Epple, Robert, Azimioara, Mihai, Russo, Ross, Xie, Yongping, Wang, Xing, Cow, Christopher, Wityak, John, Karanewsky, Donald, Bursulaya, Badry, Kreusch, Andreas, Tuntland, Tove, Gerken, Andrea, Iskandar, Maya, Saez, Enrique, Seidel, Martin and Tian, Shin-Shay (2006) 3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists. Part 2. Bioorganic & Medicinal Chemistry Letters, 16 (21). pp. 5488-5492. ISSN 0960-894X

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.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2006.08.052
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Nuclear hormone receptor; PPAR agonist; PPARδ; Energy homeostasis; Metabolic xyndrome; Isoxazoles
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez... doi:10.1016/j.bmcl.2006.08.052
Date Deposited:	14 Dec 2009 14:04
Last Modified:	31 Jan 2013 01:26
URI:	https://oak.novartis.com/id/eprint/140