Dopamine/serotonin receptor ligands. Part 17: a cross-target SAR approach: affinities of azecine-styled ligands for 5-HT(2A) versus D1 and D2 receptors.
Dibenzo- and benzindolo-azecines represent a novel class of high-affinity dopamine receptor antagonists. To further characterize these drugs as potential neuroleptics, we selected a set of azecine derivatives and ring expanded homologues and we measured their antagonist activity at the 5-HT(2A) receptor in the porcine coronary artery. SARs found for the 5-HT(2A) receptor resemble those for the D1 but not the D2 receptor. The protein-ligand interactions were discussed with respect to the different binding pockets.
Institut für Pharmazie, Lehrstuhl für Pharmazeutische/Medizinische Chemie, Friedrich-Schiller-Universität Jena, Philosophenweg 14, 07743 Jena, Germany.
Christoph
C
Enzensperger
Tilo
T
Görnemann
Heinz H
HH
Pertz
Jochen
J
Lehmann
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000737:chemistry*; D018492:Dopamine Antagonists / Q000138:chemical synthesis*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D011485:Protein Binding; D017447:Receptors, Dopamine D1 / Q000737:chemistry*; D017448:Receptors, Dopamine D2 / Q000737:chemistry*; D012701:Serotonin / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013552:Swine
D000596:Amino Acids; D018492:Dopamine Antagonists; D008024:Ligands; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012701:Serotonin; D004298:Dopamine