Process Of Forming Partially Hydrogenated Pyridine Ring Patents (Class 546/249)
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Patent number: 5530134Abstract: A process for the synthesis of compounds of the formulas Ia and Ib below, wherein R.sub.1, R.sub.2, and R.sub.3, which are the same or different, are each selected from hydrogen and C.sub.1 -C.sub.4 alkyl, including the compound Anabaseine (Ia, wherein R.sub.1 =R.sub.2 R.sub.3 =H) (3,4,5,6-tetrahydro-2', 3'-bipyridine), the process comprising reacting sodium salt of .delta.-valerolactone with substituted ethyl nicotinate derivative to produce the Claisen product sodium 3-nicotinoyl-2-tetrahydropyranone enolate derivative, heating the sodium 3-nicotinoyl-2-tetrahydropyranone enolate derivative with concentrated HCl to produce 3-(5-chloro-1-pentanone-1-yl) pyridine derivative, dissolving the 3-(5-chloro-1-pentanone-1-yl) pyridine derivative in ethanol and then heating the 3-(5-chloro-1-pentanone-1-yl) pyridine derivative in ethanol with ethanolic ammonia solution in a sealed container to produce the compound Ia.Type: GrantFiled: September 6, 1994Date of Patent: June 25, 1996Assignee: Synphar Laboratories Inc.Inventors: Mohsen Daneshtalab, Dai Nguyen, Inderjit Sidhu, Ronald G. Micetich
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Patent number: 5502050Abstract: Inhibitor of the use of tetrahydrobiopterin as a cofactor for nitric oxide synthase, e.g., substituted 4-phenyl(hydropyridines) such as 1-methyl-4-(3',4'-dihydroxyphenyl)-1,2,3,6-tetrahydropyridine or, 4-(3',4'-dihydroxyphenyl)-1,2,3,6-tetrahydropyridine) or tetrahydropterin analog which does not replace tetrahydrobiopterin as a substrate for nitric oxide synthase such as (6R,S)-6,7-dimethyl-tetrahydropterin or (6R,S)-tetrahydrofolic acid or 2,4-diamino-, 2,6-diamino, or 4,6-diamino mono- or disubstituted pyrimidines or the corresponding pyrimidine-3-oxides such as 2,4-diamino-6-(diethylamino)pyrimidine, 2,4-diamino-6-piperidino-pyrimidine-3-oxide, 2,4-diamino-6-hydroxypyrimidine, 4,6-diamino-2-hydroxypyrimidine or 2,5-diamino-4,6-dihydroxypyrimidine is administered to inhibit nitric oxide synthesis from arginine in vascular cells in a subject in need of such inhibition (e.g., for prophylaxis or treatment of cytokine- or endotoxin-induced hypotension (e.g., septic shock).Type: GrantFiled: November 29, 1993Date of Patent: March 26, 1996Assignee: Cornell Research Foundation, Inc.Inventor: Steven S. Gross
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Patent number: 5442070Abstract: This invention relates to new derivatives of fluoro quinoline carboxylic-3 acid having general formula (I), ##STR1## wherein R is a hydrogen atom or an alkyl radical and Hal is a halogen atom, as well as salts thereof, when they exist, preparation thereof and utilization as synthesis intermediary.Type: GrantFiled: April 7, 1994Date of Patent: August 15, 1995Assignee: Laboratoire Roger BellonInventors: Christophe Daubie, Jean-Jacques Legrand, Clive Pemberton
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Patent number: 5434266Abstract: Broad spectrum glycosidase inhibitors are produced from monosaccharide lactams by conversion to amidines, amidrazones, or amidoximes. The inhibitors have the general formula: ##STR1## wherein the N and C are joined as part of a monosaccharide azaanalog ring and wherein --NRQ, together with the nitrogen and carbon atoms, form a chemical group selected from amidines, amidrazones, and amidoximes.Type: GrantFiled: April 29, 1993Date of Patent: July 18, 1995Assignee: Cornell Research Foundation, Inc.Inventors: Bruce Ganem, Michael K. Tong, George Papandreou
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Patent number: 5286867Abstract: 1-Sulfonyloxy-2-pyridones of the formula I ##STR1## show good radiation sensitivity over a wide spectral range and are therefore valuable as photoactive compounds in radiation-sensitive mixtures.Type: GrantFiled: April 20, 1992Date of Patent: February 15, 1994Assignee: Hoechst AktiengesellschaftInventors: Gerhard Lohaus, Walter Spiess, Georg Pawlowski
