title: Identification of novel alpha7 nAChR positive allosteric modulators with the use of pharmacophore in silico screening methods.
abstract: The pharmacophore model of in house potent and selective alpha7 nAChR positive allosteric modulators is reported. The model was used to fish out commercially-available compounds from corporate 3D databases. As a result, novel alpha7 positive modulator chemotypes were identified. A rat full PK profile of a representative compound is also described.
authors.affiliation: GlaxoSmithKline, Molecular Discovery Research, Verona, Italy. Anna-Maria.M.Capelli@gsk.com
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Capelli
authors.forename: Laura
authors.initials: L
authors.lastname: Castelletti
authors.forename: Cristian
authors.initials: C
authors.lastname: Salvagno
authors.forename: Beatrice
authors.initials: B
authors.lastname: Oliosi
authors.forename: Elisa
authors.initials: E
authors.lastname: Di Lenarda
authors.forename: Caterina
authors.initials: C
authors.lastname: Virginio
authors.forename: Andrew
authors.initials: A
authors.lastname: Lightfoot
authors.forename: James N C
authors.initials: JN
authors.lastname: Kew
authors.forename: Simon
authors.initials: S
authors.lastname: Teague
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D002460:Cell Line; D016208:Databases, Factual; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry / Q000493:pharmacokinetics; D008862:Microsomes, Liver / Q000378:metabolism; D008958:Models, Molecular; D010671:Phenylurea Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C508388:1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)urea; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D007555:Isoxazoles; D010671:Phenylurea Compounds; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor