Novel GluN2B selective NMDA receptor antagonists: relative configuration of 7-methoxy-2-methyl-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ols

Abstract

The title compounds, C22H29NO2 (3) and C22H29NO2 (4) [systematic names: (1S*,2R*)-7-methoxy-2-methyl-3-(4-phenylbutyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-1-ol and (1R*,2R*)-7-methoxy-2-methyl-3-(4-phenylbutyl)-2,3,4,5-tetrahydro-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-phenylbutyl 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, molecules are linked via C—H...O hydrogen bonds, forming slabs parallel to the ac plane. In the crystal of (R*,R*)-4, molecules 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.

Keywords

• crystal structure
• NMDA receptor antagonists
• GluN2B antagonists
• ifenprodil analogs
• tetrahydro-3-benzazepines
• relative configuration
• conformational restriction