Synthesis, conformational analysis and antinociceptive activity of 1-[N-methyl-(2-phenylethyl)amino]methyl-1,2,3,4-tetrahydroisoquinoline derivatives

New derivatives of 1-[N-methyl-(2-phenylethyl)amino]methyl-1,2,3,4-tetrahyd roisoquinoline were synthesized. The antinociceptive activity of the compou nds, determined by the mouse tail-flick test, showed that the introduction of a hydroxy substituent in position 5 of the isoquinoline nucleus generate d compounds 4c and 5c, which were as potent as codeine. Conformational anal ysis and superimposition of energy minima conformers of the compounds on ph enazocine revealed that the main proposed opioid pharmacophores were well m atched.