title: Novel heterocyclic scaffolds of GW4064 as farnesoid X receptor agonists.
abstract: The farnesoid X receptor (FXR) may play a crucial role in a number of metabolic diseases and, as such, could potentially serve as a target for the development of therapeutics as a treatment for those diseases. Previous work has described GW4064 as an FXR agonist with an interesting activity profile. This manuscript will describe the synthesis of novel analogs of GW4064 and the activity profile of those analogs.
authors.affiliation: Muscle Metabolism DPU, Metabolic Pathways & Cardiovascular Discovery Performance Unit, GlaxoSmithKline, Inc., Five Moore Drive, Research Triangle Park, NC 27709, United States. Electronic address: terry.l.smalley@gsk.com.
authors.forename: Terrence L
authors.initials: TL
authors.lastname: Smalley
authors.affiliation: Muscle Metabolism DPU, Metabolic Pathways & Cardiovascular Discovery Performance Unit, GlaxoSmithKline, Inc., Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Sharon
authors.initials: S
authors.lastname: Boggs
authors.affiliation: Computational and Structural Sciences, Platform Technology & Science, GlaxoSmithKline, Inc., Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Caravella
authors.affiliation: Enteroendocrine DPU, Metabolic Pathways & Cardiovascular Discovery Performance Unit, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.affiliation: Molecular Discovery Research, Platform Technology & Science, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Creech
authors.affiliation: Muscle Metabolism DPU, Metabolic Pathways & Cardiovascular Discovery Performance Unit, GlaxoSmithKline, Inc., Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: David N
authors.initials: DN
authors.lastname: Deaton
authors.affiliation: Muscle Metabolism DPU, Metabolic Pathways & Cardiovascular Discovery Performance Unit, GlaxoSmithKline, Inc., Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Istvan
authors.initials: I
authors.lastname: Kaldor
authors.affiliation: Molecular Discovery Research, Platform Technology & Science, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Parks
mesh_terms: D004353:Drug Evaluation, Preclinical; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D023303:Oxazolidinones / Q000737:chemistry / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013329:Structure-Activity Relationship; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D007555:Isoxazoles; D023303:Oxazolidinones; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C412815:GW 4064
keywords: FXR agonist; Heterocycles; Liver