Source:http://linkedlifedata.com/resource/pubmed/id/11020277
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
20
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| pubmed:dateCreated |
2000-10-24
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| pubmed:abstractText |
Racemic cis-6-(phenylacetamido)carbapenem (21), 2-hydroxycarbonyl-cis-6-(phenylacetamido)carbapenem (22), 2-methoxycarbonyl-cis-6-(phenylacetamido)carbapenem (30), 2-methoxycarbomethyl-cis-6-(phenylacetamido)carbapenem (33), 2-hydroxyethyl-cis-6-(phenylacetamido)carbapenem (34), and 2-acetoxyethyl-cis-6-(phenylacetamido)carbapenem (35) were synthesized. Formation of the carbapenem nuclei in 21, 22, and 30 involved dehydrophosphonation of the corresponding 2-diphenylphosphono-6-(phenylacetamido)carbapenam precursors 14, 15, and 28 using trimethylsilyl triflate and 1,8-diazabicyclo[5.4.0]undec-7-ene in THF. Syntheses of carbapenems 33-35 involved a Wittig reaction of carbapenam 14 with methyl glyoxylate in the presence of lithium 2,2,6,6-tetramethylpiperidine in THF. For the antibacterial activities against Staphylococcus aureus FDA 209P, S. aureus 95, Escherichia coli ATCC 39188, Klebsiellapneumoniae NCTC 418, Pseudomonas aeruginosa 1101-75, and P. aeruginosa 18S-H, carbapenems (+/-)-21, (+/-)-22, (+/-)-30, and (+/-)-33-35 were found comparable with imipenem ((+)-3), yet they were notably more potent than (+)-3 against Xanthomonas maltophilia GN 12873. On the other hand, unlike (+)-3, carbapenems (+/-)-21, (+/-)-22, (+/-)-30, and (+/-)-33-35 were stable to X. maltophilia oxyiminocephalosporinase type II. Their beta-lactamase inhibitory properties, however, were found to be more comparable with those of penicillin G ((+)-4) than to those of imipenem ((+)-3). A combination of imipenem ((+)-3) with (+/-)-21, (+/-)-22, (+/-)-30, and (+/-)-33-35 resulted in synergistic antibacterial activity against X. maltophilia GN 12873. Results from the biological tests were correlated with the distribution of the electron density at C(2)=C(3) of carbapenems upon reaction with transpeptidases or beta-lactamases.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
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| pubmed:issn |
0022-2623
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
5
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| pubmed:volume |
43
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3632-40
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:11020277-Carbapenems,
pubmed-meshheading:11020277-Colony Count, Microbial,
pubmed-meshheading:11020277-Drug Resistance, Microbial,
pubmed-meshheading:11020277-Enzyme Inhibitors,
pubmed-meshheading:11020277-Microbial Sensitivity Tests,
pubmed-meshheading:11020277-Models, Molecular,
pubmed-meshheading:11020277-Stenotrophomonas maltophilia,
pubmed-meshheading:11020277-Stereoisomerism,
pubmed-meshheading:11020277-Structure-Activity Relationship,
pubmed-meshheading:11020277-beta-Lactamases
|
| pubmed:year |
2000
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| pubmed:articleTitle |
Design, synthesis, and SAR of novel carbapenem antibiotics with high stability to Xanthomonas maltophilia oxyiminocephalosporinase type II.
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| pubmed:affiliation |
Institute of Chemistry and Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China. hosein@chem.sinica.edu.tw
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|