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Patent number: 5231185Abstract: Broad spectrum glycosidase inhibitors are produced from monosaccharide lactams by conversion to amidines, amidrazones, or amidoximes. The inhibitors have the general formula: ##STR1## wherein the N and C are joined as part of a monosaccharide azaanalog ring and wherein --NRQ, together with the nitrogen and carbon atoms, form a chemical group selected from amidines, amidrazones, and amidoximes.Type: GrantFiled: July 23, 1991Date of Patent: July 27, 1993Assignee: Cornell Research Foundation, Inc.Inventors: Bruce Ganem, Michael K. Tong, George Papandreou
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Patent number: 5206369Abstract: An improved process for dehydrating dialkyl 2,6-bis(trifluoromethyl)-2,6-dihydroxy-4-(alkyl)-3,5-piperidinedicarboxyla tes using concentrated sulfuric acid essentially in the absence of a solvent to prepare the corresponding dialkyl 2,6-bis(trifluoromethyl)dihydro-4-(alkyl)-3,5-pyridinedicarboxylates.Type: GrantFiled: January 21, 1992Date of Patent: April 27, 1993Assignee: Monsanto CompanyInventor: William H. Miller
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Patent number: 5126457Abstract: The invention is directed to processes for the preparation of dimethyl-1,4-dihydro-2,6-dimethyl-4-(2'-nitrophenyl)-pyridine-3,5-dicarbox ylate by reacting 1-methoxy-1-(2'-nitrophenyl)-N-(2'-nitrophenyl)methylene methanamie or 1-(2'-nitrophenyl)-N,N'-bis-(2'-nitrophenyl) methylene methanediamine with methyl acetoacetate in the presence of an amine compound or by reacting the monomeric or trimeric from of 2-nitrobenzaldimine with methyl acetoacetate.Type: GrantFiled: March 8, 1989Date of Patent: June 30, 1992Assignee: Egis GyogyszergyarInventors: Pal Benko, Daniel Bozsing, Laszlo Levai, Gyorgyi Kovanyi nee Lax, Gyorgy Mikite, Peter Tompe, Eva Furdyga, Ilona Dinnyes nee Nagy, Eva Poczik, Gyorgyi Zalavari nee Dosa, Ivan Beck, Istvan Simonyi, Kalman Nagy, Janos Imre, Erzsebet Kiss nee Bertok, Eva J. Tajthy nee Juhasz, Attila Mandi, Frigyes Gorgenyi
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Patent number: 5104880Abstract: An acetylcholinesterase inhibitor is provided of the general formula (I): ##STR1## wherein R.sub.1 is H, (C.sub.1 -C.sub.8)alkyl or halo; R.sub.2 is H or (C.sub.1 -C.sub.8)alkyl; R.sub.3 and R.sub.4 are individually H, (C.sub.1 -C.sub.8)alkyl, NO.sub.2, hydroxy or halo; R.sub.5 and R.sub.6 are individually H, (C.sub.1 -C.sub.8)akyl, aryl or aralkyl; R.sub.7 is H, halo or (C.sub.1 -C.sub.8)alkyl, R.sub.8 is halo or (C.sub.1 -C.sub.8)alkyl; R.sub.9 is absent or is H; and the bonds represented by--are individually absent or, together with the adjacent bond, form the unit C.dbd.C, with the proviso that if both of the bonds represented by--are present, R.sub.3 and R.sub.4 cannot both be H unless R.sub.7 or R.sub.8 is halo; and the pharmaceutically acceptable salts thereof.Type: GrantFiled: May 1, 1991Date of Patent: April 14, 1992Assignee: Mayo Foundation for Medical Education and ResearchInventor: Alan P. Kozikowski
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Patent number: 4958024Abstract: A process for preparing a 2-carbamoylocxyalkyl-1,4-dihydropyridine derivative represented by the general formula: ##STR1## which comprises: (a) reacting a 3-amino-3-carbamoyloxyalkylacrylic acid derivative represented by the general formula: ##STR2## with a benzylidene compound represented by the general formula: ##STR3## (b) reacting the 3-amino-3-carbamoyloxyalkylacrylic acid derivative of the general formula II with an aldehyde compound represented by the general formula: ##STR4## and a .beta.-keto-ester compound represented by the general formula:R.sup.4 --CO--CH.sub.2 --COOR.sup.2 (V)(c) reacting a 3-carbamoyloxyalkylpropiolic acid derivative represented by the general formula: ##STR5## with the benzylidene compound of the general formula III and ammonia or its salt; or(d) reacting the 3-carbamoyloxyalkylpropiolic acid derivative of the general formula VI with the aldehyde compound of the general formula IV, the .beta.-keto-ester compound of the general formula V and ammonia or its salt.Type: GrantFiled: August 10, 1988Date of Patent: September 18, 1990Assignee: Banyu Pharmaceutical Company, Ltd.Inventors: Tetsuji Miyano, Kunio Suzuki, Ryosuke Ushijima, Susumu Nakagawa
