Synthesis and biological evaluation of (phenylpiperazinyl-propyl)arylsulfonamides as selective 5-HT(2A) receptor antagonists.
A novel series of 5-HT(2A) ligands that contain a (phenylpiperazinyl-propyl)arylsulfonamides skeleton was synthesized. Thirty-seven N-(cycloalkylmethyl)-4-methoxy-N-(3-(4-arylpiperazin-1-yl)propyl)-arylsulfonamide and N-(4-(4-arylpiperazin-1-yl)butan-2-yl)-arylsulfonamide compounds were obtained. The binding of these compounds to the 5-HT(2A), 5-HT(2C), and 5-HT(7) receptors was evaluated. Most of the compounds showed IC(50) values of less than 100 nM and exhibited high selectivity for the 5-HT(2A) receptor. Among the synthesized compounds, 16a and 16d showed good affinity at 5-HT(2A) (IC(50)=0.7 nM and 0.5 nM) and good selectivity over 5-HT(2C) (50-100 times) and 5-HT(7) (1500-3000 times).
Yoo
Euna
E
College of Pharmacy & Division of Life & Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
Yoon
Juhee
J
Pae
Ae Nim
AN
Rhim
Hyewhon
H
Park
Woo-Kyu
WK
Kong
Jae Yang
JY
Park Choo
Hea-Young
HY
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D009682:Magnetic Resonance Spectroscopy; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011869:Radioligand Assay; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
D010879:Piperazines; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D013449:Sulfonamides