title: Peroxisome proliferator-activated receptor agonists with phenethylphenylphthalimide skeleton derived from thalidomide-related liver X receptor antagonists: relationship between absolute configuration and subtype selectivity.
abstract: Introduction of an alkylcarboxylic acid unit, which is a partial structure of endogenous peroxisome proliferator-activated receptor (PPAR) ligands, into a phenethylphenylphthalimide skeleton, which possesses liver X receptor (LXR) antagonistic activity, afforded novel PPAR ligands. The results of structure-activity relationship analysis and docking studies led us to the potent PPAR agonists 13c-e. The absolute configuration of 13c-e affects the PPAR subtype selectivity.
authors.affiliation: Institute of Molecular & Cellular Bioscience, The University of Tokyo, Yayoi, Bunkyo-ku, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Motoshima
authors.forename: Minoru
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sugita
mesh_terms: D002460:Cell Line; D015195:Drug Design; D006801:Humans; D008024:Ligands; D000071518:Liver X Receptors; D008958:Models, Molecular; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism*; D010797:Phthalimides / Q000737:chemistry* / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013329:Structure-Activity Relationship; D013792:Thalidomide / Q000737:chemistry*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047492:Peroxisome Proliferator-Activated Receptors; D010797:Phthalimides; D018160:Receptors, Cytoplasmic and Nuclear; D013792:Thalidomide; D000099150:Receptor, Farnesoid X-Activated