Di-isobutyryl-apomorphin | 42337-29-1

• 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: Di-isobutyryl-apomorphin
• 英文别名: diisobutyryl apomorphine；10,11-bis-isobutyryloxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline；[6-methyl-11-(2-methylpropanoyloxy)-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-10-yl] 2-methylpropanoate
• CAS: 42337-29-1
• 化学式: C₂₅H₂₉NO₄
• 分子量: 407.51
• InChiKey: VNUZLUGZUNVCTB-UHFFFAOYSA-N

物化性质

• 沸点：
  534.1±50.0 °C(Predicted)
• 密度：
  1.161±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.56
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  55.84
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  apomorphine hydrochloride 在 sodium carbonate 作用下， 以 水 为溶剂， 反应 4.0h， 生成 Di-isobutyryl-apomorphin
  参考文献：
  名称：

  Enhancement of transdermal apomorphine delivery with a diester prodrug strategy

  摘要：

  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.

  DOI：

  10.1016/j.ejpb.2011.01.024

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.