oxoapomorphine | 18605-40-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: oxoapomorphine
• 英文别名: Apomorphine o-quinone；10-methyl-10-azatetracyclo[7.7.1.02,7.013,17]heptadeca-1(16),2(7),5,8,13(17),14-hexaene-3,4-dione
• CAS: 18605-40-8
• 化学式: C₁₇H₁₃NO₂
• 分子量: 263.296
• InChiKey: DZZIOGKZAPZOCK-UHFFFAOYSA-N

物化性质

• 熔点：
  254-258 °C(Solv: chloroform (67-66-3); hexane (110-54-3))
• 沸点：
  521.4±50.0 °C(Predicted)
• 密度：
  1.337±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  oxoapomorphine 在 potassium diclorochromate 、 溶剂黄146 作用下， 以 水 为溶剂， 生成 1-Methyl-2,3-dihydro-1H-1-aza-phenalene-7,8-dione
  参考文献：
  名称：

  Opposite vascular activity of (R)-apomorphine and its oxidised derivatives. Endothelium-dependent vasoconstriction induced by the auto-oxidation metabolite

  摘要：

  We have synthetised a series of oxidised apomorphine derivatives (orto and para quinones 2-5), in order to analyse their vascular activity. We have performed radioligand binding assays on rat cortical membranes and functional studies on rat aortic rings. Instead the relaxant activity exhibited by (R)-apomorphine, o-quinones 2, 4, show contractile activity dependent on endothelium in rat aortic rings. Compound 2, the main metabolite of (R)-apomorphine auto-oxidation, was the product which showed enhanced contractile activity by a complex mechanism related to activation of Ca(2+) channels through release and/or inhibition of endothelial factors. Moreover, this compound disrupts the endothelial function as shows the lack of response to acetylcholine observed in vessels pretreated with it.

  DOI：

  10.1016/s0223-5234(03)00057-6
• 作为产物：
  描述：

  盐酸去水吗啡 在 sodium hydrogensulfite 、 维生素 C 作用下， 以 水 为溶剂， 反应 3.0h， 生成 oxoapomorphine
  参考文献：
  名称：

  阿朴吗啡在含有抗坏血酸和亚硫酸氢盐的溶液中的稳定性以及抗氧化剂对阿朴吗啡诱导的笼爬和低温的作用

  摘要：

  抗坏血酸（100 mg / ml）和亚硫酸氢钠（0.5和20 mg / ml）在1-3天的室温下可防止盐酸阿扑吗啡盐酸盐的氧化超过10％。在5度的冰箱中冷冻1周可防止盐酸阿扑吗啡在水溶液中的氧化。抗坏血酸和亚硫酸氢钠都不会影响鼠药定型的笼爬或由阿朴吗啡引起的体温过低。

  DOI：

  10.1002/jps.2600690830

文献信息

• Mechanistic analyses of the suppression of amyloid β42 aggregation by apomorphine
  作者：Mizuho Hanaki、Kazuma Murakami、Sumie Katayama、Ken-ichi Akagi、Kazuhiro Irie

  DOI：10.1016/j.bmc.2018.01.028

  日期：2018.5

  His13,14, Gln15, and Lys16 of the Aβ42 monomer. These regions form intermolecular β-sheets in Aβ42 aggregates. Since 3 did not perturb the chemical shift of monomeric Aβ42, we performed aggregation experiments using 1,1,1,3,3,3-hexafluoro-2-propanol-treated Aβ42 to investigate whether 3 associates with Aβ42 oligomers. Compounds 1 and 3 delayed the onset of the oligomer-driven nucleation phase. Despite their

