title: Design and synthesis of substituted phenylpropanoic acid derivatives as human peroxisome proliferator-activated receptor alpha/delta dual agonists.
abstract: A series of phenylpropanoic acids was prepared as candidate dual agonists of peroxisome proliferator-activated receptors (PPAR) alpha and delta. Structure-activity relationship studies indicated that the shape of the linker moiety and the nature of the substituent at the distal benzene ring play key roles in determining the potency and selectivity of PPAR subtype transactivation. Optically active alpha-ethylphenylpropanoic acid derivatives were identified as potent human PPAR alpha and delta dual agonists with potential for the treatment of metabolic syndrome.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kasuga
authors.forename: Makoto
authors.initials: M
authors.lastname: Makishima
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyachi
mesh_terms: D015195:Drug Design; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy; D047493:PPAR alpha / Q000819:agonists*; D047494:PPAR delta / Q000819:agonists*; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D047493:PPAR alpha; D047494:PPAR delta; D010666:Phenylpropionates