Synthesis and biological investigation of triazolopyridinone derivatives as potential multireceptor atypical antipsychotics

doi:10.1016/j.bmcl.2020.127027

	Synthesis and biological investigation of triazolopyridinone derivatives as potential multireceptor atypical antipsychotics
	Shi, Wenqiang 1,2; Wang, Yu 1; Wu, Chunhui 3; Yang, Feipu 1; Zheng, Wei 1,2; Wu, Song 3; Liu, Yongjian 3; Wang, Zhen 1; He, Yang 1,2; Shen, Jingshan 1,2
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2020-04-15
卷号	30 期号:8 页码:6
关键词	Triazolopyridinone Antipsychotic Multireceptor 5-HT1A receptor
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2020.127027
通讯作者	Wang, Zhen(wangzhen@simm.ac.cn) ; He, Yang(heyang@simm.ac.cn)
英文摘要	A series of triazolopyridinone derivatives originating from the antidepressant trazodone was designed and pharmacologically evaluated. Most of the compounds with a multireceptor functional profile exhibited high potency at the D-2, 5-HT1A, and 5-HT2A receptors. Compounds S1, S3, S9 and S12 were selected for further evaluation of druggable potential. Among these compounds, S1, as a D-2 receptor partial agonist, demonstrated very potent inhibition of quipazine-induced head-twitch response, which validated its 5-HT2A receptor antagonistic efficacy in vivo. S1 also demonstrated a dose-dependent effect on PCP-induced hyperactivity when administered orally. Thus, S1 endowed with a triazolopyridinone scaffold represents a valuable lead for the development of novel atypical antipsychotics.
资助项目	Special Foundation of Chinese Academy of Sciences for strategic pilot technology[XDA12040105] ; Special Foundation of Chinese Academy of Sciences for strategic pilot technology[XDA12040331] ; Youth Program of National Natural Science Foundation of China[81703338] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002] ; Science and Technology Commission of Shanghai Municipality[18431907100]
WOS关键词	PHARMACOLOGICAL-TREATMENT ; NEGATIVE SYMPTOMS ; ANXIETY SYMPTOMS ; SCHIZOPHRENIA ; 5-HT1A ; RECEPTORS ; METAANALYSIS ; MANAGEMENT ; TRAZODONE ; COGNITION
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000519194300024
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281131]
专题	中国科学院上海药物研究所
通讯作者	Wang, Zhen; He, Yang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Topharman Shanghai Co Ltd, 388 Jialilue Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Shi, Wenqiang,Wang, Yu,Wu, Chunhui,et al. Synthesis and biological investigation of triazolopyridinone derivatives as potential multireceptor atypical antipsychotics[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2020,30(8):6.
APA	Shi, Wenqiang.,Wang, Yu.,Wu, Chunhui.,Yang, Feipu.,Zheng, Wei.,...&Shen, Jingshan.(2020).Synthesis and biological investigation of triazolopyridinone derivatives as potential multireceptor atypical antipsychotics.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,30(8),6.
MLA	Shi, Wenqiang,et al."Synthesis and biological investigation of triazolopyridinone derivatives as potential multireceptor atypical antipsychotics".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 30.8(2020):6.