29029-45-6Relevant academic research and scientific papers
Novel bisaryl substituted thiazoles and oxazoles as highly potent and selective peroxisome proliferator-activated receptor δ agonists
Epple, Robert,Cow, Christopher,Xie, Yongping,Azimioara, Mihai,Russo, Ross,Wang, Xing,Wityak, John,Karanewsky, Donald S.,Tuntland, Tove,Nguyê?-Tran, Van T. B.,Ngo, Cara Cuc,Huang, David,Saez, Enrique,Spalding, Tracy,Gerken, Andrea,Iskandar, Maya,Seidel, H. Martin,Tian, Shin-Shay
experimental part, p. 77 - 105 (2010/04/30)
The discovery, synthesis, and optimization of compound 1 from a high-throughput screening hit to highly potent and selective peroxisome proliferator-activated receptor δ (PPARδ) agonists are reported. The synthesis and structure-activity relationship in this series are described in detail. On the basis of a general schematic PPAR pharmacophore model, scaffold 1 was divided into headgroup, linker, and tailgroup and successively optimized for PPAR activation using in vitro PPAR transactivation assays. A (2-methylphenoxy)acetic acid headgroup, a flexible linker, and a five-membered heteroaromatic center ring with two hydrophobic aryl substituents were required for efficient and selective PPARδ activation. The fine-tuning of these aryl substituents led to an array of highly potent and selective compounds such as compound 38c, displaying an excellent pharmacokinetic profile in mouse. In an in vivo acute dosing model, selected members of this array were shown to induce the expression of pyruvate dehydrogenase kinase-4 (PDK4) and uncoupling protein-3 (UCP3), genes that are known to be involved in energy homeostasis and regulated by PPARδ in skeletal muscle.
COMPOUNDS AND COMPOSITIONS AS PPAR MODULATORS
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Page/Page column 31-32, (2010/02/14)
The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) families, particularly the activity of PPAR.
Certain 2,4,5-tri-substituted thiazoles, pharmaceutical compositions containing same and methods of using same
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, (2008/06/13)
2,4,5-Trisubstituted thiazoles of the formula STR1 in which each of R1 and R2, independently of the other, represents an aryl or optionally N-oxidized heteroaryl radical each of which is unsubstituted or substituted by aliphatic hydr
