Discovery of 7alpha-substituted dihydrotestosterones as androgen receptor pure antagonists and their structure-activity relationships.

Article Details

Citation

Tachibana K, Imaoka I, Yoshino H, Emura T, Kodama H, Furuta Y, Kato N, Nakamura M, Ohta M, Taniguchi K, Ishikura N, Nagamuta M, Onuma E, Sato H

Discovery of 7alpha-substituted dihydrotestosterones as androgen receptor pure antagonists and their structure-activity relationships.

Bioorg Med Chem. 2007 Jan 1;15(1):174-85. Epub 2006 Oct 4.

PubMed ID
17064916 [ View in PubMed
]
Abstract

A series of 7alpha-substituted dihydrotestosterone derivatives were synthesized and evaluated for androgen receptor (AR) pure antagonistic activity. From reporter gene assay (RGA), the compound with a side chain containing N-n-butyl-N-methyl amide (19a) showed pure antagonistic activity (IC(50)=340nM, FI(5)>10,000nM), whereas known AR antagonists showed partial agonistic activities. The optimization of 19a led to compound 23 (CH4892280), which showed more potent pure antagonistic activity (IC(50)=190nM, FI(5)>10,000nM). The SARs of tested compounds suggested that the length of the side chain and the substituents on the amide nitrogen are important for pure antagonistic activities.

DrugBank Data that Cites this Article

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