N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6-tetra-O-acetyl-β-D-glucopyranose

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6-tetra-O-acetyl-β-D-glucopyranose
• 英文别名: RIG200；N-(S-Nitroso-N-acetyl-D,L-penicillamine)-2-amino-2-deoxy-1,3,4,6-tetra-O-acetyl-beta-D-glucopyranose；[(2R,3S,4R,5R,6S)-5-[(2-acetamido-3-methyl-3-nitrososulfanylbutanoyl)amino]-3,4,6-triacetyloxyoxan-2-yl]methyl acetate
• 化学式: C₂₁H₃₁N₃O₁₂S
• 分子量: 549.556
• InChiKey: VISYVRBZWPNIOD-DYZQRANXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  37
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  227
• 氢给体数：
  2
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  N-乙酰基-D-青霉胺 在 盐酸 、 1-cyclohexyl-3-(2-morpholino-ethyl)carbodiimide metho-p-.. 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6-tetra-O-acetyl-β-D-glucopyranose
  参考文献：
  名称：

  Prolonged effect of a novel S-nitrosated glyco-amino acid in endothelium-denuded rat femoral arteries: potential as a slow release nitric oxide donor drug

  摘要：

  我们研究了一种新型的S-亚硝基糖氨RIG200在离体大鼠股动脉中的血管扩张特性，并与母体S-亚硝基硫醇化合物S-亚硝基-N-乙酰半胱氨酸(SNAP)进行了比较。分光光度分析显示，在24°C的克氏液中，RIG200的2.5 m微米溶液的分解速度较慢(半衰期(t₁/₂)=216.2±26.7 分钟)，而SNAP的半衰期(t₁/₂)=37.2±13.8 分钟。此外，SNAP但非RIG200的分解速率显著降低了Cu(I)螯合剂新杯凝血素的速率。我们得出结论，RIG200的相对稳定性部分由于其对抗微量Cu(I)催化的分解。通过NO电极证实了SNAP和RIG200的NO生成。在从成年雄性Wistar大鼠(400–550 克)离体的股动脉中进行了研究RIG200血管扩张作用的实验。将动脉段(7–8 毫米长)进行插管，分离并以恒定流速(0.6 毫升/分钟)的克氏液灌注。血管预先用苯肾上腺素(10.2±0.3 微米)收缩，上游检测到91.8±4 毫米汞柱的压力，由差压传感器测定。将SNAP或RIG200(10 微升;浓度为10⁻⁸–10⁻³ 微米)以剂量注射到内皮完整血管的灌注液中，浓度依赖性的血管扩张反应短暂，可在20分钟内恢复至注射前压力。内皮去除血管中对等剂量SNAP的注射反应也是短暂的，而对浓度大于10⁻⁵ 微米的RIG200的反应则持续。10⁻³ 微米RIG200的反应持续时间超过4小时。由NO清除剂高铁血红蛋白(10 微米)逆转持续的血管扩张，而对NO合酶抑制剂L-精氨酸甲酯无影响，表明显存NO介导的来源。我们推测RIG200长时间效应的可能原因是内皮去除后促进药物在血管壁中的保留。在原位缓慢分解RIG200可释放足够的NO，维持超过4小时的“血管扩张音调”。受损害血管的选择性保留可能对NO靶向递送具有重要的治疗意义，为剥夺内源性NO的区域恢复保护，同时避免不必要的低血压。

  DOI：

  10.1038/sj.bjp.0701557

文献信息

• Prolonged effect of a novel S-nitrosated glyco-amino acid in endothelium-denuded rat femoral arteries: potential as a slow release nitric oxide donor drug
  作者：I. L. Megson、I. R. Greig、G. A. Gray、D. J. Webb、A. R. Butler

