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Microwave assisted synthesis and AChE inhibition studies of novel thiazolo and thiadiazolo [3,2-a]pyrimidinone fused dihydrofuran compounds

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Abstract

Novel dihydro-5H-furo[2,3-d]thiazolo[3,2-a]pyrimidin-5-ones (3a–r) and 6H-furo[2,3-d][1,3,4]thiadiazolo[3,2-a]pyrimidin-8(7H)-ones (3s–v) were designed and obtained from radical cyclizations between 7-hydroxy-5H-thiazolo[3,2-a]pyrimidin-5-one derivatives (1a–d) and 7-hydroxy-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one (1e) with various alkenes (2a–h) mediated by Mn(OAc)3. Obtained compounds were characterized with 1H NMR, 13C NMR, 19F NMR, FTIR and HRMS techniques. In vitro AChE inhibitory results of these compounds show that compounds (3i–p) are the most active AChEI’s (AChE inhibitor) with IC50 values between 0.15 and 15.16 µM. Also, ligand protein interactions of two most active compounds (3i and 3j) were investigated by molecular docking studies. Furthermore, druglikeness and ADME analyses of 3i–p were performed. All tested compounds showed satisfactory druglike characteristics.

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Acknowledgements

This study was financially supported by the Scientific and Technical Research Council of Turkey (TBAG-112T884). AUI thanks to TUBITAK for doctoral fellowship.

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  1. Department of Chemistry, Faculty of Arts and Sciences, Kocaeli University, 41380 Umuttepe, Kocaeli, Turkey

    Mehmet Yilmaz, Aslı Ustalar Inal & Sait Sari

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Yilmaz, M., Inal, A.U. & Sari, S. Microwave assisted synthesis and AChE inhibition studies of novel thiazolo and thiadiazolo [3,2-a]pyrimidinone fused dihydrofuran compounds. Med Chem Res 32, 957–974 (2023). https://doi.org/10.1007/s00044-023-03044-8

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