[Synthesis and CNS-activity of spirocyclic pethidine and prodine analogs].
The bromoacetals 5a and 5b react with n-butyllithium and the piperidone 7 to yield the hydroxyacetals 8b and 8c, respectively. Cyclization of 8b and 8c followed by acid hydrolysis affords the spirocyclic hemiacetals 10b and 10c which are oxidized by PCC to give the spirocyclic prodine analogues 4b and 4c. The corresponding spirocyclic pethidine derivative 2 is prepared by alkylation of the 2-benzopyran-3-one 16 with N-Lost (17). In the mouse writhing test the spiropethidine 2 is not analgesic active up to a dose of 20 mg/kg body weight (bw). In the spirocyclic prodine series the methylated lactone 4c is the most active analgesic with an ED50-value (ED50 = 9.2 mg/kg bw) in the range of the ED50-value of tramadol.
Wünsch
B
B
Institut für Pharmazie und Lebensmittelchemie, Universität München.
Höfner
G
G
Bauschke
G
G
D000522:Alphaprodine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D008614:Meperidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects
D000700:Analgesics; D000522:Alphaprodine; D008614:Meperidine
Synthese und ZNS-Aktivität spirocyclischer Pethidin- und Prodin-Analoga.