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

…, L Zhu, G Dong, C Zhuang, Y Wu, S Wang…

Index: Miao, Zhenyuan; Zhu, Lingjian; Dong, Guoqiang; Zhuang, Chunlin; Wu, Yuelin; Wang, Shengzheng; Guo, Zizao; Liu, Yang; Wu, Shanchao; Zhu, Shiping; Fang, Kun; Yao, Jianzhong; Li, Jian; Sheng, Chunquan; Zhang, Wannian Journal of Medicinal Chemistry, 2013 , vol. 56, # 20 p. 7902 - 7910

Full Text: HTML

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- ...