Noncompetitive NMDA antagonists: a novel synthesis of 1-phenyltetrahydro-3-benzazepines.
The key step in the synthesis of the pharmacologically interesting 1-phenyltetrahydro-3-benzazepine skeleton is the Michael addition of (2-lithiophenyl)acetaldehyde acetals, which are generated in situ upon treatment of the bromo acetals 5a,b with n-butyllithium, to beta-nitrostyrene (6). The reductive ring closure of the nitro acetals 7a,b succeeded with zinc dust and hydrochloric acid to give the 3-benzazepines 11a,b in good yields. The unsubstituted 3-benzazepine 11a showed a considerable affinity for the phencyclidine binding site of the NMDA receptor (Ki = 6.41 microM), whereas donor substituents in the aryl moiety (11b,c) reduce the affinity for the NMDA receptor.
Wünsch
B
B
Pharmazeutisches Institut, Universität Freiburg.
Nerdinger
S
S
Bauschke
G
G
Höfner
G
G
D001552:Benzazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D001667:Binding, Competitive; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D001552:Benzazepines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate