Clocinnamox | 117332-69-1

• 物质功能分类: 有机原料 - 氨基化合物 - 磺酸类氨基化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: Clocinnamox
• 英文别名: C-CAM；(E)-N-[(4R,4aS,7aR,12bR)-3-(cyclopropylmethyl)-9-hydroxy-7-oxo-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-4a-yl]-3-(4-chlorophenyl)prop-2-enamide
• CAS: 117332-69-1
• 化学式: C₂₉H₂₉ClN₂O₄
• 分子量: 505.013
• InChiKey: RAURUSFBVQLAPW-DNIKMYEQSA-N

物化性质

• 溶解度：
  在 DMSO 中溶解度为 100 mM，在乙醇中溶解度为 25 mM

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-溴丙烯 、 Clocinnamox 在 potassium carbonate 作用下， 以 水 、 丙酮 为溶剂， 反应 60.0h， 以86%的产率得到C-CAM-3-allyl ether
  参考文献：
  名称：

  3-Alkyl Ethers of Clocinnamox:  Delayed Long-Term μ-Antagonists with Variable μ Efficacy

  摘要：

  In recent years there has been considerable interest in the relationship between clocinnamox (C-CAM) and its methyl ether methoclocinnamox (MC-CAM). While C-CAM appears to be an insurmountable mu-antagonist, MC-CAM has been shown to be a potent partial agonist at mu-opioid receptors. To further investigate this relationship we prepared other ethers of C-CAM and evaluated these in opioid receptor binding assays and in vivo in mouse antinociceptive assays and in morphine-dependent monkeys. In opioid binding assays, the ethers were generally mu-selective with affinity equivalent to that of C-CAM itself: Although they displayed little or no efficacy in vitro, some of the ethers showed substantial agonist activity in the in vivo antinociceptive tests. Two of the ethers, the propargyl ether 7 and the cyclopropylmethyl ether 5, were chosen for more detailed analysis in vivo. 7 was shown to have, significant mu-agonist character and was able to substitute for morphine in morphine-dependent monkeys. Interestingly, when this agonist effect abated, 7 displayed long-lasting mu-antagonism. In contrast, 5 displayed little agonist activity in vivo and. was characterized as a potent, long-acting mu antagonist. Although further work is needed to determine whether metabolism is a crucial factor in determining the pharmacological profile of these ethers, it is clear that 3-O-alkylation is a useful means of varying the mu efficacy displayed by this class of acyl-substituted 14-aminomorphinones. MC-CAM itself has generated considerable interest as a potential pharmacotherapy for opiate abuse. These analogues with differing mu efficacy but retaining the long-lasting mu-antagonist effects provide further opportunities for the development of treatment drugs.

  DOI：

  10.1021/jm9810248

文献信息

• ABUSE RESISTANT TRANSDERMAL DELIVERY DEVICES AND COMPOSITIONS COMPRISING AN OPIOID AGONIST AND A NON-TRANSDERMALLY DELIVERED N-OXIDE DERIVATIVE OF AN OPIOID ANTAGONIST FOR THE TREATMENT OF PAIN
  申请人：Euro-Celtique S.A.

  公开号：EP3377048B1

  公开（公告）日：2020-04-22