Synthesis of 1,2‐Dihydrofuro[3,4‐d]pyrimidine Derivatives as Potential VEGFR‐2 Inhibitors, and Proposed Mechanism for the 5,6‐Dihydro‐4H‐furo[3,4‐c]pyrrol‐4‐one

Abstract

AbstractThe fourteen novel 1,2‐dihydrofuro[3,4‐d]pyrimidine compounds were synthesized from 4‐(2‐azido‐2‐oxoethyl)furan‐3‐carbonyl azide, by the two selected Curtius rearrangement, nucleophilic addition, and intramolecular cyclization reactions. Molecular docking studies of these compounds were performed with vascular endothelial growth factors receptor‐2 (VEGFR‐2) tyrosine kinase (PDB ID:3WZE). Cytotoxicity studies against human prostate cancer cells (DU145), revealed that compound 8 e has cytotoxic potential. Additionally, in‐silico ADME studies appeared that most of the synthesized compounds obeyed Lipinski's rule. Also, the mechanism for 5,6‐dihydro‐4H‐furo[3,4‐c]pyrrol‐4‐one, which occurs in the reaction of isocyanate 2 with thiols, was proposed. The azide group acts as the leaving group in this reaction.