Identification of Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists

doi:10.1021/acschemneuro.9b00563

	Identification of Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists
	Mao, Qi 3,4; Zhang, Bingjie1,2 ; Li, Wanwan 3,4; Tian, Sheng 3,4; Shui, Wenqing1,2 ; Ye, Na 3,4
	2020-02-19
发表期刊	ACS CHEMICAL NEUROSCIENCE (IF:4.1[JCR-2023],4.3[5-Year])
ISSN	1948-7193
卷号	11 期号:4 页码:549-559
发表状态	已发表
DOI	10.1021/acschemneuro.9b00563
摘要	The 5-HT2C receptor has emerged as a promising target in the treatment of a variety of central nervous system disorders. We have first identified aporphines as a new class of 5-HT2C receptor agonists. Structure-activity relationship results indicate that the aporphine core may be required for 5-HT2C receptor activity, and substitutions at its C1 position are important for 5-HT2C receptor activity. Our efforts to optimize our hit 15781 lead to the identification of the highly potent and selective 5-HT2C agonist 18b (MQ02-439) with an EC50 value of 104 nM and weak antagonism at the 5-HT2A and 5-HT2B receptors. The findings may serve as good starting points for the development of more potent and selective 5-HT2C agonists as valuable pharmacological tools or potential drug candidates.
关键词	Serotonin 5-HT2C receptor 5-HT2B receptor 5-HT2A receptor agonist aporphine
收录类别	SCI ; SCIE
语种	英语
资助项目	Jiangsu Key Laboratory of Neuropsychiatric Diseases[BM2013003]
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Neurosciences & Neurology
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Neurosciences
WOS记录号	WOS:000515195800006
出版者	AMER CHEMICAL SOC
WOS关键词	THERAPEUTIC OPPORTUNITIES ; DUAL-AGONIST ; SEROTONIN ; 2C ; DOPAMINE-D-2 ; DISCOVERY ; LIGANDS ; OBESITY ; DESIGN
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/114814
专题	iHuman研究所_PI研究组_水雯箐组生命科学与技术学院
通讯作者	Shui, Wenqing; Ye, Na
作者单位	1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Soochow Univ, Jiangsu Key Lab Neuropsychiat Dis, Suzhou 215123, Jiangsu, Peoples R China 4.Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Jiangsu, Peoples R China
通讯作者单位	iHuman研究所; 生命科学与技术学院
推荐引用方式 GB/T 7714	Mao, Qi,Zhang, Bingjie,Li, Wanwan,et al. Identification of Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists[J]. ACS CHEMICAL NEUROSCIENCE,2020,11(4):549-559.
APA	Mao, Qi,Zhang, Bingjie,Li, Wanwan,Tian, Sheng,Shui, Wenqing,&Ye, Na.(2020).Identification of Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists.ACS CHEMICAL NEUROSCIENCE,11(4),549-559.
MLA	Mao, Qi,et al."Identification of Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists".ACS CHEMICAL NEUROSCIENCE 11.4(2020):549-559.