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| Design, synthesis and antibacterial activity of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain |
| Chen-Yu Linga, Yun-Liang Taob, Wen-Jing Chua, Hui Wangc, Hai-Dong Wangb, Yu-She Yanga |
a. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
b. School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China;
c. Department of Microbiology, China Pharmaceutical University, Nanjing 210009, China |
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Abstract A series of novel pleuromutilin derivatives with 4H-pyran-4-one and pyridin-4-one substitution in the C-14 side chain have been designed and synthesized. In vitro antibacterial activity evaluation showed that most of the derivatives exhibited potent antibacterial activity against drug resistant Gram-positive strains. Compounds 12a, 12d, and 28 are the most active derivatives in this series, displaying activity comparable to that of retapamulin and BC-3781. As the metabolic stability of this series is not satisfactory, further modifications are going on to improve their pharmacokinetic profile.
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Received: 10 March 2015
Published: 28 September 2015
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Corresponding Authors:
Hai-Dong Wang, Yu-She Yang
E-mail: whdoctor@163.com;ysyang@simm.ac.cn
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