Discovery of an orally-active nonsteroidal androgen receptor pure antagonist and the structure-activity relationships of its derivatives

Autor:	Etsuro Onuma, Hiromitsu Kawata, Toshiaki Tsunenari, Takuya Shiraishi, Hitoshi Yoshino, Kenji Takanashi, Mitsuaki Nakamura, Kenji Taniguchi, Masahiro Nagamuta, Nobuyuki Ishikura, Toshito Nakagawa, Ikuhiro Imaoka, Masateru Ohta, Hidemi Saito, Kazutaka Tachibana, Haruhiko Sato
Rok vydání:	2008
Předmět:	Male Models Molecular medicine.medical_specialty CHO Cells Pharmacology Crystallography X-Ray Binding Competitive chemistry.chemical_compound Prostate cancer Mice Structure-Activity Relationship Cricetulus Genes Reporter Internal medicine Cricetinae Drug Discovery medicine Agonistic behaviour Androgen Receptor Antagonists Animals Humans IC50 ED50 Mice Inbred ICR Nonsteroidal Antagonist Seminal Vesicles Androgen Antagonists General Chemistry General Medicine medicine.disease Androgen receptor Endocrinology Orally active chemistry Thiohydantoins Microsomes Liver Indicators and Reagents HeLa Cells
Zdroj:	Chemicalpharmaceutical bulletin. 56(11)
ISSN:	0009-2363
Popis:	The 3-(4-cyano-3-trifluoromethylphenyl)-5,5-dimethylthiohydantoin derivatives which have carboxy-terminal side chains were synthesized and their agonistic/antagonistic activities against androgen receptor (AR) measured. Among them, compound 13b showed antagonistic activity (IC50=130 nM) with no agonistic activity even at 10000 nM. This compound exhibited significant metabolic stability and oral antiandrogenic activity (ED50=7 mg/kg).
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3543001fcbf1d2ef9dce6f168da28546 https://pubmed.ncbi.nlm.nih.gov/18981605 Zobrazit plný text záznamu