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Front Cover: Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor (ChemMedChem 11/2018)
Author(s) -
TrivediParmar Vinay,
Robertson Michael J.,
Cisneros José A.,
Krimmer Stefan G.,
Jorgensen William L.
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800277
Subject(s) - front cover , macrophage migration inhibitory factor , chemistry , docking (animal) , cover (algebra) , stereochemistry , combinatorial chemistry , biology , cytokine , engineering , mechanical engineering , medicine , nursing , genetics
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).