The discovery of ( R)-2-( sec-butylamino)- N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)—A potent and efficacious p38α MAP kinase inhibitor

The discovery of ( R)-2-( sec-butylamino)- N-(2-methyl-5-(methylcarbamoyl)phenyl) thiazole-5-carboxamide (BMS-640994)—A potent and efficacious p38α MAP kinase inhibitor

SAR studies leading to the identification of the orally active anti-inflammatory agent BMS-640994 ( 6e) are disclosed. A novel structural class of p38α MAP kinase inhibitors has been identified via iterative SAR studies of a focused deck screen hit. Optimization of the lead series generated 6e, BMS-...

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Veröffentlicht in:Bioorganic & medicinal chemistry 2008-03, Vol.18 (6), p.1762-1767
Hauptverfasser: Hynes, John, Wu, Hong, Pitt, Sidney, Shen, Ding Ren, Zhang, Rosemary, Schieven, Gary L., Gillooly, Kathleen M., Shuster, David J., Taylor, Tracy L., Yang, XiaoXia, McIntyre, Kim W., McKinnon, Murray, Zhang, Hongjian, Marathe, Punit H., Doweyko, Arthur M., Kish, Kevin, Kiefer, Susan E., Sack, John S., Newitt, John A., Barrish, Joel C., Dodd, John, Leftheris, Katerina
Format: Artikel
Sprache:eng
Schlagworte:
Aminothiazole
MAP kinase
p38
TNF
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Zusammenfassung:SAR studies leading to the identification of the orally active anti-inflammatory agent BMS-640994 ( 6e) are disclosed. A novel structural class of p38α MAP kinase inhibitors has been identified via iterative SAR studies of a focused deck screen hit. Optimization of the lead series generated 6e, BMS-640994, a potent and selective p38α inhibitor that is orally efficacious in rodent models of acute and chronic inflammation.
ISSN:0960-894X
0968-0896
1464-3405
1464-3391
DOI:10.1016/j.bmcl.2008.02.031