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- W1974495329 abstract "Flurbiprofen (FLU) lipophilic prodrugs with lipoamino acids (LAA) 6a- e were synthesized for brain delivery. Chemical and plasmatic stability of prodrugs 6a- e as well as pharmacokinetic distribution studies for the prodrugs 6b and 6d were carried out. FLU prodrugs 6a- e were compared to the parent drug for their ability to inhibit binding of [F-18]FDDNP to in vitro formed beta-amyloid protein (Abeta fibrils). FLU-LAA conjugates showed a typical prodrug stability profile, being stable in PBS at pH 7.4 and releasing the active drug in plasma. Compound 6d yielded a slow accumulation of FLU in the brain. In the in vitro inhibition assay, all prodrugs except for the prodrug with the longest alkyl side chain ( 6e) were effective as inhibitors of [F-18]FDDNP binding to Abeta fibrils with EC50 values in the 10-300 nM range. The different brain accumulation kinetics shown by FLU and its LAA conjugate 6d suggested a possible slow-releasing activity of FLU by these prodrugs in the brain or a differential pharmacological effect deserving further, detailed studies on their biodistribution and pharmacological profile." @default.
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- W1974495329 date "2007-12-12" @default.
- W1974495329 modified "2023-09-24" @default.
- W1974495329 title "Flurbiprofen Derivatives in Alzheimer’s Disease: Synthesis, Pharmacokinetic and Biological Assessment of Lipoamino Acid Prodrugs" @default.
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- W1974495329 doi "https://doi.org/10.1021/bc700312y" @default.
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