Design, synthesis, and structural analysis of phenylpropanoic acid-type PPARγ-selective agonists: discovery of reversed stereochemistry-activity relationship.
Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-mediated transcription factor with roles in glucose, lipid, and lipoprotein homeostasis, and PPARγ ligands are expected have therapeutic potential in these as well as other areas. We report here the design, synthesis, crystallographic analysis, and computational studies of α-benzylphenylpropanoic acid PPARγ agonists. Interestingly, these compounds show a reversal of the stereochemistry-transactivation activity relationship observed with other phenylpropanoic acid ligands.
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.
Masao
M
Ohashi
Takuji
T
Oyama
Izumi
I
Nakagome
Mayumi
M
Satoh
Yoshino
Y
Nishio
Hiromi
H
Nobusada
Shuichi
S
Hirono
Kosuke
K
Morikawa
Yuichi
Y
Hashimoto
Hiroyuki
H
Miyachi
D001665:Binding Sites; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry / Q000235:genetics; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
D047495:PPAR gamma; D010666:Phenylpropionates