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

• Main Authors: Bartosz Bieszczad, Damian Garbicz, Damian Trzybiński, Damian Mielecki, Krzysztof Woźniak, Elżbieta Grzesiuk, Adam Mieczkowski
• Format: Article
• Language: English
• Published: MDPI AG 2020-02-01
• Series: Molecules
• Subjects: unsymmetrical dibenzo[<i>b,f</i>][1,5]diazocines; isatoic anhydrides; crystallographic analysis; cytotoxicity; heterocycles
• Online Access: https://www.mdpi.com/1420-3049/25/4/906

A novel approach for the synthesis of unsymmetrically substituted dibenzo[<i>b,f</i>][1,5]diazocine-6,12(5<i>H</i>,11<i>H</i>)diones has been developed. This facile three-step method uses variously substituted 1<i>H</i>-benzo[<i>d</i>][1,3]oxazine-2,4-diones (isatoic anhydrides) and 2-aminobenzoic acids as a starting materials. The obtained products were further transformed into <i>N</i>-alkyl-, <i>N</i>-acetyl- and dithio analogues. Developed procedures allowed the synthesis of unsymmetrical dibenzo[<i>b,f</i>][1,5]diazocine-6,12(5<i>H</i>,11<i>H</i>)diones and three novel heterocyclic scaffolds: benzo[<i>b</i>]naphtho[2,3-<i>f</i>][1,5]diazocine-6,14(5<i>H</i>,13<i>H</i>)dione, pyrido[3,2-<i>c</i>][1,5]benzodiazocine-5,11(6<i>H</i>,12<i>H</i>)-dione and pyrazino[3,2-<i>c</i>][1,5]benzodiazocine-6,12(5<i>H</i>,11<i>H</i>)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[<i>b,f</i>][1,5]diazocine(5<i>H</i>,11<i>H</i>)6,12-dione framework could serve as a privileged structure for the drug design and development.