Kang, Suk Youn Park, Eun-Jung Park, Woo-Kyu Kim, Hyun Jung Choi, Gildon Jung, Myung Eun Seo, Hee Jeong Kim, Min Ju Pae, Ae Nim Kim, Jeongmin Lee, Jinhwa 2024-01-20T18:34:51Z 2024-01-20T18:34:51Z 2021-09-05 2010-08-15 0968-0896 https://pubs.kist.re.kr/handle/201004/131176 In the continuing search for novel compounds targeting serotonin 5-HT2A, 5-HT2C, and serotonin transporter, new arylpiperazine-containing pyrrole 3-carboxamide derivatives were synthesized and evaluated. Based on the lead reported previously, structural modifications regarding N-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propyl)-1,2-dimethyl-5-phenyl-1H-pyrrole-3-carboxamide 5, were accomplished for improvements in not only binding affinity against serotonin receptors and transporter, but also in hERG channel inhibition. Along the line, both the forced swimming tests and spontaneous locomotor activity tests were performed to distinguish between antidepressant activity and false positive results. As potential antidepressant agents, both 2,4-dimethyl-5-phenyl-1H-pyrrole-3-carboxamide and 5-tert-butyl-2-methyl-1H-pyrrole-3-carboxamide derivatives exhibited favorable in vitro and in vivo activities, warranting further investigation around these scaffolds. (C) 2010 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD RECEPTOR ANTAGONIST UPTAKE INHIBITORS DEPRESSION NEFAZODONE DOPAMINE PINDOLOL D-3 FLUOXETINE LIGANDS DISEASE Further optimization of novel pyrrole 3-carboxamides for targeting serotonin 5-HT2A, 5-HT2C, and the serotonin transporter as a potential antidepressant Article 10.1016/j.bmc.2010.06.037 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.18, no.16, pp.6156 - 6169 BIOORGANIC & MEDICINAL CHEMISTRY 18 16 6156 6169 scie scopus 000280664100041 2-s2.0-77955469113 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article RECEPTOR ANTAGONIST UPTAKE INHIBITORS DEPRESSION NEFAZODONE DOPAMINE PINDOLOL D-3 FLUOXETINE LIGANDS DISEASE Depression Antidepressant Serotonin Piperazine Pyrrole