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Design, Synthesis and Bioactivity of [3.3.3]Propellane-Based Voltage-Gated Calcium Channel alpha 2 delta Subunit Ligands

文献类型：期刊论文

作者He Jinyan1,2,3; Tian Fuyun2,3; Wu Qingqing2; Zheng Yueming3; Chen Yuting2; Xu Haiyan3; Jin Zhengsheng2; Zhan Li3; Cheng Xinqiang2; Gu Yueling3
刊名CHINESE JOURNAL OF ORGANIC CHEMISTRY
出版日期2023-06-01
卷号43期号:6页码:2226-2238
ISSN号0253-2786
关键词propellane voltage-gated calcium channel alpha 2 delta subunit synthesis bioactivity structure-activity relationship
DOI10.6023/cjoc202210007
通讯作者Gao Zhaobing(zbgao@simm.ac.cn) ; Zhao Guilong(zhao_guilong@126.com)
英文摘要Voltage-gated calcium channel (VGCC) alpha 2 delta subunit ligands represent one of the most efficacious and safest classes of drugs for the treatment of chronic neuropathic pain. In order to investigate the effect of the sterically bulky alkyl moieties with constrained conformation on the bioactivity of VGCC alpha 2 delta subunit ligands, three.-aminobutyric acids (GABAs) substitued with [3.3.3]propellane and one GABA with bicyclo[3.3.0]octane were designed and synthesized. All the syntheszied compounds were characterzied by H-1 NMR, C-13 NMR and high-resolution mass spectrometry (HRMS), and subjected to in vitro human VGCC alpha 2 delta subunit binding assay. The bioactivity results indicated that: [3.3.3]propellane can be tolerated in the VGCC alpha 2 delta ligand, but its size is bulkier than the optimal size. The amino group in GABA chain can not be modified or replaced; otherwise, the bioactivity will decrease dramatically or even be lost. The structure-activity relationship revealed in the present study may be helpful for the future design of novel VGCC alpha 2 delta subunit ligands.
WOS关键词PHARMACOLOGY ; GABAPENTIN
资助项目Zhongshan Municipal Natural Science Foundation[200805173640573] ; Zhongshan Municipal Natural Science Foundation[210730214049987] ; Guangdong Provincial Basic and Applied Basic Research Foundation[2021A1515010197] ; Guangdong Provincial High-Level New R&D Institute Strategic Special Fund[2019B090904008] ; Guangdong Provincial High-level Innovative Research Institute Strategic Special Fund[2021B0909050003]
WOS研究方向Chemistry
语种英语
出版者SCIENCE PRESS
WOS记录号WOS:001028786600028
源URL[http://119.78.100.183/handle/2S10ELR8/306845]  
专题中国科学院上海药物研究所
通讯作者Gao Zhaobing; Zhao Guilong
作者单位1.Zunyi Med Univ, Sch Pharm, Zunyi 563003, Guizhou, Peoples R China
2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Guangzhou 528400, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 He Jinyan,Tian Fuyun,Wu Qingqing,et al. Design, Synthesis and Bioactivity of [3.3.3]Propellane-Based Voltage-Gated Calcium Channel alpha 2 delta Subunit Ligands[J]. CHINESE JOURNAL OF ORGANIC CHEMISTRY,2023,43(6):2226-2238.
APA He Jinyan.,Tian Fuyun.,Wu Qingqing.,Zheng Yueming.,Chen Yuting.,...&Zhao Guilong.(2023).Design, Synthesis and Bioactivity of [3.3.3]Propellane-Based Voltage-Gated Calcium Channel alpha 2 delta Subunit Ligands.CHINESE JOURNAL OF ORGANIC CHEMISTRY,43(6),2226-2238.
MLA He Jinyan,et al."Design, Synthesis and Bioactivity of [3.3.3]Propellane-Based Voltage-Gated Calcium Channel alpha 2 delta Subunit Ligands".CHINESE JOURNAL OF ORGANIC CHEMISTRY 43.6(2023):2226-2238.

入库方式： OAI收割

来源：上海药物研究所

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