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The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are primary targets in attenuating the symptoms of neurodegenerative diseases. Their inhibition results in elevated concentrations of the neurotransmitter acetylcholine which supports communication among nerve cells. It was previously shown for trans- 4/5-arylethenyloxazole compounds to have moderate AChE and BChE inhibitory properties. A preliminary docking study showed that elongating oxazole molecules and adding a new NH group could make them more prone to bind to the active site of both enzymes. Therefore, new trans- amino-4-/5-arylethenyl-oxazoles were designed and synthesised by the Buchwald-Hartwig amination of a previously synthesised trans- chloro-arylethenyloxazole derivative. Additionally, naphthoxazole benzylamine photoproducts were obtained by efficient photochemical electrocyclization reaction. Novel compounds were tested as inhibitors of both AChE and BChE. All of the compounds exhibited binding preference for BChE over AChE, especially for trans- amino-4-/5-arylethenyl-oxazole derivatives which inhibited BChE potently (IC 50 in µM range) and AChE poorly (IC 50 ≫100 µM). Therefore, due to the selectivity of all of the tested compounds for binding to BChE, these compounds could be applied for further development of cholinesterase selective inhibitors.HIGHLIGHTSSeries of oxazole benzylamines were designed and synthesisedThe tested compounds showed binding selectivity for BChENaphthoxazoles were more potent AChE inhibitors.

This paper describes the results obtained in the study of the photobehaviour of heteroanalogs of stilbene bearing oxazole and pyridine rings at the opposite sides of the ethene moiety. The effect of the positional isomerism of the n -pyridyl group ( n = 2, 3 and 4) on the competitive relaxation processes of the excited states (fluorescence, isomerization and cyclization) was investigated and compared with the behaviour previously reported for the 5-styryloxazole analogue. The group in Zagreb prepared the compounds and followed their photochemistry in preparative conditions while the group in Perugia studied the spectral properties of the trans/cis isomers and the cyclization products and measured the quantum yields of the competitive processes in mild conditions with the main aim to clarify the mechanism of the primary stages after excitation. The photobehaviour revealed an important deactivation effect of the n,π* states introduced by the nitrogen atom. This effect reflects the one reported for styrylpyridines, the analogous compounds with a phenyl instead of an oxazolyl ring. Quantum-mechanical Hyperchem calculations proved to be useful to describe the conformational equilibria and the role of conformers on photoreactivity while more refined DFT calculations on the Z isomers allowed the structure dependent competition between their isomerization/cyclization processes and the possible role of intramolecular H-bonds on the deactivation pathways to be explained. For the compound with n = 4, side processes of hydrogen shift in the primary dihydrophenanthrene-like intermediate and of solvent addition accompanying the photocyclization process were evidenced. [ABSTRACT FROM AUTHOR]

This paper describes the results obtained in the study of the photobehaviour of heteroanalogs of stilbene bearing an oxazole ring. The competitive relaxation processes (fluorescence, isomerization and cyclization) of the excited states of n -styryloxazoles ( n = 2 and 4) were investigated and compared with the behaviour previously reported for n = 5. After preparation of the unknown compound with n = 4 and of its positional isomer with n = 2 (the latter with a new method of synthesis), their photobehaviour was firstly investigated in preparative conditions by NMR analysis to measure the chemical yields of their photoproducts. The study was then continued in mild irradiation conditions to measure the quantum yields of the competitive photoreactions in the primary irradiation steps. The effects of the position of the styryl group at the oxazole ring, the relative abundance of the various conformers and the possible formation of intramolecular H bonds on the deactivation pathways are described. Quantum-mechanical Hyperchem calculations proved to be very useful to describe the conformational equilibria and the role of conformers on photoreactivity while more refined DFT calculations on the Z isomers allowed to explain the structure dependent competition between their isomerization/cyclization processes. The effect of the replacement of the phenyl ring with a second heteroaromatic group of electron donor character was investigated for the 5-(2-(furan-2-yl) ethenyl) oxazole. [ABSTRACT FROM AUTHOR]