Synthesis and SAR of tetrahydroisoquinolines as Rev-erbα agonists

Romain Noel; Xinyi Song; Youseung Shin; Subhashis Banerjee; Douglas Kojetin; Li Lin; Claudia H Ruiz; Michael D Cameron; Thomas P Burris; Theodore M Kamenecka

doi:10.1016/j.bmcl.2012.04.023

Synthesis and SAR of tetrahydroisoquinolines as Rev-erbα agonists

Bioorg Med Chem Lett. 2012 Jun 1;22(11):3739-42. doi: 10.1016/j.bmcl.2012.04.023. Epub 2012 Apr 13.

Authors

Romain Noel¹, Xinyi Song, Youseung Shin, Subhashis Banerjee, Douglas Kojetin, Li Lin, Claudia H Ruiz, Michael D Cameron, Thomas P Burris, Theodore M Kamenecka

Affiliation

¹ Department of Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458, USA.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Brain / drug effects
Brain / metabolism
Injections, Intraperitoneal
Isoquinolines / chemical synthesis
Isoquinolines / chemistry*
Isoquinolines / pharmacokinetics
Naphthalenes / chemical synthesis*
Naphthalenes / chemistry
Naphthalenes / pharmacokinetics
Nuclear Receptor Subfamily 1, Group D, Member 1 / agonists*
Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism
Rats
Structure-Activity Relationship

Substances

Isoquinolines
Naphthalenes
Nuclear Receptor Subfamily 1, Group D, Member 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding