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

• Published in: Medicinal chemistry research 2023-05, Vol.32 (5), p.957-974
• Main Authors: Yilmaz, Mehmet, Inal, Aslı Ustalar, Sari, Sait
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Inorganic Chemistry; Medicinal Chemistry; Molecular docking; NMR; Nuclear magnetic resonance; Original Research; Pharmacology/Toxicology; Protein interaction
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-023-03044-8

Novel dihydro-5 H -furo[2,3- d ]thiazolo[3,2- a ]pyrimidin-5-ones ( 3a–r ) and 6 H -furo[2,3- d ][1,3,4]thiadiazolo[3,2- a ]pyrimidin-8(7 H )-ones ( 3s–v ) were designed and obtained from radical cyclizations between 7-hydroxy-5 H -thiazolo[3,2- a ]pyrimidin-5-one derivatives ( 1a–d) and 7-hydroxy-5 H -[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 1 H NMR, 13 C NMR, 19 F 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 IC 50 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.