Synthesis, physico-chemical properties and penetration activity of alkyl-6-(2,5-dioxopyrrolidin-1-yl)-2-(2-oxopyrrolidin-1-yl)hexanoates as potential transdermal penetration enhancers

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• 作者：Katerina Brychtova ; Josef Jampilek ; Radka Opatrilova ; Ivan Raich ; Oldrich Farsa ; Jozef Csollei
• 关键词：Transdermal penetration enhancers ; ω ; -Lactam derivatives ; 6-Aminohexanoic acid derivatives ; Lipophilicity ; Ab initio/DFT calculations ; 3D structures
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：1 January 2010
• 年：2010
• 卷：18
• 期：1
• 页码：73-79
• 全文大小：310 K

文摘

Skin penetration enhancers are used to allow formulation of transdermal delivery systems for drugs that are otherwise insufficiently skin-permeable. The series of seven esters of substituted 6-aminohexanoic acid as potential transdermal penetration enhancers was formed by multistep synthesis. The synthesis of all newly prepared compounds is presented here. Structure confirmation of all generated compounds was accomplished by ¹H NMR, ¹³C NMR, IR and MS spectroscopy. All the prepared compounds were analyzed using RP-HPLC method for the lipophilicity measurement and their lipophilicity (log k) was determined. Hydrophobicities (log P/C log P) of the studied compounds were also calculated using two commercially available programs and 3D structures of the selected compounds were investigated by means of ab initio/DFT calculations of geometry. All the synthesized esters were tested for their in vitro transdermal penetration enhancer activity. The relationships between the lipophilicity and the chemical structure (SLR) of the studied compounds as well as the relationships between their chemical structure and transdermal penetration activity are mentioned.