isopropyl 2-methyl-2-(4-(4-(tributylstannyl)benzoyl)phenoxy)propanoate | 1383569-22-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: isopropyl 2-methyl-2-(4-(4-(tributylstannyl)benzoyl)phenoxy)propanoate
• CAS: 1383569-22-9
• 化学式: C₃₂H₄₈O₄Sn
• 分子量: 615.441
• InChiKey: HZMDONQCIQBDLR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.08
• 重原子数：
  37.0
• 可旋转键数：
  16.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  52.6
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  isopropyl 2-methyl-2-(4-(4-(tributylstannyl)benzoyl)phenoxy)propanoate 在 sodium iodide 、 双氧水 、 sodium hydroxide 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 0.25h， 生成 C₂₀H₂₁⁽¹³¹⁾IO₄
  参考文献：
  名称：

  Radioiodinated dechloro-4-iodofenofibrate: A hydrophobic model drug for molecular imaging studies

  摘要：

  Radiolabeling is a valuable option for tracking drug molecules in biodistribution experiments. In the development of innovative drug delivery systems the influence of the pharmaceutical formulation on the drugs' pharmacokinetics has to be investigated. The hypolipidemic agent fenofibrate is an ideal model drug for testing the performance of drug delivery systems designed for poorly soluble compounds. Herein, we report a de novo synthesis of a fenofibrate derivative, dechloro-4-iodofenofibrate, as well as its conversion into its radioiodinated derivatives containing (125)I or (131)I. The enzymatic stability of the radiolabeled compounds synthesized was determined in vitro. A scintigraphic imaging study supplemented by biodistribution experiments and analysis of excreted metabolites revealed the stability required for in vivo applications and its similarity to fenofibrate. Therefore a convenient method is presented to synthesize radioiodinated derivatives of fenofibrate. These tracers show excellent in vitro and in vivo properties to study the behavior of lipophilic drugs.

  DOI：

  10.1016/j.ijpharm.2012.04.039
• 作为产物：
  描述：

  甲酮,(4-羟基苯基)(4-碘苯基)- 在 bis-triphenylphosphine-palladium(II) chloride 、 magnesium sulfate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 isopropyl 2-methyl-2-(4-(4-(tributylstannyl)benzoyl)phenoxy)propanoate
  参考文献：
  名称：

  Radioiodinated dechloro-4-iodofenofibrate: A hydrophobic model drug for molecular imaging studies

  摘要：

  Radiolabeling is a valuable option for tracking drug molecules in biodistribution experiments. In the development of innovative drug delivery systems the influence of the pharmaceutical formulation on the drugs' pharmacokinetics has to be investigated. The hypolipidemic agent fenofibrate is an ideal model drug for testing the performance of drug delivery systems designed for poorly soluble compounds. Herein, we report a de novo synthesis of a fenofibrate derivative, dechloro-4-iodofenofibrate, as well as its conversion into its radioiodinated derivatives containing (125)I or (131)I. The enzymatic stability of the radiolabeled compounds synthesized was determined in vitro. A scintigraphic imaging study supplemented by biodistribution experiments and analysis of excreted metabolites revealed the stability required for in vivo applications and its similarity to fenofibrate. Therefore a convenient method is presented to synthesize radioiodinated derivatives of fenofibrate. These tracers show excellent in vitro and in vivo properties to study the behavior of lipophilic drugs.

  DOI：

  10.1016/j.ijpharm.2012.04.039

文献信息

• Using in vitro lipolysis and SPECT/CT in vivo imaging to understand oral absorption of fenofibrate from lipid-based drug delivery systems
  作者：Thuy Tran、Peter Bønløkke、Cristina Rodríguez-Rodríguez、Zeynab Nosrati、Pedro Luis Esquinas、Nrupa Borkar、Jakob Plum、Sophie Strindberg、Stoyan Karagiozov、Thomas Rades、Anette Müllertz、Katayoun Saatchi、Urs O. Häfeli

  DOI：10.1016/j.jconrel.2019.11.024

  日期：2020.1

  Using lipid-based drug delivery systems (LbDDS) is an efficient strategy to enhance the low oral bioavailability of poorly water-soluble drugs. Here the oral absorption of fenofibrate (FF) from LbDDS in rats was investigated in pharmacokinetic, in vitro lipolysis, and SPECT/CT in vivo imaging studies. The investigated formulations were soybean oil solution (SBO), a mixture of soybean oil and monoacyl phosphatidylcholine (MAPC) (SBO-MAPC), self-nanoemulsifying drug delivery systems with and without MAPC (SNEDDS-MAPC and SNEDDS, respectively), and an aqueous suspension (SUSP) as a reference. Oral bioavailability of the LbDDS ranged from 27 to 35%. A two-step in vitro lipolysis model simulating rat gastro-intestinal digestion provided in vitro FF solubilisation data to understand oral absorption. During the in vitro lipolysis, most FF was undissolved for SUSP and distributed into the poorly dispersed oil phase for SBO. For the SNEDDS without MAPC, practically all FF solubilised into the aqueous phase during the dispersion and digestion. Adding MAPC to SBO enhanced the dispersion of the oil phase into the digestion media while adding MAPC to SNEDDS resulted in a distribution of 29% of FF into the oil phase at the beginning of in vitro lipolysis. FF distribution into both oil and aqueous phases explained the higher and prolonged oral absorption of LbDDS containing MAPC. To elucidate the relatively low bioavailability of all formulations, FF and triolein were labeled with I-123 and I-125, respectively, to study the biodistribution of drug and lipid excipients in a dual isotope SPECT/CT in vivo imaging study. The concentration of radiolabeled drug as a function of time in the heart correlated to the plasma curves. A significant amount of radiolabeled drug and lipids (i.e., 28-59% and 24-60% of radiolabeled drug and lipids, respectively) was observed in the stomach at 24 h post administration, which can be linked to the low bioavailability of the formulations. The current study for the first time combined in vitro lipolysis and dual isotope in vivo imaging to find the root cause of different fenofibrate absorption profiles from LbDDS and an aqueous suspension.