A novel series of 1,2,3-triazole derivatives containing 1,4-benzothiazin-3-one ring (7a–9a, 7b–9b), (10a–12a, 10b–12b) and (13–15) were synthesized by 1,3-dipolar cycloaddition reactions of azides α-d-galactopyranoside azide F, 2,3,4,6-tetra-O-acetyl-(d)-glucopyranosyl azide G and methyl-N-benzoyl-α-azidoglycinate H with compounds 4–6. Initially, the reactions were conducted under thermal conditions in ethanol. The reaction leads, each time, to the formation of two regioisomers: (Schemes 2, 3) with yields of 17 to 21% for 1,5-disubstituted 1,2,3-triazole-regioisomers (7b–12b) and yields ranging from 61 to 65% for the 1,4-disubstituted regioisomers (7a–12a). In order to report an unequivocal synthesis of the 1,4-regioisomers and confirm the structures of the two regioisomers obtained in thermal conditions (Huisgen reactions), the method click chemistry (Copper-Catalyzed Azide-Alkyne Cycloaddition) has been used. The newly synthesized compounds using cycloaddition reactions were evaluated in vitro for their antibacterial activities against some Gram positive and Gram negative microbial strains. Among the compounds tested, the compound 8a showed excellent antibacterial activities against PA ATCC and Acin ESBL (MIC = 31.2 μg/ml).

This study focuses on synthesizing a new series of isoxazolinyl-1,2,3-triazolyl-[1,4]-benzoxazin-3-one derivatives 5a–5o. The synthesis method involves a double 1,3-dipolar cycloaddition reaction following a “click chemistry” approach, starting from the respective [1,4]-benzoxazin-3-ones. Additionally, the study aims to evaluate the antidiabetic potential of these newly synthesized compounds through in silico methods. This synthesis approach allows for the combination of three heterocyclic components: [1,4]-benzoxazin-3-one, 1,2,3-triazole, and isoxazoline, known for their diverse biological activities. The synthesis procedure involved a two-step process. Firstly, a 1,3-dipolar cycloaddition reaction was performed involving the propargylic moiety linked to the [1,4]-benzoxazin-3-one and the allylic azide. Secondly, a second cycloaddition reaction was conducted using the product from the first step, containing the allylic part and an oxime. The synthesized compounds were thoroughly characterized using spectroscopic methods, including ¹H NMR, ¹³C NMR, DEPT-135, and IR. This molecular docking method revealed a promising antidiabetic potential of the synthesized compounds, particularly against two key diabetes-related enzymes: pancreatic α-amylase, with the two synthetic molecules 5a and 5o showing the highest affinity values of 9.2 and 9.1 kcal/mol, respectively, and intestinal α-glucosidase, with the two synthetic molecules 5n and 5e showing the highest affinity values of −9.9 and −9.6 kcal/mol, respectively. Indeed, the synthesized compounds have shown significant potential as antidiabetic agents, as indicated by molecular docking studies against the enzymes α-amylase and α-glucosidase. Additionally, ADME analyses have revealed that all the synthetic compounds examined in our study demonstrate high intestinal absorption, meet Lipinski’s criteria, and fall within the required range for oral bioavailability, indicating their potential suitability for oral drug development.

In the title compound, C₁₉H₁₉NOS, the thiazin-3-one ring of the 1,4-thiazin-3-one moiety adopts a screw-boat conformation. The dihedral angle between the benzene rings is 31.0 (5)°. An intramolecular C—H...S hydrogen bond forms anS(6) ring motif. In the crystal, C—H...π(ring) contacts form inversion dimers and weak π–π stacking interactions, with a centroid-to-centroid distance of 3.8766 (2) Å, also occur.

The title compound, C₁₉H₁₆ClNO₃S, consists of chlorophenyl methylidene and dihydrobenzothiazine units linked to an acetate moiety, where the thiazine ring adopts a screw-boat conformation. In the crystal, two sets of weak C—H_Ph...O_Dbt (Ph = phenyl and Dbt = dihydrobenzothiazine) hydrogen bonds form layers of molecules parallel to the bc plane. The layers stack along the a-axis direction with intercalation of the ester chains. The crystal studied was a two component twin with a refined BASF of 0.34961 (5). The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H...H (37.5%), H...C/C...H (24.6%) and H...O/O...H (16.7%) interactions. Hydrogen-bonding and van der Waals interactions are the dominant interactions in the crystal packing. Computational chemistry indicates that in the crystal, C—H_Ph...O_Dbt hydrogen bond energies are 38.3 and 30.3 kJ mol⁻¹. Density functional theory (DFT) optimized structures at the B3LYP/ 6–311 G(d,p) level are compared with the experimentally determined molecular structure in the solid state. The HOMO–LUMO behaviour was elucidated to determine the energy gap. Moreover, the antibacterial activity of the title compound has been evaluated against gram-positive and gram-negative bacteria.

In the crystal of the title compound, C₉H₉NOS, the molecules are linked by C—H...O hydrogen bonds to generate bilayers lying parallel to (001).