Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064

Journal Article · Mon Sep 27 00:00:00 EDT 2010 · Bioorg. Med. Chem. Lett.

DOI:https://doi.org/10.1016/j.bmcl.2009.04.047· OSTI ID:1006154

Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Parks, Derek J; Todd, Dan; Williams, Shawn P; Wisely, G Bruce

Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, with the 2,6-dimethyl phenol analog 1t having greater FRET FXR potency than GW 4064 1a.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States)
• Sponsoring Organization: USDOE
• OSTI ID: 1006154
• Journal Information: Bioorg. Med. Chem. Lett., Vol. 19, Issue (11) ; 06, 2009; ISSN 0960-894X
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
OXAZOLES
SYNTHESIS
BIOLOGICAL FUNCTIONS
RECEPTORS