Synthesis and Biological Evaluation of Five-Atom-Linker-Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile

doi:10.1002/cmdc.201900439

	Synthesis and Biological Evaluation of Five-Atom-Linker-Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile
	Wu, Chunhui 2,3; Wang, Yu 1,3; Yang, Feipu 1; Shi, Wenqiang 1; Wang, Zhen 1; He, Ling 3; He, Yang 1; Shen, Jingshan 1
刊名	CHEMMEDCHEM
	2019-11-20
页码	11
关键词	D-2 5-HT1A 5-HT2A serotonin SERT PCP-induced hyperactivity
ISSN号	1860-7179
DOI	10.1002/cmdc.201900439
通讯作者	He, Ling(heling92@hotmail.com) ; He, Yang(heyang@simm.ac.cn)
英文摘要	Herein we describe a focused set of new arylpiperazine derivatives as potential broad-spectrum antipsychotics. The general structure contains a quinolinone-like moiety, an arylpiperazine moiety, and a five-atom linker. Among them, 7-(5-(4-(benzo[d]isothiazol-4-yl)piperazin-1-yl)pentyl)quinolin-2(1H)-one (S6) shows a promising preclinical profile. Compound S6, characterized by partial D2R agonism, 5-HT1AR agonism, 5-HT2AR antagonism, and blockade of SERT activities, was found to decrease psychosis- and depressive-like symptoms in rodents. The polypharmacological profile of S6 could provide opportunities for the treatment of various other central nervous system disorders such as anxiety, depression, and psychoses associated with dementia. Furthermore, S6 demonstrated acceptable safety, toxicology, and pharmacokinetic profiles, and has been selected as a preclinical candidate for further evaluation in schizophrenia.
资助项目	Special Foundation of Chinese Academy of Sciences for strategic pilot technology[XDA12040105] ; Youth Program of National Natural Science Foundation of China[81703338] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002]
WOS关键词	SEROTONIN 5-HT1A RECEPTORS ; WEIGHT-GAIN ; SCHIZOPHRENIA ; BREXPIPRAZOLE ; ANTIDEPRESSANTS ; PHARMACOTHERAPY ; RATIONALE ; UPDATE ; SERIES ; DRUGS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000497202100001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281900]
专题	中国科学院上海药物研究所
通讯作者	He, Ling; He, Yang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Key Lab Receptor Res, Shanghai 201203, Peoples R China 2.Topharman Shanghai Co Ltd, Dept Druggabil Evaluat, Shanghai 201203, Peoples R China 3.China Pharmaceut Univ, Dept Pharmacol, Nanjing 210009, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Wu, Chunhui,Wang, Yu,Yang, Feipu,et al. Synthesis and Biological Evaluation of Five-Atom-Linker-Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile[J]. CHEMMEDCHEM,2019:11.
APA	Wu, Chunhui.,Wang, Yu.,Yang, Feipu.,Shi, Wenqiang.,Wang, Zhen.,...&Shen, Jingshan.(2019).Synthesis and Biological Evaluation of Five-Atom-Linker-Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile.CHEMMEDCHEM,11.
MLA	Wu, Chunhui,et al."Synthesis and Biological Evaluation of Five-Atom-Linker-Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile".CHEMMEDCHEM (2019):11.