3选自烷基、芳基、脂环烷基和芳基烷基的群；R12选自—H和较低的酰基的群；M选自附着在PO32−、P2O63−或P3O94−上的生物活性剂，并通过碳、氧、硫或氮原子与公式I中的磷相连接；以及其药学上可接受的前药和盐。
• Novel phosphorus-containing prodrugs
  申请人：Erion D. Mark

  公开号：US20070249564A1

  公开（公告）日：2007-10-25

  Novel cyclic phosphoramidate prodrugs of drugs of formula I their use in delivery of drugs to the liver, their use in enhancing oral bioavailability, and their method of preparation are described.

  本文介绍了式I药物的新型环状磷酰胺酰化预药，其在药物传递到肝脏方面的应用、增强口服生物利用度方面的应用以及其制备方法。
• Novel Phosphorus-Containing Prodrugs
  申请人：Erion Mark D.

  公开号：US20080125605A1

  公开（公告）日：2008-05-29

  Novel cyclic phosphoramidate prodrugs of drugs of formula I their use in delivery of drugs to the liver, their use in enhancing oral bioavailability, and their method of preparation are described.

  本发明涉及一种新型环磷酰胺酰胺酯前药，其为公式I药物的前药，其在药物传递到肝脏方面的应用，其在增强口服生物利用度方面的应用，以及其制备方法。