Identification of a series of oxadiazole-substituted alpha-isopropoxy phenylpropanoic acids with activity on PPARalpha, PPARgamma, and PPARdelta.
A series of oxadiazole-substituted alpha-isopropoxy phenylpropanoic acids with dual agonist activity on PPARalpha and PPARgamma is described. Several of these compounds also showed partial agonist activity on PPARdelta. Resolution of one analogue showed that PPARalpha and PPARgamma activity resided in mainly one enantiomer, whereas PPARdelta activity was retained in both enantiomers.
Liu
K G
KG
Nuclear Receptor Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. kevin_liu@stromix.com
Smith
J S
JS
Ayscue
A H
AH
Henke
B R
BR
Lambert
M H
MH
Leesnitzer
L M
LM
Plunket
K D
KD
Willson
T M
TM
Sternbach
D D
DD
D002851:Chromatography, High Pressure Liquid; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007536:Isomerism; D010069:Oxadiazoles / Q000737:chemistry; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000819:agonists*
D010069:Oxadiazoles; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors