There has been significant attention concerning the biased agonism of G protein-coupled receptors (GPCRs), and it has resulted in various pharmacological benefits. 5-HT<sub>7</sub>R belongs to a GPCR, and it is a promising pharmaceutical target for the treatment of neurodevelopmental and neuropsychiatric disorders. Based on our previous research, we synthesized a series of 6-chloro-2'-methoxy biphenyl derivatives <b>1</b>, <b>2</b>, and <b>3</b> with a variety of amine scaffolds. These compounds were evaluated for their binding affinities to 5-HTR subtypes and their functional selectivity toward the Gs protein and the β-arrestin signaling pathways of 5-HT<sub>7</sub>R. Among them, 2-(6-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)-<i>N</i>-ethylethan-1-amine, <b>2b</b>, was found to be a G-protein-biased ligand of 5-HT<sub>7</sub>R. In an <i>in vivo</i> study with <i>Shank3</i> transgenic mice, the self-grooming behavior test was performed with <b>2b</b>, which increased the duration of self-grooming. The experiments further suggested that 5-HT<sub>7</sub>R is associated with autism spectrum disorders (ASDs) and could be a therapeutic target for the treatment of stereotypy in ASDs.