9 alpha- and 9 beta-Hydroxyphenylmorphans.
Platinum-oxide hydrogenation of 5-m-methoxyphenyl-2-methyl-9-oxomorphan (I) gave the 9 alpha-hydroxy racemate (II) whose phenolic analogue (III) is a strong antinociceptive agent, fully supportive of morphine dependence in rhesus monkeys. The di-O-acetyl derivative (VI) of III was similar to III in its profile of activity. The diastereoisomer of III (VII), obtained by hydrogenation of the methobromide of I (IV), extrusion of methyl bromide, and O-demethylation of the resultant free base (VIII), was almost inactive antinociceptively and did not suppress withdrawal symptoms in morphine-dependent monkeys. The orientation of the C-9 hydroxyl groups was deduced from spectral data and by analogy.
D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D016227:Benzoquinones; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced; D011809:Quinones; D011930:Reaction Time / Q000187:drug effects; D013237:Stereoisomerism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
D000700:Analgesics; D016227:Benzoquinones; D009019:Morphinans; D011809:Quinones; C029322:phenylbenzoquinone