p38 MAP kinase inhibitors: metabolically stabilized piperidine-substituted quinolinones and naphthyridinones.

作者信息

Bao Jianming, Hunt Julianne A, Miao Shouwu, Rupprecht Kathleen M, Stelmach John E, Liu Luping, Ruzek Rowena D, Sinclair Peter J, Pivnichny James V, Hop Cornelis E C A, Kumar Sanjeev, Zaller Dennis M, Shoop Wesley L, O'neill Edward A, O'keefe Stephen J, Thompson Chris M, Cubbon Rose M, Wang Ruixiu, Zhang Wen Xiao, Thompson James E, Doherty James B

机构信息

Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA.

出版信息

Bioorg Med Chem Lett. 2006 Jan 1;16(1):64-8. doi: 10.1016/j.bmcl.2005.09.065. Epub 2005 Oct 18.

DOI:10.1016/j.bmcl.2005.09.065

PMID:16242322

Abstract

Quinolinones and naphthyridinones with C7 N-t-butyl piperidine substituents were found to be potent p38 MAP kinase inhibitors. These compounds significantly suppress TNF-alpha release in both cellular and LPS-stimulated whole blood assays. They also displayed excellent PK profiles across three animal species. Quinolinone at 10 mpk showed comparable oral efficacy to that of dexamethasone at 1 mpk in a murine collagen-induced arthritis model.

摘要

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