[Synthesis and central effects of 4-hydroxy-(alkyl)- and 4-amino-(alkyl)-substituted 2,6-epoxy-3-benzoxocines].
The tricyclic hemiacetal 1 is transformed with amines to the N/O-acetals 3 and 10, with nitromethane to the 4-nitromethyl derivative 13, and with the Wittig reagents 15a and 15b to the 2-benzopyrans 16 and 19. Reduction and methylation of 13 yield the tertiary amine 4; through three steps the secondary amine 18 and the tertiary amine 5 are prepared from 16 and 19, respectively. The 1,3-dioxane ring of all these 2,6-epoxy-3-benzoxocine derivatives exists in the chair conformation with an equatorial C-4 substituent. After application of the amines 5, 11c, and 18 mice do not show any symptoms of central activity; weak CNS-effects are observed with the alcohols 1 and 2. For the tertiary amine 4, which causes considerable central effects (Straubtail-phenomenon, convulsions, etc.), an ED50 of 78 mg/kg is determined in the mouse "writhing"-test.
Wünsch
B
B
Institut für Pharmazie und Lebensmittelchemie, Universität München.
Bauschke
G
G
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004147:Dioxins / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice
D000700:Analgesics; D001578:Benzopyrans; D002491:Central Nervous System Agents; D004147:Dioxins
Synthese und zentrale Wirkungen von 4-hydroxy-(alkyl)- und 4-amino-(alkyl)-substituierten 2,6-epoxy-3-benzoxocinen.