Hexahydro-1H-1-pyrindines from acid rearrangement of 9-alkylidene-5-(m-methoxyphenyl)-2-methylmorphans. A new structural type of narcotic antagonists.
9-Methylene- and 9-ethylidene-5-(m-methoxyphenyl)-2-methylmorphans (1, 2) and refluxing 48% HBr have given rearrangement products 3 and 4, respectively. The structure of 4 [4a-ethyl-2,4a,5,6,7,7a-hexahydro-4-(3-hydroxyphenyl)-1-methyl-1H-1- pyrindine] was determined by X-ray crystallography and that of 3 [1,4a-dimethyl-2,4a,5,6,7,7a-hexahydro-4-(3-hydroxyphenyl)-1-methyl-1H- pyrindine] follows from analogy and NMR data. Compounds 3 and 4 are opioid antagonists of about the potency of nalorphine in the tail-flick vs. morphine assay and precipitate a complete abstinence syndrome in morphine-dependent monkeys. Both are nearly devoid of antinociceptive activity and they have about 0.025 times the affinity of nalorphine for the mu opioid receptor.
D000470:Alkaloids / Q000378:metabolism / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors; D009269:Nalorphine / Q000378:metabolism / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D011725:Pyridines; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism; D017450:Receptors, Opioid, mu; D012964:Sodium / Q000494:pharmacology; D014961:X-Ray Diffraction
D000470:Alkaloids; D009292:Narcotic Antagonists; D011725:Pyridines; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C052351:1,4a-dimethyl-2,4a,5,6,7,7a-hexahydro-4-(3-hydroxyphenyl)-1-methyl-1H-1-pyrindine; C052352:4a-ethyl-2,4a,5,6,7,7a-hexahydro-4-(3-hydroxyphenyl)-1-methyl-1H-1-pyrindine; D009270:Naloxone; D009020:Morphine; D012964:Sodium; D009269:Nalorphine