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.
MeSH terms
-
Animals
-
Benzylamines / chemical synthesis*
-
Benzylamines / chemistry
-
Benzylamines / pharmacology
-
Binding Sites
-
Binding, Competitive
-
Cerebral Cortex / metabolism
-
Dioxanes / chemical synthesis*
-
Dioxanes / chemistry
-
Dioxanes / pharmacology
-
Ethylamines / chemical synthesis*
-
Ethylamines / chemistry
-
Ethylamines / pharmacology
-
Guinea Pigs
-
Ligands
-
Phencyclidine / metabolism
-
Radioligand Assay
-
Receptors, N-Methyl-D-Aspartate / metabolism*
-
Receptors, sigma / metabolism*
-
Stereoisomerism
-
Swine
Substances
-
2-(2-ethyl-2-phenyl-1,3-dioxan-4-yl)ethan-1-amine
-
Benzylamines
-
Dioxanes
-
Ethylamines
-
Ligands
-
N-benzyl-2-(2-phenyl-1,3-dioxan-4-yl)ethan-1-amine
-
Receptors, N-Methyl-D-Aspartate
-
Receptors, sigma
-
Phencyclidine