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

Jarrad M. Altimari, Birunthi Niranjan, Gail P. Risbridger, Stephanie S. Schweiker, Anna E. Lohning, Luke C. Henderson

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6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4948-4953
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number21
DOIs
Publication statusPublished - 1 Nov 2014

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Androgen Receptor Antagonists
Triazoles
Androgens
Enantiomers
Androgen Receptors
Computer Simulation
Inhibitory Concentration 50
Prostatic Neoplasms
bicalutamide
Therapeutics

Cite this

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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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Synthesis and preliminary investigations into novel 1,2,3-triazole-derived androgen receptor antagonists inspired by bicalutamide. / Altimari, Jarrad M.; Niranjan, Birunthi; Risbridger, Gail P.; Schweiker, Stephanie S.; Lohning, Anna E.; Henderson, Luke C.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 24, No. 21, 01.11.2014, p. 4948-4953.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Altimari, Jarrad M.

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AU - Henderson, Luke C.

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