573762-62-6Relevant articles and documents
Discovery of pyridine tetrahydroisoquinoline thiohydantoin derivatives with low blood-brain barrier penetration as the androgen receptor antagonists
Bian, Jinlei,Chen, Xijing,Du, Qianming,Ge, Raoling,Li, Yan,Li, Zhiyu,Lu, Xiaoyu,Meng, Ying,Wang, Jubo,Wu, Hongxi,Xu, Xi,Xue, Siqi,Yang, Yong,Zhao, Zhili
, (2020/03/11)
Prostate cancer (PC) is the most diagnosed type of malignancy in men and the major frequently cause of cancer-related death worldwide. The androgen receptor (AR) has become a promising drug target for the treatment of PC. Here, we reported the design, optimization and evaluation of pyridine tetrahydroisoquinoline thiohydantoin derivatives with improved activity and safety as potent AR antagonists. The most promising compound 42f exhibited potent inhibitory activity on AR and strongly blocked AR nuclear translocation. Moreover, 42f displayed promising in vitro antitumor activity toward AR-dependent prostate cancer cell lines (LNCaP) and also demonstrated therapeutic effects in LNCaP xenograft tumor model in mice (TGI: 79%) with no apparent toxicity observed in vivo. More importantly, 42f showed negligible penetration of the brain-blood barrier (BBB) compared with enzalutamide. These results provide a foundation for the development of a new class of androgen receptor antagonists for potential therapeutics against PC with lower seizurogenic risk for patients.
Prostatic cancer treatment medicine
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, (2019/03/26)
The invention relates to a compound with a prostatic cancer treatment function and nontoxic pharmaceutically acceptable salt of the compound. The structure of the compound is as shown in a formula I,wherein X is C or N, R1 is alkyl of C1-C3 or halogen substituted alkyl, R2 is alkyl of C1-C3 and halogen substituted alkyl or halogen, R3 and R4 are independently selected from H, alkyl and substituted alkyl, and R3 and R4 are connected to form cycloalkyl. The compound has high inhibiting effects on in-situ prostate cancer and transfer of the prostate cancer, and eclamptogenic side effects are lower.
Design, synthesis, and biological evaluation of deuterated apalutamide with improved pharmacokinetic profiles
Pang, Xuehai,Wang, Yingwei,Chen, Yuanwei
, p. 2803 - 2806 (2017/05/29)
A series of deuterated apalutamide were designed and prepared. Compared to its prototype compound 18, deuterated analogues 19 and 21 showed obviously higher plasma concentrations and better PK parameters after oral administration in mice. In rats, N-trideuteromethyl compound 19 displayed 1.8-fold peak concentration (Cmax), and nearly doubled its drug exposure in plasma (AUC0–∞) compared to compound 18. Unsurprisingly, compounds 18 and 19 had similar affinity for AR in vitro. In summary, the deuteration strategy could obviously improve PK parameters of apalutamide.