The conditions for the C-N bond forming reaction (C-N coupling reaction) between alpha-bromocarboxylate and nitrogen-containing non-aromatic heterocyclic rings under heterogeneous copper(I) oxide catalysis are investigated in this paper. All the generated compounds were fully characterized by IR, NMR and MS spectroscopy. Ab initio/DFT calculations of partial charges on nitrogen atoms in all the discussed heterocycles and on C((2)) of carboxylate under applied conditions were predicted. These in silico results correlate relatively with the experimental observations.

• MeSH
• heterocyklické sloučeniny chemie   MeSH
• hmotnostní spektrometrie MeSH
• katalýza MeSH
• magnetická rezonanční spektroskopie MeSH
• měď chemie   MeSH
• molekulární struktura MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cupric oxide MeSH Prohlížeč
• heterocyklické sloučeniny MeSH
• měď MeSH

PURPOSE: Series of N,N-dimethylamino acid esters was synthesized to study their transdermal permeation-enhancing potency, biodegradability and reversibility of action. Effects of chirality, linking chain length and polyfluorination were investigated. MATERIALS AND METHODS: In vitro activities were evaluated using porcine skin and four model drugs-theophylline, hydrocortisone, adefovir and indomethacin. Biodegradability was determined using porcine esterase, reversibility was measured using electrical resistance. RESULTS: No differences in activity were found between (R), (S) and racemic dodecyl 2-(dimethylamino)propanoate (DDAIP). Substitution of hydrocarbon tail by fluorocarbon one resulted in loss of activity. Replacement of branched linking chain between nitrogen and ester of DDAIP by linear one markedly improved penetration-enhancing activity with optimum in 4-6C acid derivatives. Dodecyl 6-(dimethylamino)hexanoate (DDAK) was more potent than clinically used skin absorption enhancer DDAIP for theophylline (enhancement ratio of DDAK and DDAIP was 17.3 and 5.9, respectively), hydrocortisone (43.2 and 11.5) and adefovir (13.6 and 2.8), while DDAIP was better enhancer for indomethacin (8.7 and 22.8). DDAK was rapidly metabolized by porcine esterase, and displayed low acute toxicity. Electrical resistance of DDAK-treated skin barrier promptly recovered to control values. CONCLUSION: DDAK, highly effective, broad-spectrum, biodegradable and reversible transdermal permeation enhancer, is promising candidate for future research.

• MeSH
• adenin analogy a deriváty   metabolismus   MeSH
• alanin aplikace a dávkování   analogy a deriváty   chemická syntéza   farmakologie   MeSH
• aplikace kožní MeSH
• časové faktory MeSH
• chemie farmaceutická MeSH
• dimethylaminy MeSH
• dodekanol MeSH
• elektrická impedance MeSH
• esterasy metabolismus   MeSH
• halogenace MeSH
• hydrokortison metabolismus   MeSH
• hydrolýza MeSH
• indomethacin metabolismus   MeSH
• isomerie MeSH
• kapronáty aplikace a dávkování   chemická syntéza   farmakologie   MeSH
• kožní absorpce účinky léků   MeSH
• kůže účinky léků   metabolismus   MeSH
• methylaminy aplikace a dávkování   chemická syntéza   farmakologie   MeSH
• molekulární struktura MeSH
• nosiče léků MeSH
• organofosfonáty metabolismus   MeSH
• prasata MeSH
• příprava léků MeSH
• stabilita léku MeSH
• theofylin metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• adefovir MeSH Prohlížeč
• adenin MeSH
• alanin MeSH
• dimethylaminy MeSH
• dodecyl 2-(N,N-dimethylamino)propionate MeSH Prohlížeč
• dodecyl 6-(dimethylamino)hexanoate MeSH Prohlížeč
• dodekanol MeSH
• esterasy MeSH
• hydrokortison MeSH
• indomethacin MeSH
• kapronáty MeSH
• methylaminy MeSH
• nosiče léků MeSH
• organofosfonáty MeSH
• theofylin MeSH