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

Chul Min Park; So Young Kim; Woo Kyu Park; Jung Hwan Choi; Churl Min Seong

doi:10.1016/j.bmcl.2010.06.150

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

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5221-4. doi: 10.1016/j.bmcl.2010.06.150. Epub 2010 Jul 23.

Authors

Chul Min Park¹, So Young Kim, Woo Kyu Park, Jung Hwan Choi, Churl Min Seong

Affiliation

¹ Medicinal Chemistry Research Center, Bio-Organic Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon, South Korea. [email protected]

PMID: 20655748
DOI: 10.1016/j.bmcl.2010.06.150

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.

MeSH terms

Antipsychotic Agents / chemical synthesis
Antipsychotic Agents / chemistry*
Antipsychotic Agents / pharmacology*
Piperazines / chemistry
Receptors, Serotonin / classification
Receptors, Serotonin / drug effects
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry*
Sulfonamides / pharmacology*

Substances

Antipsychotic Agents
Piperazines
Receptors, Serotonin
Sulfonamides