2‐(3‐Iodo‐4‐Methylphenyl)‐4‐(aryl)oxazol‐5(4H)‐one Analogs: Synthesis, Anticancer Screening, SAR, in silico Molecular Docking, and ADMET Studies

Abstract In this study, ten analogues of 2‐(3‐iodo‐4‐methylphenyl)‐4‐(aryl)oxazol‐5(4H)‐one ( 3a‐j ) were synthesized using the Erlenmeyer reaction condition, achieving satisfactory yields of the 5‐oxazolone scaffold. The process involved coupling 3‐iodo‐4‐methylbenzoic acid with tert ‐butyl glycinate to form tert‐butyl (3‐iodo‐4‐methylbenzoyl) glycinate ( 1 ), followed by ester hydrolysis to obtain (3‐iodo‐4‐methylbenzoyl) glycine ( 2 ). Condensation of compound ( 2 ) with various aromatic aldehydes yielded the desired derivatives ( 3a‐j ). The compounds were characterized using various spectroscopic techniques. To evaluate their potential, the anticancer activity of compounds ( 3a‐j ) was assessed against nine panels of different cancer cell lines following the National Cancer Institute (NCI US) protocol at a concentration of 10 −5 M. Growth percentage (GP) and percentage growth inhibition (PGI) were calculated for each compound. Additionally, the new analogues were subjected to molecular docking studies to explore their interactions within the active binding site of 7JKZ and 6YID target protein, aiming to understand their binding modes and the favourable interactions of the active compounds. Furthermore, ADMET predictions revealed that most of the synthesized compounds displayed drug‐like properties with minimal adverse effects and toxicity. These results represent substantial progress in cancer research and offer promising potential for future advancements.