Naphthannelated azepinones: synthesis and antitumor activity.

5H-Benzo[b]naphth[2,3-e]azepine-6,13-diones 4a, 4b and 4H-naphtho[2,3-e]thieno[3,2-b]azepine-5,12-dione (6) were prepared by aldol condensation of phthalic dialdehyde (3) with the fused azepinediones 2a, 2b and 5, respectively. The Schmidt reaction of naphthacene-5,12-quinone (7) yielded 6H-benzo[e]naphth[2,3-b]azepine-7,12-dione (10). Several derivatives of the heterocyclic basic scaffolds 4, 6 and 10 were prepared by standard procedures, e.g. Grignard reaction, deoxygenation with triethylsilane, and sodium borohydride reduction. Evaluation of the synthesized compounds in the NCI in vitro cell line screening revealed a modest antitumor activity without marked cell line selectivity for the majority of the derivatives. The 2-bromo-5H-benzo[b]naphth[2,3-e]azepin-6(13H)-one (19) was the only representative in this series exhibiting a noteworthy growth inhibitory effect for human tumor cells.