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ABSTRACT: Optimization of our previously described pyrrolopiperidone series led to the identification of a new benzamide sub-series, which exhibits consistently high potency in biochemical and cell-based assays throughout the series. Strong inhibition of LPS-induced production of the cytokine TNFα is coupled to the regulation of HSP27 phosphorylation, indicating that the observed cellular effects result from the inhibition of MK2. X-ray crystallographic and computational analyses provide a rationale for the high potency of the series.
Bioorganic & medicinal chemistry letters 11/2011; 22(1):613-8. DOI:10.1016/j.bmcl.2011.10.071 · 2.42 Impact Factor