title: Synthesis and activity of substituted heteroaromatics as positive allosteric modulators for α4β2α5 nicotinic acetylcholine receptors.
abstract: The design and synthesis of a series of substituted heteroaromatic α4β2α5 positive allosteric modulators is reported. The optimization and development of the heteroaromatic series was carried out from NS9283, and several potent analogues, such as 3-(5-(pyridin-3-yl)-2H-tetrazol-2-yl)benzonitrile (5k) and 3,3'-(2H-tetrazole-2,5-diyl)dipyridine (12 h) with good in vitro efficacy were discovered.
authors.affiliation: Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors.forename: Pasha
authors.initials: P
authors.lastname: Khan
authors.affiliation: Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors.forename: Youseung
authors.initials: Y
authors.lastname: Shin
authors.affiliation: Department of Neuroscience, University of Pennsylvania, 217 Stemmler Hall, 36th & Hamilton Walk, Philadelphia, PA 19104, USA.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Cameron
authors.affiliation: Department of Neuroscience, University of Pennsylvania, 217 Stemmler Hall, 36th & Hamilton Walk, Philadelphia, PA 19104, USA.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Lindstrom
authors.affiliation: Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kenny
authors.affiliation: Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #A2A, Jupiter, FL 33458, USA. Electronic address: kameneck@scripps.edu.
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Kamenecka
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: C561896:3-(3-(pyridine-3-yl)-1,2,4-oxadiazol-5-yl)benzonitrile; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D010069:Oxadiazoles; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C577601:nicotinic receptor alpha5 subunit, human
keywords: Positive allosteric modulators; Substituted heteroaromatics; α4β2α5