D4R antagonist-2 is a potent and selective D4R antagonist (IC50= 6.52 μM) with favorable in vitro pharmacokinetic parameters and good brain penetration, making it a potential research candidate for Parkinson’s disease.

D4R antagonist-2 (compound 11a) demonstrates significant activity with a K i of 299.4 nM [1].

D4R antagonist-2 exhibits highly favorable pharmacokinetic (PK) parameters in vitro and demonstrates significant brain penetration (Kp=2.9) [1]. In rats, administered intravenously at a dose of 0.25 mg/kg, it shows a clearance rate (CL) of 22.0 ml/min/kg, a half-life (T1/2) of 4.4 hours, an initial concentration (C0) of 91 ng/ml, a steady-state volume of distribution (Vss) of 5.5 L/kg, and an area under the curve (AUC) of 747 h*ng/mL [1]. These results underscore D4R antagonist-2's potential for efficacious brain targeting.