Novel biphenylcarboxylic acid peroxisome proliferator-activated receptor (PPAR) delta selective antagonists.
We designed and synthesized novel PPARdelta antagonists based on the crystal structure of the PPARdelta full agonist TIPP-204 bound to the PPARdelta ligand-binding domain, in combination with our nuclear receptor helix 12 folding modification hypothesis. Representative compound 3a exhibits PPARdelta-preferential antagonistic activity.
Kasuga
Jun-ichi
J
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
Ishida
Seiichi
S
Yamasaki
Daisuke
D
Makishima
Makoto
M
Doi
Takefumi
T
Hashimoto
Yuichi
Y
Miyachi
Hiroyuki
H
D001665:Binding Sites; D002087:Butyrates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D047494:PPAR delta / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002087:Butyrates; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D047494:PPAR delta; C542588:TIPP-204