A Facile Synthesis and Chemical Properties of 3,4-Dihydro-2H-1,5,2-benzo[f]dithiazepin-3-ones with Potential Anticancer Activity

The syntheses of 3,4-dihydro-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1dioxides (8-11, 14, 17-20) and corresponding 1,1,5,5-tetraoxides (12, 13) are described.Reactivity of these compounds in their alcoholysis, alkaline hydrolysis and alkylation is also reported.Evaluation performed at the US National Cancer Institute (Bethesda) revealed the in vitro antitumor activity of 7-chloro-3,4dihydro-8-methyl-4-phenyl-2H-1,5,2-benzo[f]dithiazepin-3-one 1,1-dioxide (11).Arylsulfonamides represent a class of drugs with a well-established safety profile. 1 Currently there is intense interest in the discovery and development of novel arylsulfonamides for the treatment of cancer 2 and HIV infections. 3As part of a broad investigation of structures containing 2-mercaptoarylsulfonamide moiety, a series of anticancer compounds 4 and potent inhibitors of HIV-1 integrase was discovered in our laboratories (MBSAs, Figure 1). 5We also found that cyclic sulfonamides of type (A) possess interesting biological properties, particularly as anticancer agents. 6This prompted us to investigate further the chemistry and biological activity of the related heterocyclic system (B) which may be considered "bridged" version of MBSAs (Figure 1).