3-(4-chlorophenyl)-3-methylpentanedioic acid | 91393-73-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 3-(4-chlorophenyl)-3-methylpentanedioic acid
• 英文别名: 3-methyl-3-(p-chlorophenyl)glutaric acid；3-(4-chlorophenyl)-3-methylglutaric acid；3-<4-Chlor-phenyl>-3-methyl-glutarsaeure
• CAS: 91393-73-6
• 化学式: C₁₂H₁₃ClO₄
• mdl: MFCD19359301
• 分子量: 256.686
• InChiKey: PAXACUQJJAFHOY-UHFFFAOYSA-N

物化性质

• 沸点：
  397.7±27.0 °C(Predicted)
• 密度：
  1.348±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-chlorophenyl)-3-methylpentanedioic acid 在 吡啶 、 lithium aluminium tetrahydride 、 硫酸 、 三溴化磷 作用下， 以 乙醚 、 苯 为溶剂， 生成 3-(4-Chlorphenyl)-3-methyl-1,5-dibrom-pentan
  参考文献：
  名称：

  Conformational Analysis. XXXIV. The Phenyl Group^1,2

  摘要：

  DOI：

  10.1021/jo01059a112
• 作为产物：
  描述：

  3-<4-Chlor-phenyl>-2-cyan-but-2-en-saeure-aethylester 在 硫酸 、 sodium ethanolate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 44.0h， 生成 3-(4-chlorophenyl)-3-methylpentanedioic acid
  参考文献：
  名称：

  Indeno[1,2-b]pyrazin-2,3-diones: A New Class of Antagonists at the Glycine Site of the NMDA Receptor with Potent in Vivo Activity

  摘要：

  Indeno[1,2-b]pyrazin-2,3-diones have been identified as a novel series of potent ligands on the glycine site of the NMDA receptor. To improve their in vivo activities, an acetic acid-type side chain was introduced to the 5-position, giving water-soluble compounds when formulated as the sodium salt (> 10 mg/mL). Introduction of a chlorine atom in the 8-position led to a dramatic improvement of anticonvulsant activity and this was surprising since this change did not improve binding affinity. A plausible explanation is a reduced recognition by a Na+,K+-ATPase active transport system responsible for the excretion of these compounds from the brain and kidney. This promising new chemical series led to the optically active isomer (-)-10i (RPR 118723), a glycine/NMDA antagonist with nanomolar binding affinity and in vivo activity in animal model of convulsions and electrophysiology at doses in the range of 2-3 mg/kg following iv administration.

  DOI：

  10.1021/jm990957g

文献信息

• 5H-indeno\x9b1,2-b!pyrazine-2,3-dione derivatives, their preparation and
  申请人：Rhone-Poulenc Rorer S.A.

  公开号：US05922716A1

  公开（公告）日：1999-07-13

  Compounds of formula (I): ##STR1## wherein R represents a CR.sub.4 R.sub.5, CHR.sub.6, or C.dbd.R.sub.7 radical and R.sub.3 represents an oxygen atom, salts thereof, the preparation thereof and drugs containing same. The compounds of formula (I) have valuable pharmacological properties and are alpha-amino-3-hydroxy-5-methyl-4-osoxaziepropionic acid (AMPA) receptor antagonists, said receptor also being known as the quisqualate receptor. Furthermore, the compounds of formula (I) are non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, and particularly NMDA receptor glycine modulation site ligands.

  式(I)化合物：##STR1##其中R表示CR₄R₅、CHR₆或C≡R₇基团，R₃表示氧原子，及其盐类，它们的制备方法以及含有这些化合物的药物。式(I)化合物具有宝贵的药理学特性，是α-氨基-3-羟基-5-甲基-4-异噁唑丙酸(AMPA)受体拮抗剂，该受体也称为quisqualate受体。此外，式(I)化合物是非竞争性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂，特别是NMDA受体甘氨酸调节位点的配体。
• Structures and fluorescence of secondary products produced from the cope-knoevenagel reaction of 2-phenylpropionaldehyde with methyl cyanoacetate
  作者：Wakatu Nagai、Yumiko Hirata、Masao Kawai、Kiyoaki Tanaka

  DOI：10.1002/jhet.5570330122

  日期：1996.1

  of 2-phenylpropionaldehyde (7) with methyl cyanoacetate (8) produced methyl (E)-2-cyano-4-phenylpent-2-enoate (9) and the two highly fluorescent secondary products, 2-amino-3-carbomethoxy-6-phenyl-4-(1-phenylethyl)pyridine (10) and 3-cyano-6-phenyl-4-(1-phenylethyl)-2-pyridone (11). The structure of 10 was determined by X-ray crystallography while the structure of 11 was confirmed by the conversion

  2-苯基丙醛（7）与氰基乙酸甲酯（8）的Cope-Knoevenagel反应产生了（E）-2-氰基-4-苯基戊-2-烯酸甲酯（9）和两种高荧光副产物2-氨基- 3-碳甲氧基-6-苯基-4-（1-苯乙基）吡啶（10）和3-氰基-6-苯基-4-（1-苯乙基）-2-吡啶酮（11）。通过X射线晶体学确定10的结构，同时通过将9转化为11来确认11的结构。讨论了它们的形成机理。10和11的荧光 还描述了相关化合物。
• US5922716A
  申请人：——

  公开号：US5922716A

  公开（公告）日：1999-07-13
• Conformational Analysis. XXXIV. The Phenyl Group^1,2
  作者：Norman L. Allinger、Janet Allinger、Margaret A. DaRooge、Seymour Greenberg

  DOI：10.1021/jo01059a112

  日期：1962.12
• Indeno[1,2-<i>b</i>]pyrazin-2,3-diones: A New Class of Antagonists at the Glycine Site of the NMDA Receptor with Potent in Vivo Activity
  作者：Patrick Jimonet、Yves Ribeill、Georg Andrees Bohme、Alain Boireau、Michel Chevé,、Dominique Damour、Adam Doble、Arielle Genevois-Borella、Frédéric Herman、Assunta Imperato、Sylvain Le Guern、Franco Manfré、Jeremy Pratt、John C. R. Randle、Jean-Marie Stutzmann、Serge Mignani

  DOI：10.1021/jm990957g

  日期：2000.6.1

  Indeno[1,2-b]pyrazin-2,3-diones have been identified as a novel series of potent ligands on the glycine site of the NMDA receptor. To improve their in vivo activities, an acetic acid-type side chain was introduced to the 5-position, giving water-soluble compounds when formulated as the sodium salt (> 10 mg/mL). Introduction of a chlorine atom in the 8-position led to a dramatic improvement of anticonvulsant activity and this was surprising since this change did not improve binding affinity. A plausible explanation is a reduced recognition by a Na+,K+-ATPase active transport system responsible for the excretion of these compounds from the brain and kidney. This promising new chemical series led to the optically active isomer (-)-10i (RPR 118723), a glycine/NMDA antagonist with nanomolar binding affinity and in vivo activity in animal model of convulsions and electrophysiology at doses in the range of 2-3 mg/kg following iv administration.