5-HT2C receptor selectivity and structure-activity relationship of N-methyl-N-(1-methylpiperidin-4-yl)benzenesulfonamide analogs

Authors
Jang, Jae WanBaek, Je-sookChoi, Gil DonPark, Woo-KyuCho, Yong SeoBaek, Du-JongPae, Ae Nim
Issue Date
2012-01-01
Publisher
Pergamon Press Ltd.
Citation
Bioorganic & Medicinal Chemistry Letters, v.22, no.1, pp.347 - 352
Abstract
Agonists of the 5-HT2C receptor have attracted much attention as therapeutic agents for the treatment of obesity. Subtype selectivity against other 5-HT2 receptors is one of the most important prerequisites for reducing side effects. We present the synthesis of N-methyl-N-(1-methylpiperidin-4-yl) benzenesulfonamide analogs and their structure-activity relationship studies on 5-HT2A and 5-HT2C receptors. Although the compounds showed nanomolar activity to the 5-HT2C receptor, their selectivity against the 5-HT2A receptor was modest to low. Molecular modeling studies using homology modeling and docking simulation revealed that selectivity originated from subtype specific residues. The observed binding modes and receptor-ligand interactions provided us a clue for optimizing the selectivity against the 5-HT2A receptor. (C) 2011 Elsevier Ltd. All rights reserved.
Keywords
BINDING; 5-HYDROXYTRYPTAMINE(2A); PACKING; ENERGY; MICE; BINDING; 5-HYDROXYTRYPTAMINE(2A); PACKING; ENERGY; MICE; 5-HT2c ligands; Obesity; Selectivity; Homology; modeling
ISSN
0960-894X
URI
https://pubs.kist.re.kr/handle/201004/129655
DOI
10.1016/j.bmcl.2011.11.001
Appears in Collections:
KIST Article > 2012
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