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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
|
| pubmed:dateCreated |
1989-1-26
|
| pubmed:abstractText |
The synthesis and structure-activity relationships of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-[( Z)-1- propenyl]-3-cephem-4-carboxylic acid (BMY-28232), its 3-alkenyl analogs (6 and 7) and O-substituted derivatives of the oxyimino moiety (10) are described, as well as the oral pharmacokinetics and in vivo activities of the 1-acetoxyethyl ester of BMY-28232 (BMY-28271) and its analogous esters (11). The 3-alkenyl groups were introduced by the Wittig reaction of the ylide (2) prepared from the 3-chloromethyl cephem (1) to afford the Z (main) and E (minor) isomers regarding the 3-side chain. The O-substituted derivatives (10) were prepared by 7-N-acylation of the 7-amino cephem (4a) with the corresponding O-substituted side chain acids (8). The prodrug esters (11) were prepared by esterification of BMY-28232 with an appropriate halide. BMY-28232 was the most active among the 3-alkenyl analogs tested against Gram-negative organisms and much more active than the O-substituted derivatives against Gram-positive bacteria. BMY-28271 showed good oral bioavailability (66%) and good in vivo efficacy in mice against infections of Staphylococcus aureus Smith (PD50, 0.68 mg/kg) and Escherichia coli Juhl (0.54 mg/kg).
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0021-8820
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
41
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
N
|
| pubmed:pagination |
1602-16
|
| pubmed:dateRevised |
2003-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:3198494-Administration, Oral,
pubmed-meshheading:3198494-Animals,
pubmed-meshheading:3198494-Cephalosporins,
pubmed-meshheading:3198494-Esters,
pubmed-meshheading:3198494-Male,
pubmed-meshheading:3198494-Mice,
pubmed-meshheading:3198494-Prodrugs,
pubmed-meshheading:3198494-Structure-Activity Relationship
|
| pubmed:year |
1988
|
| pubmed:articleTitle |
Synthesis and biological activity of a new cephalosporin, BMY-28232 and its prodrug-type esters for oral use.
|
| pubmed:affiliation |
Bristol-Myers Research Institute, Ltd., Tokyo Research Center, Japan.
|
| pubmed:publicationType |
Journal Article
|