Novel biphenylcarboxylic acid peroxisome proliferator-activated receptor (PPAR) delta selective antagonists

Jun-ichi Kasuga; Seiichi Ishida; Daisuke Yamasaki; Makoto Makishima; Takefumi Doi; Yuichi Hashimoto; Hiroyuki Miyachi

doi:10.1016/j.bmcl.2009.10.021

Novel biphenylcarboxylic acid peroxisome proliferator-activated receptor (PPAR) delta selective antagonists

Bioorg Med Chem Lett. 2009 Dec 1;19(23):6595-9. doi: 10.1016/j.bmcl.2009.10.021. Epub 2009 Oct 8.

Authors

Jun-ichi Kasuga¹, Seiichi Ishida, Daisuke Yamasaki, Makoto Makishima, Takefumi Doi, Yuichi Hashimoto, Hiroyuki Miyachi

Affiliation

¹ Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.

PMID: 19853439
DOI: 10.1016/j.bmcl.2009.10.021

Abstract

We designed and synthesized novel PPARdelta antagonists based on the crystal structure of the PPARdelta full agonist TIPP-204 bound to the PPARdelta ligand-binding domain, in combination with our nuclear receptor helix 12 folding modification hypothesis. Representative compound 3a exhibits PPARdelta-preferential antagonistic activity.

MeSH terms

Binding Sites
Butyrates / chemical synthesis
Butyrates / chemistry
Butyrates / pharmacology*
Crystallography, X-Ray
Drug Design
Hydrocarbons, Fluorinated / chemical synthesis
Hydrocarbons, Fluorinated / chemistry
Hydrocarbons, Fluorinated / pharmacology*
Ligands
Models, Molecular
Molecular Structure
PPAR delta / antagonists & inhibitors*
Stereoisomerism
Structure-Activity Relationship

Substances

Butyrates
Hydrocarbons, Fluorinated
Ligands
PPAR delta
TIPP-204