Design of potent PPARalpha agonists.
Computational analysis of the ligand binding pocket of the three PPAR receptor subtypes was utilized in the design of potent PPARalpha agonists. Optimum PPARalpha potency and selectivity were obtained with substituents having van der Waals volume around 260. Compound 6 had a PPARalpha potency of 0.002 microM and a selectivity ratio to PPARgamma and PPARdelta of 410 and 2000, respectively.
Sauerberg
Per
P
Novo Nordisk A/S, Novo Nordisk Park, 2760 Måløv, Denmark.
Mogensen
John P
JP
Jeppesen
Lone
L
Bury
Paul S
PS
Fleckner
Jan
J
Olsen
Grith S
GS
Jeppesen
Claus B
CB
Wulff
Erik M
EM
Pihera
Pavel
P
Havranek
Miroslav
M
Polivka
Zdenek
Z
Pettersson
Ingrid
I
D000818:Animals; D003201:Computers; D003461:Crystallography; D015195:Drug Design; D008024:Ligands; D047493:PPAR alpha / Q000819:agonists* / Q000737:chemistry; D010666:Phenylpropionates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D008024:Ligands; D047493:PPAR alpha; D010666:Phenylpropionates