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
  • 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).