Front Cover: Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor (ChemMedChem 11/2018)

Abstract

The Front Cover reflects the optimization of inhibitors of the tautomerase activity of macrophage migration inhibitory factor (MIF) that feature a 4‐phenylpyrazole core. Starting from a weak docking hit (113 μM) at the bottom left of the gauge, structure‐based and computer‐aided design led to inhibitors of increasing potency, finally yielding the 67 nM biphenyl analog on the far right. Four crystal structures of complexes are reported, including the illustrated one for the 2‐naphthyl analog. Cover artwork by V. Trivedi‐Parmar and M. J. Robertson. More information can be found in the Communication by William L. Jorgensen et al. on page 1092 in Issue 11, 2018 (DOI: 10.1002/cmdc.201800158).