Synthesis and antidepressant activity of a series of arylalkanol and aralkyl piperazine derivatives targeting SSRI/5-HT1A/5-HT7

A series of arylalkanol and aralkyl piperazine derivatives have been synthesized and evaluated for 5-HT reuptake inhibitory abilities and binding affinities at the 5-HT_1A/5-HT₇ receptors. Antidepressant activities of the compounds in vivo were screened using the forced swimming test (FST). The results indicated that the compound 8j exhibited high affinities for the 5-HT_1A/5-HT₇ receptors (5-HT_1A, k_i?=?0.84?nM; 5-HT₇, k_i?=?12?nM) coupling with moderate 5-HT reuptake inhibitory activity (RUI, IC₅₀?=?100?nM) and showed a marked antidepressant-like activity in the FST model.