Synthesis and biological activity of 5-methyl-5-ethyl-4-oxobenzo[h]quinazolines

Abstract

9-Methyl-9-ethyl-8-oxo-2,3,4,5,6,7,9,10-octahydrobenzo[h]azepino[2,l-b]quinazoline was obtained via the interaction between 1-amino-3-methyl-3-ethyl-2-ethoxycarbonyl-3,4-dihydronaphthalene (aminoester) and caprolactam in the presence of phosphorus oxychloride. 5-Methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazoline was synthesized using the reaction of aminoester with formamide under the conditions of the Niementowski reaction. This aminoester reacts with benzoyl isothiocyanate at room temperature with the formation of an N′-benzoylthioureido derivative, which exhibits cyclization in the presence of an alkali, yielding 5-methyl-5-ethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazoline. The latter is converted into 2-substituted 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines by reactions with alkyl-, allyl-, benzyl-and metalylhalogenides, 2-bromoethanol, chloroacetic acid ester, and amides of halogen-substituted acetic acids. The effect of the synthesized compounds on monoamine oxidase (MAO) activity in vitro, and the antitumor properties of some compounds in vivo were evaluated. It is established that most compounds exhibit significant antitumor and anti-MAO activity.