Design, Synthesis, and Antibacterial Studies of 7‐ IMINO‐[ 1,2,4 ] TRIAZOLO[ 1,5‐a ] PYRIMIDINE‐ 6 ‐CARBONITRILE Derivatives With ADMET Profiling, DFT, and Molecular Docking Insights

ABSTRACT A series of novel iminotriazolopyrimidine carbonitrile derivatives was synthesized by reacting 2 ‐(bis(methylthio)methylene) malononitrile with 1H‐1,2,4 ‐triazol‐3‐amine in N, N ‐dimethylformamide (DMF) using anhydrous potassium carbonate as a base. Subsequent reaction with various heteroaryl amines and substituted phenols afforded structurally diverse analogues. The structure of the synthesized compounds was confirmed by IR, EI‐MS, 1 H‐NMR, and 1 3 C‐NMR spectroscopy. Biological potential was evaluated through molecular docking and ADMET profiling. Selected compounds (5b, 5d, 5g, and 5j) underwent density functional theory (DFT) calculations at the RB3LYP/6‐31++G(d,p) level to obtain optimized geometries, thermodynamic parameters, global reactivity descriptors, and HOMO–LUMO energy gap. Bond lengths and angles were also determined. Docking results revealed strong binding affinities for compounds 5j, 5d, 5b, and 5g, while in silico ADMET analysis suggested favorable oral bioavailability and low predicted toxicity. The combination of experimental and computational studies highlights the potential of these triazolopyrimidine derivatives as promising therapeutic agents.