2. Academic Validation
  3. Synthesis and biological investigations of dopaminergic partial agonists preferentially recognizing the D4 receptor subtype

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.
Stefan Löber 1,  Harald Hübner,  Peter Gmeiner
Affiliations

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).

Figures