Heterocycle-fused phenylcyclohexylamines as novel multi-target antagonists of N-methyl-D-aspartate (NMDA) receptor and monoamine transporter for treating depression
文献类型：期刊论文
| 作者 | Zheng, Fuqiang6,7; Hu, Zhengtao1,8; Chen, Hai1; Cheng, Jiaxin2,8; Hou, Qiongqiong3; Zheng, Jiefang2,8; Gong, Xudong3; Ji, Jing2,5; Zayniddin, Nuriddinov2,8; Abduahadi, Safomuddin2,8 |
| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
 |
| 出版日期 | 2025-07-05 |
| 卷号 | 291页码:20 |
| 关键词 | Heterocycle-fused phenylcyclohexylamines Multi-target antagonists NMDAR Monoamine transporter Antidepressants |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2025.117538 |
| 英文摘要 | Simultaneously modulating the glutamatergic and monoaminergic systems represents a promising strategy for treating depression. In this study, a series of multi-target antagonists targeting both NMDAR and monoamine transporters (SERT, DAT, and NET) was designed and evaluated for their antidepressant potential in vitro and in vivo. Among these heterocycle-fused phenylcyclohexylamine derivatives, compound A16 demonstrated potent and relatively balanced multi-target activity (A16: IC50(NMDAR): IC50(SERT): IC50(DAT): IC50(NET) = 1.8:1.0:1.9:1.3) compared to the lead compound S1. Pharmacokinetic studies revealed that A16 exhibited moderate clearance in microsomes and favorable oral brain exposure in mice. In vivo assessments showed that A16 and its R-isomer A17 exhibited significant antidepressant-like effects in the forced swim test and tail suspension test in mice. Notably, A17 demonstrated significant antidepressant-like effects at doses as low as 1 mg/ kg, with no indication of addiction risk at 20 mg/kg. Collectively, these findings identify A17, a heterocyclefused phenylcyclohexylamine as a promising scaffold for developing non-addictive, rapid-acting antidepressants. |
| WOS关键词 | MAJOR DEPRESSION ; KETAMINE ; ANTIDEPRESSANTS ; LANICEMINE ; EFFICACY ; INSIGHTS ; BINDING ; POTENT |
| 资助项目 | National Science and Technology Innovation 2030 Major Program[2021ZD0200900] ; State Key Laboratory of Drug Research[SKLDR-2022-LH-09] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001464569000001 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317440]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Aisa, Haji Akber; Shen, Jingshan; He, Yang |
| 作者单位 | 1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Vigonvita Shanghai Co Ltd, Shanghai 201210, Peoples R China 4.Xinjiang Med Univ, Sch Pharm, Urumqi 830054, Peoples R China 5.Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, State Key Lab Basis Xinjiang Indigenous Med Plants, Urumqi 830011, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 7.Lingang Lab, Shanghai 200031, Peoples R China 8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zheng, Fuqiang,Hu, Zhengtao,Chen, Hai,et al. Heterocycle-fused phenylcyclohexylamines as novel multi-target antagonists of N-methyl-D-aspartate (NMDA) receptor and monoamine transporter for treating depression[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2025,291:20. |
| APA | Zheng, Fuqiang.,Hu, Zhengtao.,Chen, Hai.,Cheng, Jiaxin.,Hou, Qiongqiong.,...&He, Yang.(2025).Heterocycle-fused phenylcyclohexylamines as novel multi-target antagonists of N-methyl-D-aspartate (NMDA) receptor and monoamine transporter for treating depression.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,291,20. |
| MLA | Zheng, Fuqiang,et al."Heterocycle-fused phenylcyclohexylamines as novel multi-target antagonists of N-methyl-D-aspartate (NMDA) receptor and monoamine transporter for treating depression".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 291(2025):20. |
入库方式： OAI收割
来源：上海药物研究所
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