Nitrite Esters Or Chalcogen Analogues Thereof (i.e., Compounds Having (x=)n X- Bonded Directly To Carbon, Which Carbon May Be Single Bonded To Any Atom But May Be Multiple Bonded Only To Carbon; The X's May Be The Same Or Diverse Chalcogens) Patents (Class 558/488)
  • Patent number: 9115043
    Abstract: The present invention relates to a novel a process for the preparation of 9-dichloromethylene-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-ylamine which process comprises a) reacting cyclopentadiene in the presence of a radical initiator and CXCI3, wherein X is chloro or bromo, to a compound of formula I1, or aa) reacting cyclopentadiene with CXCI3, wherein X is chloro, in the presence of a metal catalyst to a compound of formula I1, wherein X is chloro, b) reacting the compound of formula I1 with a base in the presence of an appropriate solvent to the compound of formula III, c) and converting the compound of formula III in the presence of 1,2-dehydro-6-nitrobenzene to the compound of formula IV, and d) hydrogenating the compound of formula IV in the presence of a metal catalyst.
    Type: Grant
    Filed: September 28, 2009
    Date of Patent: August 25, 2015
    Assignee: Syngenta Crop Protection, LLC
    Inventors: Denis Gribkov, Bjorn Antelmann, Fanny Giordano, Harald Walter, Alain De Mesmaeker
  • Publication number: 20150105475
    Abstract: The present disclosure relates to devices and methods for the preparation of amyl nitrite formulations at a point of use location from relatively shelf-stable reagents employing acidic cationic exchange resins.
    Type: Application
    Filed: October 15, 2013
    Publication date: April 16, 2015
    Inventors: Joseph A. McDONOUGH, Darrel W. JOHNSTON, Paul M. THOMPSON
  • Patent number: 8987496
    Abstract: The present disclosure relates to devices and methods for the preparation of amyl nitrite formulations at a point of use location from relatively shelf-stable reagents employing acidic cationic exchange resins.
    Type: Grant
    Filed: October 15, 2013
    Date of Patent: March 24, 2015
    Assignee: Southwest Research Institute
    Inventors: Joseph A. McDonough, Darrel W. Johnston, Paul M. Thompson
  • Publication number: 20140221316
    Abstract: This disclosure relates to novel compounds containing an H2S releasing moiety and a nitric oxide (NO) releasing moiety covalently linked with a core (e.g., a salicylic acid moiety) and the use of such compounds in treating inflammatory diseases, including cancers. Therapeutic potency of these compounds is significantly higher than NSAIDs containing a H2S-releasing moiety alone (HS-NSAIDs) and NSAID containing a NO-releasing moiety alone (NO-NSAIDs). The compounds, in addition, exhibit reduced side effect, e.g., reduced stomach ulcers, upon administration.
    Type: Application
    Filed: August 15, 2012
    Publication date: August 7, 2014
    Applicant: RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK
    Inventors: Khosrow Kashfi, Ravinder Kodela
  • Patent number: 8795649
    Abstract: The present invention relates to baits, especially baits to be used in humane methods for controlling feral omnivore populations. The invention also relates to methods of manufacturing the baits.
    Type: Grant
    Filed: February 28, 2008
    Date of Patent: August 5, 2014
    Assignee: Invasive Animals Ltd.
    Inventors: Linton Drew Staples, Steven Lapidge, Brendan Cowled, Simon Humphrys
  • Patent number: 8722918
    Abstract: The present invention relates to a process for producing C1-C4 alkyl nitrite, comprising loading a resin catalyst layer and/or a porous filler layer into a reactor, passing nitrogen oxide, oxygen and C1-C4 alkanol as raw materials through the resin catalyst layer and/or porous filler layer in a counter current, parallel current or cross current manner, reacting under the conditions including a reaction temperature of from 0 to 150° C., a reaction pressure of from ?0.09 to 1.5 MPa, a molar ratio of C1-C4 alkanol/nitrogen oxide of 1-100:1, a molar ratio of nitrogen oxide/oxygen of 4-50:1, to obtain an effluent containing C1-C4 alkyl nitrite, wherein said nitrogen oxide is NO, or a mixed gas containing NO and one or more selected from N2O3 and NO2.
    Type: Grant
    Filed: April 15, 2011
    Date of Patent: May 13, 2014
    Assignees: China Petroleum & Chemical Corporation, Shanghai Research Institute of Petrochemical Technology Sinopec
    Inventors: Juntao Liu, Siqin Li, Lei Li, Linna Zhang
  • Patent number: 8536366
    Abstract: A process for the continuous production of a compound of Formula (II), HO—R1—ONO2 (II) wherein R1 is a straight chain alkyl radical having from 3 to 6 carbon atoms, in a two-phase solvent system, comprising contacting a compound of Formula (I), HO—R1—OH (I) wherein R1 is as defined above, with nitric acid in the presence of a first solvent, wherein the compound of Formula (II) is continuously extracted into a second solvent, and the reaction is carried out in a mixing microreactor which provides a power loss of at least 1.3 times the power loss provided under identical conditions by a circular cross-section straight-channel microreactor having an internal diameter equal to the average hydraulic diameter of the mixing microreactor and a length equal to the length of the mixing microreactor.
