Further optimization of novel pyrrole 3-carboxamides for targeting serotonin 5-HT2A, 5-HT2C, and the serotonin transporter as a potential antidepressant

被引：18

作者：

Kang, Suk Youn ^{[1
]}

Park, Eun-Jung ^{[1
]}

Park, Woo-Kyu ^{[2
]}

Kim, Hyun Jung ^{[1
]}

Choi, Gildon ^{[2
]}

Jung, Myung Eun ^{[1
]}

Seo, Hee Jeong ^{[1
]}

Kim, Min Ju ^{[1
]}

Pae, Ae Nim ^{[3
]}

Kim, Jeongmin ^{[1
]}

Lee, Jinhwa ^{[1
]}

机构：

[1] Green Cross Co, Res Ctr, Yongin 446770, South Korea

[2] Korea Res Inst Chem Technol, Pharmacol Res Ctr, Taejon 305343, South Korea

[3] Korea Inst Sci & Technol, Biochem Res Ctr, Seoul 136791, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 16期

关键词：

Depression; Antidepressant; Serotonin; Piperazine; Pyrrole; RECEPTOR ANTAGONIST; UPTAKE INHIBITORS; DEPRESSION; NEFAZODONE; DOPAMINE; PINDOLOL; D-3; FLUOXETINE; LIGANDS; DISEASE;

D O I：

10.1016/j.bmc.2010.06.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：6156 / 6169

页数：14

共 29 条

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