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

文献类型：期刊论文

作者Wu, Chunhui2,3; Wang, Yu1,3; Yang, Feipu1; Shi, Wenqiang1; Wang, Zhen1; He, Ling3; He, Yang1; Shen, Jingshan1
刊名CHEMMEDCHEM
出版日期2019-11-20
页码11
关键词D-2 5-HT1A 5-HT2A serotonin SERT PCP-induced hyperactivity
ISSN号1860-7179
DOI10.1002/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.
WOS关键词SEROTONIN 5-HT1A RECEPTORS ; WEIGHT-GAIN ; SCHIZOPHRENIA ; BREXPIPRAZOLE ; ANTIDEPRESSANTS ; PHARMACOTHERAPY ; RATIONALE ; UPDATE ; SERIES ; DRUGS
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研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000497202100001
出版者WILEY-V C H VERLAG GMBH
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.

入库方式： OAI收割

来源：上海药物研究所

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