Thienopyrimidine–piperazine hybrids as multifunctional pharmacophores: design, synthesis, and biological evaluation

A series of novel 5,6-dimethylthieno[2,3-d]pyrimidine-piperazine hybrids was rationally designed, synthesized, and evaluated to explore their potential as multifunctional bioactive agents. The target compounds were synthesized via nucleophilic substitution of 4-chloro-5,6-dimethylthieno[2,3-d]pyrimidine with structurally diverse substituted piperazines, affording the desired derivatives in good yields. Structural confirmation was achieved through elemental analysis and comprehensive spectroscopic techniques, which were consistent with the proposed molecular frameworks. Derivatives 4h and 4i showed the most potent antimicrobial activity, while 4f and 4g exhibited superior antioxidant effects. Compounds 4g, 4j, and 4k demonstrated comparatively higher anti-inflammatory activity. Structure–activity relationship (SAR) analysis revealed that electron-withdrawing groups enhance antimicrobial activity, whereas aromatic and electron-rich substituents favor antioxidant and anti-inflammatory responses. Although the activity was lower than that of standard drugs, several compounds displayed meaningful biological potential. These results suggest that the thienopyrimidine–piperazine scaffold is a promising framework for the development of multifunctional therapeutic agents.