Novel selective PPARdelta agonists: optimization of activity by modification of alkynylallylic moiety.
Y-shaped molecules bearing alkynylallylic moieties were found to be potent and selective PPARdelta activators. The alkynylallylic moiety was synthesized from alkyn-1-ols by hydroalumination followed by a cross-coupling reaction. Series of active compounds 6 were obtained by stepwise changing the structure of the known PPARpan agonist 5 into Y-shaped compounds. The most active and selective compound, 6f, had a PPARdelta potency of 0.13 microM, which is 50-fold more potent than compound 5.
Havranek
Miroslav
M
RE&D VUFB, s.r.o., Podebradská 56/186, 180 66 Praha 9, Czech Republic. havranek@readvufb.cz
Sauerberg
Per
P
Mogensen
John P
JP
Kratina
Pavel
P
Jeppesen
Claus B
CB
Pettersson
Ingrid
I
Pihera
Pavel
P
D008958:Models, Molecular; D015394:Molecular Structure; D047494:PPAR delta / Q000819:agonists*
D047494:PPAR delta