943543-80-4Relevant academic research and scientific papers
Design, synthesis, and evaluation of potent, structurally novel peroxisome proliferator-activated receptor (PPAR) δ-selective agonists
Kasuga, Jun-ichi,Nakagome, Izumi,Aoyama, Atsushi,Sako, Kumiko,Ishizawa, Michiyasu,Ogura, Michitaka,Makishima, Makoto,Hirono, Shuichi,Hashimoto, Yuichi,Miyachi, Hiroyuki
, p. 5177 - 5190 (2007)
A series of 3-(4-alkoxyphenyl)propanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) δ-selective agonists, based on our previously discovered potent human PPARα/δ dual agonist TIPP-401 as a lead compound. Structure-activity relationship studies clearly indicated the importance of the chain length of the alkoxy group at the 4-position, and the n-butoxy compound exhibited the most potent PPARδ transactivation activity and highest PPARδ selectivity. The (S)-enantiomer of a representative compound exhibited extremely potent PPARδ transactivation activity, comparable with or somewhat superior to that of the known PPARδ-selective agonist, GW-501516. The representative compound regulated the expression of genes involved in lipid and glucose homeostasis, and should be useful not only as a chemical tool to study PPARδ function, but also as a candidate drug for the treatment of metabolic syndrome.
