Jang, Jae Wan Baek, Je-sook Choi, Gil Don Park, Woo-Kyu Cho, Yong Seo Baek, Du-Jong Pae, Ae Nim 2024-01-20T15:33:36Z 2024-01-20T15:33:36Z 2021-09-04 2012-01-01 0960-894X https://pubs.kist.re.kr/handle/201004/129655 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. English Pergamon Press Ltd. BINDING 5-HYDROXYTRYPTAMINE(2A) PACKING ENERGY MICE 5-HT2C receptor selectivity and structure-activity relationship of N-methyl-N-(1-methylpiperidin-4-yl)benzenesulfonamide analogs Article 10.1016/j.bmcl.2011.11.001 1 Bioorganic & Medicinal Chemistry Letters, v.22, no.1, pp.347 - 352 Bioorganic & Medicinal Chemistry Letters 22 1 347 352 scie scopus 000298636700066 2-s2.0-84655167900 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article BINDING 5-HYDROXYTRYPTAMINE(2A) PACKING ENERGY MICE 5-HT2c ligands Obesity Selectivity Homology modeling