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Aminocarbonyloxymethyl esters based on (S)-amino acid carriers were synthesised and evaluated as potential prodrugs of carboxylic acid agents. In addition, the compounds were evaluated as topical prodrugs with the aim of improving the dermal delivery of two non-steroidal anti-inflammatory agents: naproxen and flufenamic acid. The lipophilicities of these(More)
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with several target proteins contributing to its aetiology. Pathological, genetic, biochemical, and modeling studies all point to a critical role of Aβ aggregation in AD. Though there are still many enigmatic aspects of the Aβ cascade, none of the gaps invalidate the hypothesis. The(More)
Aminocarbonyloxymethyl ester prodrugs are known to undergo rearrangement in aqueous solutions to form the corresponding N-acylamine side product via an O-->N intramolecular acyl transfer from the carbamate conjugate base. Novel aminocarbonyloxymethyl esters of diclofenac and flufenamic acid containing amino acid amide carriers were synthesized and evaluated(More)
The synthesis and pharmacological analyses of a number of pyrazolo[3,4-b]quinoline and benzo[b]pyrazolo[4,3-g][1,8]naphthyridine derivatives are reported. We have synthesized the diversely substituted tacrine analogues 1-6, by Friedländer-type reaction of readily available o-amino-1-methyl-pyrazole-dicarbonitriles with cyclohexanone. The biological(More)
Since cyanide potentiates the inhibitory activity of several monoamine oxidase (MAO) inhibitors, a series of carbonitrile-containing aminoheterocycles was examined to explore the role of nitriles in determining the inhibitory activity against MAO. Dicarbonitrile aminofurans were found to be potent, selective inhibitors against MAO A. The origin of the MAO A(More)
The synthesis, molecular modeling, and pharmacological analysis of phenoxyalkylamino-4-phenylnicotinates (2-7), phenoxyalkoxybenzylidenemalononitriles (12, 13), pyridonepezils (14-18), and quinolinodonepezils (19-21) are described. Pyridonepezils 15-18 were found to be selective and moderately potent regarding the inhibition of hAChE, whereas(More)
Purpose. Novel tertiary amidomethyl esters were synthesized and evaluated as potential prodrugs of carboxylic acid agents. Methods. The hydrolyses of the title compounds in buffer solutions and in plasma were studied by UV spectroscopy and HPLC. Results. Amidomethyl esters were hydrolyzed by acid-catalyzed, base-catalyzed and pH-independent pathways. Both(More)
The hydrolysis of tertiary amidomethyl ester prodrugs of carboxylic acids by rat liver homogenates is reported. Amidomethyl esters are rapidly and quantitatively converted to the corresponding acid and secondary amide. Reactivity is inversely dependent upon the molar refractivity and lipophilicity of the ester, as well as with steric bulk in the carboxylic(More)
Six novel urea triazene prodrugs have been synthesized to apply in antibody-directed enzyme prodrug therapy (ADEPT). The chemical and plasmatic stability of l-glutamate triazene prodrugs were evaluated and the chemical reactivity was mainly attributed to an intramolecular catalysis promoted by the neighbouring carboxylate group of the glutamic moiety. These(More)
Purpose. O-(N-alkylamido)methyl esters of penicillin G were studied as a new class of prodrugs. Methods. Their hydrolysis in aqueous buffers containing 20 % (v/v) of acetonitrile was investigated by HPLC. Results. A U-shaped pH-rate profile was seen with a pH-independent process extending from pH ca. 2 to pH ca. 10. This pathway is characterised by kinetic(More)