Synthesis and SAR of (piperazin-1-yl-phenyl)-arylsulfonamides: a novel series of atypical antipsychotic agents.

Abstract (Piperazin-1-yl-phenyl)-arylsulfonamides were synthesized and identified to show high affinities for both 5-HT 2C and 5-HT 6 receptors. Among them, naphthalene-2-sulfonic acid isopropyl-[3-(4-methyl-piperazin-1-yl)-phenyl]-amide ( 6b ) exhibits the highest affinity towards both 5-HT 2C (IC 50  = 4 nM) and 5-HT 6 receptors (IC 50  = 3 nM) with good selectivity over other serotonin (5-HT 1A , 5-HT 2A , and 5-HT 7 ) and dopamine (D 2 –D 4 ) receptor subtypes. In 5-HT 2C and 5-HT 6 receptor functional assays, this compound showed considerable antagonistic activity for both receptors.