The identification of GPR3 inverse agonist AF64394; the first small molecule inhibitor of GPR3 receptor function

Thomas Jensen; Lisbeth Elster; Søren Møller Nielsen; Suresh Babu Poda; Frosty Loechel; Christiane Volbracht; Ib Vestergaard Klewe; Laurent David; Stephen P Watson

doi:10.1016/j.bmcl.2014.09.077

The identification of GPR3 inverse agonist AF64394; the first small molecule inhibitor of GPR3 receptor function

Bioorg Med Chem Lett. 2014 Nov 15;24(22):5195-8. doi: 10.1016/j.bmcl.2014.09.077. Epub 2014 Oct 2.

Authors

Thomas Jensen¹, Lisbeth Elster¹, Søren Møller Nielsen¹, Suresh Babu Poda¹, Frosty Loechel¹, Christiane Volbracht¹, Ib Vestergaard Klewe¹, Laurent David¹, Stephen P Watson¹

Affiliation

¹ Neuroscience Drug Discovery, H-Lundbeck A/S, 2500 Valby, Copenhagen, Denmark.

PMID: 25442311
DOI: 10.1016/j.bmcl.2014.09.077

Abstract

The identification of the novel and selective GPR3 inverse agonist AF64394, the first small molecule inhibitor of GPR3 receptor function, is described. Structure activity relationships and syntheses based around AF64394 are reported.

Keywords: AF64394; G protein coupled receptor; GPR12; GPR3; GPR6; Inverse agonist; Orphan receptor.

MeSH terms

Animals
Drug Inverse Agonism*
Mice
Pyrimidines / chemistry*
Pyrimidines / pharmacology
Receptors, G-Protein-Coupled / antagonists & inhibitors*
Receptors, G-Protein-Coupled / physiology*
Triazoles / chemistry*
Triazoles / pharmacology

Substances

GPR3 protein, mouse
Pyrimidines
Receptors, G-Protein-Coupled
Triazoles
pyrimidine