A new strategy to improve the metabolic stability of lactone: Discovery of (20 S, 21 S)-21-fluorocamptothecins as novel, hydrolytically stable topoisomerase I inhibitors

…, K Fang, J Yao, J Li, C Sheng, W Zhang

Index: Miao, Zhenyuan; Sheng, Chunquan; Zhang, Wannian; Ji, Haitao; Zhang, Jing; Shao, Luecheng; You, Liang; Zhang, Min; Yao, Jianzhong; Che, Xiaoyin Bioorganic and Medicinal Chemistry, 2008 , vol. 16, # 3 p. 1493 - 1510

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Citation Number: 12

Abstract

Lactone is a common structural motif in biologically active natural products. However, the metabolic instability of lactone significantly reduces their in vivo potency. In the present investigation, a new strategy to improve the metabolic stability of lactone was provided by the design of α-fluoro ether as a novel bioisostere of lactone. The effectiveness of the α- fluoro ether/lactone replacement was validated by the discovery of (20 S, 21 S)-21- ...