Compound 4h, also known as 5-HT7R antagonist 2, is a selective inhibitor of the 5-HT7R that disrupts both G protein and β-arrestin signaling pathways. It exhibits a K_i value of 67 nM, with IC_50 values of 2.59 μM in cAMP assays and 39.57 μM in Tango tests. This antagonist is noted for its potential to mitigate repetitive behaviors associated with autism spectrum disorder (ASD) and to foster the restoration of neurogenesis impaired by ASD [1]. Pharmacokinetic analysis in ICR male mice following intravenous and intraperitoneal administration shows a T_max of 0.08 hours and 0.25 hours, a T_1/2 of 0.77 hours and 1.06 hours, and a C_max of 33.07 ng/mL and 156.44 ng/mL, respectively. The AUC_last was recorded at 28.31 ng·h/mL and 143.27 ng·h/mL, with a clearance rate (CL) of 41.61 L/h/kg for intravenous administration. The volume of distribution at steady state (V_ss) was 32.43 L/kg, the mean residence time (MRT) was 0.79 hours and 0.93 hours, and the bioavailability (F) was calculated at 50.60% [1].

5-HT 7 Receptor:67 nM (Ki)

5-HT7R antagonist 2 (compound 4h) (microsomes, 30 分钟) 在代谢稳定性方面表现出色，并且对细胞无毒性 [1]。此化合物是 G 蛋白和 β-阻滞蛋白信号通路中的竞争性拮抗剂 [1]。Cell Line: Concentration: Incubation Time: Result: Cell Line: Concentration: Incubation Time: Result:

5-HT7R antagonist (compound 4h)（腹腔内注射，5 mg/kg，30 分钟）在 ASD 动物模型中对调节 ASD 重复行为有潜力，并能增加 ASD 动物模型中未成熟神经元的数量[1]。 Animal Model: ASD animal models Dosage: 5 mg/kg Administration: Intraperitoneal injection Result: 4h can increase the number of immature ASD neurons.