| Abstract
| - Inhibition of the biosynthesis of proinflammatory cytokines such as tumor necrosis factor andinterleukin-1 via p38 has been an approach toward the development of a disease modifyingagent for the treatment of chronic inflammation and autoimmune diseases. The developmentof a new core structure of p38 inhibitors, 3-(4-fluorophenyl)-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b]pyridine, is described. X-ray crystallographic data of the lead bound to the active site of p38was used to guide the optimization of the series. Specific focus was placed on modulating thephysical properties of the core while maintaining potent inhibition of p38. These efforts identified42c as a potent inhibitor of p38, which also possessed the required physical properties worthyof advanced studies.
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