Substituted 3-R-2,8-Dioxo-7,8-dihydro-2H-pyrrolo[1,2-a][1,2,4] triazino [2,3-c]quinazoline-5a(6H)carboxylic Acids and their Salts-a Promising Class of Anti-inflammatory Agents

Abstract

Abstract: Background: Fragment-based drug design as well as in silico pre-screening of affinity to biological targets are among the most effective methods of medicinal chemistry. Abovementioned approaches were used for purposeful search of anti-inflammatory agents among quinazoline condensed derivatives. Objective: Purposeful synthesis of novel 3-R-2,8-dioxo-7,8-dihydro-2H-pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazoline-5a(6H)carboxylic acids and their salts as promising anti-inflammatory agents, evaluation of their structure by physicochemical methods and establishing of their anti-inflammatory activity. Method: The structures of target compounds were proposed due to principles of fragment-based drug design. The features of the synthesized compounds structures were evaluated by IR-, NMR spectroscopy and chromatography-mass spectrometry and were discussed in detail. Probable molecular mechanisms of activity were predicted due to molecular docking. The anti-inflammatory activity was determined by their ability to reduce the formalin- and carrageenan-induced paw edema in rats.