Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064 |
| |
| Authors: | Jonathan Y Bass Richard D Caldwell Justin A Caravella Lihong Chen Katrina L Creech David N Deaton Kevin P Madauss Harry B Marr Robert B McFadyen Aaron B Miller Derek J Parks Dan Todd Shawn P Williams G Bruce Wisely |
| |
| Institution: | 1. Department of Medicinal Chemistry, GlaxoSmithKline, Research Triangle Park, NC 27709, USA;2. Molecular Discovery Research, Computational and Structural Chemistry Research, GlaxoSmithKline, Research Triangle Park, NC 27709, USA;3. Department of Metabolic Diseases, GlaxoSmithKline, Research Triangle Park, NC 27709, USA;4. Molecular Discovery Research, Screening & Compound Profiling, GlaxoSmithKline, Research Triangle Park, NC 27709, USA;5. Department of Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Research Triangle Park, NC 27709, USA;6. Molecular Discovery Research, Biological Reagents and Assay Development, GlaxoSmithKline, Research Triangle Park, NC 27709, USA;7. Department of Pharmaceutical Development, Physical Properties and Developability, GlaxoSmithKline, Research Triangle Park, NC 27709, USA |
| |
| Abstract: | 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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
