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 (IC₅₀ in µM range) and AChE poorly (IC₅₀≫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.

• HIGHLIGHTS

• Series of oxazole benzylamines were designed and synthesised

• The tested compounds showed binding selectivity for BChE

• Naphthoxazoles were more potent AChE inhibitors

乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）是减轻神经退行性疾病症状的主要靶标。它们的抑制导致升高浓度的神经递质乙酰胆碱，其支持神经细胞之间的通讯。先前已证明反式4 / 5-芳基乙烯基恶唑化合物具有中等的AChE和BChE抑制特性。初步的对接研究表明，延长恶唑分子并添加新的NH基团可使它们更易于结合两种酶的活性位点。因此，由先前合成的反式氨基化合物的布赫瓦尔德-哈特维格胺胺化设计并合成了新的反式氨基-4- / 5-芳基乙烯基恶唑。氯-芳基乙烯基恶唑衍生物。另外，通过有效的光化学电环化反应获得了萘并恶唑苄胺光产物。测试了新型化合物作为AChE和BChE的抑制剂。所有的化合物的乙酰胆碱酯酶上表现出的结合偏好的BChE，特别是对反式-其抑制的BChE有力氨基-4- / 5-arylethenyl -恶唑衍生物（IC ₅₀以μM范围）和乙酰胆碱酯酶差（IC ₅₀ »100μM）。因此，由于所有测试的化合物对结合BChE的选择性，这些化合物可用于胆碱酯酶选择性抑制剂的进一步开发。

• 强调

• 设计合成了恶唑苄胺系列

• 所测试的化合物显示出对BChE的结合选择性

• 萘并恶唑是更有效的AChE抑制剂