HY-078020 (compound III-4), a selective and orally active histamine H1 receptor antagonist, demonstrates an IC50 of 24.12 nM. It exhibits anti-inflammatory effects in allergic diseases [1].

H1 Receptor:24.12 nM

HY-078020 is a potent H1R inhibitor with an IC50 of 24.12 nM, while showing weaker inhibition of M3R and hERG, with IC50 values of >10 μM and 17.6 μM, respectively [1]. It exhibits moderate permeability (efflux ratio <2) and is stable in liver microsomes, demonstrating a long half-life (T1/2 = 86.625 min) in humans, beagle dogs, and mice [1]. Additionally, HY-078020 inhibits cytochrome P450 (CYP) isoenzyme CYP3A4 in rats [1].

HY-078020, administered at 5 mg/kg via oral gavage in an ICR/KM mouse model, effectively inhibited histamine-induced vasodilation and increased vascular permeability of the skin, achieving an inhibition rate of 58.71%[1]. When the dose was increased to 10 mg/kg and administered intravenously, HY-078020 displayed mild anticholinergic effects in Wistar rats, with a 10.8% reduction in saliva secretion[1]. Detailed pharmacokinetic analysis in male Wistar rats revealed that intravenous injection (iv) at 4 mg/kg resulted in a half-life (T 1/2) of 0.653 ± 0.12 hours, total exposure (AUC 0-inf) of 1822.38 ± 224.97 ng·h/mL, distribution volume (V d) of 1.77 ± 0.22 L/kg, and a clearance (CL) of 37.00 ± 4.62 mL/h/kg. Oral administration (po) at 25 mg/kg showed a peak concentration time (T max) of 0.38 ± 0.16 hours, maximum concentration (C max) of 1722.06 ± 337.11 ng/mL, and exposure (AUC 0-t) of 6246.92 ± 1443.28 ng·h/mL.