Tandem Synthesis of Novel thiazole-substituted pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one Derivatives and their Theoretical Pharmacokinetic Profiles

Kuzu E., Kuzu B.

Chemistry of Heterocyclic Compounds, cilt.59, sa.1-2, ss.80-87, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 59 Sayı: 1-2
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1007/s10593-023-03165-3
  • Dergi Adı: Chemistry of Heterocyclic Compounds
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica
  • Sayfa Sayıları: ss.80-87
  • Anahtar Kelimeler: pyrrolotriazinones, thiazole, ADMET profile, DFT, tandem synthesis
  • Van Yüzüncü Yıl Üniversitesi Adresli: Evet

Özet

[Figure not available: see fulltext.] In this study, a new tandem method was developed for the synthesis of thiazole-substituted pyrrolo[1,2-d][1,2,4]triazin-4(3H)-one derivatives. The method consists of a tandem reaction involving a subsequent formation of first the thiazole and then the triazine ring upon the addition of phenacyl bromide to a product of the condensation reaction between ethyl 2-formyl-1H-pyrrole- 1-carboxylate and thiosemicarbazide. The tandem cyclization step was completed in just 30 minutes. In order to predict the reaction mechanism, the charge densities of atoms and HOMO and LUMO energy were calculated by DFT method for the compounds obtained in the intermediate stage. In addition, a series of pyrrolotriazinone derivatives synthesized in high yields by this method were found to be suitable drug candidates according to their druglikeness and theoretical pharmacokinetic profiles.