Design, synthesis, and evaluation of simple phenol amides as ERR gamma agonists

作者：Lin, Hua; Doebelin, Christelle; Patouret, Remi; Garcia-Ordonez, Ruben D.; Chang, Mi Ra; Dharmarajan, Venkatasubramanian; Bayona, Claudia Ruiz; Cameron, Michael D.; Griffin, Patrick R.; Kamenecka, Theodore M.^*

来源：Bioorganic & Medicinal Chemistry Letters, 2018, 28(8): 1313-1319.

DOI：10.1016/j.bmcl.2018.03.019

• Nuclear receptor
• ERR gamma
• Selective ligand
• Amide
• Agonist

Herein we report the design and synthesis of a series of simple phenol amide ERR gamma 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 ERR gamma and aid in the development of more potent ligands.

• 出版日期2018-5-1