Halogen Containing Or Process Utilizing Halogen Or Halogen Containing Compound Patents (Class 546/258)
  • Patent number: 4787931
    Abstract: N-phenyl-N'-(pyridinyl-N-oxide)ureas of the formula ##STR1## and their use as plant regulators are disclosed and exemplified.
    Type: Grant
    Filed: June 17, 1986
    Date of Patent: November 29, 1988
    Assignee: FMC Corporation
    Inventors: Robert Henrie, II, Christine M. Green, Robert E. Sticker
  • Patent number: 4786641
    Abstract: Blood-sugar-lowering dihydropyridines of the formula ##STR1## in which R.sup.1 represents phenyl, naphthyl, thienyl, pyridyl, chromenyl or thiochromenyl, it being possible for the radicals mentioned each to carry up to 2 identical or different substituents from the series comprising halogen, alkyl, alkoxy and alkylthio with in each case up to 6 carbon atoms, fluoroalkyl and fluoroalkoxy with in each case up to 3 carbon atoms and 3 fluorine atoms, nitro and cyano,R.sup.2 represents straight-chain, branched or cyclic alkyl which has up to 8 carbon atoms, can be interrupted in the alkyl chain by an oxygen or a sulphur atom and can be substituted by halogen, phenyl, cyano, hydroxyl, amino, alkylamino or dialkylamino with in each case up to 3 carbon atoms per alkyl group or by N-benzylmethylamino,R.sup.
    Type: Grant
    Filed: August 20, 1987
    Date of Patent: November 22, 1988
    Assignee: Bayer Aktiengesellschaft
    Inventors: Siegfried Goldmann, Hans-Jurgen Ahr, Walter Puls, Hilmar Bischoff, Dieter Petzinna, Klaus Schlossmann, Joachim Bender
  • Patent number: 4764516
    Abstract: Pure enantiomers of 5-nitrodihydropyridine of the formula ##STR1## are mixed, wherein one of the enantiomers has a high vasodilative action and a low negative inotropic activity on heart muscle, the other enantiomer has a low vasoconstrictive action and a high positive inotropic activity on heart muscle, the mixture being high in vasodilative activity and in positive inotropic activity on heart muscle.
    Type: Grant
    Filed: December 6, 1985
    Date of Patent: August 16, 1988
    Assignee: Bayer Aktiengesellschaft
    Inventors: Gerhard Franckowiak, Rolf Grosser, Gunter Thomas, Matthias Schramm, Rainer Gross
  • Patent number: 4737506
    Abstract: This invention relates to a 1,4-dihydropyridine-3,5-dicarboxylate derivative represented by the following general formula (I): ##STR1## wherein R means an imidazolyl or pyridyl group, R.sub.1 denotes a hydrogen or halogen atom or a nitro or trifluoromethyl group, R.sub.2 is a lower alkyl group, X is CH or N, A means a lower alkylene group, ##STR2## B being a lower alkylene or O-lower alkylene group, ##STR3## R.sub.4 being a hydrogen atom or lower alkyl group, or ##STR4## m denotes a number of 1-3, and n stands for 1 or 2. The derivative has vasodilative effects, hyperkinemic effects, platelet aggregation inhibitory effects, thromboxane A.sub.2 formation inhibitory effects and so on, and are hence useful as a pharmaceutical product such as vasodilator, antihypertensive, antithrombotic agent, antiarteriosclerotic agent or the like.
    Type: Grant
    Filed: April 7, 1986
    Date of Patent: April 12, 1988
    Assignee: Kowa Co., Ltd.
    Inventors: Noboru Shimizu, Hiroyuki Ishiwata, Tomio Ohta, Hiroshi Ishihama, Yasumi Uchida
  • Patent number: 4705794
    Abstract: Pyridinecarboxylic acid esters of the formula ##STR1## in which R is an optionally substituted aryl or heterocyclic radical,R.sup.1 and R.sup.2 are hydrogen, alkyl, aryl, aralkyl, acyloxyalkyl or hydroxyalkyl, or R.sup.1 with X forms a carbonyl-containing heterocyclic ring,X is --CN, --CO--R.sup.4, --COOR.sup.5 or --SO.sub.2 R.sup.6,R.sup.4, R.sup.5 and R.sup.6 are various optionally substituted radicals, andR.sup.3 is different from R.sup.5 and is a substituted or interrupted hydrocarbon radical,or pharmaceutically acceptable salts thereof control the otherwise negative effects of ischaemia and/or hypoxia.
    Type: Grant
    Filed: February 28, 1983
    Date of Patent: November 10, 1987
    Assignee: Bayer Aktiengesellschaft
    Inventors: Egbert Wehinger, Horst Meyer, Ulrich Benz
  • Patent number: 4698352
    Abstract: This invention relates to a novel 4-oxo-1,4-dihydronicotinic acid derivative ##STR1## or a salt thereof, wherein R.sup.1 is hydrogen or carboxyl-protecting group;R.sup.2 is substituted phenyl and naphthyl, or a substituted or unsubstituted heterocyclic group; andR.sup.3 is haloalkyl, aminoalkyl, or substituted or unsubstituted alkenyl, phenylalkenyl, naphthylalkenyl, phenylalkyl, naphthylalkyl, phenylalkynyl, naphthylalkynyl, heterocyclic alkyl, heterocyclic alkenyl, phenyl, naphthyl, cycloalkyl, cycloalkenyl, carboxylic acyl, iminoalkyl, heterocyclic or bridged hydrocarbon, which has a broad antibacterial spectrum and a low toxicity, and are useful for treatment of diseases of human beings and animals, to a process for producing the same and to an antibacterial agent containing the same.
    Type: Grant
    Filed: October 27, 1983
    Date of Patent: October 6, 1987
    Assignee: Toyama Chemical Co., Ltd.
    Inventors: Hirokazu Narita, Yoshinori Konishi, Jun Nitta, Shunjiro Misumi, Hideyoshi Nagaki, Isao Kitayama, Yoriko Nagai, Yasuo Watanabe, Nobuyuki Matsubara, Shinzaburo Minami, Isamu Saikawa
  • Patent number: 4686217
    Abstract: There are described compounds of formula I, ##STR1## in which R.sub.1 represents benzofurazanyl, pyridyl or phenyl, the pyridyl or phenyl being substituted,--COOR.sub.2 and --COOR.sub.3 are various ester groups,one of R.sub.7 and R.sub.8 represents alkyl Cl to 6 and the other represents --CONR.sub.10 R.sub.11 ; --CSNH.sub.2 ; --C(.dbd.NH)SR.sub.9 ; --S(O).sub.m R.sub.9 ; phenyl optionally substituted by one or more of alkyl Cl to 6, halogen, alkoxy Cl to 6 or nitro; alkyl Cl to 6 substituted by halogen; or furanyl;m is 0 or 1R.sub.9 is alkyl Cl to 6, andR.sub.10 and R.sub.11 each independently represent hydrogen or alkyl Cl to 6, or together with the nitrogen atom to which they are attached form a 5 or 6 membered heterocyclic ring.There are also described processes for making the compounds, and pharmaceutical, e.g. calcium antagonist, formulations containing them.
    Type: Grant
    Filed: April 17, 1984
    Date of Patent: August 11, 1987
    Assignee: Fisons plc
    Inventors: Andrew J. G. Baxter, John Dixon, Kenneth J. Gould, Alan C. Tinker
  • Patent number: 4672118
    Abstract: Corrosion of metal surfaces in contact with an aqueous medium is inhibited by incorporating a N-(hydrophobe aromatic)pyridinium compound such as N-(p-dodecylphenyl)-2,4,6-trimethylpyridinium sulfoacetate into the aqueous medium.
    Type: Grant
    Filed: January 9, 1984
    Date of Patent: June 9, 1987
    Assignee: The Dow Chemical Company
    Inventors: Thomas E. Fisk, Christopher J. Tucker
  • Patent number: 4654353
    Abstract: Compounds of the formula: ##STR1## where R is an optionally substituted aryl or heteroaryl group;R.sup.1 and R.sup.2 are each independently C.sub.1 -C.sub.4 alkyl or 2-methoxyethyl; and Y is --(CH.sub.2).sub.n -- where n is 2, 3 or 4, --CH.sub.2 CH(CH.sub.3)-- or --Ch.sub.2 C(CH.sub.3).sub.2 --; and their pharmaceutically acceptable salts.The compounds have utility as anti-ischaemic and antihypertensive agents and as synthetic intermediates to other dihydropyridine calcium antagonists.
    Type: Grant
    Filed: April 26, 1985
    Date of Patent: March 31, 1987
    Assignee: Pfizer Inc.
    Inventors: David Alker, Simon F. Campbell, Peter E. Cross
  • Patent number: 4618607
    Abstract: 1,4-Dihydropyridine-3,5-dicarboxylic acid ester derivatives of the general formula: ##STR1## or acid addition salts thereof, wherein W is --CH.dbd. or --N.dbd.; Y is --CH.dbd.CH--, --O--, --S--, --CH.dbd.N(O)p-- (p is zero or 1) or --N(R)-- (R is hydrogen or lower alkyl); X.sup.1, X.sup.2 and X.sup.3 are the same or different, and are each hydrogen, halogen, nitro, trifluoromethyl, cyano or lower alkylthio; Z is aryl or 5- or 6-membered aromatic heterocyclic ring (which may have a substituent or two or three substituents which may be the same or different, and the substituent may be halogen, lower alkyl, lower alkoxy, lower alkanoylamino, cyano, nitro, lower alkylthio, trifluoromethyl, sulfamoyl, di-lower alkylsulfamoyl, amino or di-lower alkylamino); ##STR2## is 5- to 7-membered heterocyclic ring which may have nitrogen atom, oxygen atom, sulfur atom or unsaturated bond on the ring, and may be substituted by lower alkyl, lower alkoxycarbonyl, lower alkanoylamino, ethylenedioxy or --(CH.sub.2).sub.m --OR.sup.
    Type: Grant
    Filed: December 10, 1982
    Date of Patent: October 21, 1986
    Assignee: Yoshitomi Pharmaceutical Industries, Ltd.
    Inventors: Kazuhiko Araki, Hideki Ao, Jun Inui, Kenichi Aihara
  • Patent number: 4579859
    Abstract: The invention relates to novel dihydropyridine derivatives of vasodilating activity of the formula: ##STR1## in which R.sup.1 is aryl selected from the group consisting of phenyl, tolyl, xylyl, cumenyl and mesityl which may have one or more substituents selected from the group consisting of halogen, nitro, hydroxy, carboxy and lower alkoxy, or a heterocyclic group containing at least one hetero atom selected from the group consisting of oxygen, nitrogen and sulfur,R.sup.2 is lower alkoxy-carbonyl or N,N-disubstituted amino(lower)alkoxycarbonyl,R.sup.3 is lower alkyl, alkanoyl, protected alkanoyl or cyano,R.sup.4 is lower alkyl andA is lower alkylene, and pharmaceutically acceptable salt thereof.
    Type: Grant
    Filed: May 17, 1984
    Date of Patent: April 1, 1986
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventors: Ikuo Ueda, Daizo Morino, Koichi Takimoto
  • Patent number: 4558058
    Abstract: 1,4-dihydropyridines of the formula I ##STR1## in which R denotes, for example, --CO.sub.2 R.sup.3 or cyano, R.sup.1 denotes, for example, an optionally substituted phenyl, pyridyl or thienyl, R.sup.2 denotes the radical of a 5-membered, optionally substituted, ring having at least one double bond and at least 2 heteroatoms or heteroatom groups from the series comprising O, N, NH and S, and R.sup.3 denotes, for example, alkyl or alkoxyalkyl, and their acid addition salts, have valuable pharmacological properties.
    Type: Grant
    Filed: December 9, 1983
    Date of Patent: December 10, 1985
    Assignee: Cassella Aktiengesellschaft
    Inventors: Karl Schonafinger, Helmut Bohn, Melitta Just, Piero Martorana
  • Patent number: 4551467
    Abstract: The invention relates to 1,4-dihydropyridines as well as methods for the preparation of said 1,4-dihydropyridines and compositions contained therein. The invention also includes the use of said compounds and compositions for influencing circulation.
    Type: Grant
    Filed: October 11, 1979
    Date of Patent: November 5, 1985
    Assignee: Bayer Aktiengesellschaft
    Inventors: Egbert Wehinger, Friedrich Bossert, Wulf Vater, Kurt Stoepel
  • Patent number: 4549022
    Abstract: The invention relates to 4-pyridone-3-carboxylic acid derivatives, a process for the preparation thereof and pharmaceutical compositions containing same. The 4-pyridone-3-carboxylic acid derivatives are useful as antibacterial agents and/or as agents having a stimulating activity on the central nervous system.
    Type: Grant
    Filed: November 2, 1984
    Date of Patent: October 22, 1985
    Assignee: Hoffmann-La Roche Inc.
    Inventor: Alexander E. Wick
  • Patent number: 4532342
    Abstract: N-substituted amino acids are described which when coupled with 1,2,3,4-tetrahydroisoquinolines result in substituted acyl derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids as anti-hypertensive agents. The novel intermediates are in turn prepared by reacting an amino acid such as alanine with 2-bromo-4-phenyl butanoic acid or an ester thereof.
    Type: Grant
    Filed: June 8, 1982
    Date of Patent: July 30, 1985
    Assignee: Warner-Lambert Company
    Inventors: Milton L. Hoefle, Sylvestor Klutchko
  • Patent number: 4520131
    Abstract: Antihypertensive compounds of the formula ##STR1## where the substituents are as herein defined and where Z is alkylene, R.sub.3 is alkoxyalkyl and R.sub.4 is hydroxyalkyl.
