title: 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.
abstract: 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 (1)H NMR, (13)C NMR, IR and MS spectroscopy. All the prepared compounds were analyzed using RP-HPLC method for the lipophilicity measurement and their lipophilicity (logk) was determined. Hydrophobicities (logP/ClogP) 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.
authors: Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic. brychtovak@vfu.cz
authors: Katerina
authors: K
authors: Brychtova
authors: Josef
authors: J
authors: Jampilek
authors: Radka
authors: R
authors: Opatrilova
authors: Ivan
authors: I
authors: Raich
authors: Oldrich
authors: O
authors: Farsa
authors: Jozef
authors: J
authors: Csollei
mesh_terms: D000279:Administration, Cutaneous; D015119:Aminocaproic Acid / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology*; D008055:Lipids / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D010539:Permeability / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine; D013806:Theophylline / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D008055:Lipids; D013806:Theophylline; D015119:Aminocaproic Acid