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Among them, 7\u2010(5\u2010(4\u2010(benzo[<jats:italic>d<\/jats:italic>]isothiazol\u20104\u2010yl)piperazin\u20101\u2010yl)pentyl)quinolin\u20102(1<jats:italic>H<\/jats:italic>)\u2010one (<jats:bold>S6<\/jats:bold>) shows a promising preclinical profile. Compound <jats:bold>S6<\/jats:bold>, characterized by partial D<jats:sub>2<\/jats:sub>R agonism, 5\u2010HT<jats:sub>1A<\/jats:sub>R agonism, 5\u2010HT<jats:sub>2A<\/jats:sub>R antagonism, and blockade of SERT activities, was found to decrease psychosis\u2010 and depressive\u2010like symptoms in rodents. The polypharmacological profile of <jats:bold>S6<\/jats:bold> could provide opportunities for the treatment of various other central nervous system disorders such as anxiety, depression, and psychoses associated with dementia. Furthermore, <jats:bold>S6<\/jats:bold> demonstrated acceptable safety, toxicology, and pharmacokinetic profiles, and has been selected as a preclinical candidate for further evaluation in schizophrenia.<\/jats:p>","DOI":"10.1002\/cmdc.201900439","type":"journal-article","created":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T06:10:14Z","timestamp":1574230214000},"page":"2042-2051","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Synthesis and Biological Evaluation of Five\u2010Atom\u2010Linker\u2010Based Arylpiperazine Derivatives with an Atypical Antipsychotic Profile"],"prefix":"10.1002","volume":"14","author":[{"given":"Chunhui","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pharmacology China Pharmaceutical University  Nanjing 210009 China"},{"name":"Department of Druggability Evaluation Topharman Shanghai Co. Ltd.  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