title: Biarylether amide quinolines as liver X receptor agonists.
abstract: A series of 4-(amido-biarylether)-quinolines was prepared as potential LXR agonists. Appropriate substitution with amide groups provided high affinity LXR ligands, some with excellent potency and efficacy in functional assays of LXR activity. Novel amide 4g had a binding IC(50)=1.9 nM for LXRbeta and EC(50)=34 nM (96% efficacy relative to T0901317) in an ABCA1 gene expression assay in mouse J774 cells, demonstrating that 4-(biarylether)-quinolines with appropriate amide substitution are potent LXR agonists.
authors.affiliation: Chemical and Screening Sciences, Wyeth Pharmaceuticals, 500 Arcola Road, Collegeville, PA 19426, USA. bernotr@wyeth.com
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Bernotas
authors.forename: Robert R
authors.initials: RR
authors.lastname: Singhaus
authors.forename: David H
authors.initials: DH
authors.lastname: Kaufman
authors.forename: John
authors.initials: J
authors.lastname: Ullrich
authors.forename: Horace
authors.initials: H
authors.lastname: Fletcher
authors.forename: Elaine
authors.initials: E
authors.lastname: Quinet
authors.forename: Ponnal
authors.initials: P
authors.lastname: Nambi
authors.forename: Rayomand
authors.initials: R
authors.lastname: Unwalla
authors.forename: Anna
authors.initials: A
authors.lastname: Wilhelmsson
authors.forename: Annika
authors.initials: A
authors.lastname: Goos-Nilsson
authors.forename: Mathias
authors.initials: M
authors.lastname: Farnegardh
authors.forename: Jay
authors.initials: J
authors.lastname: Wrobel
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D007700:Kinetics; D008024:Ligands; D000071518:Liver X Receptors; D051379:Mice; D008958:Models, Molecular; D057093:Orphan Nuclear Receptors; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000577:Amides; D004268:DNA-Binding Proteins; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011804:Quinolines; D018160:Receptors, Cytoplasmic and Nuclear