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Azepino‐ and Diazepinoindoles: Synthesis and Dopamine Receptor Binding Profiles
Author(s) -
Kraxner Johannes,
H?bner Harald,
Gmeiner Peter
Publication year - 2000
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 - 10.1002/1521-4184(20009)333:9<287::aid-ardp287>3.0.co;2-r
Subject(s) - chemistry , radioligand , benzazepine , agonist , reductive amination , stereochemistry , affinities , chemical synthesis , dopamine , indole test , receptor , biochemistry , in vitro , endocrinology , biology , catalysis
Starting from the readily available building blocks 7 , 10 , 11 , and 15 , the synthesis of the fused indoles 1 , 2 , 5 , and 6 , respectively, is reported. The syntheses involved Pictet‐Spengler cyclizations, Michael addition reactions, lactamization, directed metallation, and reductive amination as the key reaction steps. Radioligand displacement studies comprising the dopamine receptor subtypes D 1 , D 2long D 2short , D 3 , and D 4.4 were performed when the diazepinoindole 6 revealed D 1 and D 4 affinities ( K i = 0.11 μM and 1.7 μM, respectively) which are comparable to the partial D 1 agonist SKF 38393 ( 3b ). In contrast to the benzazepine 3b , the indole based test compounds turned out less selective over the D 2 and D 3 receptor subtype.