Design, Synthesis, and Cholinesterase Inhibitory Activity of 4‐Substituted‐6‐(trihalomethyl)‐2‐methylsulfanyl Pyrimidines

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 te...

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Bibliographic Details
Published in:	ChemistrySelect (Weinheim) Vol. 6; no. 6; pp. 1204 - 1209
Main 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
Format:	Journal Article
Language:	English
Published:	10-02-2021
Subjects:	Cholinesterase Heterocycles Nucleophilic substitution Pyrimidines Trichloromethyl
Online Access:	Get full text
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Summary:	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. 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.
ISSN:	2365-6549 2365-6549
DOI:	10.1002/slct.202100125