Synthesis and structure-activity relationships of a series of 3-aryl-4-isoxazolecarboxamides as a new class of TGR5 agonists.
| Autor: | Budzik BW; Discovery Medicinal Chemistry, Discovery Research, GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA 19426-0989, USA., Evans KA, Wisnoski DD, Jin J, Rivero RA, Szewczyk GR, Jayawickreme C, Moncol DL, Yu H |
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| Jazyk: | angličtina |
| Zdroj: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Feb 15; Vol. 20 (4), pp. 1363-7. Date of Electronic Publication: 2010 Jan 07. |
| DOI: | 10.1016/j.bmcl.2010.01.003 |
| Abstrakt: | A series of 3-aryl-4-isoxazolecarboxamides identified from a high-throughput screening campaign as novel, potent agonists of the human TGR5 G-protein-coupled receptor is described. Many analogues were readily accessible via solution-phase synthesis which resulted in the rapid identification of key structure-activity relationships (SAR), and the discovery of potent exemplars (up to pEC50=9). Details of the SAR and optimization of this series are presented herein. (Copyright 2010 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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