Novel triazolopyridylbenzamides as potent and selective p38伪 inhibitors

详细信息	查看全文 | 推荐本文 |

• 作者：Josep Aiguadé ; ; ^{josep.aiguade@almirall.com} ; Cristina Balagué ; Iné ; s Carranco ; Francisco Caturla ; Marí ; a Domí ; nguez ; Paul Eastwood ; Cristina Esteve ; Jacob Gonzá ; lez ; Wenceslao Lumeras^&dagger ; ; Adelina Orellana ; Sara Preciado^&Dagger ; ; Ram&oacute ; n Roca^§ ; ; Laura Vidal ; Bernat Vidal
• 关键词：p38伪 Inhibitors ; Biaryl-triazolopyridine scaffold ; TNF伪 ; LPS-induced endotoxemia ; Rat adjuvant-induced arthritis
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 May, 2012
• 卷：22
• 期：10
• 页码：3431-3436
• 文件大小：1080 K

摘要

A new class of p38伪 inhibitors based on a biaryl-triazolopyridine scaffold was investigated. X-ray crystallographic data of the initial lead compound cocrystallised with p38伪 was crucial in order to uncover a unique binding mode of the inhibitor to the hinge region via a pair of water molecules. Synthesis and SAR was directed towards the improvement of binding affinity, as well as ADME properties for this new class of p38伪 inhibitors and ultimately afforded compounds showing good in vivo efficacy.