European Journal of Medicinal Chemistry p. 1325 - 1344 (2018)
Update date:2022-08-23
Topics:
Xu, Xi
Ge, Raoling
Li, Lei
Wang, Jubo
Lu, Xiaoyu
Xue, Siqi
Chen, Xijing
Li, Zhiyu
Bian, Jinlei
Prostate cancer (PC) is a major cause of cancer-related male death in worldwide and the identification of new and improved potent anti-PC molecules is constantly required. A novel scaffold of tetrahydroisoquinoline thiohydantoin was rationally designed based on the enzalutamide structures and our pre-work, leading to the discovery of a series of new antiproliferative compounds. Several new analogues displayed improved androgen receptor (AR) antagonistic activity, while maintaining the higher selective toxicity toward LNCaP cells (AR-rich) versus DU145 cells (AR-deficient) compared to enzalutamide. In fact, compound 55 exhibited promising in vitro antitumor activity by impairing AR unclear translocation. More importantly, 55 showed better pharmacokinetic properties compared to the compound 1 reported in our pre-work. These results demonstrate a step towards the development of novel and improved AR antagonists.
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Doi:10.1039/a708691a
(1998)Doi:10.1016/S0277-5387(00)87207-1
(1983)Doi:10.1002/jps.2600710814
(1982)Doi:10.1016/j.tetlet.2015.10.050
(2015)Doi:10.1016/j.jcat.2012.02.001
(2012)Doi:10.1021/ja00714a066
(1970)