Synthesis and biological investigations of dopaminergic partial agonists preferentially recognizing the D4 receptor subtype

Stefan Löber; Harald Hübner; Peter Gmeiner

doi:10.1016/j.bmcl.2006.02.075

Synthesis and biological investigations of dopaminergic partial agonists preferentially recognizing the D4 receptor subtype

Bioorg Med Chem Lett. 2006 Jun 1;16(11):2955-9. doi: 10.1016/j.bmcl.2006.02.075. Epub 2006 Mar 24.

Authors

Stefan Löber¹, Harald Hübner, Peter Gmeiner

Affiliation

¹ Department of Medicinal Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstrasse 19, D-91052 Erlangen, Germany.

PMID: 16563764
DOI: 10.1016/j.bmcl.2006.02.075

Abstract

Aminomethyl-substituted biaryls bearing a pyrazole or triazole moiety were synthesized and investigated for dopamine and serotonin receptor binding. The N-arylpyrazoles 3b,f,g and 4 revealed Ki values in the subnanomolar range (0.28-0.70 nM) for the dopamine D4 receptor subtype. Employing both mitogenesis and GTPgammaS assays, ligand efficacy was evaluated indicating partial agonist properties. Interestingly, the tetrahydropyrimidine 4 (FAUC 2020) displayed significant intrinsic selectivity for D2(long) over D2(short).

MeSH terms

Molecular Structure
Protein Binding
Receptors, Dopamine D4 / agonists*
Receptors, Dopamine D4 / chemistry
Receptors, Dopamine D4 / metabolism*
Structure-Activity Relationship

Substances

Receptors, Dopamine D4