Identification of a series of PPAR gamma/delta dual agonists via solid-phase parallel synthesis.
We have developed a general solid-phase synthesis for identification of PPAR ligands. Synthesis of a 480-member library led to the identification of a potent PPAR gamma/delta dual agonist 23. Compound 23 showed good plasma exposure in rats and demonstrated antihyperglycemic and antihyperlipidemic efficacy in diabetic fatty Zucker rats.
Liu
K G
KG
Nuclear Receptor Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. kevin_liu@stromix.com
Lambert
M H
MH
Leesnitzer
L M
LM
Oliver
W
W
Ott
R J
RJ
Plunket
K D
KD
Stuart
L W
LW
Brown
P J
PJ
Willson
T M
TM
Sternbach
D D
DD
D000818:Animals; D004268:DNA-Binding Proteins / Q000819:agonists*; D003920:Diabetes Mellitus / Q000628:therapy; D020536:Enzyme Activators / Q000138:chemical synthesis* / Q000494:pharmacology; D006943:Hyperglycemia / Q000517:prevention & control; D006949:Hyperlipidemias / Q000517:prevention & control; D008024:Ligands; D051381:Rats; D011924:Rats, Zucker; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D014157:Transcription Factors / Q000819:agonists*
D004268:DNA-Binding Proteins; D020536:Enzyme Activators; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors