Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK)

  • J Med Chem. 2015 Feb 12;58(3):1426-41. doi: 10.1021/jm5017494.
Adrian L Smith  1 ,  Kristin L Andrews ,  Holger Beckmann ,  Steven F Bellon ,  Pedro J Beltran ,  Shon Booker ,  Hao Chen ,  Young-Ah Chung ,  Noel D D'Angelo ,  Jennifer Dao ,  Kenneth R Dellamaggiore ,  Peter Jaeckel ,  Richard Kendall ,  Katja Labitzke ,  Alexander M Long ,  Silvia Materna-Reichelt ,  Petia Mitchell ,  Mark H Norman ,  David Powers ,  Mark Rose ,  Paul L Shaffer ,  Michelle M Wu ,  J Russell Lipford
Affiliations
  • 1. Departments of †Medicinal Chemistry, ‡Molecular Structure and Characterization, §Oncology Research, and ∥Pharmacokinetics and Drug Metabolism, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
PMID: 25587754 DOI: 10.1021/jm5017494
Abstract

The structure-based design and optimization of a novel series of selective PERK inhibitors are described resulting in the identification of 44 as a potent, highly selective, and orally active tool compound suitable for PERK pathway biology exploration both in vitro and in vivo.

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