title: Evolution of a Novel, Orally Bioavailable Series of PI3Kδ Inhibitors from an Inhaled Lead for the Treatment of Respiratory Disease.
abstract: A four-step process of high-quality modeling of existing data, deconstruction, identification of replacement cores, and an innovative synthetic regrowth strategy led to the rapid discovery of a novel oral series of PI3Kδ inhibitors with promising selectivity and excellent in vivo characteristics.
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Augustin
authors.initials: A
authors.lastname: Amour
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Nick
authors.initials: N
authors.lastname: Barton
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Anthony W J
authors.initials: AW
authors.lastname: Cooper
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Graham
authors.initials: G
authors.lastname: Inglis
authors.affiliation: Department of Pure and Applied Chemistry, University of Strathclyde , 295 Cathedral Street, Glasgow G1 1XL, U.K.
authors.forename: Craig
authors.initials: C
authors.lastname: Jamieson
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Luscombe
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Josie
authors.initials: J
authors.lastname: Morrell
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Simon
authors.initials: S
authors.lastname: Peace
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: David
authors.initials: D
authors.lastname: Perez
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Paul
authors.initials: P
authors.lastname: Rowland
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Tame
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Sorif
authors.initials: S
authors.lastname: Uddin
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitulli
authors.affiliation: GlaxoSmithKline R&D , Gunnels Wood Road, Stevenage SG1 2NY, U.K.
authors.forename: Natalie
authors.initials: N
authors.lastname: Wellaway
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001682:Biological Availability; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012140:Respiratory Tract Diseases / Q000188:drug therapy* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D058543:Class Ia Phosphatidylinositol 3-Kinase