Structure-activity relationships of bioisosteric replacement of the carboxylic acid in novel androgen receptor pure antagonists.

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Yoshino H, Sato H, Tachibana K, Shiraishi T, Nakamura M, Ohta M, Ishikura N, Nagamuta M, Onuma E, Nakagawa T, Arai S, Ahn KH, Jung KY, Kawata H

Structure-activity relationships of bioisosteric replacement of the carboxylic acid in novel androgen receptor pure antagonists.

Bioorg Med Chem. 2010 May 1;18(9):3159-68. doi: 10.1016/j.bmc.2010.03.036. Epub 2010 Mar 19.

PubMed ID

20381361 [ View in PubMed

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Abstract

A series of 5,5-dimethylthiohydantoin derivatives were synthesized and evaluated for androgen receptor pure antagonistic activities for the treatment of hormone refractory prostate cancer. CH4933468 (32d) with a sulfonamide side chain not only exhibited antagonistic activity with no agonistic activity in the reporter gene assay but also inhibited the growth of bicalutamide-resistant cell lines. This compound also inhibited tumor growth of the LNCaP xenograft in mice dose-dependently.

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)	550	N/A	N/A	Details