Carbon-silicon switch led to the discovery of novel synthetic cannabinoids with therapeutic effects in a mouse model of multiple sclerosis

doi:10.1016/j.ejmech.2021.113878

	Carbon-silicon switch led to the discovery of novel synthetic cannabinoids with therapeutic effects in a mouse model of multiple sclerosis
	Duan, Wenwen1 ; Sun, Ying 2; Wu, Meng1 ; Zhang, Zhiyuan1 ; Zhang, Taotao 3; Wang, Huan1 ; Li, Fei1 ; Yang, Lingyun1 ; Xu, Yueming1 ; Liu, Zhi-Jie1,4 ; Hua, Tian1,4 ; Nie, Hong 2; Cheng, Jianjun1
	2021-12-15
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (IF:6.0[JCR-2023],6.1[5-Year])
ISSN	0223-5234
EISSN	1768-3254
卷号	226
发表状态	已发表
DOI	10.1016/j.ejmech.2021.113878
摘要	Cannabinoids are widely studied as therapeutic agents for the treatment of various diseases. Among them, THC and CBD are two important phytocannabinoids which have served as structural templates for the design of synthetic analogs. In this study, we designed and synthesized a variety of novel cannabinoids based on the structural backbones of THC and CBD using the carbon-silicon switch strategy. A dimethyl silyl group was introduced as the tail group and two series of novel compounds were designed and synthesized, which showed a wide range of binding affinity for CB1 and CB2 receptors. Among them, compound 15b was identified as a non-selective CB1 and CB2 agonist and 38b as a selective agonist for the CB2 receptor. Preliminary screening showed that both compounds have improved metabolic stability than their carbon analogs and good in vivo pharmacokinetic profiles. Furthermore, both 15b and 38b significantly alleviated the phenotype of experimental autoimmune encephalomyelitis (EAE) in mice. (C) 2021 Elsevier Masson SAS. All rights reserved.
关键词	Cannabinoid Tetrahydrocannabinol Cannabidiol G protein-coupled receptor Multiple sclerosis
收录类别	SCIE ; IC
语种	英语
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000708735400011
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128501
专题	iHuman研究所_公共科研平台_IT平台生命科学与技术学院 iHuman研究所 iHuman研究所_公共科研平台_生命科学NMR平台 iHuman研究所_PI研究组_程建军组 iHuman研究所_PI研究组_华甜组
通讯作者	Hua, Tian; Nie, Hong; Cheng, Jianjun
作者单位	1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China; 2.Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Dept Immunol & Microbiol, Sch Med, Shanghai 200025, Peoples R China; 3.Kunming Med Univ, Biomed Engn Res Ctr, Kunming 650500, Yunnan, Peoples R China; 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
第一作者单位	iHuman研究所
通讯作者单位	iHuman研究所; 生命科学与技术学院
第一作者的第一单位	iHuman研究所
推荐引用方式 GB/T 7714	Duan, Wenwen,Sun, Ying,Wu, Meng,et al. Carbon-silicon switch led to the discovery of novel synthetic cannabinoids with therapeutic effects in a mouse model of multiple sclerosis[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2021,226.
APA	Duan, Wenwen.,Sun, Ying.,Wu, Meng.,Zhang, Zhiyuan.,Zhang, Taotao.,...&Cheng, Jianjun.(2021).Carbon-silicon switch led to the discovery of novel synthetic cannabinoids with therapeutic effects in a mouse model of multiple sclerosis.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,226.
MLA	Duan, Wenwen,et al."Carbon-silicon switch led to the discovery of novel synthetic cannabinoids with therapeutic effects in a mouse model of multiple sclerosis".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 226(2021).