Synthesis and Structure鈥揂ctivity Relationships of 伪-Amino-纬-lactone Ketolides: A Novel Class of Macrolide Antibiotics
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- 作者：Dra啪en Pavlovi膰 ; Stjepan Mutak ; Daniele Andreotti ; Stefano Biondi ; Francesca Cardullo ; Alfredo Paio ; Elisa Piga ; Daniele Donati ; Sergio Lociuro
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2014
- 出版时间：October 9, 2014
- 年：2014
- 卷：5
- 期：10
- 页码：1133-1137
- 全文大小：269K
- ISSN：1948-5875
文摘
An efficient synthesis of 伪-amino-纬-lactone ketolide (3) was developed, which provided a versatile intermediate for the incorporation of a variety of aryl and heteroaryl groups onto the C-21 position of clarithromycin via HBTU-mediated amidation. The biological data for this important new class of macrolides revealed significantly potent activity against erythromycin-susceptible strains as well as efflux-resistant and erythromycin MLSB-resistant strains of S. pneumoniae and S. pyogenes. In addition, ketolide 11o showed excellent in vitro antibacterial activity against H. influenzae strain as compared to telithromycin. These results indicate that C-21 substituted 纬-lactone ketolides have potential as a next generation macrolide antibiotics.