morphine-3-hemisuccinate | 37993-25-2

• 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: morphine-3-hemisuccinate
• 英文别名: Morphine 3-hemisuccinate；4-[[(4R,4aR,7S,7aR,12bS)-7-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl]oxy]-4-oxobutanoic acid
• CAS: 37993-25-2
• 化学式: C₂₁H₂₃NO₆
• 分子量: 385.417
• InChiKey: YHUCNUSGZWWORH-FTUYCGPFSA-N

物化性质

• 沸点：
  616.1±55.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  96.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-O-[(4R,4aR,7S,7aR,12bS)-7-hydroxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] 4-O-tert-butyl butanedioate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 morphine-3-hemisuccinate
  参考文献：
  名称：

  Plasma-mediated release of morphine from synthesized prodrugs

  摘要：

  Two morphine prodrugs ('PDA' and 'PDB') were synthesized and the kinetics of esterase-mediated morphine release from these prodrugs were determined when incubated with plasma from different animal species. Morphine was rapidly released from PDA by all species plasma with the maximum reached within 5-10 min; the released morphine was biologically active as determined by an in vitro cAMP assay. The morphine was released from PDB at a slower and species-dependent rate (mouse > rat > guinea pig > human). Morphine's release from PDB appeared to be mediated by carboxyl esterases as the release was inhibited by the carboxyl esterase inhibitor benzil. PDA nor PDB induce cytotoxicity in the neuronal cell lines SK-NSH and SH-SY5Y. The carboxyl and amino functional moieties present on the linker portions of PDA and PDB, respectively, may facilitate their conjugation to nanoparticles to tailor morphine pharmacokinetics and specific targeting. These studies suggest the potential clinical utility of these prodrugs for morphine release at desired rates by administration of their mixture at selected ratios. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.08.098

文献信息

• Radioimmunoassay for quantitative determination of morphine in capsules of Papaver somniferum
  作者：An-Fei Hsu、Dorothy Brower、Ronald B. Etskovitz、Peter K. Chen、Donald D. Bills

  DOI：10.1016/0031-9422(83)80107-1

  日期：1983.1

  Abstract A radioimmunoassay (RIA) procedure for the determination of pmol quantitites of morphine in capsule samples of Papaver somniferum was developed. An antiserum developed against a conjugate of morphine-3-hemisuccinate-BSA was relatively specific for morphine and possessed moderated cross-reactivity with codeine and mild cross-reactivity with thebaine, but none with narceine, papaverine, or noscapine

  摘要 开发了一种用于测定嗜眠罂粟胶囊样品中吗啡 pmol 含量的放射免疫分析 (RIA) 程序。针对吗啡-3-半琥珀酸酯-BSA 缀合物开发的抗血清对吗啡具有相对特异性，并且与可待因具有适度的交叉反应性，与蒂巴因具有轻度交叉反应性，但与那赛因、罂粟碱或那斯卡品均无交叉反应性。标准曲线在 0.01–0.20 ng 范围内呈线性。该测定允许快速、灵敏和精确地测定胶囊样品未纯化水提取物中的吗啡。通过放射免疫测定法测定的水性提取物中吗啡的量通过高效液相色谱法 (HPLC) 进行验证。这两种方法显示出很高的相关系数（r = 0。
• [EN] POLYPEPTIDE-OPIOID CONJUGATES AND USES THEREOF<br/>[FR] CONJUGUÉS POLYPEPTIDES OPIOÏDES ET UTILISATIONS ASSOCIÉES
  申请人：ANGIOCHEM INC

  公开号：WO2013056096A1

  公开（公告）日：2013-04-18

  The invention features polypeptide-opioid conjugates capable of crossing the blood-brain barrier. The polypeptide-opioid conjugates can be used to treat a condition that is modulated by opioid receptors such as pain (e.g., postoperative pain, cancer pain, acute pain, and chronic pain).

  这项发明涉及能够穿越血脑屏障的多肽-阿片类肽共轭物。这些多肽-阿片类肽共轭物可用于治疗受阿片类受体调节的疾病，如疼痛（例如术后疼痛、癌症疼痛、急性疼痛和慢性疼痛）。
• SUSTAINED-RELEASE ANALGESIC COMPOUNDS
  申请人：Control Delivery Systems

  公开号：EP1399161B1

  公开（公告）日：2011-04-20
• Plasma-mediated release of morphine from synthesized prodrugs
  作者：Thommey P. Thomas、Baohua Huang、Ankur Desai、Hong Zong、Xue-min Cheng、Alina Kotlyar、Pascale R. Leroueil、Thomas Dunham、Abraham van der Spek、Brent B. Ward、James R. Baker

  DOI：10.1016/j.bmcl.2010.08.098

  日期：2010.11

  Two morphine prodrugs ('PDA' and 'PDB') were synthesized and the kinetics of esterase-mediated morphine release from these prodrugs were determined when incubated with plasma from different animal species. Morphine was rapidly released from PDA by all species plasma with the maximum reached within 5-10 min; the released morphine was biologically active as determined by an in vitro cAMP assay. The morphine was released from PDB at a slower and species-dependent rate (mouse > rat > guinea pig > human). Morphine's release from PDB appeared to be mediated by carboxyl esterases as the release was inhibited by the carboxyl esterase inhibitor benzil. PDA nor PDB induce cytotoxicity in the neuronal cell lines SK-NSH and SH-SY5Y. The carboxyl and amino functional moieties present on the linker portions of PDA and PDB, respectively, may facilitate their conjugation to nanoparticles to tailor morphine pharmacokinetics and specific targeting. These studies suggest the potential clinical utility of these prodrugs for morphine release at desired rates by administration of their mixture at selected ratios. (C) 2010 Elsevier Ltd. All rights reserved.