Synthesis, Conformational Analysis and Antinociceptive Activity of 1-[N-Methyl-(2-phenylethyl)amino]methyl-1,2,3,4-tetrahydroisoquinoline Derivatives

Summary

New derivatives of 1-[N-methyl-(2-phenylethyl)amino]methyl-1,2,3,4-tetrahydroisoquinoline were synthesized. The antinociceptive activity of the compounds, determined by the mouse tail-flick test, showed that the introduction of a hydroxy substituent in position 5 of the isoquinoline nucleus generated compounds 4c and 5c, which were as potent as codeine. Conformational analysis and superimposition of energy minima conformers of the compounds on phenazocine revealed that the main proposed opioid pharmacophores were well matched.

Zusammenfassung

Synthese, Strukturanalyse und schmerzstillende Wirkung von 1-[N-Methyl-(2-phenylethyl)- amino]methyl-1,2,3,4-tetrahydroisochinolin-Derivaten

Neue Derivate von 1-[N-Methyl-(2-phenylethyl)amino]methyl-1,2,3,4-tetrahydroisochinolin wurden synthetisiert. Die im Mäuse-”Tail-flick”-Test bestimmte schmerzstillende Wirkung der synthetisierten Verbindungen zeigte, daß die Einführung eines Hydroxy-Substituenten in Position 5 in den Isochinolin-Kern Verbindungen liefert (4c und 5c), die so wirksam sind wie Codein. Strukturanalysen und Überlagerungen implizieren, daß der vorgeschlagene Hauptopioid-Pharmakophor eine gute Übereinstimmung aufweist.

Key words

1,2,3,4-Tetrahydroisoquinoline derivatives, antinociceptive activity - conformational analysis, synthesis