Design, 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

Abstract

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.