• Archives of Pharmacal Research
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• v.21 no.5
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• pp.527-530
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• 1998

The antibacterial activity of novel ${\beta}$-lactamase inhibitors, 6-exomethylene penamsulfones (CH1240, CH2140), has been compared in vivo with that of sulbactam and clavulanic acid against b-lactamase producing strains. In vivo microbiological assessment was used as experimental mouse infection model by gram negative strains. Against Pseudomonas aeruginosa F0013, cefoperazone/CH 1240 was slightly less active than sulbactam. ampicillin/CH 2140 was less effective than sulbactam against escheriachia coli 3457. Especially against Citrobacter diversus 2046E, amoxicillin/CH 2140 was the most potent and amoxicillin/CH 1240 was slightly more active than clavulanic acid. consequently the difference in efficacy between the drug combinations appers to be related to the degree of protection afforded the animals by the b-lactamasse inhibitors. CH1240 and CH2140 are promising new agents and should undergo further investigations.

• Biomolecules & Therapeutics
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• v.14 no.4
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• pp.220-225
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• 2006

Derivatives of penicillanic acid sulfones are known to be irreversible inhibitors of $\beta$-lactamase. Eight 6-tricyclic methylene penicillanic acid sulfones were prepared, and their $\beta$-lactamase inhibitory activities were evaluated against $\beta$-lactamase types I, II, III and IV. Among the tricycles attached to 6-exomethylenepenam sulfones, thiazolobenzimidazole(12a-12b), fluorene(12c), and carbazole(12e), showed inhibitory activity on type I, II and III $\beta$-lactamase. But phenanthrene(12d), and anthracene(12f-12h) derivatives showed little $\beta$-lactamase inhibitory activity. The synergic effects of the selected compound(l2b) in 1:4 combination with piperacillin showed some protection to piperacillin for the resistant strains of E. coli DC2 and P. aeruginosa 1771.

• Archives of Pharmacal Research
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• v.20 no.6
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• pp.647-651
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• 1997

The 6, 6-dibromopenam 6 was treated with $CH_{3}/MgBr$ and carbaldehyde 5 to afford the 6-bromo-6-(1-hydroxy-1-methyl)penicillanate 7, which was reacted with acetic anhybride to give acetoxy compound 8. The deacetobromination of 8 with zinc and acetic acid gave 6-exomethylenpenams, Z-isomer 9 and E-isomer 10, which were oxidized to sulfones 11 and 12 by m-CPBA. The p-methoxybenzyl compounds were deprotected by $AlCl_{3}$ and neutralized to give the sodium salts 13, 14, and 15.