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

Abstract

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.

Design, synthesis, and biological evaluation of new thalidomide–donepezil hybrids as neuroprotective agents targeting cholinesterases and neuroinflammation

“…Anticholinesterase activity was determined according to Ellman's method 27 modified for 96-well plates as previously described. 19 All solutions were prepared in Tris-HCl buffer (0.02 M, pH 7.5) and stock solutions of the test compounds were prepared in DMSO (50 mM). To 96-well plates were added solutions with the inhibitor compound at 30 μM final concentration.…”

“…Thalidomide is currently successfully used to treat different chronic diseases, including leprosy, multiple myeloma, cancer, Crohn's disease and AIDS, but with severe restrictions and under FDA supervision. 17 However, thalidomide has also been shown to have therapeutic effects on NDs 18,19 due to its ability to modulate several proinflammatory cytokines 20 and also to promote anti-apoptotic and antioxidant effects. 21 Taking into account the anti-inflammatory effects of thalidomide (2), especially related to modulation of TNF-α, and the AChE inhibitory properties of donepezil (1), and based on the MTDL strategy, we designed a new series of potentially active multifunctional ligands (3a-h) by combining the N-benzylpiperazine subunit as a bioisosteric fragment of the N-benzylpiperidine pharmacophore of donepezil and the isoindoline-1,3-dione fragment from the thalidomide structure in a single scaffold (Fig.…”

The Riveting Chemistry of Poly‐aza‐heterocycles Employing Microwave Technique: A Decade Review

“…The microwave exposure for 40 min at 100 °C afforded N ‐protected products 14 a ; whereas increase in time and temperature to 150 °C for 60 min produced deprotected 1,2,4‐triazoles 14 b (Scheme 5). [11] …”

Butyrylcholinesterase - BuChE: A Potential Target for Development of Drugs for Alzheimer's Disease Treatment

“…111 Novos derivados 3-amino-1,2,4-triazóis (52ad, Figura 34), planejados através da hibridação molecular com a donepezila (3) e bioisosterismo não clássico, foram descritos por Santos e colaboradores. 115 Os autores desenvolveram uma nova rota sintética regiosseletiva para obtenção dos derivados e os mesmos foram avaliados quanto sua capacidade inibitória frente as enzimas eeAChE e eqBChE. O amino-triazol 52c (n = 5) foi o mais seletivo para BuChE (CI 50 eeAChE = 11,00 µM e ICI 50 eqBChE = 1,65 µM) demonstrando ser mais potente em eqBChE que o padrão utilizado (donepezila: IC 50 eqBChE = 2,39 µM).…”