METHODS OF SYNTHESIS OF QUINAZOLINES AND THEIR CONDENSED ANALOGUES-POTENTIAL ANTI-INFLAMMATORY AGENTS (REVIEW)

Present review is critical analysis of recently published data devoted to the search of the novel anti-inflammatory agents among substituted and condensed quinazolines. It has been shown that anti-inflammatory activity is typical for various quinazoline-containing compounds including substituted quinazolin-4-ones, quinazolin-4-amines, condensed and spiro-condensed quinazolines. The features of target compounds synthesis were systematized and discussed. It was shown that synthesis of quinazoline-containing anti-inflammatory agents in most of cases based on modification of anthranilic acid derivatives, substituted 2-aminobenzonitriles or isatoic anhydride. Particular attention was paid to the discussion of 2-azaheterylanilines as original initial compounds for synthesis of condensed quinazolines with promising anti-inflammatory activity. The mechanisms of quinazolines biological activity have been presented and discussed as well. It has been shown that described compounds can effect on COX -1, COX-2, LOX-15, NO, PGE2, IL-1b, IL-6, TNF-a and other typical for anti-inflammatory agents' biomolecular targets. For some series of compounds, the structure-biological activity relationships were discussed. The data presented in review substantiates the reasonability of the search of new highly effective and low-toxic drugs with anti-inflammatory activity among quinazoline containing compounds.