19685-10-0Relevant articles and documents
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
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
, p. 7902 - 7910 (2013)
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 (20S,21S)-21-fluorocamptothecins as hydrolytically stable topoisomerase I inhibitors. A highly potent camptothecin derivative, 8l, was successfully identified, which showed excellent in vitro and in vivo antitumor activities and represents a promising lead for the discovery of novel antitumor agents. Interestingly, this study also provided a new structure-activity relationship for the C21-carbonyl group of camptothecin, which has been regarded as an essential pharmacophore. Our results revealed that the conserved C21-carbonyl group can be replaced by a fluorine substituent. α-Fluoro ether may have general application in improving the metabolic stability of lactone.
CONJUGATES OF A CELL-BINDING MOLECULE WITH CAMPTOTHECIN ANALOGS
-
Page/Page column 144, (2021/10/30)
Provided are conjugates of camptothecin analogs with a cell-binding molecule of formula (I), wherein R1, R2, R3, R4, R5, X, L, n, m, T and ----- are defined herein. It also provides methods of making the conjugates of camptothecin analogs to a cell-binding agent, as well as methods of using the conjugates in targeted treatment of cancer, infection, and immunological disorders.
Visible-Light-Induced Radical Cascade Cyclization: Synthesis of (20S)-Camptothecin, SN-38 and Irinotecan
Yuan, Yao,Dong, Wuheng,Gao, Xiaoshuang,Xie, Xiaomin,Curran, Dennis P.,Zhang, Zhaoguo
, p. 1035 - 1040 (2018/09/25)
(20S)-Camptothecin, irinotecan and SN-38 were successfully synthesized by a photocatalyzed radical cascade cyclization from an N-propargyl iodopyridinone and an arylisonitrile under visible light with a ruthenium catalyst. This synthetic method provided a useful entry into composing camptothecin family of antitumor agents in good yields under mild reaction conditions without the use of heavy metal reagents.
Synthesis and anticancer evaluation of novel 10-methoxycamptothecin derivatives
Zhu, Meixuan,Jing, Lijia,Wang, Shaoming,Zhang, Sheng,Wang, Yang
, p. 932 - 934 (2015/02/05)
As part of our continuing search for potential anticancer drug candidates, we have synthesized four 10-methoxycamptothecin derivatives. The compounds were synthesized by facile procedures and characterized by 1H NMR, 13C NMR and mass spectra study. The synthesized compounds were examined for their cytotoxic effect on a panel of five human cancer cell lines. Three out of five compounds were found to exhibit moderate anticarcinogenic activities in all cell lines. The result of the present investigation encourage us to develop more other related compounds and to screen them for a wide range of biological activity.