Synthesis and SAR of tetrahydroisoquinolines as Rev-erbα agonists

https://doi.org/10.1016/j.bmcl.2012.04.023Get rights and content

Abstract

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 abstract

The 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.

  1. Download : Download full-size image

Section snippets

Acknowledgement

This work was supported, in whole or in part, by National Institutes of Health Grants DK080201 and MH093429 (to T. P. B.).

References and notes (16)

  • I.G. Schulman

    Adv. Drug Delivery Rev.

    (2010)
  • T.P. Burris et al.

    Chem. Biol.

    (2012)
  • M. Levi et al.

    Contrib. Nephrol.

    (2011)
  • S. Raghuram et al.

    Nat. Struct. Mol. Biol.

    (2007)
  • L. Yin et al.

    Science

    (2007)
  • T.P. Burris

    Mol. Endocrinol.

    (2008)
  • N. Kumar et al.

    Endocrinology

    (2010)
  • B. Dumas et al.

    Mol. Endocrinol.

    (1994)
There are more references available in the full text version of this article.

Cited by (0)

View full text
Copyright © 2012 Elsevier Ltd. All rights reserved.