Regioselective microwave synthesis and derivatization of 1,5-diaryl-3-amino-1,2,4-triazoles and a study of their cholinesterase inhibition properties

• Published in: RSC advances Vol. 9; no. 35; pp. 2356 - 2369
• Main Authors: Santos, Sabrina Neves, Alves de Souza, Gabriela, Pereira, Thiago Moreira, Franco, Daiana Portella, de Nigris Del Cistia, Catarina, Sant'Anna, Carlos Mauricio R, Lacerda, Renata Barbosa, Kümmerle, Arthur Eugen
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 01.07.2019; The Royal Society of Chemistry
• Subjects: Biological activity; Chemistry; Cholinesterase; Organic chemistry; Regioselectivity; Synthesis; Triazoles
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/c9ra04105b

Herein we describe the development of an efficient one-pot regioselective synthesis protocol to obtain N -protected or N -deprotected 1,5-diaryl-3-amino-1,2,4-triazoles from N -acyl- N -Boc-carbamidothioates. This improved protocol using microwave irradiation and low reaction times (up to 1 h) furnished desired compounds in yields ranging from 50 to 84%. This chemistry is useful for a variety of aromatic groups with electronically diverse substituents. The design and correct derivation of the amino group led to compounds able to inhibit cholinesterases with good IC 50 of up to 1 μM. Also, the mode of action (mixed-type) and SAR analysis for this series of compounds was described by means of kinetic and molecular modelling evaluations, showing potential for this class of compounds as new scaffolds for this biological activity. Regioselective microwave synthesis of N -protected and N -deprotected 1,5-diaryl-3-amino-1,2,4-triazoles in up to 1 h. Derivatizations furnish new scaffolds for cholinesterase mixed-type inhibition.