Desing, synthesis and anti-inflammatory activity of dirivatives10-R-3-aryl-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones of spiro-fused cyclic frameworks

Acta Chimica Slovenica

Vitaliy Palchikov¹  Oleksii Voskoboynik²  Sergiy Kovalenko²  Galyna Berest²  Oleksandra Kolomoets²  Inna Nosulenko²  Oleksii Antypenko²  Olexandr Karpenko³ 

[1] Dnipropetrovsk National University;Zaporozhye State Medical University;“Enamine Ltd.”;

关键词: 6,7-dihydro-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones;    spiro-fused cycle;    synthesis;    molecular docking;    anti-inflammatory activity;   

DOI  :  10.17344/acsi.2017.3575

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown