Department of Medicinal Chemistry and Biology, Scios, Inc, 6500 Paseo Padre Parkway, Fremont, CA 94555, USA.
Bioorg Med Chem Lett. 2010 Feb 1;20(3):1059-62. doi: 10.1016/j.bmcl.2009.12.031. Epub 2009 Dec 11.
The design and synthesis of a new class of p38alpha MAP kinase inhibitors based on 4-fluorobenzylpiperidine heterocyclic oxalyl amides are described. Many of these compounds showed low-nanomolar activities in p38alpha enzymatic and cell-based cytokine TNFalpha production inhibition assays. The optimal linkers between the piperidine and the oxalyl amide were found to be [6,5] fused ring heterocycles. Substituted indoles and azaindoles were favored structural motifs in the cellular assay.
描述了一类基于 4-氟苄基哌啶杂环草酰酰胺的新型 p38α MAP 激酶抑制剂的设计和合成。这些化合物中有许多在 p38α 酶和基于细胞的细胞因子 TNFα 产生抑制测定中表现出低纳摩尔的活性。发现哌啶和草酰酰胺之间的最佳连接基团为[6,5]稠合环杂环。在细胞测定中，取代的吲哚和氮杂吲哚是优选的结构基序。
