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Noncompetitive NMDA Antagonists: A Novel Synthesis of 1‐Phenyltetrahydro‐3‐benzazepines
Author(s) -
Wünsch Bernhard,
Nerdinger Sven,
Bauschke Gerd,
Höfner Georg
Publication year - 1997
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19973300705
Subject(s) - chemistry , benzazepine , benzazepines , moiety , nmda receptor , stereochemistry , phencyclidine , receptor , biochemistry
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 β‐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 ( K i = 6.41 μM), whereas donor substituents in the aryl moiety ( 11b,c ) reduce the affinity for the NMDA receptor.