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3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists. Part 2. | LitMetric
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3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists. Part 2.

Robert Epple Mihai Azimioara Ross Russo Yongping Xie Xing Wang Christopher Cow John Wityak Don Karanewsky Badry Bursulaya Andreas Kreusch Tove Tuntland Andrea Gerken Maya Iskandar Enrique Saez H Martin Seidel Shin-Shay Tian

Bioorg Med Chem Lett

Department of Medicinal Chemistry, The Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.

Published: November 2006

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.

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http://dx.doi.org/10.1016/j.bmcl.2006.08.052DOI Listing

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