codeine-6-O-sulfate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: codeine-6-O-sulfate
• 英文别名: C6SU；C6S；[(4R,4aR,7S,7aR,12bS)-9-methoxy-3-methyl-1,2,3,4,4a,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium-7-yl] sulfate
• 化学式: C₁₈H₂₁NO₆S
• 分子量: 379.434
• InChiKey: JIYGLXDCNSTUSY-XSSYPUMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  97.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  可待因 在 吡啶 、 三氧化硫吡啶 作用下， 反应 3.5h， 以36.6%的产率得到codeine-6-O-sulfate
  参考文献：
  名称：

  吗啡衍生物的硫酸酯：合成与表征。

  摘要：

  通过吡啶-SO（3）络合物和硫酸/ N，N'-二环己基碳二亚胺的硫酸盐化反应，合成了十六种吗啡，可待因的3-O-和6-O-硫酸酯及其一些N-甲基季衍生物。基于一维和二维同核和异核测量，为每个合成的化合物给出了完整的（1）H-和（13）C-NMR分配。通过圆二色性和旋光色散对手性进行的比较分析表明，由于水溶液中强氢键的电荷，极性和分子内缔合的变化，光谱特征存在差异。将合成的硫酸酯是缺乏中央副作用潜在周止痛药，并且也作为用于涉及硫酸酯代谢物的各种分析研究参考物质是有用的。

  DOI：

  10.1016/j.ejps.2010.10.007

文献信息

• Sulfate esters of morphine derivatives: Synthesis and characterization
  作者：András Váradi、András Gergely、Szabolcs Béni、Péter Jankovics、Béla Noszál、Sándor Hosztafi

  DOI：10.1016/j.ejps.2010.10.007

  日期：2011.1

  of sulfation with pyridine-SO(3) complex and sulfuric acid/N,N'-dicyclohexylcarbodiimide. Complete (1)H- and (13)C-NMR assignments are given for each of the synthesized compounds based on one- and two-dimensional homo- and heteronuclear measurements. Comparative analysis of chiral properties by circular dichroism and optical rotatory dispersion revealed characteristic differences in the spectra due

  通过吡啶-SO（3）络合物和硫酸/ N，N'-二环己基碳二亚胺的硫酸盐化反应，合成了十六种吗啡，可待因的3-O-和6-O-硫酸酯及其一些N-甲基季衍生物。基于一维和二维同核和异核测量，为每个合成的化合物给出了完整的（1）H-和（13）C-NMR分配。通过圆二色性和旋光色散对手性进行的比较分析表明，由于水溶液中强氢键的电荷，极性和分子内缔合的变化，光谱特征存在差异。将合成的硫酸酯是缺乏中央副作用潜在周止痛药，并且也作为用于涉及硫酸酯代谢物的各种分析研究参考物质是有用的。
• Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners
  作者：Peter A. Crooks、Santosh G. Kottayil、Abeer M. Al-Ghananeem、Stephen R. Byrn、D. Allan Butterfield

  DOI：10.1016/j.bmcl.2006.05.060

  日期：2006.8

  A series of 3-O-acyl-6-O-sulfate esters of morphine, dihydromorphine, N-methylmorphinium iodide, codeine, and dihydrocodeine were prepared and evaluated for their ability to bind to mu-, delta-, kappa(1)-, kappa(2)-, and kappa(3)-opiate receptors. Several compounds exhibited good affinity for the p-opiate receptor. Morphine-3-O-propionyl-6-O-sulfate had four times greater affinity than morphine at the mu-opiate receptor and was the most selective compound at this receptor subtype. (c) 2006 Elsevier Ltd. All rights reserved.
• Comparisons of In Vivo and In Vitro Opioid Effects of Newly Synthesized 14-Methoxycodeine-6-O-sulfate and Codeine-6-O-sulfate
  作者：Ferenc Zádor、Amir Mohammadzadeh、Mihály Balogh、Zoltán S. Zádori、Kornél Király、Szilvia Barsi、Anna Rita Galambos、Szilvia B. László、Barbara Hutka、András Váradi、Sándor Hosztafi、Pál Riba、Sándor Benyhe、Susanna Fürst、Mahmoud Al-Khrasani

  DOI：10.3390/molecules25061370

  日期：——

  The present work represents the in vitro (potency, affinity, efficacy) and in vivo (antinociception, constipation) opioid pharmacology of the novel compound 14-methoxycodeine-6-O-sulfate (14-OMeC6SU), compared to the reference compounds codeine-6-O-sulfate (C6SU), codeine and morphine. Based on in vitro tests (mouse and rat vas deferens, receptor binding and [35S]GTPγS activation assays), 14-OMeC6SU has µ-opioid receptor-mediated activity, displaying higher affinity, potency and efficacy than the parent compounds. In rats, 14-OMeC6SU showed stronger antinociceptive effect in the tail-flick assay than codeine and was equipotent to morphine, whereas C6SU was less efficacious after subcutaneous (s.c.) administration. Following intracerebroventricular injection, 14-OMeC6SU was more potent than morphine. In the Complete Freund’s Adjuvant-induced inflammatory hyperalgesia, 14-OMeC6SU and C6SU in s.c. doses up to 6.1 and 13.2 µmol/kg, respectively, showed peripheral antihyperalgesic effect, because co-administered naloxone methiodide, a peripherally acting opioid receptor antagonist antagonized the measured antihyperalgesia. In addition, s.c. C6SU showed less pronounced inhibitory effect on the gastrointestinal transit than 14-OMeC6SU, codeine and morphine. This study provides first evidence that 14-OMeC6SU is more effective than codeine or C6SU in vitro and in vivo. Furthermore, despite C6SU peripheral antihyperalgesic effects with less gastrointestinal side effects the superiority of 14-OMeC6SU was obvious throughout the present study.

  这项研究代表了新型化合物14-甲氧基可待因-6-O-硫酸酯（14-OMeC6SU）的体外（效力、亲和力、功效）和体内（镇痛、便秘）阿片类药理学，与参考化合物可待因-6-O-硫酸酯（C6SU）、可待因和吗啡进行比较。根据体外实验（小鼠和大鼠输精管、受体结合和[35S]GTPγS激活实验），14-OMeC6SU具有µ-阿片受体介导的活性，显示出比母体化合物更高的亲和力、效力和功效。在大鼠中，14-OMeC6SU在尾巴反射实验中显示出比可待因更强的镇痛效果，并且与吗啡具有相同的效力，而C6SU在皮下给药后的效力较低。经脑室内注射后，14-OMeC6SU比吗啡更有效。在完全弗氏佐剂诱导的炎症性高敏感性实验中，14-OMeC6SU和C6SU在皮下剂量分别为6.1和13.2 µmol/kg时显示出外周抗高敏感性效果，因为共同给予的外周作用阿片受体拮抗剂纳洛酮甲碘化物拮抗了测得的抗高敏感性。此外，皮下给药的C6SU对胃肠道传递的抑制作用较14-OMeC6SU、可待因和吗啡为轻。这项研究首次证明了14-OMeC6SU在体内和体外比可待因或C6SU更有效。此外，尽管C6SU具有外周抗高敏感性作用且胃肠道副作用较轻，但在整个研究中14-OMeC6SU的优越性是显而易见的。