Synthesis and biological evaluation of 3,6-diaryl-7H-thiazolo[3,2-b] [1,2,4]triazin-7-one derivatives as acetylcholinesterase inhibitors

Abstract

Acetylcholinesterase (AChE) inhibitors played an important role in developing a cure for Alzheimer' s disease. In order to study on the influence of modifications at different groups and side chains on the AChE inhibitory ability and the active sites of 7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives, fourteen 3,6-diaryl-7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives were designed and synthesized. The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control drug. Most of the target compounds exhibited more than 50% inhibition at 10 μM. Some target compounds showed strong inhibition against AChE. The molecular fields analysis and preliminary structure-activity relationships are discussed.

Synthesis, Characterization, and Biological Evaluation of Novel 7-Oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic Acid Derivatives

“…The known approaches for the synthesis of 7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acid derivatives can be divided into two main paths: the construction of the thiazole ring from 1,2,4-triazin-5-one derivatives [15,17] and construction of the 1,2,4-triazine ring from 2-aminothiazole derivatives [18][19][20]. There are several limitations to the second approach such as a scarcity of raw materials, low yields, and several side reactions with less selectivity of the process.…”

Design, synthesis and antibacterial activity of novel 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives

“…The synthesis of the intermediates and the target compounds was accomplished according to the steps depicted in Schemes 1 . The starting material 6-substituted-3-mercapto-1,2,4-triazin-5-ones 1a-1g were synthesized as previously described [ [23] , [24] , [25] ]. Condensation of equimolar amounts of 1a-1g with ethyl 4-chloroacetoacetate in DMF in the presence of base afforded the corresponding S -alkylated derivatives 2a-2g .…”

Design, Synthesis, Biological Evaluation, and Molecular Modeling of Coumarin–Piperazine Derivatives as Acetylcholinesterase Inhibitors

“…) yielded the following insights: The hydrophobicity conferred by aromatic groups in the synthesized coumarin–piperazine molecules indicated the uniform distribution of hydrophobic small fields over the entire surface span; this property is very essential as the lining residues of PAS established interaction with aromatic residues, which may also additionally contribute Π–Π mode of interactions as observed similarly in the docking experiments and it is compatible with high anti‐ h AChE potency. The nitrogen atoms in the piperazine group of the molecules act as positive charge center, a molecular property observed in many potent AChE inhibitors which developed a cloud of positive region at the middle of the aligned dataset conformers. In addition, acetamide linker having H bond tendency owing to its nitrogen and oxygen atoms can line the surface wall of h AChE cavity.…”