A NOVEL ROUTE TO NEW DIBENZO[b,f][1,5]DIAZOCINE DERIVATIVES AS CHEMOSENSITIZERS

Unsymmetrically-Substituted 5,12-dihydrodibenzo[b,f][1,4]diazocine-6,11-dione Scaffold—A Useful Tool for Bioactive Molecules Design

“…The performed single-crystal X-ray structural analysis revealed the structural features of newly synthesized compounds, which supports design and development of new chemical materials or therapeutic agents with given or assumed chemical or biological properties. The investigated method, also allowing the synthesis of novel pentacyclic scaffold, consists of three benzene and two diazocine rings (9a-c), and led to the observation of a new type of rearrangement, contraction of the diazocine ring to the isoindoline ring (10). Although the synthesized compounds, tested on selected cancerous and non-cancerous cell lines, exhibited a rather weak cytotoxic effect, our synthetic methods are useful to design compounds with improved biological activity.…”

“…Contrary to dibenzoazepines, azolobenzodiazepines and their structural analogues, tricyclic heterocyclic scaffolds, possessing two non-polar phenyl rings separated by an eight-membered heterocycle ( Figure 1 ), such as dibenzodiazocines 2 [ 9 ] and 3 , are rarely recognized and considered to be potential privileged structures for design and development of new drugs, despite great structural similarity to their seven-membered heterocyclic analogues. The sparse reports in the literature of application of such molecules include compound 2 (R 1 = R 2 = 2,8-di-OMe, R 3 = R 4 = Bn) developed as a chemosensitizer [ 10 , 11 ] or compound 3 (R 1 = R 2 = R 3 = R 4 = H) developed as a ligand for GABA A R receptors exhibiting anticonvulsant activity [ 12 ].…”

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

“…This situation is caused by the lack of appropriate synthetic routes leading to this type of compounds. A rare example of the application of such heterocyclic scaffolds in the design of compounds exhibiting biological activity involves the use of compound 9 (Figure 2) as a chemosensitizer, abolishing the activity of a glycoprotein (GP 170) located in the cell membrane, and increasing the penetration of the drug into the cell [9,10]. In our continuous research on the development of medicinally relevant compounds possessing the dilactam structure [7,8], we recently focused on the dibenzo[b,f][1,5]diazocine scaffold 10 as a possible framework for the design of biologically active substances.…”

“…This situation is caused by the lack of appropriate synthetic routes leading to this type of compounds. A rare example of the application of such heterocyclic scaffolds in the design of compounds exhibiting biological activity involves the use of compound 9 (Figure 2) as a chemosensitizer, abolishing the activity of a glycoprotein (GP 170) located in the cell membrane, and increasing the penetration of the drug into the cell [9,10].…”

“…These methods, based on the dimerization of two moieties of 2-aminobenzoic acids or their esters, allow for high-yield syntheses of symmetrical dibenzo[b,f][1,5]diazocines but In our continuous research on the development of medicinally relevant compounds possessing the dilactam structure [7,8], we recently focused on the dibenzo[b,f ][1,5]diazocine scaffold 10 as a possible framework for the design of biologically active substances. Our literature survey revealed that symmetrical compounds type 10 (R 1 = R 2 , R 3 = R 4 ) could be obtained in the dimerization reaction of substituted 2-aminobenzoic acids (anthranilic acids) in the presence of phosphorus oxychloride [9] or in the dimerization reaction of alkyl 2-aminobenzoates after treatment with sodium hydride [11]. These methods, based on the dimerization of two moieties of 2-aminobenzoic acids or their esters, allow for high-yield syntheses of symmetrical dibenzo[b,f ][1,5]diazocines but are completely unsuitable for synthesis of more complex and unsymmetrical compounds type 10, possessing various substituents in the aromatic and dilactam rings (R 1 R 2 , R 3 R 4 ).…”