Synthesis and SAR of tetrahydroisoquinolines as Rev-erbα agonists

The design and synthesis of a novel series of Rev-erbα agonists is described. The development and optimization of the tetrahydroisoquinoline series was carried out from an earlier acyclic series of Rev-erbα agonists. Through the optimization of the scaffold 1, several potent compounds with good in vivo profiles were discovered.

Graphical abstractThe design and synthesis of a novel series of Rev-erbα agonists is described. The development of N-acylated tetrahydroisoquinolines from an earlier acyclic series of Rev-erbα agonists has led to potent and efficacious compounds like 6j with good in vivo exposure.Figure optionsDownload full-size imageDownload as PowerPoint slide