Acta Chimica Slovenica (Dec 2017)

Desing, synthesis and anti-inflammatory activity of dirivatives 10-R-3-aryl-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones of spiro-fused cyclic frameworks

  • Oleksandra Kolomoets,
  • Oleksii Voskoboynik,
  • Oleksii Antypenko,
  • Galyna Berest,
  • Inna Nosulenko,
  • Vitaliy Palchikov,
  • Olexandr Karpenko,
  • Sergiy Kovalenko

DOI
https://doi.org/10.17344/acsi.2017.3575
Journal volume & issue
Vol. 64, no. 4
pp. 902 – 910

Abstract

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Present work is devoted to the purposeful search of novel promising anti-inflammatory agents among the insufficiently known 3'-R-10'-R1-spiro[hetaryl-3(4),6'-[1,2,4]triazino[2,3-c]quinazolin]-2'(7'H)-ones. The virtual combinatorial library of previously unknown spiro-condensed derivatives of [1,2,4]triazino[2,3-c]quinazolines was formed and promising COX-2 inhibitors were identified by molecular docking method. Potential anti-inflammatory agents were synthesized by [5+1]-cyclocondensation of substituted 3-(2-aminophenyl)-6-R-1,2,4-triazin-5(2H)-ones with heterocyclic ketones. The structures of synthsized compounds were verified by complex of physicochemical methods and spectral characteristics features were discussed. Obtained compounds were studied for anti-inflammatory activity using formalin induced paw edema model and highly active compounds were identified. Conducted SAR-analysis showed that combination of triazino[2,3-c]quinazoline moiety with spiro-condensed fragments is a reasonable approach for creating novel anti-inflammatory agents.

Keywords