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Patent number: 4929731Abstract: The present invention relates to a method for the synthesis of certain bridged fused ring pyridines. Such bridged fused ring pyridines can be converted to huperzine A and analogs of huperzine A. The present invention also covers such bridged fused ring pyridines, compounds utilized for the preparation of the bridged fused ring pyridines and analogs of huperzine A.Type: GrantFiled: February 21, 1989Date of Patent: May 29, 1990Assignee: University of PittsburghInventors: Alan P. Kozikowski, Yan Xia
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Patent number: 4908398Abstract: Poly-dihydro-2,6-dimethylpyridine-3,5-dicarboxylesters of general formula (I) ##STR1## in which A, B, m, n, k, j, R, R.sup.1 and R.sup.2 have the meanings defined in the text, useful as thermal stabilizers for synthetic polymers, in particular for polyvinylchloride-based masses.The compounds of formula (I) are preferably used in combination with the usual stabilizers based on organic metal derivatives. They can also be used combined with agents which exert a synergic action in maintaining a low color of manufactured articles subjected to heating, and in particular with betadicarbonyl compounds of formula (II):R.sup.3 --CO--CH.sub.2 --CO--R.sup.4 (II)in which R.sup.3 and R.sup.4 have the meanings defined in the text, in masses containing organic calcium and zinc salts as basic stabilizers.Type: GrantFiled: March 29, 1988Date of Patent: March 13, 1990Assignee: Lagor S.p.A.Inventors: Giuseppe Li Bassi, Roberto Ortica
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Patent number: 4857475Abstract: Labellable reagents for fluormetric assays comprise a cyclic condensation product of a .beta.-diketone, an aldehyde and an NH.sub.2 -bearing macromolecule, for example an antigen or antibody or a substance having an active group to which an antibody or antigen is linked. The reagents can chelate lanthanide metal ions such as Eu(II) and Tb(III) to form fluorescing complexes which can be used as labelled reagents for fluorometric assay of organic substances, for example antigens, antibodies and other substances occurring in body fluids.Type: GrantFiled: April 17, 1986Date of Patent: August 15, 1989Assignee: Roger Philip EkinsInventor: Salifu Dakubu
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Patent number: 4795814Abstract: Process for preparing dihydropyridine derivatives and salts and esters thereof represented by the general formula ##STR1## from a phenyl derivative and an enamine derivative in which the phenyl derivative is prepared by reacting a compound of the formula ##STR2## with a compound of the formula ##STR3## in the presence of an aromatic amine selected from o-, m-, p- anisidine; m-, p-toluidine; p-chloroaniline; aniline and o-phenetidine.Type: GrantFiled: December 18, 1986Date of Patent: January 3, 1989Assignee: Otsuka Pharmaceutical Co., Ltd.Inventors: Shinji Nishitani, Junichi Minamikawa, Masanobu Kano, Junichiro Otsubo, Yoshiaki Manabe
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Patent number: 4780538Abstract: A process for the preparation of 1,4-dihydropyridine compounds, especially N-substituted 1,4-dihydropyridine compounds, is disclosed. The compounds are useful as cardiovascular agents and also as starting materials for the preparation of certain cyclized compounds which have properties as calcium entry blockers.Type: GrantFiled: February 12, 1986Date of Patent: October 25, 1988Assignee: Merck & Co., Inc.Inventors: Steven M. Pitzenberger, Barry M. Trost
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Patent number: 4757147Abstract: This invention relates to novel highly branched amines and to a process of preparing same which comprises:(1) the preparation of a vinylimine from branched aldehydes and ammonia;(2) the dimerization and intermolecular condensation of such vinylimines to cyclic diamines; and(3) hydrolysis of such cyclic diamines to other diamines.Type: GrantFiled: September 5, 1985Date of Patent: July 12, 1988Assignee: Petrolite CorporationInventors: Benjamin T. Outlaw, Bernardus A. Oude Alink
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Patent number: 4703119Type: GrantFiled: June 4, 1985Date of Patent: October 27, 1987Assignee: Bayer AktiengesellschaftInventors: Egbert Wehinger, Horst Meyer
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Patent number: 4600778Abstract: In the preparation of a 1,4-dihydropyridine of the formula ##STR1## in which R is a phenyl radical which is optionally substituted once or twice by nitro and/or chlorine,R.sub.1 is a C.sub.1 -C.sub.4 -alkyl radical which is optionally substituted by a C.sub.1 -C.sub.4 -alkoxy group, andR.sub.2 is a C.sub.1 -C.sub.12 -alkyl radical which is optionally substituted by a C.sub.1 -C.sub.4 -alkoxy group, a trifluoromethyl group or the radical (C.sub.6 H.sub.5 CH.sub.2) (CH.sub.3)N,by preparing an ylidene compound of the formula ##STR2## and reacting such ylidene compound with an enamine compound of the formula ##STR3## the improvement which comprises preparing the ylidene compound by reaction of a ketocarboxylic ester of the formula ##STR4## with an aldehyde of the formula RCHO, in a solvent in the presence of a catalytic amount of any acetate salt of an amine, at a temperature from about -10.degree. C. up to 100.degree. C. The products symmetrical or unsymmetrical, are produced in high yield and purity.Type: GrantFiled: March 20, 1984Date of Patent: July 15, 1986Assignee: Bayer AktiengesellschaftInventors: Werner Teller, Wolfgang Koebernick, Arthur Haaf, Paul Naab, Michael Preiss
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Patent number: 4469871Abstract: One aspect of the invention resides in the three step process for preparing cardiotonically active 1,2-dihydro-6-(lower-alkyl)-2-oxo-5-(pyridinyl)nicotinonitriles or 1,2-dihydro-6-(lower-alkyl)-2-oxo-5-(pyridinyl)nicotinamides which comprises reacting a pyridinylmethyl lower-alkyl ketone with tri-(lower-alkyl) orthoformate, acetic anhydride and acetic acid to produce 2-(lower-alkoxy)-1-(pyridinyl)ethenyl lower-alkyl ketone reacting the latter with cyanoacetamide or malonamide in the presence of a basic condensing agent and neutralizing the reaction mixture, where pyridinyl is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. Other aspects of the invention reside in the intermediate 2-(lower-alkoxy)-1-(pyridinyl)ethenyl lower-alkyl ketones, their salts and their two step conversion, as described above, to 1,2-dihydro-6-(lower-alkyl)-2-oxo-5-(pyridinyl)-nicotinonitriles or corresponding nicotinamides.Type: GrantFiled: March 3, 1983Date of Patent: September 4, 1984Assignee: Sterling Drug Inc.Inventor: Karl O. Gelotte
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Patent number: 4417054Abstract: One aspect of the invention resides in the three step process for preparing cardiotonically active 1,2-dihydro-6-(lower-alkyl)-2-oxo-5-(pyridinyl)nicotinonitriles (III, Q is CN) or 1,2-dihydro-6-(lower-alkyl)-2-oxo-5-(pyridinyl)nicotinamides (III, Q is CONH.sub.2) which comprises reacting a pyridinylmethyl lower-alkyl ketone (I) with tri-(lower-alkyl) orthoformate, acetic anhydride and acetic acid to produce 2-(lower-alkoxy)-1-(pyridinyl)ethenyl lower-alkyl ketone (II), reacting II with cyanoacetamide or malonamide in the presence of a basic condensing agent and neutralizing the reaction mixture, where pyridinyl is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. Other aspects of the invention resides in the intermediate 2-(lower-alkoxy)-1-(pyridinyl)ethenyl lower-alkyl ketones (II) and its two step conversion, as described above, to said compounds (III, Q is CN or CONH.sub.2).Type: GrantFiled: May 24, 1982Date of Patent: November 22, 1983Assignee: Sterling Drug Inc.Inventor: Karl O. Gelotte
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Patent number: 4413127Abstract: The invention resides in a process for preparing cardiotonically active 1,2-dihydro-6-(lower-alkyl)-2-oxo-5-(pyridinyl)nicotinonitriles (III) which comprises reacting a pyridinylmethyl lower-alkyl ketone (I) with tri-(lower-alkyl) orthoformate, acetic anhydride and acetic acid to produce 2-(lower-alkoxy)-1-(pyridinyl)ethenyl lower-alkyl ketone (II) and then reacting II with malononitrile in a lower-alkanol, where pyridinyl is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents.Type: GrantFiled: May 24, 1982Date of Patent: November 1, 1983Assignee: Sterling Drug Inc.Inventor: Baldev Singh
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Patent number: 4387230Abstract: Dihydropyridines of formula ##STR1## where R.sup.6 is lower alkyl and R.sup.5 is lower alkyl or aryl (lower)alkyl are prepared by a novel process from sodium or potassium salts of 1-substituted-1,6-dihydro-5-hydroxy-3[2H]-pyridones. The dihydropyridines are useful as intermediates for pharmacologically active 1-optionally substituted-3-phenyl or substituted phenylpiperidin-5-ols and esters. Some of the piperidinols and esters are novel; those where the 1-substituent is aryl(lower)alkyl are intermediates, those where the 1-substituent is cycloalkyl(lower)alkyl are analgesics or antidepressants and those in which the 1-position is unsubstituted are anti-secretory agents.Type: GrantFiled: August 20, 1981Date of Patent: June 7, 1983Assignee: John Wyeth and Brother LimitedInventors: Alan C. White, Robin G. Shepherd
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Patent number: 4386207Abstract: An improved process for the preparation of pyridines and/or hydrogened pyridines that have been substituted with a hydrocarbon group at one or more carbon atoms. .gamma.-cyanoketone, in a gaseous phase and in the presence of hydrogen, is passed over a first catalyst in a reaction zone to form a reaction mixture containing substituted pyridines and/or hydrogenated pyridines and hydrogen. A hydrogen-containing gas is separated from the reaction mixture and, prior to being recycled, is subjected to a two-step catalytic treatment. In the first catalytic treatment step, the hydrogen-containing gas is passed over an iron, nickel, cobalt, or platinum-containing catalyst at a temperature of between about 250.degree. and 550.degree. C. In the second catalytic treatment step, the hydrogen-containing gas is passed over an iron, nickel, or cobalt catalyst at a temperature of between about 550.degree. and 800.degree. C.Type: GrantFiled: November 13, 1981Date of Patent: May 31, 1983Assignee: Stamicarbon B.V.Inventors: Theodorus F. M. de Graaf, Charles H. Geersheuvels
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Patent number: 4347363Abstract: A process for preparing cardiotonically active 1,2-dihydro-6-methyl-2-oxo-5-(pyridinyl)nicotinonitriles which comprises reacting a pyridinylmethyl methyl ketone with ethoxymethylenemalononitrile, where pyridinyl is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents.Type: GrantFiled: September 17, 1981Date of Patent: August 31, 1982Assignee: Sterling Drug Inc.Inventor: Baldev Singh
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Patent number: 4276419Abstract: An improved process for the preparation of pyridines and/or hydrogenated pyridines that have been substituted with a hydrocarbon group at one or more carbon atoms, .gamma.-cyanoketone, in a gaseous phase and in the presence of hydrogen, is passed in a reaction zone over a first catalyst containing a catalytically active metal or compound of a metal selected from the group copper, silver, gold, iron, nickel, cobalt, ruthenium, rhodium, palladium, osmium, iridium and platinum to form a reaction mixture. A hydrogen-containing gas is separated from the reaction mixture, passed over a second catalyst containing a catalytically active metal or compound of a metal selected from the group iron, nickel and cobalt at a temperature of between 300.degree. and 800.degree. C., and the hydrogen-containing gas so treated is recycled to the reaction zone.Type: GrantFiled: September 19, 1979Date of Patent: June 30, 1981Assignee: Stamicarbon, B.V.Inventors: Egidius J. M. Verheijen, Charles H. Geersheuvels
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Patent number: 4264609Abstract: Amrinone intermediates are prepared by reacting 4-picoline with at least three mole equivalents of phosgene per mole of 4-picoline and excess dimethylformamide to produce N-[3-dimethylamino-2-(4-pyridinyl)-2-propenylidene]-N-methylmethaniminium chloride hydrochloride, then reacting the latter with Q-CH.sub.2 CONH.sub.2 and at least three mole equivalents of base in anhydrous medium and then neutralizing the reaction mixture to produce 5-Q-[3,4'-bipyridin]-6(1H)-one, where Q is cyano or carbamyl. Other aspects of the invention are the separate steps of preparing said iminium salt and then converting it to said 5-Q-[3,4'-bipyridin]-6(1H)-one, and also cardiotonic composition and method for increasing cardiac contractility using said iminium salt or pharmaceutically-acceptable acid-addition salt thereof as the active cardiotonic.Type: GrantFiled: February 26, 1980Date of Patent: April 28, 1981Assignee: Sterling Drug Inc.Inventors: Karl O. Gelotte, Chester J. Opalka, Jr.
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Patent number: 4234484Abstract: Special cyclic enamides are prepared by splitting off alcohols catalytically from the corresponding alkoxylated cyclic amides, in the presence of at least one tetraalkylammonium and/or alkali metal salt of tetrafluoroboric acid and/or of hexafluorophosphoric acid as the catalyst, at a temperature of from about 120.degree. to 250.degree. C., distilling off the detached alcohol and isolating the formed enamide in known manner. Particularly preferred starting compounds are those cyclic amides which have been obtained by anodic alkoxylation of corresponding cyclic N-compounds in an alcohol in the presence of supporting electrolytes which are identical with the catalysts subsequently used for splitting off the alcohol, and by distilling off the alcohol from the reaction batch. The enamides are valuable starting products and intermediates for various syntheses, for example, syntheses of prostaglandins and of other pharmaceuticals.Type: GrantFiled: April 25, 1978Date of Patent: November 18, 1980Assignee: Hoechst AktiengesellschaftInventors: Michael Mitzlaff, Klaus Warning
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Patent number: 4205174Abstract: Process for the production of 6-substituted-4-methyl-2-pyridones having the formula: ##STR1## wherein R is a branched or unbranched alkyl group, a halogenated branched or unbranched alkyl group or a substituted or unsubstituted aryl group. Senecioic acid amide having the formula: ##STR2## is reacted in a solvent at an elevated temperature in the presence of a Lewis acid (as a catalyst) with an acyl chloride having the formula: ##STR3## wherein R has the same meaning as above. The reaction mixture is subsequently placed in an aqueous phase for hydrolysis. The 6-substituted-4-methyl-2-pyridone is separated by extraction through the buffering of the reaction mixture at a pH of 4 to 5.Type: GrantFiled: January 11, 1979Date of Patent: May 27, 1980Assignee: Lonza, Ltd.Inventor: Urs Michel
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Patent number: 4192946Abstract: A process for the production of 3-hydroxy-5-chloropyridine and 3-hydroxy-5-bromopyridine is disclosed which process comprises reacting 2-furfurylamine in aqueous mineral-acid solution at -20.degree. to +5.degree. C. with chlorine or bromine, neutralizing the hydrohalic acid formed, heating the reaction mixture at reflux temperature, and isolating the formed 3-hydroxy-5-halopyridine. The 3-hydroxy-5-halopyridines obtained are intermediates for the production of insecticides.Type: GrantFiled: June 29, 1978Date of Patent: March 11, 1980Assignee: Ciba-Geigy CorporationInventors: Niels Clauson-Kaas, Gunter Mattern, Walter Traber