Design, Synthesis, and Cholinesterase Inhibitory Activity of 4‐Substituted‐6‐(trihalomethyl)‐2‐methylsulfanyl Pyrimidines. Issue 6 (5th February 2021)

• Record Type: Journal Article
• Authors: Da Silva, Andreia M. P. W.; Mittersteiner, Mateus; Da Silva, Fabio M.; D'Avila, Fernanda; Nogara, Pablo A.; Nogara, Karise F.; Rocha, João B. T.; Bonacorso, Helio G.; Martins, Marcos A. P.; Zanatta, Nilo
• Is Part Of: ChemistrySelect. Volume 6:Issue 6(2021)
• Page Start: 1204
• Page End: 1209
• Publication Date: 2021-02-05
• Subjects: Cholinesterase -- Heterocycles -- Nucleophilic substitution -- Pyrimidines -- Trichloromethyl; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202100125
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: A chemoselective approach is reported for the synthesis of 4‐(bromo/chloro)methyl‐2‐methylsulfanyl‐6‐trihalomethyl pyrimidines and subsequent nucleophilic substitution of the halomethyl moiety with aminoalcohols. The final compounds were choline derivatives (bearing a pyrimidine ring). These were tested as AChE and BChE inhibitors, and presented IC50 values in the range of 13.8–81.6 μM. Remarkably, the trichloromethyl pyrimidines were the most active compounds. Docking studies and ADMET properties are also reported. Abstract : Several pyrimidine‐based choline derivatives were prepared aiming the synthesis of novel cholinesterase inhibitors. Remarkably, trichloromethyl pyrimidines were more active, reaching IC50 values in the range of 13.8–34.1 μM for acetylcholinesterase and 25.2–81.6 μM for butyrylcholinesterase.