1.
Bioorg Med Chem Lett
; 22(1): 613-8, 2012 Jan 01.
Article
in English
| MEDLINE
| ID: mdl-22119462
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.