中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 国家级研究中心
  5. 原创新药研究全国重点实验室
Design, synthesis, and biological profiling of novel aryl-spirocyclic diamine derivatives with potential antidepressant-like properties

文献类型：期刊论文

作者Zheng, Jiefang1,2; Tian, Yaxin1,2; Cheng, Jiaxin1,2; Hu, Zhengtao1,4; Zhang, Junchi1,2; Yang, Feipu1,2; Li, Pengcheng3; Jiang, Zhijuan3; Gong, Xudong3; Hou, Qiongqiong3
刊名EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
出版日期2026-01-05
卷号301页码:23
关键词Antidepressants Multimodal monoaminergic compounds Triple monoamine reuptake inhibitors 5-HT 3A R antagonist Aryl-spirocyclic diamine derivatives
ISSN号0223-5234
DOI10.1016/j.ejmech.2025.118198
英文摘要To meet the clinical need for therapeutic efficacy against cognitive impairment and pain comorbidities in depression, a rational drug design approach was used in the current study to synthesize a series of spirocyclic diamine derivatives. Among them, (R)-D24 exhibited triple monoamine reuptake inhibitory activity (SERT, NET, and DAT), while D6 and D17 showed potent inhibitory activity against both SERT and 5-HT3AR. D6 and D17 have acceptable systemic exposure and oral bioavailability in mice and low clearance in human liver microsomes. D6 and D17 exhibited favorable safety profiles in hepatic, renal, and hERG toxicity assays and showed potent antidepressant-like effects in the forced swim test, supporting their potential for further preclinical investigation. In addition, the compound-target interactions of the key compounds were analyzed through molecular docking. These results highlight the rationality of our design and provide new perspectives for the development of antidepressant drugs.
WOS关键词TRIPLE REUPTAKE INHIBITORS ; DOPAMINE ; SEROTONIN ; PAIN ; VORTIOXETINE ; MODULATION ; RELEASE ; DRUG
资助项目STI2030-Major Projects[2021ZD0200900] ; Science and Technology Commission of Shanghai Municipality[20S11903300]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001596382000002
出版者ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/320709]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Tian, Guanghui; Zhu, Weiliang; He, Yang
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Vigonvita Shanghai Co Ltd, Shanghai 201210, Peoples R China
4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
推荐引用方式
GB/T 7714		 Zheng, Jiefang,Tian, Yaxin,Cheng, Jiaxin,et al. Design, synthesis, and biological profiling of novel aryl-spirocyclic diamine derivatives with potential antidepressant-like properties[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2026,301:23.
APA Zheng, Jiefang.,Tian, Yaxin.,Cheng, Jiaxin.,Hu, Zhengtao.,Zhang, Junchi.,...&Shen, Jingshan.(2026).Design, synthesis, and biological profiling of novel aryl-spirocyclic diamine derivatives with potential antidepressant-like properties.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,301,23.
MLA Zheng, Jiefang,et al."Design, synthesis, and biological profiling of novel aryl-spirocyclic diamine derivatives with potential antidepressant-like properties".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 301(2026):23.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。