3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists. Part 2.
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Epple R, Azimioara M, Russo R, Xie Y, Wang X, Cow C, Wityak J, Karanewsky D, Bursulaya B, Kreusch A, Tuntland T, Gerken A, Iskandar M, Saez E, Martin Seidel H, Tian SS
3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists. Part 2.
Bioorg Med Chem Lett. 2006 Nov 1;16(21):5488-92. Epub 2006 Aug 22.
- PubMed ID
- 16931011 [ View in PubMed]
- Abstract
A series of PPARdelta-selective agonists was investigated and optimized for a favorable in vivo pharmacokinetic profile. Isoxazole LCI765 (17d) was found to be a potent and selective PPARdelta agonist with good in vivo PK properties in mouse (C(max)=5.1 microM, t(1/2)=3.1 h). LCI765 regulated expression of genes involved in energy homeostasis in relevant tissues when dosed orally in C57BL6 mice. A co-crystal structure of compound LCI765 and the LBD of PPARdelta is discussed.