Microwave‐Assisted Synthesis of Trifluoromethylated Amino‐Pyrimidines: Exploring EGFR and HER2 Therapeutic Potential with In Silico Docking

Abstract Microwave‐assisted (MW) synthesis has emerged as a pivotal advancement in synthetic chemistry, offering accelerated reaction rates, higher yields, and improved product purities under milder conditions. In this study, we synthesized a series of trifluoromethylated pyrimidine derivatives using MW‐aided techniques and evaluated their potential as dual inhibitors of EGFR (Epidermal Growth Factor Receptor) and HER2 (Human Epidermal Growth Factor Receptor‐2). Molecular docking studies were conducted to assess the binding affinities and hydrogen bonding interactions of the synthesized compounds with EGFR and HER2. Notably, compounds 6b, 6d, 6e, and 6m demonstrated strong binding affinities with EGFR (−8.2 to −8.5 kcal/mol), while compounds 6b, 6d, 6e, and 6f showed similar affinities with HER2 (−7.5 to −8.3 kcal/mol). These results are comparable to or better than the affinities of known chemotherapy drugs, such as erlotinib, neratinib, and TAK‐285. Our findings indicate that the designed trifluoromethylated pyrimidines have significant potential as multitarget inhibitors, which may lead to the development of more effective therapeutic agents for breast cancer treatment. Further biological evaluations are warranted to explore their full therapeutic potential.