Kolomoets Oleksandra, Voskoboynik Оleksii, Antypenko Oleksii, Berest Galyna, Nosulenko Inna, Palchikov Vitaliy, Karpenko Olexandr, Kovalenko Sergiy
Acta Chim Slov. 2017 Dec;64(4):902-910. doi: 10.17344/acsi.2017.3575.
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.
目前的工作致力于在鲜为人知的3'-R-10'-R1-螺[杂芳基-3(4),6'-[1,2,4]三嗪并[2,3-c]喹唑啉]-2'(7'H)-酮中，有目的地寻找新型有前景的抗炎药。构建了此前未知的[1,2,4]三嗪并[2,3-c]喹唑啉螺稠合衍生物的虚拟组合库，并通过分子对接方法鉴定出有前景的COX-2抑制剂。通过取代的3-(2-氨基苯基)-6-R-1,2,4-三嗪-5(2H)-酮与杂环酮的[5+1]环缩合反应合成了潜在的抗炎药。通过多种物理化学方法对合成化合物的结构进行了验证，并对光谱特征进行了讨论。使用福尔马林诱导的爪肿胀模型对所得化合物的抗炎活性进行了研究，并鉴定出高活性化合物。进行的构效关系分析表明，三嗪并[2,3-c]喹唑啉部分与螺稠合片段的结合是开发新型抗炎药的合理方法。
