title: 1-(3-Aryloxyaryl)benzimidazole sulfones are liver X receptor agonists.
abstract: A series of 1-(3-aryloxyaryl)benzimidazoles incorporating a sulfone substituent (6) was prepared. High affinity LXR ligands were identified (LXRbeta binding IC(50) values <10nM), some with excellent agonist potency and efficacy in a functional assay of LXR activity measuring ABCA1 mRNA increases in human macrophage THP1 cells. The compounds were typically stable in liver microsome preparations and had good oral exposure in mice.
authors.affiliation: Chemical Sciences, Wyeth Pharmaceuticals, 500 Arcola Road, Collegeville, PA 19426, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Travins
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Bernotas
authors.forename: David H
authors.initials: DH
authors.lastname: Kaufman
authors.forename: Elaine
authors.initials: E
authors.lastname: Quinet
authors.forename: Ponnal
authors.initials: P
authors.lastname: Nambi
authors.forename: Irene
authors.initials: I
authors.lastname: Feingold
authors.forename: Christine
authors.initials: C
authors.lastname: Huselton
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: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D002460:Cell Line; D006801:Humans; D000071518:Liver X Receptors; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000737:chemistry*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001562:Benzimidazoles; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D013450:Sulfones