N-(cyclopropylmethyl)-5β-methylnorthebaine | 152660-73-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: N-(cyclopropylmethyl)-5β-methylnorthebaine
• CAS: 152660-73-6
• 化学式: C₂₃H₂₇NO₃
• 分子量: 365.472
• InChiKey: OTPAPAIQPLMQKH-VSDWSMLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.59
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  30.93
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(cyclopropylmethyl)-5β-methylnorthebaine 在 palladium on activated charcoal sodium periodate 、 氢气 、 sodium acetate 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 14.0h， 生成 5β-methyl-14β-<(p-nitrocinnamoyl)amino>-7,8-dihydro-N-(cyclopropylmethyl)norcodeinone
  参考文献：
  名称：

  14.beta.-[(p-Nitrocinnamoyl)amino]morphinones, 14.beta.-[(p-nitrocinnamoyl)amino]-7,8-dihydromorphinones, and their codeinone analogs: synthesis and receptor activity

  摘要：

  A series of 14beta-[(nitrocinnamoyl)amino]codeinones and morphinones, some of which contain a 5beta-Methyl group, were prepared from 14beta-aminocodeinones and 14beta-[N-(cyclopropylmethyl)-amino]norcodeinones. The affinities of the target compounds for the mu, delta, and kappa opioid receptors were determined by radiolabeled binding experiments using bovine brain membranes. An analogous series of 7,8-dihydrocodeinones and morphinones was prepared and assayed in the same systems. The 3-methoxy derivatives 3 and 4 were more selective than the corresponding morphinones for the mu receptor. The 5beta-methylcodeinones 25 and 27 had lower affinity at all receptors than the corresponding morphinones, but the 5beta-methylmorphinones had affinities similar to the morphinones 5 and 6. A similar pattern was observed in the 7,8-dihydro series. Two compounds, 5beta-methyl-14beta-[(p-nitrocinnamoyl)amino]-7,8-dihydromorphinone, 20 (MET-CAMO), and N-(cyclopropylmethyl)-14beta-[(p-nitrocinnamoyl)amino]-7,8-dihydronormorphinone, 22 (N-CPM-MET-CAMO), acted as nonequilibrium ligands in antinociception and membrane binding studies. In mice after icv administration, neither ligand showed any agonist activity but 8-24 h after administration both compounds acted as potent mu antagonists. A Scatchard plot of the effect of N-CPM-MET-CAMO on [H-3]DAMGO ([H-3]D-Ala2, (Me)-Phe4, Gly(ol)5]enkephalin) binding to bovine striatal membranes showed that there was a significant decrease in the B(max) value and a marginal effect on the K(d) value suggesting that the number of binding sites was reduced. When taken together, these results support the view that 20 and 22 bind covalently to the mu receptor. On the other hand, when N-acetylcysteine and 22 were allowed to react in a buffered solution, 22 was recovered unchanged. Under these conditions no Michael reaction was observed.

  DOI：

  10.1021/jm00073a015
• 作为产物：
  描述：

  N-(cyclopropylmethyl)northebaine 、 硫酸二甲酯 在 正丁基锂 作用下， 生成 N-(cyclopropylmethyl)-5β-methylnorthebaine
  参考文献：
  名称：

  14.beta.-[(p-Nitrocinnamoyl)amino]morphinones, 14.beta.-[(p-nitrocinnamoyl)amino]-7,8-dihydromorphinones, and their codeinone analogs: synthesis and receptor activity

  摘要：

  A series of 14beta-[(nitrocinnamoyl)amino]codeinones and morphinones, some of which contain a 5beta-Methyl group, were prepared from 14beta-aminocodeinones and 14beta-[N-(cyclopropylmethyl)-amino]norcodeinones. The affinities of the target compounds for the mu, delta, and kappa opioid receptors were determined by radiolabeled binding experiments using bovine brain membranes. An analogous series of 7,8-dihydrocodeinones and morphinones was prepared and assayed in the same systems. The 3-methoxy derivatives 3 and 4 were more selective than the corresponding morphinones for the mu receptor. The 5beta-methylcodeinones 25 and 27 had lower affinity at all receptors than the corresponding morphinones, but the 5beta-methylmorphinones had affinities similar to the morphinones 5 and 6. A similar pattern was observed in the 7,8-dihydro series. Two compounds, 5beta-methyl-14beta-[(p-nitrocinnamoyl)amino]-7,8-dihydromorphinone, 20 (MET-CAMO), and N-(cyclopropylmethyl)-14beta-[(p-nitrocinnamoyl)amino]-7,8-dihydronormorphinone, 22 (N-CPM-MET-CAMO), acted as nonequilibrium ligands in antinociception and membrane binding studies. In mice after icv administration, neither ligand showed any agonist activity but 8-24 h after administration both compounds acted as potent mu antagonists. A Scatchard plot of the effect of N-CPM-MET-CAMO on [H-3]DAMGO ([H-3]D-Ala2, (Me)-Phe4, Gly(ol)5]enkephalin) binding to bovine striatal membranes showed that there was a significant decrease in the B(max) value and a marginal effect on the K(d) value suggesting that the number of binding sites was reduced. When taken together, these results support the view that 20 and 22 bind covalently to the mu receptor. On the other hand, when N-acetylcysteine and 22 were allowed to react in a buffered solution, 22 was recovered unchanged. Under these conditions no Michael reaction was observed.

  DOI：

  10.1021/jm00073a015