Design and synthesis of novel PPARalpha/gamma/delta triple activators using a known PPARalpha/gamma dual activator as structural template.
Using a known dual PPARalpha/gamma activator (5) as a structural template, SAR evaluations led to the identification of triple PPARalpha/gamma/delta activators (18-20) with equal potency and efficacy on all three receptors. These compounds could become useful tools for studying the combined biological effects of PPARalpha/gamma/delta activation.
Mogensen
John P
JP
Novo Nordisk A/S, Novo Nordisk Park, 2760 Måløv, Denmark. jpm@novonordisk.com
Jeppesen
Lone
L
Bury
Paul S
PS
Pettersson
Ingrid
I
Fleckner
Jan
J
Nehlin
Jan
J
Frederiksen
Klaus S
KS
Albrektsen
Tatjana
T
Din
Nanni
N
Mortensen
Steen B
SB
Svensson
L Anders
LA
Wassermann
Karsten
K
Wulff
Erik M
EM
Ynddal
Lars
L
Sauerberg
Per
P
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry / Q000187:drug effects*
D001786:Blood Glucose; D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors