Synthesis and biological activity of a novel series of indole-derived PPARgamma agonists.
The synthesis and structure-activity relationships of a novel series of indole 5-carboxylic acids that bind and activate peroxisome proliferator-activated receptor gamma (PPARgamma) are reported. These new analogs are selective for PPARgamma vs the other PPAR subtypes, and the most potent compounds in this series are comparable to in vitro potencies at PPARgamma reported for the thiazolidinedione-based antidiabetic drugs currently in clinical use.
Henke
B R
BR
Department of Medicinal Chemistry, Glaxo Wellcome Research and Development, Research Triangle Park, NC 27709, USA.
Adkison
K K
KK
Blanchard
S G
SG
Leesnitzer
L M
LM
Mook
R A
RA
Plunket
K D
KD
Ray
J A
JA
Roberson
C
C
Unwalla
R
R
Willson
T M
TM
D000818:Animals; D001682:Biological Availability; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000819:agonists*
D007211:Indoles; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors