Synthesis of the PPARbeta/delta-selective agonist GW501516 and C4-thiazole-substituted analogs.
Sequential, position-selective, Pd-catalyzed cross-coupling reactions of 2,4-dibromo-5-hydroxymethylthiazole provided the scaffold for the synthesis of GW501516, the most potent PPARbeta/delta agonist yet described, and equally selective analogs at the thiazole-C4 position.
Pereira
Raquel
R
Departamento de Química Orgánica, Universidade de Vigo, 36310 Vigo, Spain.
Gaudon
Claudine
C
Iglesias
Beatriz
B
Germain
Pierre
P
Gronemeyer
Hinrich
H
de Lera
Angel R
AR
D002384:Catalysis; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D017930:Genes, Reporter; D005821:Genetic Techniques; D005914:Globins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D062385:Hydroxybenzoates / Q000737:chemistry*; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D008956:Models, Chemical; D047494:PPAR delta / Q000819:agonists*; D048068:PPAR-beta / Q000819:agonists*; D010165:Palladium / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
C508740:CB676475; C425931:GW 501516; D062385:Hydroxybenzoates; D008024:Ligands; D008055:Lipids; D047494:PPAR delta; D048068:PPAR-beta; D011799:Quinazolines; D013844:Thiazoles; D010165:Palladium; D005914:Globins