    Type: Grant
    Filed: December 19, 2008
    Date of Patent: September 17, 2013
    Assignee: DSM Fine Chemicals Austria NFG GmbH & Co KG
    Inventors: Sascha Braune, Stefan Steinhofer, Peter Poechlauer, Rafael Wilhelmus E. G. Reintjens, Nicole Theodora W. Linssen, Mehul Thathagar
  • Patent number: 8476469
    Abstract: A process of producing C1-C4 alkyl nitrite, comprising the following steps: a) firstly feeding nitrogen oxide and oxygen into Reactor I, contacting with an aluminosilicate catalyst, and reacting to produce an effluent I containing NO2 and unreacted NO; b) feeding the effluent I and C1-C4 alkanol into Reactor II, and reacting to produce an effluent II containing C1-C4 alkyl nitrite; and c) separating the effluent II containing C1-C4 alkyl nitrite to obtain C1-C4 alkyl nitrite; wherein reactor I is a fixed bed reactor, and Reactor II is a rotating high-gravity reactor; said nitrogen oxide in step a) is NO, or a mixed gas containing NO and one or more of N2O3 and NO2, wherein the molar number of NO is greater than that of NO2, if any; and the molar ratio of NO in nitrogen oxide to oxygen is 4-25:1.
    Type: Grant
    Filed: April 14, 2011
    Date of Patent: July 2, 2013
    Assignees: China Petroleum & Chemical Corporation, Shanghai Research Institute of Petrochemical Technology SINOPEC
    Inventors: Juntao Liu, Weimin Yang, Wanmin Wang, Linna Zhang
  • Patent number: 8044224
    Abstract: The invention relates to a chiral iridium aqua complex of formula (1): wherein R1 and R2 are the same or different and each is an aryl group optionally having at least one substituent selected from the group consisting of a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a haloalkoxy group having 1 to 6 carbon atoms, a nitro group, a carboxyl group and a cyano group, or the like; and wherein R3 and R4 are the same or different and each is an alkyl group or the like, as well as the use of such a chiral iridium aqua complex for asymmetric transfer hydrogenation.
    Type: Grant
    Filed: January 29, 2008
    Date of Patent: October 25, 2011
    Assignees: Sumitomo Chemical Company, Limited
    Inventor: Erick M. Carreira
  • Publication number: 20110257424
    Abstract: A process of producing C1-C4 alkyl nitrite, comprising the following steps: a) firstly feeding nitrogen oxide and oxygen into Reactor I, contacting with an aluminosilicate catalyst, and reacting to produce an effluent I containing NO2 and unreacted NO; b) feeding the effluent I and C1-C4 alkanol into Reactor II, and reacting to produce an effluent II containing C1-C4 alkyl nitrite; and c) separating the effluent II containing C1-C4 alkyl nitrite to obtain C1-C4 alkyl nitrite; wherein reactor I is a fixed bed reactor, and Reactor II is a rotating high-gravity reactor; said nitrogen oxide in step a) is NO, or a mixed gas containing NO and one or more of N2O3 and NO2, wherein the molar number of NO is greater than that of NO2, if any; and the molar ratio of NO in nitrogen oxide to oxygen is 4-25:1.
    Type: Application
    Filed: April 14, 2011
    Publication date: October 20, 2011
    Applicants: Shanghai Research Institute of Petrochemical Technology SINOPEC, China Petroleum & Chemical Corporation
    Inventors: Juntao LIU, Weimin YANG, Wanmin WANG, Linna ZHANG
  • Publication number: 20110257425
    Abstract: The present invention relates to a process for producing C1-C4 alkyl nitrite, comprising loading a resin catalyst layer and/or a porous filler layer into a reactor, passing nitrogen oxide, oxygen and C1-C4 alkanol as raw materials through the resin catalyst layer and/or porous filler layer in a counter current, parallel current or cross current manner, reacting under the conditions including a reaction temperature of from 0 to 150° C., a reaction pressure of from ?0.09 to 1.5 MPa, a molar ratio of C1-C4 alkanol/nitrogen oxide of 1-100:1, a molar ratio of nitrogen oxide/oxygen of 4-50:1, to obtain an effluent containing C1-C4 alkyl nitrite, wherein said nitrogen oxide is NO, or a mixed gas containing NO and one or more selected from N2O3 and NO2.
