14β-amino-7,8-dihydrocodeinone | 87307-35-5

• 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: 14β-amino-7,8-dihydrocodeinone
• 英文别名: (4R,4aS,7aR,12bR)-4a-amino-9-methoxy-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 87307-35-5
• 化学式: C₁₈H₂₂N₂O₃
• 分子量: 314.384
• InChiKey: UJSAHUBHOFQOHO-XFKAJCMBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  14β-amino-7,8-dihydrocodeinone 在 盐酸 、 三溴化硼 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 14β-acetylamino-morphindole
  参考文献：
  名称：

  14-Amino, 14-Alkylamino, and 14-Acylamino Analogs of Oxymorphindole. Differential Effects on Opioid Receptor Binding and Functional Profiles

  摘要：

  The 14-amino analogue of oxymorphindole (OMI) was synthesized and found to possess delta-opioid binding affinity and selectivity similar to OMI. Substitution of the amino group with alkyl, arylalkyl, and acyl groups had relatively little effect on delta-affinity but delta-selectivity was reduced. In functional assays the 14-phenylacetylamino derivative 6d was a selective delta-agonist whereas the phenethylamino analogue 5d was a mu-agonist and low efficacy delta partial agonist that warrants further investigation as an analgesic with low tolerance and dependence.

  DOI：

  10.1021/jm021073r
• 作为产物：
  描述：

  19-(2,2,2-trichloroethoxycarbonyl)-6,14-dihydro-6β,14β-epoxyimininothebaine 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 水 为溶剂， 反应 2.5h， 生成 14β-amino-7,8-dihydrocodeinone
  参考文献：
  名称：

  选择性且耐清洗的荧光二氢可待因酮衍生物可实现 μ-阿片受体二聚化的单分子成像。

  摘要：

  μ-阿片受体 (μ-OR) 在疼痛调节中发挥着关键作用，并介导最强大的镇痛药物的作用。尽管付出了广泛的努力，但人们对μ-ORs如何在活细胞中产生特定作用的了解仍然不够。我们开发了基于 μ-OR 拮抗剂对硝基肉桂酰氨基二氢可待因酮 (CACO) 的新型荧光配体，该配体具有高亲和力、长停留时间和显着的选择性。使用这些配体，我们实现了活细胞表面生理表达水平μ-OR的单分子成像。我们的结果揭示了 μ-OR 扩散的高度异质性，以及相关的固定部分。使用一对不同颜色的荧光配体，我们提供了 μ-OR 相互作用的证据，在质膜上形成短寿命的同型二聚体。这种方法提供了一种在单分子水平上研究μ-OR药理学的新策略。

  DOI：

  10.1002/anie.201912683

文献信息

• 14.beta.-(2-bromoacetamido)morphine and 14.beta.-(2-bromoacetamido)morphinone
  作者：Sydney Archer、Ahmad Seyed-Mozaffari、Peter Osei-Gyimah、Jean M. Bidlack、Leo G. Abood

  DOI：10.1021/jm00366a024

  日期：1983.12

  14 beta-(2-Bromoacetamido)morphine (6) and 14 beta-(2-bromoacetamido)morphinone (9) were prepared preferably from the adduct of thebaine and 1-chloro-1-nitrosocyclohexane, which on reduction in methanol solution gave 14-aminocodeinone (2) and the corresponding ketal (3). When tested in a receptor-binding assay, the IC50 values of 6 and 9 were 15 and 10 nM, respectively. If the incubation time during

  优选从蒂巴因和1-氯-1-亚硝基环己烷的加合物制备14-β-（2-溴乙酰氨基）吗啡（6）和14-β-（2-溴乙酰氨基）吗啡酮（9），将其在甲醇溶液中还原后得到14。 -氨基可待因酮（2）和相应的缩酮（3）。在受体结合试验中测试时，IC50值6和9分别为15和10 nM。如果将测定期间的孵育时间从15分钟增加到30分钟，则观察到两种配体的不可逆结合。
• Structural Determinants of Opioid Activity in Derivatives of 14-Aminomorphinones:  Effect of Substitution in the Aromatic Ring of Cinnamoylaminomorphinones and Codeinones
  作者：Nick P. R. Nieland、Humphrey A. Moynihan、Simon Carrington、Jillian Broadbear、James H. Woods、John R. Traynor、Stephen M. Husbands、John W. Lewis

  DOI：10.1021/jm0604777

  日期：2006.8.1

  In recent years there has been substantial interest in the 14-aminodihydromorphinone derivatives methoclocinnamox (MC-CAM) and clocinnamox (C-CAM). To investigate the importance of the cinnamoyl ring substituent, a series of analogues have been prepared with chloro, methyl, and nitro substituents in the 2' and 4' positions. Despite some discrepancies between the in vitro and in vivo data, a clear SAR could be observed where the 2'-chloro and 2'-methyl ligands consistently displayed higher efficacy than their 4'-substituted analogues. The new series also followed the well-established SAR that 17-methyl ligands have greater efficacy at the A opioid receptor than their 17-cyclopropylmethyl counterparts.
• 14.beta.-[(p-Nitrocinnamoyl)amino]morphinones, 14.beta.-[(p-nitrocinnamoyl)amino]-7,8-dihydromorphinones, and their codeinone analogs: synthesis and receptor activity
  作者：Alice Sebastian、Jean M. Bidlack、Qi Jiang、Darlene Deecher、Milton Teitler、Stanley D. Glick、Sydney Archer

  DOI：10.1021/jm00073a015

  日期：1993.10

  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.
• Synthesis and opioid binding properties of 2-chloroacrylamido derivatives of 7,8-dihydromorphinans
  作者：Ian Hutchinson、Sydney Archer、Kevin P. Hill、Jean M. Bidlack

  DOI：10.1016/s0960-894x(96)00274-0

  日期：1996.7

  14 beta-2-chloroacrylamido-7,8-dihydromorphinones 7 and 8 and the corresponding 6 beta,8-dihydromorphinans 19 and 20 were prepared and the binding affinities to mu, delta and kappa receptors in bovine striatal membranes were determined. Only 20 produced wash-resistant inhibition of m binding despite the fact that it formed adducts with N-acetylcysteine at pH 10 and not at pH 8. Copyright (C) 1996 Elsevier Science Ltd