(Rs)-(四唑-5-基)甘氨酸 | 138199-51-6

• 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
• 中文名称: (Rs)-(四唑-5-基)甘氨酸
• 英文名称: D,L-(tetrazol-5-yl)-glycine
• 英文别名: (RS)-(tetrazol-5-yl)glycine；(Tetrazol-5-yl)glycine；2-amino-2-(2H-tetrazol-5-yl)acetic acid
• CAS: 138199-51-6
• 化学式: C₃H₅N₅O₂
• mdl: MFCD00233633
• 分子量: 143.105
• InChiKey: UKBRUIZWQZHXFL-UHFFFAOYSA-N

物化性质

• 沸点：
  447.1±55.0 °C(Predicted)
• 密度：
  1.804±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：0.25mg/mL； PBS（pH 7.2）：0.2mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  -4.1
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  6

制备方法与用途

生物活性

(RS)-(Tetrazol-5-yl)glycine (D,L-(tetrazol-5-yl)glycine) 是一种高效且选择性的 N-甲基-D-天冬氨酸 (NMDA) 受体激动剂。其对 GluN1/GluN2D 和 GluN1/GluN2A 的 EC50 分别为 99 nM 和 1.7 μM，并诱导小鼠癫痫发作反应和 Fos。

靶点

• EC50:
  • GluN1/GluN2D: 99 nM
  • GluN1/GluN2A: 1.7 μM

体外研究

( RS )-(Tetrazol-5-yl)glycine (D,L-(tetrazol-5-yl)glycine) 是兴奋性氨基酸受体 NMDA 亚型的激动剂。它能置换大鼠脑膜上的 NMDA 受体结合，以 [3H]CGS19755 (IC50 = 98 nM) 和 [3H]谷氨酸 (IC50 = 36 nM) 为配体测量。此外，(RS)-(Tetrazol-5-yl)glycine 对 D,L-α-[5-甲基-3H]氨基-3-羟基-5-甲基异噁唑-4-丙酸 (AMPA)，[3H]天冬氨酸或 [3H]甘氨酸的结合几乎没有抑制作用（IC50 > 30 μM）。

体内研究

( RS )-(Tetrazol-5-yl)glycine (D,L-(tetrazol-5-yl)glycine; 1.25, 1.5 mg/kg；IP) 能诱导 NR1+/+ 和 NR1-/- 小鼠的癫痫发作反应和 Fos。在新生大鼠中，(RS)-(Tetrazol-5-yl)glycine 是一种高度有效的惊厥剂（ED50 = 0.071 mg/kg；i.p.)。

实验结果

• 动物模型: C57BL/6 小鼠
• 剂量: 1.25, 1.5 mg/kg
• 给药途径: IP
• 结果: 引起癫痫发作反应和 Fos。

反应信息

• 作为产物：
  描述：

  [Ru(bpy)2(TzGly)(py)]Cl2 生成 (Rs)-(四唑-5-基)甘氨酸
  参考文献：
  名称：

  [EN] PHOTOLABILE COMPOUNDS
  [FR] COMPOSES PHOTOLABILES

  摘要：

  公开号：

  WO2010151879A9

文献信息

• DL-Tetrazol-5-ylglycine, a highly potent NMDA agonist: its synthesis and NMDA receptor efficacy
  作者：W. H. W. Lunn、Darryle D. Schoepp、David O. Calligaro、R. T. Vasileff、L. J. Heinz、Craig R. Salhoff、Patrick J. O'Malley

  DOI：10.1021/jm00102a015

  日期：1992.11

  At physiological pH, the spatial arrangement of the three charges Of DL-tetrazol-5-ylglycine (5) could be viewed as similar to those found in certain conformations of the two excitatory amino acids (EAAs)-aspartic and glutamic acids. Given significant binding to one or more EAA receptors, 5 would offer unique modeling and perhaps biological opportunities. We have previously shown it to be the most potent NMDA agonist known, with a unique and marked in vitro neutrotoxicity at depolarizing concentrations. Now we report the details required for its synthesis, together with its potency and efficacy in two assays of functional activation of the NMDA receptor, namely agonist-influenced [H-3]MK801 binding and agonist-induced release of the neurotransmitter [H-3]-norepinephrine from brain slices. In both these assays DL-tetrazol-5-ylglycine proved to be more potent and efficacious than NMDA and cis-methanoglutamate. It was more potent than, and equally efficacious to, L-glutamate in [H-3]MK801 binding. The structural features of 5 may well reflect optimal agonist interaction at the NMDA receptor site. (We considered the possibility that some decarboxylation of DL-tetrazol-5-ylglycine may have occurred during testing. This would give 5-(aminomethyl)tetrazole (13), the tetrazole acid analog of glycine; and glycine is involved in NMDA receptor activation. Compound 13 does not affect [H-3]glycine binding at the strychnine-insensitive glycine binding site, and [H-3]MK801 binding studies showed that the (aminomethyl)-tetrazole, even if is formed, would probably have no effect on the activity of tetrazol-5-ylglycine at the NMDA receptor.)
• [EN] PHOTOLABILE COMPOUNDS<br/>[FR] COMPOSES PHOTOLABILES
  申请人：UNIV COLUMBIA

  公开号：WO2010151879A9

  公开（公告）日：2011-03-24