Design, synthesis and structure-activity relationships of azole acids as novel, potent dual PPAR alpha/gamma agonists.
The design, synthesis and structure-activity relationships of a novel series of N-phenyl-substituted pyrrole, 1,2-pyrazole and 1,2,3-triazole acid analogs as PPAR ligands are outlined. The triazole acid analogs 3f and 4f were identified as potent dual PPARalpha/gamma agonists both in binding and functional assays in vitro. The 3-oxybenzyl triazole acetic acid analog 3f showed excellent glucose and triglyceride lowering in diabetic db/db mice.
Zhang
Hao
H
Metabolic Diseases Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, USA.
Ryono
Denis E
DE
Devasthale
Pratik
P
Wang
Wei
W
O'Malley
Kevin
K
Farrelly
Dennis
D
Gu
Liqun
L
Harrity
Thomas
T
Cap
Michael
M
Chu
Cuixia
C
Locke
Kenneth
K
Zhang
Litao
L
Lippy
Jonathan
J
Kunselman
Lori
L
Morgan
Nathan
N
Flynn
Neil
N
Moore
Lisa
L
Hosagrahara
Vinayak
V
Zhang
Lisa
L
Kadiyala
Pathanjali
P
Xu
Carrie
C
Doweyko
Arthur M
AM
Bell
Aneka
A
Chang
Chiehying
C
Muckelbauer
Jodi
J
Zahler
Robert
R
Hariharan
Narayanan
N
Cheng
Peter T W
PT
D000818:Animals; D001393:Azoles / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line / Q000201:enzymology; D018360:Crystallography, X-Ray; D015195:Drug Design; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008822:Mice, Transgenic; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D001393:Azoles; D047493:PPAR alpha; D047495:PPAR gamma