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

doi:10.3390/molecules27185867

Synthesis of Hydantoin Androgen Receptor Antagonists and Study on Their Antagonistic Activity

Molecules. 2022 Sep 10;27(18):5867. doi: 10.3390/molecules27185867.

Authors

Longjun Ma^{1

2}, Yan Zhou³, Dehua Yang³, Ming-Wei Wang³, Wei Lu², Jiyu Jin²

Affiliations

¹ Department of Applied Chemistry, School of Chemistry and Chemical Engineering, Lanzhou Jiaotong University, 88 Anning West Road, Lanzhou 730070, China.
² 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.
³ 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.

Abstract

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.

Keywords: androgen receptor; antagonist; antiproliferative; enzalutamide; hydantoin analogs.

MeSH terms

Androgen Receptor Antagonists / pharmacology
Benzamides
Cell Line, Tumor
Cell Proliferation
Humans
Hydantoins* / pharmacology
Male
Nitriles / pharmacology
Phenylthiohydantoin
Prostatic Neoplasms* / drug therapy
Pyridines / pharmacology
Receptors, Androgen

Substances

Androgen Receptor Antagonists
Benzamides
Hydantoins
Nitriles
Pyridines
Receptors, Androgen
Phenylthiohydantoin
enzalutamide

Grants and funding

This work was partially supported by the “Personalized Medicines-Molecular Signature-based Drug Discovery and Development Strategic Priority Research Program” of Chinese Academy of Sciences grants (XDA12020347 to M.-W.W.; XDA12040308 to D.Y.) and the Thousand Talents Program in China (to M.-W.W.). We are grateful for the financial support for Shanghai Science and Technology Council (16DZ2280100).