(-)-LY 235723 | 142923-40-8

• 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: (-)-LY 235723
• 英文别名: (2R,4S)-4-(2H-tetrazol-5-ylmethyl)piperidine-2-carboxylic acid
• CAS: 142923-40-8
• 化学式: C₈H₁₃N₅O₂
• 分子量: 211.224
• InChiKey: FAAVTENFCLADRE-NTSWFWBYSA-N

物化性质

• 沸点：
  488.9±55.0 °C(Predicted)
• 密度：
  1.398±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl cis-4-(cyanomethyl)-N-<(vinyloxy)carbonyl>piperidine-2-carboxylate 在 palladium on activated charcoal 盐酸 、 氢气 、 三正丁基叠氮化锡 作用下， 以 乙醇 为溶剂， 25.0~100.0 ℃ 、413.69 kPa 条件下， 反应 1.0h， 生成 (-)-LY 235723
  参考文献：
  名称：

  （+/-）-（2SR，4RS）-4-（1H-四唑-5-基甲基）哌啶-2-羧酸的NMDA拮抗剂活性与（-）-2R，4S-异构体相同。

  摘要：

  拆分了四唑取代的氨基酸（+/-）-（2SR，4RS）-4-（1H-四唑-5-基甲基）哌啶二羧酸（LY233053，（+/-）-1）通过在外消旋氨基酸合成中的关键中间体（+/-）-顺式-4-（氰甲基）-N-烯丙基哌啶-2-羧酸乙酯的合成过程中的关键中间体的组成，将其合成为对映体，3R-二-对甲苯基酒石酸。然后将这些拆分的胺的外消旋体转化为氨基酸（-）-1和（+）-1。发现该有效且选择性的NMDA拮抗剂的活性与1的（-）-异构体（LY235723）相同。X射线晶体学分析的是顺式4-（氰基甲基）-N-烯丙基哌啶-2-羧酸乙酯的2S，3S-二-对甲苯甲酰基酒石酸盐表明，分解的胺具有（-）-1的特征2R，4S绝对立体化学。使用特定的放射性配体[3H]-（2SR，4RS）-4-（膦酰基甲基）哌啶-2-羧酸（[3H] CGS 19755; IC50 = 67 +/- 6 nM）确定对NMDA受体的亲和力使用皮质切片制剂（IC50对40

  DOI：

  10.1021/jm00095a004

文献信息

• KETAMINE FORMULATIONS
  申请人：Otonomy, Inc.

  公开号：EP2932971A1

  公开（公告）日：2015-10-21

  Formulations of ketamine for administration to the inner or middle ear.

  用于内耳或中耳给药的氯胺酮制剂。
• Nanocarriers and their processing for diagnostics and therapeutics
  申请人：Rhode Island Hospital

  公开号：US10555948B2

  公开（公告）日：2020-02-11

  The compositions and methods of the invention provide compositions and methods for preferential targeting of tissues to delivery therapeutic or diagnostic agents. For example, such compounds are useful in the treatment of joint disorders those affecting articulating joints, e.g., injury-induced osteoarthritis as well as autoimmune diseases affecting joint tissue such as rheumatoid arthritis.

  本发明的组合物和方法提供了优先靶向组织递送治疗或诊断制剂的组合物和方法。例如，这类化合物可用于治疗影响关节的关节疾病，如损伤引起的骨关节炎以及影响关节组织的自身免疫性疾病，如类风湿性关节炎。
• Topical pharmaceutical composition containing phenytoin and a (co-) analgesic for the treatment of chronic pain
  申请人：Topical Innovations B.V.

  公开号：US11147799B2

  公开（公告）日：2021-10-19

  This disclosure relates to a pharmaceutical composition for topical use wherein the active pharmaceutical ingredient consists of the co-analgesic phenytoin and at least one further co-analgesic, and a method for producing the pharmaceutical composition. In addition, the disclosure relates to the pharmaceutical composition for use in the treatment of chronic pain.

  本公开涉及一种局部使用的药物组合物，其中的活性药物成分包括共镇痛剂苯妥英和至少另一种共镇痛剂，还涉及一种生产该药物组合物的方法。此外，本发明还涉及用于治疗慢性疼痛的药物组合物。
• 4-(Tetrazolylalkyl)piperidine-2-carboxylic acids. Potent and selective N-methyl-D-aspartic acid receptor antagonists with a short duration of action
  作者：Paul L. Ornstein、Darryle D. Schoepp、M. Brian Arnold、J. David Leander、David Lodge、Jonathan W. Paschal、Tom Elzey

  DOI：10.1021/jm00105a016

  日期：1991.1

  We have prepared a series of cis-4-(tetrazolylalkyl)piperidine-2-carboxylic acids as potent and selective N-methyl-D-aspartic acid (NMDA) receptor antagonists. NMDA antagonists may prove to be useful therapeutic agents, for instance, as anticonvulsants, in the treatment of neurodegenerative disorders such as Alzheimer's disease and in the prevention of neuronal damage that occurs during cerebral ischemia. The compounds prepared were evaluated in vitro in both receptor binding assays ([H-3]CGS-19755, [H-3]AMPA, and [H-3]kainic acid) and in a cortical-wedge preparation (versus NMDA, quisqualic acid, and kainic acid) to determine affinity, potency, and selectivity. The new amino acids were also evaluated in vivo for their ability to block NMDA-induced convulsions in neonatal rats and NMDA-induced lethality in mice. The most potent compound of this series, 15 (LY233053), selectively displaced [H-3]CGS-19755 binding with an IC50 of 107 +/- 7 nM and selectively antagonized responses due to NMDA in a cortical-wedge preparation with an IC50 of 4.2 +/- 0.4-mu-M. Compound 15 blocked both NMDA-induced convulsions in neonatal rats (minimum effective dose (MED) = 20 mg/kg ip) and NMDA-induced lethality in mice (MED = 5 mg/kg ip). This is the first example of an NMDA receptor antagonist that incorporates a tetrazole moiety as an omega-acid bioisostere. These amino acid antagonists are also unique from their phosphonic acid counterparts in that they have a shorter duration of action in vivo. For the treatment of acute disorders such as stroke, where an NMDA antagonist would be administered parenterally, the shorter duration of action may be beneficial, e.g., allowing for better dosage control. The combination of potent NMDA receptor antagonism and a short duration of action may make these compounds useful therapeutic agents in the treatment of a variety of neurological disorders.
• ORNSTEIN, PAUL L.;SCHOEPP, DARRYLE D.;ARNOLD, M. BRIAN;LEANDER, J. DAVID;+, J. MED. CHEM., 34,(1991) N, C. 90-97
  作者：ORNSTEIN, PAUL L.、SCHOEPP, DARRYLE D.、ARNOLD, M. BRIAN、LEANDER, J. DAVID、+

  DOI：——

  日期：——