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-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.
Tabatabai
S A
SA
Department of Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran.
Zarrindast
M R
MR
Lashkari
S B
SB
Shafiee
A
A
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010620:Phenazocine / Q000737:chemistry / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D013237:Stereoisomerism
D000700:Analgesics; D000701:Analgesics, Opioid; D007546:Isoquinolines; D009292:Narcotic Antagonists; D009270:Naloxone; D010620:Phenazocine