Synthesis, characterization, molecular docking and pharmacokinetics of new pyrimidine carboxylate derivatives as potent VEGFR inhibitors
TL;DR
This study shows that the synthesized pyrimidine carboxylates bind effectively with VEGFR active site, demonstrate favourable pharmacokinetic properties and high oral bioavailability.
Abstract
Purpose: To investigate the strategic design and synthesis of three new pyrimidine carboxylate derivatives aimed at inhibiting VEGFR signaling pathways to suppress tumor growth. Methods: A set of 3 new pyrimidine carboxylate derivatives was successfully synthesized via optimized chemical routes. Structural integrity of the synthesized compounds was characterized using advanced spectroscopic techniques, including FT-IR, 1H-NMR, and 13C-NMR. Furthermore, multidimensional in silico investigations were conducted to evaluate therapeutic potential. Results: According to the simulation of molecular docking, the three derivatives demonstrated a high potential for bonding in the vascular endothelial growth factor receptor (VEGFR) active site forming stable complex structures through a series of key hydrogen bond and hydrophobic interactions between important amino acid residues. Additionally, complete ADMET profiling indicated that the three compounds have excellent pharmacokinetic profiles and high oral bioavailability. Conclusion: This study shows that the synthesized pyrimidine carboxylates bind effectively with VEGFR active site, demonstrate favourable pharmacokinetic properties and high oral bioavailability. Keywords: