title: Enantiomerically pure 1,3-dioxanes as highly selective NMDA and σ₁ receptor ligands.
abstract: We synthesized and investigated the NMDA and σ₁ receptor affinity of enantiomerically pure 2-(2-phenyl-1,3-dioxan-4-yl)ethanamines 17-26. The primary amines (R,R)-18-20 with an axially oriented phenyl moiety in position 2 interacted with high enantioselectivity (eudismic ratios 70-130) and high affinity (K(i)((R,R)-19) = 13 nM) with the PCP binding site of the NMDA receptor. Introduction of an N-benzyl moiety led to potent σ₁ ligands including compound (S,R)-22 (K(i) = 6 nM) with an equatorially oriented phenyl moiety in position 2.
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität Münster, Hittorfstraße 58-62, D-48149 Münster, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Köhler
authors.forename: Klaus
authors.initials: K
authors.lastname: Bergander
authors.forename: Jörg
authors.initials: J
authors.lastname: Fabian
authors.forename: Dirk
authors.initials: D
authors.lastname: Schepmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wünsch
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D004146:Dioxanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005021:Ethylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D008024:Ligands; D010622:Phencyclidine / Q000378:metabolism; D011869:Radioligand Assay; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D013237:Stereoisomerism; D013552:Swine
chemical_list: C577932:2-(2-ethyl-2-phenyl-1,3-dioxan-4-yl)ethan-1-amine; D001596:Benzylamines; D004146:Dioxanes; D005021:Ethylamines; D008024:Ligands; C577933:N-benzyl-2-(2-phenyl-1,3-dioxan-4-yl)ethan-1-amine; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D010622:Phencyclidine