Novel opiates and antagonists. 5. 7-Carbethoxy-N-(cycloalkylmethyl)-3-hydroxymorphinan-6-ones and -isomorphinan-6-ones.
A direct conversion of deoxydihydrothebaine-phi (1) to 3-methoxymorphinan-6-one (3Ca) and its trans isomer 3Ta was achieved in excellent yield by the catalytic reduction of 1 in AcOH containing CF3COOH. Treatment of 3Ca or 3Ta with NaH and diethyl carbonate formed the corresponding 7-carbethoxy derivatives 4a which, on O-demethylation, furnished the 3-hydroxy compounds 4b. The analgesic N-methyl compounds 3 were converted to the 17-(cyclopropylmethyl) or 17-(cyclobutylmethyl) derivatives 6--8. Two of these compounds, one in the cis (7Ca) and the other in the trans (7Ta) series, showed mixed agonist/antagonist activity in the pentazocine range.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D051379:Mice; D009019:Morphinans / Q000138:chemical synthesis* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000138:chemical synthesis*; D009294:Narcotics / Q000138:chemical synthesis*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects
D009019:Morphinans; D009292:Narcotic Antagonists; D009294:Narcotics