One-step synthesis, crystallographic studies and antimicrobial activity of new 4-diazopyrazole derivatives

A number of new 4-diazopyrazole derivatives were prepared by the reaction of 1-R-3-methyl-5(R(1)-substituted)benzamidopyrazoles with a sevenfold excess of nitrous acid in acetic medium. The compounds were tested for activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus faecalis, Listeria monocytogenes, Candida albicans, Candida tropicalis and Paecilomyces varioti. The highest microbial susceptibility was shown by Gram-positive bacteria, with minimum inhibitory concentrations (MIG) in the range 0.5-12.5 mu g/mL. For S aureus the R(1) substituents were screened utilizing the Topliss operational scheme. The 4-nitro group was found to be the best substituent. We also tested the compounds 4l,o,p, found to be the most active in the test against S aureus ATCC 25923, on ten clinical S aureus strains, five of which were sensitive and five resistant to methicillin. The above compounds were active in the range 2-8 mu g/mL against methicillin-resistant S aureus strains. An X-ray analysis of compounds 4i and 4q is reported.