Nitrogen Or Divalent Chalcogen Double Bonded Directly To Carbocyclic Ring Of The Pentacyclo Ring System (e.g., Morphinones, Etc.) Patents (Class 546/45)
Abstract: This patent application describes the preparation and properties of novel and highly potent morphinan analgesics. The compounds include narcotic agnoists as well as narcotic antagonists and are represented by the following formula: ##STR1## R.sub.1 =OCH.sub.3, OCOCH.sub.3, H R.sub.2 =CH.sub.3, CH.sub.2 --CH.dbd.CH.sub.2, ##STR2## CH.sub.2 CH.sub.2 C.sub.6 H.sub.
Type:
Grant
Filed:
July 16, 1981
Date of Patent:
June 14, 1983
Assignee:
The United States of America as represented by Secretary of the Department of Health and Human Services
Inventors:
Arnold Brossi, Helmut Schmidhammer, Arthur E. Jacobson, Fu-Lian Hsu
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 4,5.alpha.-epoxy-3-hydroxy or methoxy-7-(1-hydroxyalkyl or 1-oxoalkyl)morphinan-6-one compounds characterized by the structural formulae: ##STR1## In the foregoing formulae R is methyl, cyclopropylmethyl, cyclobutylmethyl, propargyl, allyl, dimethylallyl, cis-chloroallyl or furfuryl; R.sub.1 is H or methyl; R.sub.2 is straight or branched chain alkyl of from 1 to 10 carbon atoms, aryl, substituted aryl or arylalkyl, in which the alkyl group contains from 1 to 6 carbon atoms, and R.sub.3 is a straight chain alkyl of 1 to 4 carbon atoms.
Type:
Grant
Filed:
December 10, 1980
Date of Patent:
August 31, 1982
Assignee:
SISA, Incorporated
Inventors:
James E. Quick, Raj K. Razdan, Haldean C. Dalzell
Abstract: Thebaine is converted to a mixture of codeinone and neopinone in aqueous formic acid solution containing as catalyst a mercuric salt. Thebaine is converted to a neopinone ketal by irradiation in an alkanol or to a mixture of neopinone and codeinone in an acidic aqueous solution. Neopinone ketals, codeinone and neopinone can be converted to codeine.
Type:
Grant
Filed:
January 25, 1980
Date of Patent:
July 7, 1981
Assignee:
The United States of America as represented by the Department of Health and Human Services
Inventors:
William G. Dauben, Craig P. Baskin, Herman C. H. A. vanRiel
Abstract: Disclosed are 7,7-dimethyl-4,5.alpha.-epoxy-morphinan-6-one compounds characterized by the formula: ##STR1## wherein R is H or CH.sub.3, R.sub.1 is H, CH.sub.3 or CH.sub.2 CH.sub.3 and R.sub.2 is cyclopropylmethyl or cyclobutylmethyl. Particular compounds circumscribed by the foregoing formula are useful as analgesics, narcotic antagonists or mixed analgesics/narcotic antagonists.
Abstract: Disclosed are 7,8 and 7-8 substituted 4,5.alpha.-epoxymorphinan-6-one compounds characterized by the structural formula: ##STR1## In the foregoing formula R.sub.1 may be H or methyl, R.sub.2 is cyclopropylmethyl, cyclobutylmethyl, allyl or tetrahydrofurfuryl, R.sub.3 is H, .beta.-methyl, .beta.-ethyl or .alpha.-ethyl and R.sub.4 is H or .alpha.-methyl. Particular compounds corresponding to the foregoing description are useful as mixed analgesics/narcotic antagonists whereas others have been found to be pure narcotic antagonists.
Type:
Grant
Filed:
July 11, 1979
Date of Patent:
June 9, 1981
Assignee:
Miles Laboratories, Inc.
Inventors:
Michael P. Kotick, Robert N. Schut, Joseph O. Polazzi, David L. Leland
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: Novel derivatives of morphine having the general formula: ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are certain specified values, and their pharmaceutically acceptable salts.The compounds exhibit activity in the central nervous system and may be presented in the form of pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or carrier.
Type:
Grant
Filed:
March 15, 1978
Date of Patent:
December 23, 1980
Assignee:
Reckitt & Colman Products Limited
Inventors:
Ryszard J. Kobylecki, Ian G. Guest, John W. Lewis, Gordon W. Kirby
Abstract: Novel derivatives of morphine having the general formula: ##STR1## wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are certain specified values, and their pharmaceutically acceptable salts.The compounds exhibit activity in the central nervous system and may be presented in the form of pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or carrier.
Type:
Grant
Filed:
March 15, 1978
Date of Patent:
December 23, 1980
Assignee:
Reckitt & Colman Products Limited
Inventors:
Ryszard J. Kobylecki, Ian G. Guest, John W. Lewis, Gordon W. Kirby
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 is 17-cyclobutylmethyl-4,5.alpha.-epoxy-3-hydroxy-14-methoxy-8.alpha.-methylm orphinan-6-one characterized by the formula: ##STR1## This compound is useful as a mixed analgesic/narcotic antagonist.
Abstract: Compounds of the formula ##STR1## wherein R is allyl or a related radical such as chloroallyl, cyclopropyl-methyl or propargyl, andX is the anion of an acid, especially a chloride, bromide, iodide or methylsulfate anion;the compounds prevent or relieve the intestinal mobility inhibiting side-effects of narcotic analgesics without interfering with the analgesic activity of the latter.
Type:
Grant
Filed:
July 28, 1978
Date of Patent:
November 27, 1979
Assignee:
Boehringer Ingelheim GmbH
Inventors:
Leon I. Goldberg, Herbert Merz, Klaus Stockhaus
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: 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: Compounds of the general formula ##STR1## in which X represents halogen. These compounds are useful in the production of codeinone and codeine substantially free from impurities.