Topiroxostat

Triazoles, nitrogen-containing heterocycles, have gained attention for their applications in medicinal chemistry, drug discovery, agrochemicals, and material sciences. In the current study, we synthesized novel derivatives of N-substituted 2-((5-(3-bromophenyl)-4-methyl-4H-1,2,4-triazol-3-yl)thio)-N-phenylpropanamide and conducted a comprehensive investigation using density functional theory (DFT). These novel structural hybrids of 1,2,4-triazole were synthesized through the multi-step chemical modifications of 3-bromobenzoic acid (1). Initially, compound 1 was converted into its methyl-3-bromobenzoate (2) which was then transformed into 3-bromobenzohydrazide (3). The final step involved the cyclization of compound 3, producing its 1,2,4-triazole derivative (4). This intermediate was then coupled with different electrophiles, resulting in the formation of the final derivatives (7a–7c). Additionally, the characterization of these triazole-based compounds (7a, 7b, and 7c) were carried out using techniques such as IR, HNMR, and UV–visible spectroscopy to understand their structural and spectroscopic properties. The DFT study utilized M06/6-311G(d,p) functional to investigate geometrical parameters, HOMO–LUMO energies, natural bond orbital analyses, transition density matrix (TDM), density of states, and nonlinear optical (NLO) properties. The FMO analysis revealed that compound 7c exhibited the lowest band gap value (4.618 eV). Notably, compound 7c exhibited significant linear polarizability (4.195 >  × 10–23) and first and second hyperpolarizabilities (6.317 >  × 10–30, 4.314 × 10–35), signifying its potential for nonlinear optical applications. These NLO characteristics imply that each of our compounds, especially 7c, plays a crucial part in fabricating materials showing promising NLO properties for optoelectronic applications.

In this study, with an aim to develop novel heterocyclic hybrids as potent enzyme inhibitors, we synthesized a series of 10 novel 2‐(4‐(4‐ethyl‐5‐(2‐(substitutedphenyl)‐2‐oxo‐ethylthio)‐4H‐1,2,4‐triazol‐3‐yl)‐phenyl)‐5,6‐dimethyl‐1H‐benzimidazole (5a–5j) derivatives and characterized by 1H‐NMR, 13C‐NMR, and HRMS. These compounds were evaluated for their inhibitory activity against hCA I and hCA II. All the compounds exhibited good hCA I and hCA II inhibitory activities with IC50 values in range of 1.288 μM–3.122 μM. Among all these compounds, compound 5e, with an IC50 value of 1.288 μM is the most active against carbonic hCA I. Compound 5h with an IC50 value of 1.532 μM is the most active against carbonic hCA‐II. Compounds 5a–5j were also evaluated for their cytotoxic effects on the L929 mouse fibroblast (normal) cell line. The compounds were also analyzed for their antioxidant capacity by TAS, FRAP, and DPPH activity. Enzyme inhibition kinetics showed all compounds 5a–5j to inhibit the enzyme by non‐competitive. The most active compound 5e for hCA I and compound 5h for hCA‐II were subjected to molecular docking, which revealed their binding interactions with the enzyme's active site, confirming the experimental findings.