    Type: Application
    Filed: April 15, 2011
    Publication date: October 20, 2011
    Inventors: Juntao Liu, Siqin Li, Lei Li, Linna Zhang
  • Patent number: 8030511
    Abstract: Organic nitrites can be produced from a compound which is a mono/polyhydric alcohol or an aldehyde- or ketone-derivate thereof after de-aeration of the same, using NO gas, and stored in an environment saturated with gaseous NO. Organic nitrites produced according to the invention exhibit less impurities and improved storage stability compared to conventionally produced nitrites. The organic nitrites of the invention can easily be formulated into pharmaceutical compositions and have utility for the treatment of various conditions.
    Type: Grant
    Filed: March 14, 2007
    Date of Patent: October 4, 2011
    Inventors: Lars E. Gustafsson, Dag Linnarsson, Kristofer Nilsson
  • Publication number: 20110207958
    Abstract: The present invention relates to a novel a process for the preparation of 9-dichloromethylene-1,2,3,4-tetrahydro-1,4-methano-naphthalen-5-ylamine which process comprises a) reacting cyclopentadiene in the presence of a radical initiator and CXCI3, wherein X is chloro or bromo, to a compound of formula I1, or aa) reacting cyclopentadiene with CXCI3, wherein X is chloro, in the presence of a metal catalyst to a compound of formula I1, wherein X is chloro, b) reacting the compound of formula I1 with a base in the presence of an appropriate solvent to the compound of formula III, c) and converting the compound of formula III in the presence of 1,2-dehydro-6-nitrobenzene to the compound of formula IV, and d) hydrogenating the compound of formula IV in the presence of a metal catalyst.
    Type: Application
    Filed: September 28, 2009
    Publication date: August 25, 2011
    Applicant: SYNGENTA CROP PROTECTION LLC
    Inventors: Denis Gribkov, Bjorn Antelmann, Fanny Giordano, Harald Walter, Alain De Mesmaeker
  • Publication number: 20110160225
    Abstract: Disclosed herein are novel compositions and methods for treating or preventing a variety of disorders and conditions associated with lipid metabolism. The methods generally include administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising one or more fibric acid or statin derivative compositions alone or in combination with one or more lipid altering agents and/or PDE inhibitors.
    Type: Application
    Filed: November 19, 2010
    Publication date: June 30, 2011
    Applicant: IRONWOOD PHARMACEUTICALS, INC.
    Inventors: Mark G. Currie, John Jeffrey Talley, Brian Cali
  • Patent number: 7714160
    Abstract: An alkyl nitrite is produced with high efficiency by bringing a nitrogen monoxide gas into contact with an aqueous solution of an alkyl alcohol and nitric acid in a reactor 2, which aqueous solution may be a liquid fraction generated in an alkyl nitrite-production process in which an alkyl alcohol is reacted with nitrogen monoxide and oxygen in a reaction column 1.
    Type: Grant
    Filed: September 21, 2004
    Date of Patent: May 11, 2010
    Assignee: Ube Industries, Ltd.
    Inventors: Ryoji Sugise, Shuji Tanaka, Hirofumi Ii, Kazuaki Mii
  • Publication number: 20100016618
    Abstract: The invention relates to a chiral iridium aqua complex of formula (1): wherein R1 and R2 are the same or different and each is an aryl group optionally having at least one substituent selected from the group consisting of a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a haloalkoxy group having 1 to 6 carbon atoms, a nitro group, a carboxyl group and a cyano group, or the like; and wherein R3 and R4 are the same or different and each is an alkyl group or the like, as well as the use of such a chiral iridium aqua complex for asymmetric transfer hydrogenation.
    Type: Application
    Filed: January 29, 2008
    Publication date: January 21, 2010
    Applicants: SUMITOMO CHEMICAL COMPANY, LIMITED
    Inventor: Erick M. Carreira
  • Publication number: 20090286968
    Abstract: Disclosed are 2-quinoxalinol salen compounds and in particular 2-quinoxalinol salen Schiff-base ligands. The disclosed 2-quinoxalinol salen compounds may be utilized as ligands for forming complexes with cations, and further, the formed complexes may be utilized as catalysts for oxidation reactions. The disclosed 2-quinoxalinol salen compounds also may be conjugated to solid supports and utilized in methods for selective solid-phase extraction or detection of cations.
    Type: Application
    Filed: April 24, 2009
    Publication date: November 19, 2009
    Applicant: Auburn University
    Inventors: Anne E. V. Gorden, Xianghong Wu
  • Publication number: 20090258944
    Abstract: Organic nitrites can be produced from a compound which is a mono/polyhydric alcohol or an aldehyde- or ketone-derivate thereof after de-aeration of the same, using NO gas, and stored in an environment saturated with gaseous NO. Organic nitrites produced according to the invention exhibit less impurities and improved storage stability compared to conventionally produced nitrites. The organic nitrites of the invention can easily be formulated into pharmaceutical compositions and have utility for the treatment of various conditions.
    Type: Application
    Filed: March 14, 2007
    Publication date: October 15, 2009
    Inventors: Lars E. Gustafsson, Dag Linnarsson, Kristofer Nilsson
  • Publication number: 20090170108
    Abstract: (Problems) The main object of the present invention is to provide a screening method for selecting a substance affecting a bond between thioredoxin and MIF. (Means for Solving Problems) The present invention provides a screening method for selecting a test substance which strengthens a bond between a polypeptide of a thioredoxin family and a macrophage migration inhibition factor, comprising: mixing a test substance with at least one binding substance selected from following (1) to (4), (1) the polypeptide belonging to the thioredoxin family, (2) a protein having an amino acid sequence of the polypeptide belonging to the thioredoxin family in which one or more amino acid is deleted, replaced or added, and having an equivalent activity to the polypeptide of the thioredoxin family, (3) a gene coding (1), (4) a gene coding (2); bonding the binding substance to the macrophage migration inhibition factor; and monitoring the bond state between the binding substance and the macrophage migration inhibition factor.
    Type: Application
    Filed: November 26, 2008
    Publication date: July 2, 2009
    Inventors: Junji Yodoi, Norihiko Knodo, Aoi Son, Noriko Kato, Tornijiro Hara, Tomohisa Horibe
  • Publication number: 20090043120
    Abstract: A process for producing a nitrite includes allowing a nitrogen oxide to react with an alcohol at a reaction temperature lower than 10° C.
    Type: Application
    Filed: August 5, 2008
    Publication date: February 12, 2009
    Inventors: Akihiro Shibamoto, Takahiro Iwahama
  • Publication number: 20090012323
    Abstract: This invention relates to a process for the production of a mixture of detergent-range alcohols having an average of between 8 and 20 carbon atoms per molecule. The process includes the steps of providing a hydrocarbon stream containing olefins and paraffins in which more than 5% by volume of olefin molecules in the hydrocarbon stream have a total number of carbon atoms which is different from the total number of carbon atoms of the most abundant two carbon numbers of olefins in the hydrocarbon stream; reacting the hydrocarbon stream with CO and an alcohol in the presence of a catalyst in a hydroesterification reaction to form a hydrocarbon stream containing esters and paraffins; separating esters from the hydrocarbon stream containing esters and paraffins; and subjecting the esters to a hydrogenation reaction to provide the mixed alcohol product.
    Type: Application
    Filed: June 30, 2008
    Publication date: January 8, 2009
    Applicant: Sasol Technology (Proprietary) Limited
    Inventors: Hendrik Van Rensburg, Craig McGregor
  • Patent number: 7439400
    Abstract: The invention disclosed a new process of asymmetric alkynylation of ketone or ketimine, involving the chiral ligand-mediated asymmetric addition of zinc or copper acetylide to a trifluoromethyl ketone or ketimine intermediate to give a chiral tertiary proparglic alcohols or amines. The adduct compounds include the key precursors to the potent HIV reverse transcriptase inhibitor Efavirenz (DMP 266), DPC 961 and DPC 083. The invention also disclosed a novel chiral amino alcohol ligand.
    Type: Grant
    Filed: June 16, 2003
    Date of Patent: October 21, 2008
    Assignee: Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences
    Inventors: Biao Jiang, Yugui Si
  • Patent number: 7314948
    Abstract: In a continuous process for the preparation of alkyl nitrites and dinitrites, an alkanol or dialkanol is first mixed with an aqueous mineral acid, the reaction mixture obtained is then reacted with an inorganic nitrite and the product obtained can then be isolated immediately.
    Type: Grant
    Filed: August 2, 2002
    Date of Patent: January 1, 2008
    Assignee: BASF Aktiengesellschaft
    Inventors: Steffen Kudis, Rene Lochtman, Manfred Ehresmann, Michael Keil, Joachim Gebhardt, Michael Rack, Ralf Schimetzek
  • Patent number: 7186753
    Abstract: Compounds or their salts of general formula (I): A—B—N(O)s wherein: s is an integer equal to 1 or 2; A=R—T1—, wherein R is the drug radical and T1=(CO)t or (X)t?, wherein X=O, S, NR1c, R1c is H or a linear or branched alkyl or a free valence, t and t? are integers and equal to zero or 1, with the proviso that t=1 when t?=0; t=0 when t?=1; B=—TB—X2—O— wherein TB=(CO) when t=0, TB=X when t?=0, X being as above defined; X2 is equal to R1B—X—R2B radical wherein X is as above defined, R1B and R2B, equal to or different from each other, are linear or branched C1–C6 alkylenes, or X2 is a radical wherein two alkylene chains C1–C4 are linked to nonadjacent positions of a central ring having 4 or 6 atoms, said ring being an unsaturated cycloaliphatic ring, or a saturated or aromatic heterocylic ring, containing one or two heteroatoms, equal or different, selected from O, S, N; wherein the unsaturated cycloaliphatic ring does not have aromatic character according to Huckel's rule.
