Unsymmetrically Substituted Dibenzo[ b,f ][1,5]-diazocine-6,12(5 H ,11 H )dione-A Convenient Scaffold for Bioactive Molecule Design.

A novel approach for the synthesis of unsymmetrically substituted dibenzo[ b,f ][1,5]diazocine-6,12(5 H ,11 H )diones has been developed. This facile three-step method uses variously substituted 1 H -benzo[ d ][1,3]oxazine-2,4-diones (isatoic anhydrides) and 2-aminobenzoic acids as a starting materials. The obtained products were further transformed into N -alkyl-, N -acetyl- and dithio analogues. Developed procedures allowed the synthesis of unsymmetrical dibenzo[ b,f ][1,5]diazocine-6,12(5 H ,11 H )diones and three novel heterocyclic scaffolds: benzo[ b ]naphtho[2,3- f ][1,5]diazocine-6,14(5 H ,13 H )dione, pyrido[3,2- c ][1,5]benzodiazocine-5,11(6 H ,12 H )-dione and pyrazino[3,2- c ][1,5]benzodiazocine-6,12(5 H ,11 H )dione. For 11 of the compounds crystal structures were obtained. The preliminary cytotoxic effect against two cancer (HeLa, U87) and two normal lines (HEK293, EUFA30) as well as antibacterial activity were determined. The obtained dibenzo[ b,f ][1,5]diazocine(5 H ,11 H )6,12-dione framework could serve as a privileged structure for the drug design and development.
Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.