Design, synthesis, and biological evaluation of deuterated apalutamide with improved pharmacokinetic profiles. Issue 12 (15th June 2017) - Pang, Xuehai
Graphical abstract: Abstract: A series of deuterated apalutamide were designed and prepared. Compared to its prototype compound18, deuterated analogues19 and21 showed obviously higher plasma concentrations and better PK parameters after oral administration in mice . In rats, N -trideuteromethyl compound19 displayed 1.8-fold peak concentration (Cmax ), and nearly doubled its drug exposure in plasma (AUC0–∞ ) compared to compound18 . Unsurprisingly, compounds18 and19 had similar affinity for AR in vitro . In summary, the deuteration strategy could obviously improve PK parameters of apalutamide.