| New ether oxime derivatives of erythromycin A. A structure-activity relationship study. | |
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MedLine Citation:
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PMID: 1827435 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The discovery of roxithromycin is the result of a rational and scientific process, based on the fact that at least one reason for erythromycin A's resorption variability after oral administration was its instability in the gastric juice. This instability is due to the reactivity of the ketone in position 9 in acidic medium and one chemical approach was to mask it by an oxime function. Both stereoisomers of this oxime were isolated. Direct O-alkylation of this oxime allowed access to various ether oxime derivatives and of the latter the E stereoisomers were more interesting than the Z ones. The choice of the nature of the oxime substitution was made according to the lipophilic or hydrophilic character of the aliphatic ether chain and these alterations were mainly carried out by introducing heteroatoms into this chain. These different derivatives were classified in 5 groups according to the chemical nature of the chain: Aliphatic, aromatic and nitrogen-, oxygen- and sulfur-containing chains. Two classes, those containing a nitrogen or an oxygen in the ether side chains, showed differential in vitro/in vivo antibiotic activities, with improved bioavailability. Some preliminary pharmacokinetic data confirmed this improvement and led to the selection of five candidates, from which roxithromycin emerged as the best compound. |
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Authors:
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J C Gasc; S G d'Ambrieres; A Lutz; J F Chantot |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of antibiotics Volume: 44 ISSN: 0021-8820 ISO Abbreviation: J. Antibiot. Publication Date: 1991 Mar |
Date Detail:
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Created Date: 1991-06-12 Completed Date: 1991-06-12 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0151115 Medline TA: J Antibiot (Tokyo) Country: JAPAN |
Other Details:
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Languages: eng Pagination: 313-30 Citation Subset: IM |
Affiliation:
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Centre de Recherches Roussel Uclaf, Romainville, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bacteria / drug effects* Biological Availability Erythromycin / analogs & derivatives*, pharmacokinetics, pharmacology, therapeutic use Magnetic Resonance Spectroscopy Mice Rats Rats, Inbred Strains Roxithromycin / pharmacokinetics, pharmacology*, therapeutic use Specific Pathogen-Free Organisms Staphylococcal Infections / drug therapy* Stereoisomerism Streptococcal Infections / drug therapy* Structure-Activity Relationship |
| Chemical | |
Reg. No./Substance:
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114-07-8/Erythromycin; 80214-83-1/Roxithromycin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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