  （R）-Apomorphine（1）具有减少淀粉样β蛋白（Aβ42）（阿尔茨海默氏病（AD）的病原体）的潜力。尽管将Aβ42聚集抑制为1归因于其酚部分的抗氧化作用，但是其在分子水平上的抑制机理仍有待充分阐明。LC-MS和UV分析显示，在孵育过程中1被自动氧化生成不稳定的邻醌形式（2），该形式与Aβ42的Lys 16和28形成了迈克尔加合物。具有邻醌和菲部分的另一种自氧化形式的1（3）抑制了Aβ42的聚集，可与1媲美，而用还原剂三（2-羧乙基）膦处理1降低了其抑制活性。1H-15N SOFAST-HMQC NMR研究表明1与Aβ42单体的Arg5，His13,14，Gln15和Lys16相互作用。这些区域在Aβ42聚集体中形成分子间β-折叠。由于3不会干扰单体Aβ42的化学位移，因此我们使用1,1,1,3,3,3-六氟-2-丙醇处理过的Aβ42进行了聚集实验，以研究3是否与Aβ42低聚物缔合
• Extensive study of the autooxidation products of apomorphine and its pharmacologically active derivatives
  作者：Antal Udvardy、Zsuzsanna Gyulai、Attila Sipos

  DOI：10.1016/j.molstruc.2011.06.041

  日期：2011.9

  The autooxidation phenomenon of apomorphine and the products of this procedure were analytically and pharmacologically studied, however we found that there have been some unclarified details of this filed. Therefore the synthesis and structure of the autooxidation products of three clinically and pharmacologically relevant aporphinoids (apomoprine, N-propyl-norapomorphine and 2-hydroxy-N-propyl-norapomorphine) were thoroughly investigated. The autooxidation of apomorphine achieved at physiological pH resulted two products; one of them is the known tetracyclic, tertiary amino ortho quinone and the hitherto unknown, fluorescent, derivatized phenanthrene-3,4-quinone. Under the same conditions N-propyl congeners resulted only the expected 1,2-dione products. The analytical structure elucidation involved the full H-1 and C-13 NMR assignment, UV and IR characterizations of the four isolated ortho quinone-type products exploiting the possibilities of DFT calculations for geometry optimization. NMR and IR simulations. The phenanthrene-3,4-quinone compound can be relevant in further pharmacological studies of aporphine-related oxidation products due to its potential toxicity and investigated fluorescent character. (C) 2011 Elsevier B.V. All rights reserved.
• Investigation of the inhibitory mechanism of apomorphine against MDM2–p53 interaction
  作者：Hiroyuki Ishiba、Taro Noguchi、Keitou Shu、Hiroaki Ohno、Kaori Honda、Yasumitsu Kondoh、Hiroyuki Osada、Nobutaka Fujii、Shinya Oishi

  DOI：10.1016/j.bmcl.2017.03.082

  日期：2017.6

  Mirror-image screening using D-proteins is a powerful approach to provide mirror-image structures of chiral natural products for drug screening. During the course of our screening study for novel MDM2-p53 interaction inhibitors, we identified that NPD6878 (R-(-)-apomorphine) inhibited both the native L-MDM2-L-p53 interaction and the mirror-image D-MDM2-D-p53 interaction at equipotent doses. In addition, both enantiomers of apomorphine showed potent inhibitory activity against the native MDM2-p53 interaction. In this study, we investigated the inhibitory mechanism of both enantiomers of apomorphine against the MDM2-p53 interaction. Achiral oxoapomorphine, which was converted from chiral apomorphines under aerobic conditions, served as the reactive species to form a covalent bond at Cys77 of MDM2, leading to the inhibitory effect against the binding to p53. (C) 2017 Elsevier Ltd. All rights reserved.
• RAPIDLY DISINTEGRATING FORMULATIONS AND METHODS OF USE
  申请人：Impax Laboratories, Inc.

  公开号：EP3068396B1

  公开（公告）日：2019-05-08
• RAPIDLY DISINTEGRATING FORMULATIONS AND METHODS THEREOF
  申请人：IMPAX LABORATORIES, INC.

  公开号：US20160296463A1

  公开（公告）日：2016-10-13

  The invention relates to a rapidly disintegrating oral dosage form that contains a drug/polymer solid solution and methods of using the oral dosage form.