    Type: Grant
    Filed: July 27, 2000
    Date of Patent: March 6, 2007
    Assignee: Nicox S.A.
    Inventor: Piero Del Soldato
  • Patent number: 7166618
    Abstract: The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or optionally, at least one therapeutic agent, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B4 (LTB4) receptor antagonists, leukotriene A4 (LTA4) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, H2antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhi
    Type: Grant
    Filed: June 18, 2003
    Date of Patent: January 23, 2007
    Assignee: NitroMed, Inc.
    Inventors: Ramani R. Bandarage, David S. Garvey, L. Gordon Letts, Joseph D. Schroeder, Sang William Tam
  • Patent number: 7160920
    Abstract: Disclosed are (i) compounds of a steroid, a ?-agonist, an anticholinergic, a mast cell stabilizer and a phosphodiesterase (PDE) inhibitor directly or indirectly linked to a NO or NO2 group or a group which stimulates endogenous production of NO or EDRF in vivo; (ii) compositions of steroids, ?-agonists, anticholinergics, mast cell stabilizers and PDE inhibitors, which can optionally be substituted with at least one NO or NO2 moiety or a group which stimulates endogenous production of NO or EDRF in vivo, and a compound that donates, transfers or releases nitric oxide as a charged species, i.e., nitrosonium (NO+) or nitroxyl (NO?), or as the neutral species, nitric oxide (NO.) or that stimulates endogenous production of NO or EDRF in vivo; and (iii) uses for them in preventing and/or treating respiratory disorders.
    Type: Grant
    Filed: May 5, 2003
    Date of Patent: January 9, 2007
    Assignee: NitroMed, Inc.
    Inventors: David S. Garvey, L. Gordon Letts, H. Burt Renfroe, Stewart K. Richardson
  • Patent number: 6844464
    Abstract: An alkyl nitrite is produced with high efficiency by bringing a nitrogen monoxide gas into contact with an aqueous solution of an alkyl alcohol and nitric acid in a reactor 2, which aqueous solution may be a liquid fraction generated in an alkyl nitrite-production process in which an alkyl alcohol is reacted with nitrogen monoxide and oxygen in a reaction column 1.
    Type: Grant
    Filed: March 13, 2003
    Date of Patent: January 18, 2005
    Assignee: Ube Industries, Ltd.
    Inventors: Ryoji Sugise, Shuji Tanaka, Hirofumi Ii, Kazuaki Mii
  • Publication number: 20040199003
    Abstract: In a continuous process for the preparation of alkylnitrites and dinitrites, an alkanol or dialkanol is first mixed with an aqueous mineral acid, the reaction mixture obtained is then reacted with an inorganic nitrite and the product obtained can then be isolated immediately.
    Type: Application
    Filed: January 29, 2004
    Publication date: October 7, 2004
    Inventors: Steffen Kudis, Rene Lochtman, Manfred Ehresmann, Michael Keil, Joachim Gebhardt, Michael Rack, Ralf Schimetzek
  • Publication number: 20040024057
    Abstract: The invention describes novel nitrosated nonsteroidal antiinflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent.
    Type: Application
    Filed: July 3, 2003
    Publication date: February 5, 2004
    Applicant: NitroMed, Inc.
    Inventors: Richard A. Earl, Maiko Ezawa, Xinqin Fang, David S. Garvey, Ricky D. Gaston, Subhash P. Khanapure, L. Gordon Letts, Chia-En Lin, Ramani R. Ranatunga, Stewart K. Richardson, Joseph D. Schroeder, Cheri A. Stevenson, Shiow-Jyi Wey
  • Publication number: 20040019105
    Abstract: Disclosed are novel NO-releasing compounds which comprise a stabilized S-nitrosyl group and a free alcohol or a free thiol group. Also disclosed is a method of preparing the NO-releasing compounds. The method comprises reacting a polythiol or a thioalcohol with a nitrosylating agent. Also disclosed are medical devices coated with the disclosed compounds, methods of delivering NO to treatments sites in a subject by utilizing the medical devices and methods of sterilizing surfaces.
    Type: Application
    Filed: March 11, 2003
    Publication date: January 29, 2004
    Applicant: Duke University
    Inventors: Eric J. Toone, Jonathan S. Stamler
  • Publication number: 20030208036
    Abstract: A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation.
    Type: Application
    Filed: May 13, 2003
    Publication date: November 6, 2003
    Inventors: Robert A. Herrmann, David Knapp
  • Publication number: 20020099330
    Abstract: Disclosed are novel NO-releasing compounds which comprise a stabilized S-nitrosyl group and a free alcohol or a free thiol group. Also disclosed is a method of preparing the NO-releasing compounds. The method comprises reacting a polythiol or a thioalcohol with a nitrosylating agent. Also disclosed are medical devices coated with the disclosed compounds, methods of delivering NO to treatments sites in a subject by utilizing the medical devices and methods of sterilizing surfaces.
