Modelling of alpha 2-adrenergic ligands.
Six different ligands, which bind to alpha 2-adrenergic receptor were studied using molecular mechanics and quantum chemical methods. Superimposition was performed using low energy conformations resulting the common binding model. Both electrostatic and structural features of different compounds were compared. It is suggested, that the reason for agonism/antagonism is based on small structural differences in ligands. In agonists the distance between the cationic nitrogen and an aromatic ring plane was about 1 A shorter than in antagonists, whereas the distance between the same nitrogen and outmost part of ring atoms was about 1 A longer in agonists than in antagonists.
Rouvinen
J
J
Department of Chemistry, University of Joensuu, Finland.
Hoffrén
A M
AM
Karjalainen
A
A
Pakkanen
T A
TA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004563:Electrochemistry; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D009584:Nitrogen / Q000737:chemistry; D011789:Quantum Theory; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry* / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D008024:Ligands; D018341:Receptors, Adrenergic, alpha-2; D009584:Nitrogen