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Synthesis and preliminary investigations into novel 1,2,3-triazole-derived androgen receptor antagonists inspired by bicalutamide.
journal contributionposted on 2014-11-01, 00:00 authored by Jarrad Altimari, B Niranjan, G P Risbridger, S S Schweiker, A E Lohning, Luke HendersonLuke Henderson
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.
JournalBioorganic & Medicinal Chemistry Letters
Pagination4948 - 4953
Publication classificationC Journal article; C1 Refereed article in a scholarly journal
Copyright notice2014, Elsevier
Androgen receptorBicalutamideClick chemistryMolecular modelingProstate cancerTriazoleScience & TechnologyLife Sciences & BiomedicinePhysical SciencesChemistry, MedicinalChemistry, OrganicPharmacology & PharmacyChemistryBIOLOGICAL EVALUATIONPROSTATE-CANCERTERMINAL ALKYNESDESIGNDERIVATIVESACIDREPLACEMENTMETABOLISMMODULATORSBINDINGIMPACTPOTENT