Novel GluN2B selective NMDA receptor antagonists: relative configuration of 7-meth-oxy-2-methyl-2,3,4,5-tetra-hydro-1H-3-benzazepin-1-ols.
The title compounds, C22H29NO2 (3) and C22H29NO2 (4) [systematic names: (1S*,2R*)-7-meth-oxy-2-methyl-3-(4-phenyl-but-yl)-2,3,4,5-tetra-hydro-1H-3-benzazepin-1-ol and (1R*,2R*)-7-meth-oxy-2-methyl-3-(4-phenyl-but-yl)-2,3,4,5-tetra-hydro-1H-3-benzazepin-1-ol, are diastereomers with the relative configuration of the adjacent hydroxyl and methyl groups at the seven-membered azepine ring being trans in (3) and cis in (4). In the crystals the orientation of these groups is -anti-periplanar (3) and +syn-clinal (4). In both cases, the crystals studied proved to be of a racemic mixture, with relative configurations (R*,S*)-3 and (R*,R*)-4. In both compounds, the seven-membered azepine ring has a chair-like conformation, and the 4-phenyl-butyl side chain adopts a extended conformation in (R*,S*)-3, but a twisted conformation in (R*,R*)-4. In the crystal of (S*,R*)-3, mol-ecules are linked via C-H⋯O hydrogen bonds, forming slabs parallel to the ac plane. In the crystal of (R*,R*)-4, mol-ecules are linked via O-H⋯N hydrogen bonds, forming chains propagating along the c-axis direction. The chains are linked by C-H⋯O hydrogen bonds, forming slabs parallel to the ac plane.
Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstrasse 48, D-48149 Münster, Germany.
Bastian
B
Tewes
Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstrasse 48, D-48149 Münster, Germany.
Bastian
B
Frehland
Organisch-chemisches Institut der Westfälischen Wilhelms-Universität Münster, Corrensstr. 40, D-48149-Münster, Germany.
Roland
R
Fröhlich
Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstrasse 48, D-48149 Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), Universität Münster, Germany.
Bernhard
B
Wünsch
GluN2B antagonists; NMDA receptor antagonists; conformational restriction; crystal structure; ifenprodil analogs; relative configuration; tetra­hydro-3-benzazepines