Title

Synthesis and preliminary investigations into novel 1,2,3-triazole-derived androgen receptor antagonists inspired by bicalutamide

Date of this Version

1-1-2014

Document Type

Journal Article

Publication Details

Citation only

Altimari, J. M., Niranjan, B., Risbridger, G. P., Schweiker, S. S., Lohning, A. E., & Henderson, L. C. (2014). Synthesis and preliminary investigations into novel 1,2,3-triazole-derived androgen receptor antagonists inspired by bicalutamide. Bioorganic and Medicinal Chemistry Letters, 24(21), 4948-4953.

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© Copyright, Elsevier Ltd, 2014

ISSN

0960-894X

Abstract

A versatile and high yielding synthesis of novel androgen receptor (AR) antagonists is presented. Using this methodology, six 1,4-substituted-1,2,3-triazole derived bicalutamide mimics were synthesised in five steps and in isolated overall yields from 41% to 85%. Evaluation of these compounds for their anti-proliferative properties against androgen dependent (LNCaP) and independent (PC-3) cells showed promising IC50 values of 34-45 μM and 29-151 μM, respectively. The data suggest that the latter compounds may be an excellent starting point for the development of prostate cancer therapeutics for both androgen dependent and independent forms of this disease. Docking of these compounds (each enantiomer) in silico into the T877A mutated androgen receptor, as possessed by LNCaP cells, was also undertaken.

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This document has been peer reviewed.