Prostate cancer (PCa) is the second cause of cancer-related death among the male population of Western society and androgen-deprivation therapy (ADT) represents the first line in PCa treatment. In spite of androgen receptor (AR) expression throughout the various stages of PCa, ADT frequently fails and prostate cancers progress towards the androgen-independent prostate cancer (AIPC) or the hormone-refractory prostate cancer, also known as castration-resistant prostate cancer  (CRPC). Clinical evidence suggests that the classical AR antagonists such as Casodex�, also known as bicalutamide, are un-effective for the treatment of advanced prostate cancers.In this study we will discuss the diastereoselective synthesis of a novel class of bicalutamide-like molecules bearing different molecular fragments at the C2-position that was achieved starting from inexpensive and commercially available starting materials. Molecular modeling studies along with in vitro and in vivo biological profiling will be provided to demonstrate that small chemical changes in the structure of non-steroidal AR ligands sensibly change the molecular mechanisms underling the pharmacological responses of AR and its mutated forms.

SAR study on novel androgen receptor pan-antagonists

248th National Meeting (2014)

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