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ID: ALA4616669

Journal: J Med Chem

Title: Bioisosteric Replacement of Arylamide-Linked Spine Residues with N-Acylhydrazones and Selenophenes as a Design Strategy to Novel Dibenzosuberone Derivatives as Type I 1/2 p38α MAP Kinase Inhibitors.

Authors: Pedreira JGB, Nahidino P, Kudolo M, Pantsar T, Berger BT, Forster M, Knapp S, Laufer S, Barreiro EJ.

Abstract: The recent disclosure of type I 1/2 inhibitors for p38α MAPK demonstrated how the stabilization of the R-spine can be used as a strategy to greatly increase the target residence time (TRT) of inhibitors. Herein, for the first time, we describe N-acylhydrazone and selenophene residues as spine motifs, yielding metabolically stable inhibitors with high potency on enzymatic, NanoBRET, and whole blood assays, improved metabolic stability, and prolonged TRT.

CiteXplore: 32462866

DOI: 10.1021/acs.jmedchem.0c00508