title: Further modification on phenyl acetic acid based quinolines as liver X receptor modulators.
abstract: A series of phenyl acetic acid based quinolines was prepared as LXR modulators. An SAR study in which the C-3 and C-8 positions of the quinoline core were varied led to the identification of two potent LXR agonists 23 and 27. Both compounds displayed good binding affinity for LXRbeta and LXRalpha, and increased expression of ABCA1 in THP-1 cells. These two compounds also had desirable pharmacokinetic profiles in mice and displayed in vivo efficacy in a 12-week Apo E knockout mouse lesion model.
authors: Chemical and Screening Sciences, Wyeth Pharmaceuticals, 500 Arcola Road, Collegeville, PA 19426, USA. hub@wyeth.com
authors: Baihua
authors: B
authors: Hu
authors: James
authors: J
authors: Jetter
authors: David
authors: D
authors: Kaufman
authors: Robert
authors: R
authors: Singhaus
authors: Ronald
authors: R
authors: Bernotas
authors: Rayomand
authors: R
authors: Unwalla
authors: Elaine
authors: E
authors: Quinet
authors: Dawn
authors: D
authors: Savio
authors: Anita
authors: A
authors: Halpern
authors: Michael
authors: M
authors: Basso
authors: James
authors: J
authors: Keith
authors: Valerie
authors: V
authors: Clerin
authors: Liang
authors: L
authors: Chen
authors: Qiang-Yuan
authors: QY
authors: Liu
authors: Irene
authors: I
authors: Feingold
authors: Christine
authors: C
authors: Huselton
authors: Farooq
authors: F
authors: Azam
authors: Annika
authors: A
authors: Goos-Nilsson
authors: Anna
authors: A
authors: Wilhelmsson
authors: Ponnal
authors: P
authors: Nambi
authors: Jay
authors: J
authors: Wrobel
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D016466:CHO Cells; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000819:agonists* / Q000235:genetics; D006801:Humans; D007202:Indicators and Reagents; D000071518:Liver X Receptors; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D012997:Solvents; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D002264:Carboxylic Acids; D004268:DNA-Binding Proteins; D007202:Indicators and Reagents; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; D057093:Orphan Nuclear Receptors; D010648:Phenylacetates; D011804:Quinolines; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D012997:Solvents; C025136:phenylacetic acid