2. Academic Validation
  3. Design, synthesis, and evaluation of simple phenol amides as ERRγ agonists

Design, synthesis, and evaluation of simple phenol amides as ERRγ agonists

  • Bioorg Med Chem Lett. 2018 May 1;28(8):1313-1319. doi: 10.1016/j.bmcl.2018.03.019.
Hua Lin 1,  Christelle Doebelin 1,  Rémi Patouret 1,  Ruben D Garcia-Ordonez 1,  M R Chang 1,  Venkatasubramanian Dharmarajan 1,  Claudia Ruiz Bayona 1,  Michael D Cameron 1,  Patrick R Griffin 1,  Theodore M Kamenecka 2
Affiliations

Affiliations

  • 1 The Scripps Research Institute, Scripps Florida, Department of Molecular Medicine, 130 Scripps Way #A2A, Jupiter, FL 33458, USA.
  • 2 The Scripps Research Institute, Scripps Florida, Department of Molecular Medicine, 130 Scripps Way #A2A, Jupiter, FL 33458, USA. Electronic address: kameneck@scripps.edu.
PMID: 29548571 DOI: 10.1016/j.bmcl.2018.03.019
Abstract

Herein we report the design and synthesis of a series of simple phenol amide ERRγ agonists based on a hydrazone lead molecule. Our structure activity relationship studies in this series revealed the phenol portion of the molecule to be required for activity. Attempts to replace the hydrazone with more suitable chemotypes led to a simple amide as a viable alternative. Differential hydrogen-deuterium exchange experiments were used to help understand the structural basis for binding to ERRγ and aid in the development of more potent ligands.

Keywords

Agonist; Amide; ERRγ; Nuclear receptor; Selective ligand.

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