Imidazoline-modified benzylimidazolines as h5-HT(1D/1B) serotonergic ligands.
Sumatriptan, a h5-HT1D and h5-HT1B receptor agonist used clinically as a migraine-abortive, produces certain side effects thought to result from its affinity for h5-HT1B receptors. The present investigation extends our work with benzylimidazolines as novel non-tryptamine h5-HT(1D/1B) ligands. The effect of N-methylation, N-benzylation, ring-aromatization, and variation of the imidazoline ring on affinity both at h5-HT1D and h5-HT1B receptors was examined. Several compounds were identified with good affinity and enhanced (i.e., > 100-fold) h5-HT1D versus hS-HT1B selectivity.
Prisinzano
T
T
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond 23298-0540, USA.
Law
H
H
Dukat
M
M
Slassi
A
A
MaClean
N
N
Demchyshyn
L
L
Glennon
R A
RA
D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D008024:Ligands; D008881:Migraine Disorders / Q000188:drug therapy; D011485:Protein Binding; D011869:Radioligand Assay; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D001593:Benzyl Compounds; C470302:HTR1B protein, human; D007093:Imidazoles; D008024:Ligands; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists