5-ht7r antagonist 1

5-HT7R antagonist 1 is a G protein-biased antagonist with a Ki of 6.5 nM for 5-HT7R.

5-HT7R antagonist 1 (free base) is a G protein-biased antagonist for the 5-HT7R receptor, with a dissociation constant (K_i) of 6.5 nM.

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].