3-O-triisopropylsilyl-6-β-aminomorphine | 797060-11-8

• 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: 3-O-triisopropylsilyl-6-β-aminomorphine
• CAS: 797060-11-8
• 化学式: C₂₆H₄₀N₂O₂Si
• 分子量: 440.701
• InChiKey: HVZWBHOGMAQEKA-GBGUOAHGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.01
• 重原子数：
  31.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  47.72
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-O-triisopropylsilyl-6-β-aminomorphine 在 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of some 6-arylamidomorphines as analogues of morphine-6-glucuronide

  摘要：

  A series of 6-beta-arylamidomorphines was synthesized and biologically evaluated. Various aryl substituents were introduced into the arylamidomorphines to examine substituent structure-activity relationships. Competition binding assays showed that compounds 10a-h bound to the p opioid receptor with high affinity (0.2-0.6uM). Functional assays showed that compounds 10a-h acted as full a opioid receptor agonists. The ED50 of compound 10e(.)HCl as an analgesic was 12.6 mg/kg in the tail flick latency test in the rat. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.08.019
• 作为产物：
  描述：

  3-O-triisopropylsilyl-6-β-phthalimidomorphine 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.33h， 以94%的产率得到3-O-triisopropylsilyl-6-β-aminomorphine
  参考文献：
  名称：

  Synthesis and biological evaluation of some 6-arylamidomorphines as analogues of morphine-6-glucuronide

  摘要：

  A series of 6-beta-arylamidomorphines was synthesized and biologically evaluated. Various aryl substituents were introduced into the arylamidomorphines to examine substituent structure-activity relationships. Competition binding assays showed that compounds 10a-h bound to the p opioid receptor with high affinity (0.2-0.6uM). Functional assays showed that compounds 10a-h acted as full a opioid receptor agonists. The ED50 of compound 10e(.)HCl as an analgesic was 12.6 mg/kg in the tail flick latency test in the rat. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.08.019

文献信息

• [EN] SYNTHESIS OF METABOLICALLY STABLE ANALGESICS, PAIN MEDICATIONS AND OTHER AGENTS<br/>[FR] SYNTHÈSE D'ANALGÉSIQUES À MÉTABOLISME STABLE, DE MÉDICAMENTS CONTRE LA DOULEUR ET D'AUTRES AGENTS
  申请人：HUMAN BIOMOLECULAR RES INST

  公开号：WO2005117589A1

  公开（公告）日：2005-12-15

  Disclosed are analgesic-related compositions and methods of using the compositions for modulation of analgesic receptor activity. The compositions and methods are useful for reducing pain, as well as for therapeutic intervention of addictions or other diseases or disorders amenable to treatment or prophylaxis by modulation of analgesic receptor signaling.

  揭示了与止痛相关的组合物及使用这些组合物调节止痛受体活性的方法。这些组合物和方法对于减轻疼痛以及治疗成瘾或其他可通过调节止痛受体信号传导进行治疗或预防的疾病或障碍是有用的。
• Synthesis and in vitro biological evaluation of a carbon glycoside analogue of morphine-6-glucuronide
  作者：James M. MacDougall、Xiao-Dong Zhang、Willma E. Polgar、Taline V. Khroyan、Lawrence Toll、John R. Cashman

  DOI：10.1016/j.bmcl.2005.01.072

  日期：2005.3

  Attachment of a glucose moiety to 6-beta-aminomorphine afforded compound 3, where the glucose moiety was linked to the C-6 nitrogen atom by a two-carbon bridge. The synthesis of 3 was accomplished in eight steps from 3-triisopropylsilyl-6-P-aminomorphine and 2,3,4,6-tetra-O-benzyl-D-glucose. The C-glycoside 3 was prepared with the objective of examining a metabolically stable analogue of morphine-6-glucuronide and determining the potency and selectivity of opioid receptor binding. Competition binding assays showed that 3 bound to the mu opioid receptor with a K-i value of 3.5 nM. The C-glycoside 3 exhibited delta/mu and kappa/mu selectivity ratios of 76 and 165, respectively. The synthetic intermediate (i.e., benzyl precursor, compound 11) bound to the mu opioid receptor with a K-i value of 0.5 nM, was less selective for the mu opioid receptor. The [S-35]GTP gamma S assay was used to evaluate the functional properties of compounds 3 and 11. Compound 3 was determined to be a full agonist at the p opioid receptor, whereas compound 11 was found to be a partial agonist. Compound 3 was determined to be very stable in the presence of human liver S9, and rat and monkey liver microsomes: no detectable loss of 3 was observed up to 90 min. Compound 3 was also very stable at pH 2 and pH 7.4, suggesting that 3 possessed properties for sustained duration of action. (c) 2005 Elsevier Ltd. All rights reserved.