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

Yılmaz A. Ş., Kaçan M.

ChemistrySelect, cilt.8, sa.17, 2023 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 8 Sayı: 17
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/slct.202300150
  • Dergi Adı: ChemistrySelect
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier
  • Anahtar Kelimeler: Azide Elimination, Curtius Rearrengement, Lipinski Rule, Protein-Ligand İnteraction, İntramolecular Cyclization
  • Trakya Üniversitesi Adresli: Evet

Özet

The 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.