title: Synthesis and biological activities of indolizine derivatives as alpha-7 nAChR agonists.
abstract: Human α7 nicotinic acetylcholine receptor (nAChR) is a promising therapeutic target for the treatment of schizophrenia accompanied with cognitive impairment. Herein, we report the synthesis and agonistic activities of a series of indolizine derivatives targeting to α7 nAChR. The results show that all synthesized compounds have affinity to α7 nAChR and some give strong agonistic activity, particularly most active agonists show higher potency than control EVP-6124. The docking and structure-activity relationship studies provide insights to develop more potent novel α7 nAChR agonists.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Molecular and Cellular Pharmacology, PKU-IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: Jingshu
authors.initials: J
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: Xiaozhuo
authors.initials: X
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: Bingxue
authors.initials: B
authors.lastname: Xie
authors.affiliation: Department of Molecular and Cellular Pharmacology, PKU-IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Molecular and Cellular Pharmacology, PKU-IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China. Electronic address: wangkw@bjmu.edu.cn.
authors.forename: Kewei
authors.initials: K
authors.lastname: Wang
authors.affiliation: Jiangsu Nhwa Pharmaceutical Co. Ltd. 69 Minzhu South Road, Xuzhou, Jiangsu, 221116, PR China.
authors.forename: Guisen
authors.initials: G
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China. Electronic address: liangren@bjmu.edu.cn.
authors.forename: Liangren
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, PR China.
authors.forename: Lihe
authors.initials: L
authors.lastname: Zhang
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000819:agonists*
chemical_list: D007212:Indolizines; D064569:alpha7 Nicotinic Acetylcholine Receptor; C035094:indolizine
keywords: Agonists; Indolizine; SAR; Schizophrenia; α7 nAChR