Synthesis of androgen receptor antagonists containing a pentafluorosulfanyl (SF5 ) moiety
Jiyu Jin1, Yan Zhou2, Dehua Yang2
1Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, P. R. China.
Abstract:
A novel scaffold of pentafluorosulfanyl (SF5 )-containing enzalutamide analogues was discovered for potent androgen receptor (AR) antagonists through rational drug design. Several compounds showed good biological profiles in AR binding. Of the derivatives studied, compound 8a had potent AR antagonist activity (IC50 = 7.1 ± 1.0 µM) and high efficacy (104.5 ± 12.8%). It exhibited an inhibitory effect comparable to that of enzalutamide (inhibition = 66.0 and 77.9%, respectively) in a prostate cancer cell line. The results point to the potential of using this scaffold to develop new AR antagonists.
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