• YAKHAK HOEJI
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• v.41 no.4
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• pp.462-472
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• 1997

In this approach, the antimicrobial activities of the compounds were compared with the ${\beta}$-lactam antibiotics against ${\beta}$-lactamase producing strains in vitro. Heteroc yclyl exomethylenepenam derivatives were several numbers of 6-exomethylenepenam sodiums (CH1240, CH1245, CH1250, CH2140, CH2145, CH2150). The inhibitory concentraion assay of six compounds were compared with clavulanic acid, sulbactam, tazobactam. Clavulanic acid, sulbactam and tazobactam are used as inhibitors of a variety of plasmid-mediated beta-lactamases. In vitro ${\beta}$-lactamase inhibitory assay, CH1240 and CH2140 were more active than clavulanic acid, sulbactam and tazobactam against ${\beta}$-lactamases overally. And in vitro comparative antimicrobial susceptibility test of six inhibitors were performed with mixed forms of ampicillin, cefotaxime, amoxicillin, ticarcillin, piperacillin, cefoperazone against ${\beta}$-lactamase producing 31 species strains. Consequently CH2140 and CH1240 among the six compounds enhanced the activity of the ${\beta}$-lactams for 31 ${\beta}$-lactamase producing strains.

• YAKHAK HOEJI
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• v.51 no.6
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• pp.447-454
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• 2007

The resistance of bacteria against ${\beta}$-lactam antibiotics is mainly caused by the production of ${\beta}$-lactamase enzymes. ${\beta}$-Lactamase inhibitors are used in combination with known antibiotics to overcome the growing problem of bacterial resistance. We prepared 6-(thienylmethylene)penam sulfones for the development of potent ${\beta}$-lactamase inhibitors and evaluated their ${\beta}$-lactamase inhibitory activities.

• 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.

• Journal of the Korean Chemical Society
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• v.49 no.5
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• pp.461-469
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• 2005

• YAKHAK HOEJI
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• v.43 no.6
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• pp.782-788
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• 1999

7-Oxocephalosporanate 1 was treated with phosphonium salts 2~4 by Wittig reaction to afford 7-exomethylene cephalosporanates 5~7. They were oxidized to sulfones 8~10 with mCPBA. Deprotecton of benzhydryl 7-exomethylene cephalosporanate with $AlCl_3$ and NaHCO_3$ gave sodium salts of 7-exomethylene cephalosporanates 11~16. The ${\beta}-lactamase$ inhibitory activity of synthesized compounds 11~16 were compared with sulbactam, tazobactam and clavulanic acid against Type I, II, III, IV and TEM-2 $\beta$-lactamase in vitro. Compound 15 showed more potent activity than sulbactam and clavulanic acid against Type III, IV ${\beta}-lactamase$ enzyme.

• Archives of Pharmacal Research
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• v.22 no.1
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• pp.68-71
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• 1999

The 6,6-dibromopenam (6) was treated with CH3MgBr and carbaldehyde 5 to afford the hydroxy compound 7, which was reacted with acetic anhydride to give acetoxy compound 8. The deacetobromination of 8 with zinc and acetic acid gave 6-exomethylenepenams, E-isomer 10 and Z-isomer 9, which was oxidized to sulfone 11 by m-CPBA. The p-methoxybenzyl compounds were deprotected by AlCl3 and neutralized to give the sodium salts 12, 13, and 14.

• YAKHAK HOEJI
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• v.52 no.4
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• pp.306-310
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• 2008

In vitro ${\beta}-lactamase$ inhibitory activity of 6-benzothiazole penicillins (1, 2, 3 and 4) was compared with clavulanic acid, sulbactam and tazobactam. The inhibitory activity of exomethylene compounds (3 and 4) was stronger than those of non-exomethylene compounds (1 and 2). The sulfide 3 showed stronger inhibitory activity than sulbactam, clavulanic acid andsimilar to tazobactam against ${\beta}-lactamase$ Type I enzymes. The inhibitory activity of 4 was stronger than those of sulbactam, clavulanic acid and tazobactam against Type III and IV enzymes. The in vitro antimicrobial activity of ampicillin or cefoperazone combined with 3 or 4 was stronger than those of ampicillin or cefoperazone alone against many ${\beta}-lactamase$ producing strains to show that compounds 3 and 4 have some synergistic effect. The synergistic activity of 3 and 4 was comparable to sulbactam in some ${\beta}-lactamase$ producing strains, but it was inferior to tazobactam.

• YAKHAK HOEJI
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• v.46 no.6
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• pp.387-391
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• 2002

In vitro $\beta$-lactamase inhibitory activity of 6-exomethylene sulbactam compounds (CH-120, 130, 140, 145, 150, 155) was compared with clavulanic acid, sulbactam and tazobactam. The inhibitory activity of CH-140 was stronger than sulbactam and clavulanic acid against Type II, III, IV, TEM enzymes and stronger than tazobactam against Type IV enzyme. The inhibitory activity of CH-145 was stronger than sulbactam and clavulanic acid against Type I, II, III, IV, TEM enzymes and stronger than tazobactam against Type III, IV enzymes. The in vitro antimicrobial activity of CH-140 and CH-145 combined with piperacillin and ceftriaxone was compared with the sulbactam and tazobactam against $\beta$-lactamase producing 31 strains. But, synergistic activity of CH-140 and CH-145 was inferior to tazobactam.

• YAKHAK HOEJI
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• v.52 no.4
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• pp.311-315
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• 2008

The synthesis of 7-arylidene cephalosporanates for ${\beta}-lactamase$ inhibitor was described. The reactions of substituted benzyl halides $[1]{\sim}[3]$ with triphenylphosphine gave triphenylphcsphonium chlorides $[4]{\sim}[6]$. These phosphonium salts were treated with n-butyllithium to give ylides, which were reated with 7-oxocephalosporanate [7] by Wittig reaction to afford the 7-exomethylene cephalosporanates $[8]{\sim}[10]$. These cephalosporanates were oxidized to cephalosporanate sulfones $[11]{\sim}[13]$ with mCPBA. The deprotection of benzhydryl cephalosporanate $[8]{\sim}[13]$ with $AlCl_3$ and $NaHCO_{3}$ gave sodium salts of 7-arylidene cephalosporanates $[14]{\sim}[19]$.