Antibacterials. Synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 2. The 'A' group
| العنوان: | Antibacterials. Synthesis and structure-activity studies of 3-aryl-2-oxooxazolidines. 2. The 'A' group |
|---|---|
| المؤلفون: | D. C. Eustice, Chia-Lin J. Wang, P. T. Bartholomew, M. Forbes, David R. Brittelli, Andrew M. Slee, M. A. Wuonola, R. J. Mcripley, W. A. Gregory, V. S. Eberly |
| المصدر: | Journal of Medicinal Chemistry. 33:2569-2578 |
| بيانات النشر: | American Chemical Society (ACS), 1990. |
| سنة النشر: | 1990 |
| مصطلحات موضوعية: | chemistry.chemical_classification, Staphylococcus aureus, Ketone, Chemical Phenomena, Stereochemistry, medicine.drug_class, Aryl, Substituent, Carboxamide, Microbial Sensitivity Tests, Electrophilic aromatic substitution, Anti-Bacterial Agents, Chemistry, Structure-Activity Relationship, chemistry.chemical_compound, Ketyl, chemistry, Drug Discovery, Enterococcus faecalis, medicine, Molecular Medicine, Oxazoles, Alkyl, Antibacterial agent |
| الوصف: | The synthesis and structure-activity relationship (SAR) studies of the effect of varying the "A" group in a series of 5-(acetamidomethyl)oxazolidonone antibacterials (2) are described. Compounds 2 were principally prepared either by the six-step synthesis described previously (J. Med. Chem. 1989, 32, 1673) or by elaboration of the synthetic intermediate 2 (A = H) via electrophilic aromatic substitution or elaboration of the intermediate 2 (A = I) by transition metal catalyzed carbon-carbon bond-forming reactions. Antibacterial evaluation of compounds 2 with A = alkyl, ethenyl, ethynyl, hydroxyalkyl, aldo and keto, oximinoakyl, carboalkoxy, nitro, amino, halo and psi-halo, alkylthio, alkylsulfinyl, and alkysulfonyl against Staphylococcus aureus and Enterococcus faecalis led to the identification of several SAR trends. In several series of homologues (alkyl, ketyl, aximinoalkyl, amino, halo and psi-halo, and alkythio), antibacterial activity increased with increasing lipophilicity. But in series with where A is a substituent with a trior tetrasubstituted (substituent larger than H) quaternary atom attached directly to the aromatic ring (hydroxyalkyl, alkylsulfinyl, alkylsufonyl), the activity peaked at the member of the series with the "tert-butyl" connectivity pattern. Conjugated electron-withdrawing substituents also had increased activity relative to nonconjugated analogues of comparable lipophilicity. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::08ae7d5de14ba9bd56c9ab466850c168 https://doi.org/10.1021/jm00171a035 |
| رقم الأكسشن: | edsair.doi.dedup.....08ae7d5de14ba9bd56c9ab466850c168 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
|---|