Design and biological evaluation of novel, balanced dual PPARalpha/gamma agonists.
An X-ray-guided design approach led to the identification of a novel, balanced class of alpha-ethoxy-phenylpropionic acid-derived dual PPARalpha/gamma agonists. The series shows a wide range of PPARalpha/gamma ratios within a rather narrow structural space. Advanced compounds possess favorable physicochemical and pharmacokinetic profiles and show a high efficacy in T2D and dyslipidemia animal models.
Grether
Uwe
U
Pharma Research, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland. uwe.grether@roche.com
Bénardeau
Agnes
A
Benz
Jörg
J
Binggeli
Alfred
A
Blum
Denise
D
Hilpert
Hans
H
Kuhn
Bernd
B
Märki
Hans Peter
HP
Meyer
Markus
M
Mohr
Peter
P
Püntener
Kurt
K
Raab
Susanne
S
Ruf
Armin
A
Schlatter
Daniel
D