CEPHALOSPORINS HAVING A HETEROCYCLIC CATECHOL IN THE C3 SIDE CHAIN II. IMPROVEMENT OF PHARMACOKINETIC PROFILE

7-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxy-(or hydroxy)-iminoacetamido]-3-[propen-l-yl]-cephalosporins having a variety of heterocyclic catechol in 3-position of the propenyl group were synthesized. Among them, 6, 7-dihydroxyisoquinoline derivatives, 2a and 2b, showed very high and prolonged blood lev...

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Published inJournal of antibiotics Vol. 46; no. 5; pp. 850 - 857
Main Authors KAMACHI, HAJIME, HASEGAWA, TOSHIFUMI, KAMEI, HIDEO, IMAE, KIYOTO, OKITA, TAKAAKI, TAMAOKA, MASAMI, MURATA, SHINJI, IIMURA, SEIJI
Format Journal Article
LanguageEnglish
Published Tokyo JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1993
Japan Antibiotics Research Association
Subjects
Animals
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacterial Infections - drug therapy
Biological and medical sciences
Ceftazidime - pharmacology
Cephalosporins - blood
Cephalosporins - chemical synthesis
Cephalosporins - pharmacokinetics
Half-Life
Medical sciences
Mice
Microbial Sensitivity Tests
Pharmacology. Drug treatments
Structure-Activity Relationship
Molecular structure
Intramuscular administration
Optimization
Synthesis
Structure activity relation
Bacteria
Heterocyclic compound
Rodentia
Bioavailability
In vitro
Infection
In vivo
Vertebrata
Antibiotic
Chemotherapy
Cephalosporin derivatives
Mammalia
Sensitivity resistance
Treatment
Mouse
Animal
Bacteriosis
Microorganism culture
Antibacterial agent
Pharmacokinetics
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Summary:7-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxy-(or hydroxy)-iminoacetamido]-3-[propen-l-yl]-cephalosporins having a variety of heterocyclic catechol in 3-position of the propenyl group were synthesized. Among them, 6, 7-dihydroxyisoquinoline derivatives, 2a and 2b, showed very high and prolonged blood levels after intramuscular administration to mice and higher in vivo antibacterial activity than expected from their in vitro activity. The former cephalosporin (2a) gave wellbalanced in vitro and in vivo antibacterial spectra including anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. The latter cephalosporin (2b) also showed good in vitro and in vivo activities against Gram-positive bacteria, especially against S. aureus A15036, a strain of MRSA, the in vivo activity being comparable to vancomycin but was lacking in anti-pseudomonal activity.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:0021-8820
1881-1469
DOI:10.7164/antibiotics.46.850