  DOI：10.1038/sj.bjp.0701557

  日期：1997.12

  The vasodilator properties of a novel S‐nitrosated glyco‐amino acid (RIG200) were investigated in isolated rat femoral arteries and compared with those of the parent S‐nitrosothiol compound, S‐nitroso‐N‐acetylpenicillamine (SNAP). Spectrophotometric analysis revealed that 2.5 mm solutions of RIG200 decomposed more slowly (half‐life (t1/2)=216.2±26.7 min) than SNAP (t1/2=37.2±13.8 min) in Krebs buffer at 24°C. Furthermore, the rate of decomposition of SNAP, but not of RIG200, was significantly reduced by the Cu(I) chelator, neocuproine. We concluded that the relative stability of RIG200 is due, at least in part, to its resistance to trace Cu(I)‐catalyzed decomposition. Nitric oxide (NO) generation from SNAP and RIG200 was confirmed by use of an NO electrode. Experiments to investigate the vasodilator effects of RIG200 were carried out on isolated femoral arteries taken from adult male Wistar rats (400–550 g). Lengths of artery (7–8 mm long) were cannulated, dissected free and perfused at constant flow rate (0.6 ml min−1) with Krebs buffer. Vessels were precontracted with phenylephrine (10.2±0.3 μm) and developed pressures of 91.8 ± 4 mmHg, detected upstream by a differential pressure transducer. Concentration‐dependent vasodilator responses to bolus injections of SNAP or RIG200 (10 μl; 10−8–10−3 m) made into the perfusate of endothelium‐intact vessels were transient, recovering the pre‐injection pressure in <20 min. Responses to equivalent bolus injections of SNAP in endothelium‐denuded vessels were also transient but those in response to concentrations of RIG200 >10−5 m were sustained. Responses to 10−3 m RIG200 were sustained for periods >4 h. Sustained vasodilatation was reversed by the NO scavenger, ferrohaemoglobin (10 μm) but was unaffected by the NO synthase inhibitor, Nω‐nitro‐L‐arginine methyl ester (200 μm), indicating involvement of NO from a source other than NO synthase. We suggest that a possible explanation for the prolonged effect of RIG200 is retention of the compound by the vascular wall, facilitated by endothelial denudation. Slow decomposition of RIG200 in situ would release sufficient NO to maintain a ‘vasodilator tone’ which persists for more than 4 h. Selective retention by damaged vessels could have important therapeutic implications with regard to targeted delivery of NO, restoring protection to areas deprived of endogenous NO, whilst avoiding unwanted hypotension.

  我们研究了一种新型的S-亚硝基糖氨RIG200在离体大鼠股动脉中的血管扩张特性，并与母体S-亚硝基硫醇化合物S-亚硝基-N-乙酰半胱氨酸(SNAP)进行了比较。分光光度分析显示，在24°C的克氏液中，RIG200的2.5 m微米溶液的分解速度较慢(半衰期(t₁/₂)=216.2±26.7 分钟)，而SNAP的半衰期(t₁/₂)=37.2±13.8 分钟。此外，SNAP但非RIG200的分解速率显著降低了Cu(I)螯合剂新杯凝血素的速率。我们得出结论，RIG200的相对稳定性部分由于其对抗微量Cu(I)催化的分解。通过NO电极证实了SNAP和RIG200的NO生成。在从成年雄性Wistar大鼠(400–550 克)离体的股动脉中进行了研究RIG200血管扩张作用的实验。将动脉段(7–8 毫米长)进行插管，分离并以恒定流速(0.6 毫升/分钟)的克氏液灌注。血管预先用苯肾上腺素(10.2±0.3 微米)收缩，上游检测到91.8±4 毫米汞柱的压力，由差压传感器测定。将SNAP或RIG200(10 微升;浓度为10⁻⁸–10⁻³ 微米)以剂量注射到内皮完整血管的灌注液中，浓度依赖性的血管扩张反应短暂，可在20分钟内恢复至注射前压力。内皮去除血管中对等剂量SNAP的注射反应也是短暂的，而对浓度大于10⁻⁵ 微米的RIG200的反应则持续。10⁻³ 微米RIG200的反应持续时间超过4小时。由NO清除剂高铁血红蛋白(10 微米)逆转持续的血管扩张，而对NO合酶抑制剂L-精氨酸甲酯无影响，表明显存NO介导的来源。我们推测RIG200长时间效应的可能原因是内皮去除后促进药物在血管壁中的保留。在原位缓慢分解RIG200可释放足够的NO，维持超过4小时的“血管扩张音调”。受损害血管的选择性保留可能对NO靶向递送具有重要的治疗意义，为剥夺内源性NO的区域恢复保护，同时避免不必要的低血压。