Synthesis and SAR of (piperazin-1-yl-phenyl)-arylsulfonamides: a novel series of atypical antipsychotic agents.
(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.
Park
Chul Min
CM
Medicinal Chemistry Research Center, Bio-Organic Division, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon, South Korea. parkcm@krict.re.kr
Kim
So Young
SY
Park
Woo Kyu
WK
Choi
Jung Hwan
JH
Seong
Churl Min
CM
D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010879:Piperazines / Q000737:chemistry; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D014150:Antipsychotic Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D013449:Sulfonamides