Studies on 1-arylpiperazine derivatives with affinity for rat 5-HT7 and 5-HT1A receptors

ABSTRACT Several 1‐aryl‐4‐(2‐arylethyl)piperazine derivatives were synthesized and tested in‐vitro for their binding affinity for 5‐HT7 and 5‐HT1A receptors. These compounds displayed 5‐HT7 receptor affinity ranging between Ki = 474 nm and Ki = 8.2 nm, besides high affinity for the 5‐HT1A receptor. Intrinsic activity of the most potent compounds was assessed. 4‐[2‐(3‐Methoxyphenyl)ethyl]‐1‐(2‐methoxyphenyl)piperazine (16) and 1‐(1,2‐benzisoxazol‐3‐yl)‐4‐[2‐(3‐methoxyphenyl)ethyl]piperazine (20) (Ki = 24.5 and 8.2 nm, respectively) behaved as partial agonist and full agonist, respectively, when tested for 5‐HT7 receptor‐mediated relaxation of substance P‐induced guinea‐pig ileum contraction.