New 2,4-diphenylaminopyrimidinothiophene derivatives: Synthesis, Spectroscopic analysis, X-ray, DFT calculation, ADMET prediction, and biological activity

Abstract

Pyrimidine derivatives have garnered significant attention due to their wide range of biological activities, including anticancer, antimicrobial, and antihypertensive effects. Leveraging the diverse pharmacological potential of pyrimidines, we designed and synthesized a series of novel 2,4-diphenylaminopyrimidinothiophene derivatives. The structures of these target compounds 2a-2h were confirmed using NMR and HRMS techniques, with compound 2 g further characterized by single-crystal X-ray diffraction and FT-IR analysis. Additionally, Density Functional Theory (DFT) calculations for compound 2g were conducted at the B3LYP/6–311++G(d,p) level. Focal adhesion kinase (FAK) inhibitory activity and in vitro antitumor efficacy of compounds 2a-2h against U87-MG cell lines were assessed, revealing that certain compounds exhibited significant antitumor activity. Molecular docking studies indicated that compound 2g effectively occupies the ATP binding site of FAK. Furthermore, the ADMET properties of compounds 2a-2h were predicted, providing valuable insights into their pharmacokinetic profiles. These findings lay a foundation for further exploration of compound 2g as a potential FAK inhibitor.