title: Structure-based design, synthesis, and nonalcoholic steatohepatitis (NASH)-preventive effect of phenylpropanoic acid peroxisome proliferator-activated receptor (PPAR) α-selective agonists.
abstract: A series of α-ethylphenylpropanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) α-selective agonists, based on our PPARα/δ dual agonist 3 as a lead compound. Structure-activity relationship studies clearly indicated that the steric bulkiness and position of the distal hydrophobic tail part are critical for PPARα agonistic activity and PPARα selectivity, as had been predicted from a molecular-modeling study. A representative compound blocked the progression of nonalcoholic steatohepatitis (NASH) in an animal model.
authors.affiliation: Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Tsushima-Naka, Kita-ku, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Ban
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kasuga
authors.forename: Izumi
authors.initials: I
authors.lastname: Nakagome
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nobusada
authors.forename: Fusako
authors.initials: F
authors.lastname: Takayama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirono
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyachi
mesh_terms: D000818:Animals; D015195:Drug Design; D005234:Fatty Liver / Q000517:prevention & control; D006801:Humans; D008297:Male; D008958:Models, Molecular; D065626:Non-alcoholic Fatty Liver Disease; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D010666:Phenylpropionates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D047493:PPAR alpha; D010666:Phenylpropionates