Open AccessDesign, Synthesis and Anti-inflammatory Activity of Derivatives 10-R-3-Aryl-6,7-dihydro-2H-[1,2,4] triazino[2,3-c]quinazolin-2-ones of Spiro-fused Cyclic Frameworks
Author(s) -
Oleksandra S. Kolomoets,
О. Yu. Voskoboynik,
Oleksii Antypenko,
Г. Г. Берест,
И. С. Носуленко,
В. А. Пальчиков,
Olexandr Karpenko,
С. И. Коваленко
Publication year - 2017
Publication title -
acta chimica slovenica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.289
H-Index - 46
eISSN - 1580-3155
pISSN - 1318-0207
DOI - 10.17344/acsi.2017.3575
Subject(s) - aryl , chemistry , combinatorial chemistry , medicinal chemistry , stereochemistry , organic chemistry , alkyl
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.