    Type: Application
    Filed: December 18, 2001
    Publication date: July 25, 2002
    Applicant: Duke University Medical Center
    Inventors: Eric J. Toone, Jonathan S. Stamler
  • Publication number: 20020062020
    Abstract: A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation.
    Type: Application
    Filed: January 14, 2002
    Publication date: May 23, 2002
    Inventors: Robert A. Herrmann, David Knapp
  • Patent number: 6359182
    Abstract: A C-nitroso compound having a molecular weight ranging from about 225 to about 1,000 (from about 225 to about 600 for oral administration) on a monomeric basis wherein a nitroso group is attached to a tertiary carbon, which is obtained by nitrosylation of a carbon acid having a pKa less than about 25, is useful as an NO donor. When the compound is obtained from a carbon acid with a pKa less than about 10, it provides vascular relaxing effect when used at micromolar concentrations and this activity is potentiated by glutathione to be obtained at nanomolar concentrations. When the compound is obtained from a carbon acid with a pKa ranging from about 15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations without glutathione. The compound is preferably water-soluble and preferably contains a carbon alpha to the nitrosylated carbon which is part of a ketone group.
    Type: Grant
    Filed: October 26, 2000
    Date of Patent: March 19, 2002
    Assignee: Duke University
    Inventors: Jonathan S. Stamler, Eric J. Toone
  • Patent number: 6191302
    Abstract: An alkyl nitrite can be produced on an industrial scale with a high efficiency and with a low yield of by-products by the process wherein nitrogen oxide-containing feed gas is brought into an alkyl alcohol liquid in a distillation column reactor while circulating a liquid fraction, produced in the reactor and containing the alkyl alcohol, through a circulation path including a lower section of the reactor and a cooler to remove the reaction heat vigorously generated in the reactor, and while controlling the weight ratio of the circulating liquid fraction to the total alkyl alcohol fed into the reactor to 50:1 to 200:1, the molar ratio of the total alkyl alcohol fed to the reactor and contained in the circulating liquid fraction to nitrogen oxide in the feed gas to 20:1 to 150:1, and the content of the alkyl alcohol in the liquid fraction to 15 to 60% by weight; and the resultant gas fraction containing the target alkyl nitrite is collected from the reactor.
    Type: Grant
    Filed: October 21, 1998
    Date of Patent: February 20, 2001
    Assignee: Ube Industries, Ltd.
    Inventors: Keigo Nishihira, Shuji Tanaka, Shinichi Yoshida
  • Patent number: 6013667
    Abstract: Compounds of formula (I): in which:R.sub.a and R.sub.b, identical or different, represent hydrogen or alkyl or together form a bond,R.sub.C represents hydroxyl optionally substituted alkoxy, or optionally substituted amino,R.sub.1 represents hydrogen or --O--NO.sub.2, --O--NO, or --S--NO,R.sub.2 and R.sub.3, identical or different, represent hydrogen, alkyl, or optionally substituted phenyl,X represents oxygen or --NH--CO--,m represents 0 or 1,n represents an integer such that 0.ltoreq.n.ltoreq.6,p represents 0 or 1,R.sub.4 represents hydrogen, optionally substituted alkyl, optionally substituted phenyl, or a group as defined in the description,R.sub.5 represents hydrogen or alkyl,R.sub.6 represents hydrogen or alkyl,or R.sub.5 and R.sub.6 together form a chain --(CH.sub.2).sub.t -- in which t represents 1 or 2,q represents 0, 1, or 2,r represents an integer such that 0.ltoreq.r.ltoreq.6,R.sub.d and R.sub.
    Type: Grant
    Filed: February 27, 1998
    Date of Patent: January 11, 2000
    Assignee: Adir Et Compagnie
    Inventors: Gilbert Lavielle, Bernard Cimetiere, Tony Verbeuren, Serge Simonet, Jean-Jacques Descombes
  • Patent number: 5859053
    Abstract: The invention relates to new derivatives of acetylsalicylic acid (called ASA in the following), which contain an NO.sub.3 structure. They are therapeutically active either as the intact active compound molecule or after cleavage (NO release). The invention also relates to processes for their preparation and their use as medicaments, in particular for the alleviation of pain, inhibition of platelet aggregation, lowering of fever and for the prevention of cardiovascular disorders and oncoses.
    Type: Grant
    Filed: October 24, 1997
    Date of Patent: January 12, 1999
    Assignee: Bayer Aktiengesellschaft
    Inventors: Eva Lesur, Dieter Neuser, Oswald Lockhoff, Elisabeth Perzborn, Peter Kurka, Johannes Peter Stasch
  • Patent number: 5674894
    Abstract: The current invention discloses novel amidine derivatives with nitric oxide donating property that can inhibit platelet aggregation and promote vasodilation in a single compound.
    Type: Grant
    Filed: May 15, 1995
    Date of Patent: October 7, 1997
    Assignee: G.D. Searle & Co.
