Synthesis and biological properties of 3-phenyl-and 3-phenethyl-5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines

Abstract

The interaction of 3-methyl-3-ethyl-1-amino-2-ethoxycarbonyl-3,4-dihydronaphthaline with phenyl-and phenethylisothiocyanates and subsequent treatment of the reaction mix with alkali led to the formation of the corresponding 3-phenyl-and 3-phenethyl-5-methyl-5-ethyl-4-oxo-2-thioxo-1,2,3,4,5,6-hexahydrobenzo[h]quinazolines (II, III). Condensation of the resulting 2-thioxobenzo[h]quinazolines II and III with halogenides of different structures was used to synthesize 2-sulfanyl-substituted 5-methyl-5-ethyl-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (IV–XXVII). Reaction of benzo[h]quinazoline II with 2-ethanolamine and 3-propanolamine yielded 5-methyl-5-ethyl-3-phenyl-2-(β-hydroxyethylamino)-and 5-methyl-5-ethyl-3-phenyl-2-(γ-hydroxypropylamino)-4-oxo-3,4,5,6-tetrahydrobenzo[h]quinazolines (XXVIII, XXIX) respectively. The effects of the resulting compounds on brain monoamine oxidase (MAO) activity were studied in in vitro experiments. Most of the compounds were found to inhibit 5-HT deamination. The antitumor activities of these compounds were studied using two models of grafted mouse tumors — Ehrlich ascites carcinoma (EAC) and sarcoma 180. Some of the study compounds had moderate therapeutic effects (suppressing tumor growth by 50–60%, p < 0.05).