title: Synthesis and SAR of potent LXR agonists containing an indole pharmacophore.
abstract: A novel series of 1H-indol-1-yl tertiary amine LXR agonists has been designed. Compounds from this series were potent agonists with good rat pharmacokinetic parameters. In addition, the crystal structure of an LXR agonist bound to LXRalpha will be disclosed.
authors.affiliation: Department of Chemistry, Molecular Discovery Research, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA. dave.g.washburn@gsk.com
authors.forename: David G
authors.initials: DG
authors.lastname: Washburn
authors.forename: Tram H
authors.initials: TH
authors.lastname: Hoang
authors.forename: Nino
authors.initials: N
authors.lastname: Campobasso
authors.forename: Angela
authors.initials: A
authors.lastname: Smallwood
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Parks
authors.forename: Christine L
authors.initials: CL
authors.lastname: Webb
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Frank
authors.forename: Melanie
authors.initials: M
authors.lastname: Nord
authors.forename: Chaya
authors.initials: C
authors.lastname: Duraiswami
authors.forename: Christopher
authors.initials: C
authors.lastname: Evans
authors.forename: Michael
authors.initials: M
authors.lastname: Jaye
authors.forename: Scott K
authors.initials: SK
authors.lastname: Thompson
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002784:Cholesterol / Q000032:analysis; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000819:agonists*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D057093:Orphan Nuclear Receptors; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D004268:DNA-Binding Proteins; D007211:Indoles; D000071518:Liver X Receptors; C000605214:Nr1h3 protein, mouse; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D002784:Cholesterol