1,3,5-Trisubstituted aryls as highly selective PPARdelta agonists.
A series of highly potent and selective PPARdelta agonists is described using the known non-selective ligand GW2433 as a structural template. Compound 1 is bioavailable, potent (10 nM), and shows no cross-activity with other PPAR subtypes up to 10 microM, making it a useful tool in studying the biological effects of selective PPARdelta activation.
Department of Medicinal Chemistry, The Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA. repple@gnf.org
Robert
R
Epple
Mihai
M
Azimioara
Ross
R
Russo
Badry
B
Bursulaya
Shin-Shay
SS
Tian
Andrea
A
Gerken
Maya
M
Iskandar
D002087:Butyrates / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D047494:PPAR delta / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002087:Butyrates; C110636:GW 2433; D008024:Ligands; D047494:PPAR delta; D010671:Phenylurea Compounds