Discovery and structure-activity relationships of new steroidal compounds bearing a carboxy-terminal side chain as androgen receptor pure antagonists.

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Citation

Tachibana K, Imaoka I, Yoshino H, Kato N, Nakamura M, Ohta M, Kawata H, Taniguchi K, Ishikura N, Nagamuta M, Onuma E, Sato H

Discovery and structure-activity relationships of new steroidal compounds bearing a carboxy-terminal side chain as androgen receptor pure antagonists.

Bioorg Med Chem Lett. 2007 Oct 15;17(20):5573-6. Epub 2007 Aug 22.

PubMed ID
17804229 [ View in PubMed
]
Abstract

Lead optimization of CH4892280 (4), an androgen receptor (AR) pure antagonist, was investigated. Compounds 6 and 7, which have a carboxylic acid at the end of the side chain at the position 7alpha of dihydrotestosterone (DHT), showed partial agonistic activities in reporter gene assay (RGA). Conversion of the steroidal core structure to 17alpha-methyltestosterone gave compound 14, which showed weak pure antagonistic activity. Optimization of the side chain by the insertion of a phenyl ring led to compounds 22 and 28-30, which showed pure antagonistic activities at submicromolar concentrations. The structure-activity relationships were clarified.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
BicalutamideAndrogen receptorIC 50 (nM)200N/AN/ADetails
BicalutamideAndrogen receptorIC 50 (nM)140N/AN/ADetails