    Inventors: Mark G. Currie, Foe S. Tjoeng, Mark E. Zupec
  • Patent number: 5649322
    Abstract: C.sub.1 -C.sub.4 -Alkyl nitrites can be prepared by reaction of C.sub.1 -C.sub.4 -alkanols with nitrogen oxides with the participation of oxygen in a reactor designed as a scrubber column, nitrogen oxides having a proportion of more than 50% of NO of the total amount of gram atoms of N of the nitrogen oxides, oxygen and optionally inert gas being fed into the lower part of the reactor. 5 to 60% of the total amount of C.sub.1 -C.sub.4 -alkanol used is likewise fed into the lower part of the reactor in vaporous or atomized form, while the remaining C.sub.1 -C.sub.4 -alkanol is delivered to the column head.
    Type: Grant
    Filed: December 11, 1995
    Date of Patent: July 15, 1997
    Assignee: Bayer Aktiengesellschaft
    Inventors: Heinz Landscheidt, Paul Wagner, Zoltan Kricsfalussy, Alexander Klausener
  • Patent number: 5646181
    Abstract: Pharmaceutical compositions in topical or parenteral form containing organic nitrites are effective in treating male impotence and erectile dysfunction through topical or intracavernosal administration to the penis. Methods of treatment utilizing the nitrite-containing compositions are also disclosed, as are certain novel organic nitrite compounds.
    Type: Grant
    Filed: May 2, 1995
    Date of Patent: July 8, 1997
    Assignee: Research Foundation of State University of New York
    Inventors: Ho-Leung Fung, John Anthony Bauer
  • Patent number: 5562887
    Abstract: Alkyl nitrite-containing exhaust gases are purified in continuous form by treating them with equimolar to excess amidosulphuric acid in the form of an aqueous solution in the manner of a counter-current scrubbing at a temperature of 0.degree.-100.degree. C.
    Type: Grant
    Filed: November 8, 1994
    Date of Patent: October 8, 1996
    Assignee: Bayer Aktiengesellschaft
    Inventors: Heinz Landscheidt, Kaspar Hallenberger, Paul Wagner, Alexander Klausener
  • Patent number: 5536723
    Abstract: The invention relates to novel S-nitroso derivatives of ACE inhibitors and to pharmaceutical compositions comprising the S-nitrosothiol derivatives of the invention together with a pharmaceutically acceptable carrier.The invention also relates to methods for treating various pathophysiological conditions including acute myocardial infarction, left ventricular dysfunction without overt heart failure, hypertension, pulmonary hypertension, congestive heart failure, angina pectoris, vascular thrombosis, Raynauds syndrome, scleroderma, toxemia of pregnancy, acute renal failure, diabetic nephropathy, and renal artery stenosis, and to methods of inhibiting ACE and effecting vasodilation comprising administering the S-nitrosothiol derivatives of the ACE inhibitors of the invention to an animal.
    Type: Grant
    Filed: October 6, 1994
    Date of Patent: July 16, 1996
    Assignee: Brigham & Women's Hospital
    Inventors: Joseph Loscalzo, John Cooke
  • Patent number: 5534648
    Abstract: A process for producing dimethyl carbonate is carried out by a first step of catalytically reacting carbon monoxide with methyl nitrite to produce dimethyl carbonate; a second step of absorbing dimethyl carbonate contained in a gas fraction withdrawn from the first step by dimethyl oxalate; a third step of regenerating methyl nitrite by contacting nitrogen monoxide contained in a gas fraction withdrawn from the second step with a molecular oxygen-containing gas and methyl alcohol; a fourth step of collecting dimethyl carbonate by distilling a liquid fraction withdrawn from the second step; and a fifth step of producing and recovering methyl nitrite from a purge gas consisting of a minor portion of a gas fraction withdrawn from one of the second step and the third step by bringing the purge gas together with an ammonia-oxidation product gas into contact with methyl alcohol in a methyl nitrite-recovering column, to thereby produce and recover methyl nitrite contained in the recovering column with a high efficie
    Type: Grant
    Filed: November 28, 1994
    Date of Patent: July 9, 1996
    Assignee: Ube Industries, Ltd.
    Inventors: Keigo Nishihira, Shinichi Yoshida, Shuji Tanaka
  • Patent number: 5412147
    Abstract: C.sub.1 -C.sub.6 -Alkyl nitrites can be prepared by reacting nitrogen dioxide with C.sub.1 -C.sub.6 -alcohols, by, in a counterflow-operated column, feeding the alcohol or an alcohol/water mixture into the upper part of the column and the nitrogen dioxide or a nitrogen dioxide/inert gas mixture into the lower part of the column. The resulting alkyl nitrite is removed from the column as the top product and the co-formed nitric acid is removed from the column as the bottom product.
