Discovery of novel spirocyclic derivates as potent androgen receptor antagonists.

• Tác giả: Caiping Chen, Xingru Chen, Yadong Chen, Zhuolin Chen, Yawen Fan, Yu Jiao, Hongmei Li, Tao Lu, Chenxiao Wang, Xian Wei, Wenqiang Zhang, Xiaoyu Zhou, Hao Zhu
• Ngôn ngữ: eng
• Thông tin xuất bản: England : Bioorganic & medicinal chemistry , 2025
• Bộ sưu tập: NCBI
• ID: 581952

Tóm tắt

We report herein the development of a series of novel AR antagonists characterized by a spirocyclic scaffold, employing scaffold hopping and structure-based drug design strategies. Most of the spirocyclic derivatives exhibited enhanced AR antagonistic activity and superior antiproliferative activity against LNCaP cells compared to enzalutamide. Among them, compound 21 demonstrated moderate antiproliferative activity against enzalutamide resistant prostate cancer cell lines and exhibited favorable in vitro metabolic stability. These findings offer valuable insights for the rational design of AR antagonists for the treatment of advanced prostate cancer.