Robust approach leading to novel densely functionalized four-cyclic benzo[e]pyrazolo[5′,1′:2,3]pyrimido[4,5-b][1,4]diazepines with antibacterial activity toward resistant strains

• Published in: Journal of the Iranian Chemical Society 2020-07, Vol.17 (7), p.1555-1566
• Main Authors: Sheikhi-Mohammareh, Seddigheh, Mashreghi, Mansour, Shiri, Ali
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Antimicrobial agents; Biochemistry; Chemical reactions; Chemistry; Chemistry and Materials Science; Drug resistance; E coli; Inorganic Chemistry; Klebsiella; NMR spectroscopy; Nucleophiles; Organic Chemistry; Original Paper; Physical Chemistry; Potassium carbonate; Substitutes
• ISSN: 1735-207X; 1735-2428
• DOI: 10.1007/s13738-020-01875-5

A straightforward approach for the regioselective synthesis of various derivatives of benzo[ e ]pyrazolo[5′,1′:2,3]pyrimido[4,5- b ] [1, 4] diazepine as a novel heterocyclic system from the annulation of 6-bromo-7-chloro-3-cyano-2-(ethylthio)-5-methylpyrazolo[1,5- a ]pyrimidine with several 2-amino- N -substituted benzamides as bident nucleophiles in the presence of K 2 CO 3 and DMF has been disclosed. The right regioisomer was elucidated by 2 D-NOESY NMR spectroscopy, as well. Most of the novel synthetic compounds exhibited antimicrobial activity though relatively at high concentrations against multi-drug-resistant Klebsiella pneumoniae and Escherichia coli clinical isolates possessed of strong biofilm formation ability. N -Cyclohexyl-substituted pyrazolopyrimidobenzodiazepine ( 3   h ) as the most potent compound represented 100% growth inhibitory on both types of bacterial strains, which brings promises for further changes to develop potential antimicrobial drugs. Graphical abstract