    Type: Grant
    Filed: November 24, 1993
    Date of Patent: May 2, 1995
    Assignee: Bayer Aktiengesellschaft
    Inventors: Heinz Landscheidt, Paul Wagner, Alexander Klausener
  • Patent number: 5098597
    Abstract: The present invention relates to a continuous process for making an alkali metal azide or an alkaline earth metal azide which comprises the steps of: (a) reacting a first reaction mixture comprising an alkali metal nitrite or alkaline earth metal nitrite, a C1--C3 alkanol, and a high boiling acid in a first reactor to form a gaseous C1-C3 alkyl nitrite, (b) controllably feeding said gaseous C1-C3 alkyl nitrite into a second reactor and reacting in a controlled manner a second reaction mixture comprising said gaseous C1-C3 alkyl nitrite, hydrazine, and an alkali metal hydroxide or alkaline earth metal hydroxide, in the presence of an organic solvent, thereby producing an alkali metal azide or alkaline earth metal azide, and (c) removing said alkali metal azide or alkaline earth metal azide from said second reactor and replenishing said reaction mixture in said second reactor to provide a continuous, controlled process for producing said alkali metal azide or alkaline earth metal azide.
    Type: Grant
    Filed: June 29, 1990
    Date of Patent: March 24, 1992
    Assignee: Olin Corporation
    Inventors: Eugene F. Rothgery, David F. Gavin, Kimberly A. Thomas
  • Patent number: 5049694
    Abstract: The invention relates to pharmaceutical compositions containing novel nitrate esters, of which it was found that they are useful for the treatment of ischemiatic heart diseases, decompensatio cordis, myocardial infarction and hypertension.
    Type: Grant
    Filed: September 14, 1989
    Date of Patent: September 17, 1991
    Assignee: Cedona Pharmaceuticals B.V.
    Inventors: Jan Bron, Geert J. Sterk, Jan F. van der Werf, Hendrik Timmerman
  • Patent number: 4980496
    Abstract: The invention provides a process for the production of C.sub.1 to C.sub.5 alkyl nitrite by forming an aqueous solution of C.sub.1 to C.sub.5 alkyl alcohol an alkali metal nitrite; cooling it; then slowly adding a hydrohalic acid solution while it is stirring; the reaction temperature is maintained in the range of from about -10.degree. C. to about 10.degree. C. until the reaction is substantially complete; and the two formed phases are separated in a separatory funnel.
    Type: Grant
    Filed: December 5, 1989
    Date of Patent: December 25, 1990
    Inventor: Olan S. Fruchey
  • Patent number: 4918250
    Abstract: This invention relates to a process for nitrating toluene to dinitrotoluene and phase separation of the product using an inorganic salt as a phase separation agent.
    Type: Grant
    Filed: April 21, 1989
    Date of Patent: April 17, 1990
    Assignee: Olin Corporation
    Inventors: Robert W. Mason, Peter C. Imm, Kent J. Bordelon
  • Patent number: 4908466
    Abstract: A process and reaction vessel for producing alkyl nitrite is disclosed the process comprising (a) contacting nitric oxide, lower alcohol and oxygen in a reaction zone such that alkyl nitrite is formed, said reaction zone comprising a reactor section and a rectification section, (b) supplying a liquid scrubbing agent to an upper portion of the rectification section, (c) withdrawing a gaseous alkyl nitrite product stream from the upper portion of the rectification section, and (d) withdrawing a liquid stream from a lower portion of the reactor section. The reactor section provides intimate vapor-liquid contact sufficient to enhance the conversion of nitric oxide to alkyl nitrite and the rectification section provides sufficient vapor residence time to enhance conversion of oxygen, as well as sufficient rectification capabilities to reduce the amounts of water and nitric acid in the gaseous alkyl nitrite product stream.
    Type: Grant
    Filed: September 29, 1987
    Date of Patent: March 13, 1990
    Assignee: Union Carbide Chemicals and Plastics Company Inc.
    Inventor: James R. Nelson
  • Patent number: 4879401
    Abstract: A process is provided for removing impurities from the gaseous product of an alkyl nitrite production zone by contacting a portion of it with lower alcohol and oxygen to convert substantially all of the nitric oxide in that portion of the gaseous product stream to alkyl nitrite, the oxygen being present in an amount such that the mole ratio of nitric oxide to oxygen is in the range of about 4:1 to about 2:1 and the lower alcohol being present in the reaction zone such that the mole ratio of nitric oxide to lower alcohol is about 1:1 or less. A recovery stream, comprising alkyl nitrite substantially free of nitric oxide, is withdrawn from the reaction zone and at least a portion of the alkyl produced in the reaction zone is removed. A least a portion of the balance of the recovery stream from which the alkyl nitrite has been removed is purged, thereby removing impurities from the process.
    Type: Grant
    Filed: September 29, 1987
    Date of Patent: November 7, 1989
    Assignee: Union Carbide Chemicals and Plastics Company Inc.
    Inventors: Arthur R. Doumaux, Jr., James R. Nelson