Novel 3-O-carbamoyl erythromycin A derivatives (carbamolides) with activity against resistant staphylococcal and streptococcal isolates

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• 作者：Thomas V. Magee^a ; ^&dagger ; ; ^{thomas.v.magee@pfizer.com} ; Seungil Han^b ; ^{seungil.han@pfizer.com} ; Sandra P. McCurdy^c ; ^&dagger ; ; Thuy-Trinh Nguyen^f ; ^&dagger ; ; Karl Granskog^f ; ^&dagger ; ; Eric S. Marr^b ; Bruce A. Maguire^d ; Michael D. Huband^e ; ^&dagger ; ; Jinshan Michael Chen^f ; Timothy A. Subashi^d ; Veerabahu Shanmugasundaram^g
• 关键词：Bacterial resistance ; cfr ; erm ; MLSb ; MRSA ; Macrolide ; Carbamolide ; Clarithromycin ; Oxazolidinone ; Linezolid ; Ribosome X-ray ; Deinococcus radiodurans
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：15 March, 2013
• 年：2013
• 卷：23
• 期：6
• 页码：1727-1731
• 全文大小：734 K

文摘

A novel series of 3-O-carbamoyl erythromycin A derived analogs, labeled carbamolides, with activity versus resistant bacterial isolates of staphylococci (including macrolide and oxazolidinone resistant strains) and streptococci are reported. An (R)-2-aryl substituent on a pyrrolidine carbamate appeared to be critical for achieving potency against resistant strains. Crystal structures showed a distinct aromatic interaction between the (R)-2-aryl (3-pyridyl for 4d) substituent on the pyrrolidine and G2484 (G2505, Escherichia coli) of the Deinococcus radiodurans 50S ribosome (3.2 ? resolution).