title: 4-(3-Aryloxyaryl)quinoline sulfones are potent liver X receptor agonists.
abstract: A series of 4-(3-aryloxyaryl)quinolines with sulfone substituents on the terminal aryl ring (7) was prepared as LXR agonists. High affinity LXR ligands with excellent agonist potency and efficacy in functional assays of LXR activity were identified. In general, these sulfone agonists were equal to or superior to previously described alcohol and amide analogs in terms of affinity, functional potency, and microsomal stability. Many of the sulfones had LXRbeta binding IC(50) values <10nM while the most potent compounds in an ABCA1 mRNA induction assay in J774 mouse cells had EC(50) values <10nM and were as efficacious as T0901317.
authors.affiliation: Chemical 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: Jeremy M
authors.initials: JM
authors.lastname: Travins
authors.forename: John W
authors.initials: JW
authors.lastname: Ullrich
authors.forename: Rayomand
authors.initials: R
authors.lastname: Unwalla
authors.forename: Elaine
authors.initials: E
authors.lastname: Quinet
authors.forename: Mark
authors.initials: M
authors.lastname: Evans
authors.forename: Ponnal
authors.initials: P
authors.lastname: Nambi
authors.forename: Andrea
authors.initials: A
authors.lastname: Olland
authors.forename: Björn
authors.initials: B
authors.lastname: Kauppi
authors.forename: Anna
authors.initials: A
authors.lastname: Wilhelmsson
authors.forename: Annika
authors.initials: A
authors.lastname: Goos-Nilsson
authors.forename: Jay
authors.initials: J
authors.lastname: Wrobel
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003198:Computer Simulation; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry / Q000494:pharmacology; D006860:Hydrogen Bonding; D000071518:Liver X Receptors; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011804:Quinolines; D013449:Sulfonamides; D013450:Sulfones; C577836:ABCA1 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides