Abstract: Disclosed is the novel analgesic/narcotic antagonist 17-cyclopropylmethyl-3-hydroxy-14-methoxy-7.alpha.-methyl-morphinan-6-one.

Abstract: A method of producing morphinan compounds which incorporates double advantages over the prior art, such as the utilization of .beta.,.gamma.-unsaturated ketones in place of the .alpha.,.beta.-unsaturated ketones previously used. Additionally, in the step where .beta.,.gamma.-unsaturated bromoketones (13 or 14) proceed to 1-bromo-N-formylnordihydrothebainone (morphinan) (17) there are utilized super acids, such as trifluoromethane sulfonic, trifluoroethane sulfonic and mixtures thereof, and also antimony pentafluoride and mixtures of hydrogen fluoride and antimony pentafluoride. Super acid works, whereas the prior art shows that cyclization in the presence of acids, even strong acids, such as sulfuric, phosphoric, do not work.

Abstract: Disclosed are certain 14-ethoxymorphinan-6-one compounds exhibiting analgesic and, in some cases, mixed analgesic/narcotic antagonist activity.

Abstract: Disclosed is the title compound which has been found to be significantly more water soluble than other acid addition salts of the morphinane nucleus.

Abstract: 6(eq)-R.sub.4 -1,2,3,4,5,6-Hexahydro-3-R.sub.1 -11(ax)-R.sub.3 -11(eq)-CH.sub.2 Z-2,6-methano-3-benzazocines, useful as analgesic agents and narcotic antagonists, prepared by heating, with formic acid in an organic solvent or with certain ammonium formates in the absence of a solvent, certain 1,2,3,4,4a,5,10,10a-octahydro-2,5-methanobenzo[g]quinolines.

Abstract: 3-Hydroxy-7-oxomorphinans and 3-hydroxy-7-oxoisomorphinans, optionally substituted on the 17-nitrogen atom, are potent, orally active antidiarrheal agents.

Abstract: Disclosed are 14-methoxy substituted 3-hydroxy or 3-methoxy -6-one morphinans characterized by the structural formula: ##STR1## wherein R is H or methyl; R.sub.1 is H, .alpha. methyl or .beta. methyl; and R.sub.2 is cyclobutylmethyl, cyclopropylmethyl, tetrahydrofurfuryl or dimethylallyl. The compounds of the present invention are variously useful as analgesics, narcotic antagonists and mixed analgesics/narcotic antagonists.

Abstract: Disclosed is 17-cyclopropylmethyl-14-hydroxy-3-methoxymorphinan-6-one. This compound is a mixed agonist (analgesic)/narcotic antagonist and therefore useful for the treatment of moderate to severe pain without the liability of inducing physical dependence.

Abstract: 6(eq)-R.sub.4 -1,2,3,4,5,6-Hexahydro-3-R.sub.1 -11(ax)-R.sub.3 -11(eq)-CH.sub.2 Z-2,6-methano-3-benzazocines, useful as analgesic agents and narcotic antagonists, prepared by heating, with formic acid in an organic solvent or with certain ammonium formates in the absence of a solvent, certain 1,2,3,4,4a,5,10,10a-octahydro-2,5-methanobenzo[g]quinolines.

Abstract: The preparation of 3-phenoxy N-substituted morphinans, useful as analgesics from 1-(p-hydroxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline or cyclohexen-(1)-yl-ethylamine and p-phenoxyphenylacetic acid is described.

Abstract: Disclosed is a novel method for the introduction of a 7-methyl group into the morphinan nucleus to thereby provide precursors for the preparation of therapeutically useful 7-methyl-4,5.alpha.-epoxy morphinan and morphinan-6-one compounds. The method involves reacting thebaine, dihydrothebaine or the enol acetate of dihydrocodeinone with lithium dimethyl cuprate to form the corresponding 7-methyl-4,5.alpha.-epoxy cleaved product.

Abstract: 1-R.sub.1 -2-Q-4a.alpha.-R.sub.3 -5.alpha.-R.sub.4 -1,2,3,4,4a,5,10,10a-Octahydro-3,5-etheno- (and 3,5-ethano) benzo[g]quinolines, useful as analgesic agents, prepared by heating, with formic acid in an organic solvent or with certain ammonium formates in the absence of a solvent, certain 1,2,3,4,4a,5,10,10a-octahydro-2,5-methanobenzo[g]quinolines, the latter prepared by acid catalyzed cyclization of a 3-benzyl-2-azabicyclo[2.2.2]oct-5-ene.

Abstract: Disclosed are 7-methyl, 8.beta.-lower alkyl and 7 methyl-8-lower alkyl substituted B/C Cis or Trans morphinan-6-one compounds characterized by the structural formula: ##STR1## Specific compounds, included within the scope of the foregoing general formula wherein R.sub.1 is H or methyl, R.sub.2 is cyclopropylmethyl or cyclobutylmethyl, R.sub.3 is H, methyl, ethyl or n-propyl and R.sub.4 is H or methyl are useful as mixed analgesics/narcotic antagonists.

Abstract: 3-R.sub.1 -6(eq)-R.sub.4 -7-R.sub.2 "-8-R.sub.2 -9-R.sub.2 '-10-R.sub.2 "'-11(ax)-R.sub.3 -11(eq)-[CH.sub.2 CH.sub.2 CO(CH.sub.2).sub.n -(2- and 3-furyl)]-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines, useful as analgesics and narcotic antagonists, are prepared either by heating, with formic acid in an organic solvent or with certain ammonium formates, certain lower-alkyl 1-R.sub.1 -4a.alpha.-R.sub.3 -5.alpha.-R.sub.4 -6-R.sub.2 "-7-R.sub.2 -8-R.sub.2 '-9-R.sub.2 "'-3-[CO(CH.sub.2).sub.n -(2- and 3-furyl)]-1,2,3,4,4 a,5,10,10a-octahydro-2,5-methanobenzo[g]quinoline-3-carboxylates or by reaction of a lower-alkyl .beta.-[3-R.sub.1 -6-(eq)-R.sub.4 -7-R.sub.2 "-8-R.sub.2 -9-R.sub.2 '-10-R.sub.2 "'-11(ax)-R.sub.3 -1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-11(eq)-yl]propionate with 2 or 3-furylacetic acid in the presence of a strong base.

Abstract: 3-R.sub.1 -6(eq)-R.sub.4 -7-R.sub.2 "-8-R.sub.2 -9-R.sub.2 '-10-R.sub.2 '''-11(ax)-R.sub.3 -11(eq)-[CH.sub.2 CH.sub.2 CO(CH.sub.2).sub.n -(2- and 3-furyl)]-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines, useful as analgesics and narcotic antagonists, are prepared either by heating, with formic acid in an organic solvent or with certain ammonium formates, certain lower-alkyl 1-R.sub.1 -4a.alpha.-R.sub.3 -5.alpha.-R.sub.4 -6-R.sub.2 "-7-R.sub.2 -8-R.sub.2 '-9-R.sub.2 '''-3-[CO(CH.sub.2).sub.n -(2- and 3-furyl]-1,2,3,4,4a,5,10,10a-octahydro-2,5-methanobenzo[g]quinoline-3-carb oxylates or by reaction of a lower-alkyl .beta.-[3-R.sub.1 -6(eq)-R.sub.4 -7-R.sub.2 "-8-R.sub.2 -9-R.sub.2 '-10-R.sub.2 '''-11(ax)-R.sub.3 -1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocin-11(eq)-yl]propionate with 2- or 3-furylacetic acid in the presence of a strong base.

Abstract: 3-R.sub.1 -7-R.sub.2 "-8-R.sub.2 -9-R.sub.2 '-10-R.sub.2 "'-11(ax)-R.sub.3 -6(eq)-R.sub.4 -11(eq)-(CH.sub.2 CH.sub.2 CH.sub.2 R.sub.5)-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines, generally useful as morphine-like analgesics and as narcotic antagonists, are prepared by reducing, under Wolff-Kishner reaction conditions, a corresponding 3-R.sub.1 -7-R.sub.2 "-8-R.sub.2 -9-R.sub.2 '-10-R.sub.2 "'-11(ax)-R.sub.3 -6(eq)-R.sub.4 -11(eq)-(CH.sub.2 CH.sub.2 COR.sub.5)-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocine and, if desired, cleaving a lower-alkoxy, methoxymethoxy or benzyloxy group to an hydroxy group.

Abstract: 3-R.sub.1 -6(eq)-R.sub.4 -7-R.sub.2 "-8-R.sub.2 -9-R.sub.2 '-10-R.sub.2 "'-11(ax)-R.sub.3 -11(eq)-[CH.sub.2 CH.sub.2 CO(CH.sub.2).sub.n -X-Alk]-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines, useful as analgesics, are prepared by heating, with formic acid in an organic solvent or with certain ammonium formates, a lower-alkyl 1-R.sub.1 -3-[Alk-X-(CH.sub.2).sub.n -CO]-4a.alpha.-R.sub.3 -5.alpha.-R.sub.4 -6-R.sub.2 "-7-R.sub.2 -8-R.sub.2 '-9-R.sub.2 "'-1,2,3,4,4a,5,10,10a-octahydro-2,5-methanobenzo[g]quinoline-3-carboxylat e.

Abstract: .beta.-[3-R.sub.1 -6(eq)-R.sub.4 -7-R.sub.2 "-8-R.sub.2 -9-R.sub.2 '-10-R.sub.2 '"-11(ax)-R.sub.3 -1,2,3,4,5,6,-hexahydro-2,6-methano-3-benzazocin-11(eq)-yl]propionic acids, esters and amides, useful as analgesics and narcotic antagonists, are prepared by heating, with formic acid in an organic solvent or with certain ammonium formates, certain di-lower-alkyl 1-R.sub.1 -4a.alpha.-R.sub.3 -5.alpha.-R.sub.4 -6-R.sub.2 "-7-R.sub.2 -8-R.sub.2 '-9-R.sub.2 "'-1,2,3,4,4a,5,10,10a-octahydro-2,5-methanobenzo[g]quinoline-3,3-dicarbox ylates, to prepare the esters, hydrolysis of the latter to prepare the acids and conversion of the acids to a mixed anhydride and reaction of the latter with ammonia or an appropriate amine to form the amides.

Abstract: There is provided a novel and high yield procedure for transforming acid salts of 14-alkanoyloxymorphinans and derivatives thereof into the corresponding N-alkyl-14-hydroxymorphinans wherein the alkyl moiety on the nitrogen contains the same number of carbon atoms as that previously in the 14-alkanoyl moiety. In the process of the present invention, the acid is neutralized to the free base, the alkanoyl moiety at the 14-oxy then spontaneously shifts to the nitrogen and is subsequently reduced to the corresponding alkyl moiety. O-dealkylation at C-3, where an alkoxy group is originally present, is carried out in the usual manner. There is also provided a readily produced and readily disassociated adduct of the corresponding 14-hydroxy-N-alkanoyl morphinan-6-alkylene ketal with benzene, tetrahydrofuran, and the like.

Abstract: Lower-alkyl 1-R.sub.1 -3-R.sub.5 CO-4a.alpha.-R.sub.3 -5.alpha.-R.sub.4 -6-R.sub.2 "-7-R.sub.2 -8-R.sub.2 '-9-R.sub.2 '"-1,2,3,4,4a,5,10,10a-octahydro-2,5-methanobenzo[g]quinoline-3-carboxylat es, useful as intermediates for the preparation of 3-R.sub.1 -6(eq)-R.sub.4 -7-R.sub.2 "-8-R.sub.2 -9-R.sub.2 '-10-R.sub.2 '"-11(ax)-R.sub.3 -11(eq)-CH.sub.2 CH.sub.2 COR.sub.5 -1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines, useful as analgesics and narcotic antagonists, are prepared by acylation of an appropriate lower-alkyl 1-R.sub.1 -4a.alpha.-R.sub.3 -5.alpha.C-R.sub.4 -6-R.sub.2 "-7-R.sub.2 -8-R.sub.2 '-9-R.sub.2 '"-1,2,3,4,4a,5,10,10a-octahydro-2,5-methanobenzo[g]quinoline-3-carboxylat e or carboxylation of an appropriate 1-R.sub.1 -3-COR.sub.5 "-4.alpha.-R.sub.3 -5.alpha.-R.sub.4 -6-R.sub.2 "-7-R.sub.2 -8-R.sub.2 '-9-R.sub.2 '"-1,2,3,4,4a,5,10,10a-octahydro-2,5-methanobenzo[g]quinoline.

Abstract: There is provided a novel, high yield, method of dealkylating N-alkylated 14-hydroxymorphinans and derivatives thereof including, inter alia, oxymorphone and oycodone. There are thus provided, inter alia, more efficient routes for the formation of naloxone, naltrexone, and nalbuphine. In the principal step of the process, the dealkylation using certain oxycarbonyl halides (or haloformates) is carried out on the N-alkyl-14-acyloxy-morphinan which it is desired to dealkylate.

Abstract: N-substituted-14-hydroxy-3-substituted-morphinan derivatives have been found to possess potent narcotic agonist or antagonist activity. In particular, the compound N-Cyclobutylmethyl-3,14-dihydroxymorpinan has been found to posess potent agonist/antagonist activity as a non-narcotic analgesic. An improved total snythesis of these compounds is described herein from the starting material 2-(p-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline. A preferred feature of the process involves borane reduction of 2-cyclobutylcarbonyl-9,10-dihydroxy-1-(p-methoxybenzyl)perhydroisoquinolin e (Va) to provide the corresponding cyclobutylmethyl derivative complexed with borane which is converted directly to N-cyclobutylmethyl-14.beta.-hydroxy-3-methoxymorphinan (LVa) by treating with acid.

Abstract: Levo-rotary 3-phenoxy N-substituted morphinans and derivatives thereof useful as analgesics and/or narcotic antagonists and their preparation form (-)-3-hydroxy-N-lower alkyl morphinan including intermediates in this preparation.