title: Discovery of novel potent and selective ligands for 5-HT2A receptor with quinazoline scaffold.
abstract: A series of compounds with quinazoline scaffold were designed, synthesized and evaluated as novel potent 5-HT2A receptor ligands. N-(4-Chlorophenyl)-2-(piperazin-1-yl)quinazolin-4-amine (5o) has a Ki value of 14.04 ± 0.21 nM, with a selectivity more than 10,000 fold over 5-HT1A receptors (D1 and D2-like receptors). The functional assay showed that this compound is an antagonist to 5-HT2A receptor with an IC50 value of 1.66 μM.
authors.affiliation: Department of Medicinal Chemistry & Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Xinxian
authors.initials: X
authors.lastname: Deng
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Medicinal Chemistry & Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-disorders & Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu Province 215123, China. Electronic address: zhenxuechu@suda.edu.cn.
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
authors.affiliation: Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Kunqian
authors.initials: K
authors.lastname: Yu
authors.affiliation: Department of Medicinal Chemistry & Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: zhaoweili@fudan.edu.cn.
authors.forename: Weili
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Medicinal Chemistry & Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. Electronic address: wfu@fudan.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Fu
mesh_terms: D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011799:Quinazolines; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists
keywords: 5-HT(2A) receptor antagonist; Molecular docking; Quinazoline derivatives; Synthesis