Discovery of 7alpha-substituted dihydrotestosterones as androgen receptor pure antagonists and their structure-activity relationships.
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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
Drug Target Property Measurement pH Temperature (°C) Bicalutamide Androgen receptor IC 50 (nM) 200 N/A N/A Details Bicalutamide Androgen receptor IC 50 (nM) 140 N/A N/A Details