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A novel and efficient route has been developed to afford 5H-dipyridoazepine derivatives from primary amines and 3,3'-(Z)-ethene-1,2-di-ylbis(4-chloropyridine). The procedure based on the double nucleophilic aromatic substitution provides a valuable synthetic tool for the synthesis of dipyridoazepines. The reaction proceeds without catalyst, under microwave irradiation condition. [Projekat Ministarstva nauke Republike Srbije, br. 172008]

A series of new 5H-pyridobenzazepine and pyridobenzothiepine derivatives was synthesized by Pd-catalyzed formation of C-N and C-S bonds. All synthesized compounds were tested for their in vitro antimicrobial activity. The 5H-pyridobenzazepine derivatives showed better antibacterial and antifungal activity than corresponding 5H-dipyridoazepine analogs. Among the synthesized azepines, derivative 8 displayed potent activity against tested bacteria (MIC = 39-78 μg/mL), while azepine 12 showed promising antifungal activity (MIC = 156-313 μg/mL). The synthesized thiepine derivatives exhibited weak antibacterial activity, but showed pronounced antifungal activity. [Projekat Ministarstva nauke Republike Srbije, br. 172008]

Lipophilicity is one of the essential properties influencing drug absorption, excretion and metabolism. It is used for screening viable drug candidates. Chromatographic behavior of thiepino[3,2- c:6,7- c′]dipyridine and 16 benzothiepino[3,2- c]pyridine derivatives as potential antifungal drugs was studied using thin-layer chromatography under typical reversed-phase conditions and two microemulsion chromatographic systems. Seventeen chromatographic and nine in silico lipophilicity measures were estimated. They were compared by classical multivariate approaches: principal component analysis, hierarchical cluster analysis, and ranked and grouped by the non-parametric method-Sum of ranking differences. Two computational and two chromatographic descriptors from the typical reversed-phase conditions using acetone/water mixtures emerged as the best candidates for lipophilicity estimation. The principal component scores related to typical reversed-phase conditions using dioxane/water were ranked as statistically insignificant (the worst). Microemulsion systems were positioned in between, performing worse than in silico estimates. Thiepine derivatives were ranked and grouped by sum of ranking differences, fusing multiple lipophilicity measures. In multicriteria maximization ranking, the compound substituted by phenyl group at position 8 was selected as the most lipophilic one. It is also the most active against Candida albicans. The ranking confirmed that introduction of phenyl core is essential for increasing the lipophilicity of the studied compounds. [ABSTRACT FROM AUTHOR]

A novel series of thiepine derivatives were synthesized and evaluated as potential antimicrobials. All the synthesized compounds were evaluated for their antimicrobial activities in vitro against the fungi Candida albicans ( ATCC 10231), C. parapsilosis (clinical isolate), Gram-negative bacterium Pseudomonas aeruginosa ( ATCC 44752), and Gram-positive bacterium Staphylococcus aureus ( ATCC 25923). Synthesized compounds showed higher antifungal activity than antibacterial activity, indicating that they could be used as selective antimicrobials. Selected thiepines efficiently inhibited Candida hyphae formation, a trait necessary for their pathogenicity. Thiepine 8-phenyl[1]benzothiepino[3,2-c]pyridine ( 16) efficiently killed Candida albicans at 15.6 μg/mL and showed no embryotoxicity at 75 μg/mL. Derivative 8-[4-(4,5-dihydro-1 H-imidazol-2-yl)phenyl][1]benzothiepino[3,2- c]pyridine ( 23) caused significant hemolysis and in vitro DNA interaction. The position of the phenyl ring was essential for the antifungal activity, while the electronic effects of the substituents did not significantly influence activity. Results obtained from in vivo embryotoxicity on zebrafish ( Danio rerio) encourage further structure optimizations. [ABSTRACT FROM AUTHOR]

The synthesis of new 5H-pyridobenzazepine and 5H-dipyridoazepine compounds using as key step a palladium-catalyzed amination-cyclization reaction is reported. By choosing an appropriate combination of ligands and reactants under standardized reaction conditions, N- and S-tricyclic products can be prepared in one step from the appropriate stilbenes. [ABSTRACT FROM AUTHOR]