diacetylapomorphine | 6191-56-6

• 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: diacetylapomorphine
• 英文别名: Apomorphin-diacetat；Diacetylapomorphin；10,11-diacetoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline；10,11-diacetoxy-6-methyl-aporphane；10,11-Diacetoxy-6-methyl-aporphan；(11-acetyloxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-10-yl) acetate
• CAS: 6191-56-6
• 化学式: C₂₁H₂₁NO₄
• 分子量: 351.402
• InChiKey: PJAGGJPKGNYFJH-UHFFFAOYSA-N

物化性质

• 熔点：
  127-128°
• 比旋光度：
  D24 -88° (c = 1.12 in 0.1N HCl)
• 沸点：
  501.9±50.0 °C(Predicted)
• 密度：
  1.237±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  乙酸酐 、 apomorphine hydrochloride 在 吡啶 作用下， 反应 24.0h， 以88%的产率得到diacetylapomorphine
  参考文献：
  名称：

  New insights into the oxidation pathways of apomorphine

  摘要：

  报道了对阿朴吗啡在水性介质中氧化行为的一项详细研究。通过合成阿朴吗啡衍生物，成功识别了与其儿茶酚和叔胺基团氧化相关的所有阳极氧化峰。这些发现至关重要，因为它们有助于更深入地理解阿朴吗啡的生物相互作用，并揭示其代谢途径。在伏安法研究过程中，还发现阿朴吗啡通过儿茶酚基团与硼酸盐形成复合物，从而提高了其氧化电位。这一特性在稳定阿朴吗啡溶液方面可能非常有用，因为它能大幅减少其自氧化作用。

  DOI：

  10.1039/b204605a

文献信息

• Enhancement of transdermal apomorphine delivery with a diester prodrug strategy
  作者：Kuo-Sheng Liu、K.C. Sung、Saleh A. Al-Suwayeh、Ming-Chuan Ku、Chin-Chen Chu、Jhi-Joung Wang、Jia-You Fang

  DOI：10.1016/j.ejpb.2011.01.024

  日期：2011.8

  Diester prodrugs of apomorphine, diacetyl apomorphine (DAA), and diisobutyryl apomorphine (DIA) were synthesized, and their partition coefficients, capacity factor (log K'), enzymatic hydrolysis, and in vitro permeation across nude mouse skin were characterized. The lipophilicity of the diesters was between that of apomorphine HCl and the apomorphine base. The prodrugs were chemically stable, but enzymatically unstable in esterase medium, skin homogenate, and human plasma. DAA showed a faster hydrolysis in plasma compared to DIA. Total fluxes (nmol/cm(2)/h) of the parent drug and prodrug were significantly greater after topical treatment with the diesters in aqueous solutions (water, 30% polyethylene glycol in water, and 30% glycerol in water) compared to treatment with HCl and base forms of apomorphine. DIA flux from deionized water was 51 nmol/cm(2)/h, which exceeded the flux of apomorphine HCl by 10-fold. The extent of parent drug regeneration after topical application ranged 51-88% and 34-61% for DAA and DIA, respectively, depending on the vehicles selected. Permeation measurements using intact and stratum corneum-stripped skins demonstrated that the viable epidermis/dermis was an important barrier to prodrug permeation. Nano-sized lipid emulsions were also used as carriers for apomorphine and its prodrugs. Diester prodrugs exhibited superior skin permeation compared to the parent drug when formulated into the emulsions. DAA and DIA fluxes from lipid emulsions were 11- and 3-fold higher than that of apomorphine HCl. The results in the present work suggest the feasibility of diester prodrugs for the transdermal delivery of apomorphine. (C) 2011 Elsevier B.V. All rights reserved.
• Tiffeneau; Porcher, Bulletin de la Societe Chimique de France, 1915, vol. <4>17, p. 119
  作者：Tiffeneau、Porcher

  DOI：——

  日期：——
• US9670200B2
  申请人：——

  公开号：US9670200B2

  公开（公告）日：2017-06-06