Synthesis of Hydantoin Androgen Receptor Antagonists and Study on Their Antagonistic Activity
Longjun Ma,
Yan Zhou,
Dehua Yang,
Ming-Wei Wang,
Wei Lu,
Jiyu Jin
Affiliations
Longjun Ma
Department of Applied Chemistry, School of Chemistry and Chemical Engineering, Lanzhou Jiaotong University, 88 Anning West Road, Lanzhou 730070, China
Yan Zhou
The National Center for Drug Screening, CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 189 Guo Shou Jing Road, Shanghai 200031, China
Dehua Yang
The National Center for Drug Screening, CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 189 Guo Shou Jing Road, Shanghai 200031, China
Ming-Wei Wang
The National Center for Drug Screening, CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), 189 Guo Shou Jing Road, Shanghai 200031, China
Wei Lu
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China
Jiyu Jin
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China
Hydroxymethylthiohydantoin, hydroxymethylthiohydantoin, and hydantoin, containing a pyridine group, were synthesized to study their androgen receptor antagonistic activities. Among them, compounds 6a/6c/7g/19a/19b exhibited excellent androgen receptor antagonistic activity, which was consistent with or even superior to enzalutamide. In addition, compounds 19a and 19b exhibited better antiproliferative activity than enzalutamide in prostate cancer cells. The results show that compound 19a has great potential as a new AR antagonist.
