title: Carboxylic acid based quinolines as liver X receptor modulators that have LXRbeta receptor binding selectivity.
abstract: A series of potent and binding selective LXRbeta agonists was developed using the previously reported non-selective LXR ligand WAY-254011 as a structural template. With the aid of molecular modeling, it was found that 2,3-diMe-Ph, 2,5-diMe-Ph, and naphthalene substituted quinoline acetic acids (such as quinoline 33, 37, and 38) showed selectivity for LXRbeta over LXRalpha in binding assays.
authors.affiliation: Chemical and Screening Sciences, Wyeth Pharmaceuticals, Collegeville, PA 19426, USA. hub@wyeth.com
authors.forename: Baihua
authors.initials: B
authors.lastname: Hu
authors.forename: Elaine
authors.initials: E
authors.lastname: Quinet
authors.forename: Rayomand
authors.initials: R
authors.lastname: Unwalla
authors.forename: Mike
authors.initials: M
authors.lastname: Collini
authors.forename: James
authors.initials: J
authors.lastname: Jetter
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dooley
authors.forename: Diane
authors.initials: D
authors.lastname: Andraka
authors.forename: Lisa
authors.initials: L
authors.lastname: Nogle
authors.forename: Dawn
authors.initials: D
authors.lastname: Savio
authors.forename: Anita
authors.initials: A
authors.lastname: Halpern
authors.forename: Annika
authors.initials: A
authors.lastname: Goos-Nilsson
authors.forename: Anna
authors.initials: A
authors.lastname: Wilhelmsson
authors.forename: Ponnal
authors.initials: P
authors.lastname: Nambi
authors.forename: Jay
authors.initials: J
authors.lastname: Wrobel
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D057093:Orphan Nuclear Receptors; D011804:Quinolines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D015533:Transcriptional Activation
chemical_list: D002264:Carboxylic Acids; D004268:DNA-Binding Proteins; D008024:Ligands; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D011804:Quinolines; D018160:Receptors, Cytoplasmic and Nuclear