    Type: Grant
    Filed: March 3, 1983
    Date of Patent: May 28, 1985
    Assignee: USV Pharmaceutical
    Inventors: Bernard Loev, Howard Jones, John T. Suh
  • Patent number: 4483985
    Abstract: The invention relates to a process for the production of 1,4-dihydropyridinecarboxylic acid compounds which involves hydrolysis, under alkaline conditions and in a temperature range from 10.degree. to 100.degree. C., of an ester group which contains an electron-attracting group. The invention also includes novel compounds made according to the invention as well as compositions containing said novel compounds. Also included in the invention are methods for the use of said compounds and compositions. The compounds obtained according to the process of the invention are useful because of their circulation-influencing action and are also useful as intermediates for the preparation of compounds having circulation-influencing action.
    Type: Grant
    Filed: January 19, 1981
    Date of Patent: November 20, 1984
    Assignee: Bayer Aktiengesellschaft
    Inventors: Egbert Wehinger, Friedrich Bossert
  • Patent number: 4472584
    Abstract: Compounds of the formula: ##STR1## wherein Ar is heteroaryl, cycloalkyl having from 3 to 7 carbon atoms, naphthyl, indanyl, indenyl, tetrahydro naphthyl, or a radical of the formula ##STR2## wherein each of R.sub.5, R.sub.6 and R.sub.7 is independently H, alkyl, aryl, halo, lower alkoxy, nitro, amino, alkylmercapto, cyano, carboxy, carbalkoxy, sulfamyl, trifluoromethyl, hydroxy, acyloxy, methanesulfonyl, alkylamino or acylamino; and R.sub.5 and R.sub.6 when taken together, form a methylenedioxy; Z is alkylene containing 1 to about 5 carbon atoms in the principal chain; each R.sub.1 is independently hydrogen, alkyl or alkoxyalkyl, with the proviso that only one R.sub.1 may be hydrogen; R.sub.2 is lower alkyl; R.sub.3 is hydroxyalkyl containing 2 to 4 carbon atoms and R.sub.4 is H, alkyl, cycloalkyl or hydroxyalkyl containing 2 to 4 carbon atoms; wherein the alkyl, alkoxy, and acyl groups contain up to 10 carbon atoms, and their pharmaceutically-acceptable salts are disclosed.
    Type: Grant
    Filed: March 3, 1983
    Date of Patent: September 18, 1984
    Assignee: USV Pharmaceutical Corporation
    Inventors: Bernard Loev, Howard Jones, John T. Suh
  • Patent number: 4463008
    Abstract: 2-(R.sub.1 O)-3-Q-5-PY-6-R-pyridine (I) or pharmaceutically acceptable acid-addition salts thereof are useful cardiotonics, where R.sub.1 is methyl or ethyl, R is hydrogen or lower-alkyl, PY is 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two lower-alkyl substituents, and Q is hydrogen, chloro or COOR' where R' is lower-alkyl, or Q is cyano only when R is hydrogen. The preparation of I and their cardiotonic use are shown.
    Type: Grant
    Filed: November 10, 1982
    Date of Patent: July 31, 1984
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Chester J. Opalka, Jr., Baldev Singh
  • Patent number: 4362734
    Abstract: Shown are cardiotonically active 2-RR'N-5-PY-6-Q-nicotinonitriles where R is methyl or ethyl, R' is hydrogen or methyl, PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two substituents, and Q is hydrogen or methyl, the latter only when R' is hydrogen, or pharmaceutically acceptable acid-addition salts thereof. Also shown are cardiotonic compositions and a method for increasing cardiac contractility using as active components 2-RR'N-5-PY-6-Q-nicotinonitriles or pharmaceutically acceptable acid-addition salts thereof, where R, R', PY and Q are defined as above. Also shown is the process for preparing said 2-RR'N-5-PY-6-Q-nicotinonitriles by reacting a 2-halo-5-PY-6-Q-nicotinonitrile with an amine of the formula RR'NH.
    Type: Grant
    Filed: August 26, 1981
    Date of Patent: December 7, 1982
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
  • Patent number: 4351941
    Abstract: 2-[R.sub.1 NHN(R)]-3-Q'-5-PY-6-Q-pyridines or pharmaceutically-acceptable acid-addition salts thereof are useful as cardiotonic agents, where Q is hydrogen or lower-alkyl, PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, Q' is hydrogen or halo, R is hydrogen, lower-alkyl or lower-hydroxyalkyl, and R.sub.1 is hydrogen or when R is other than hydrogen R.sub.1 is the same as R. These compounds are prepared by reacting a 2-halo-3-Q'-5-PY-6-Q-pyridine with R.sub.1 NHNHR where 2-halo is bromo or chloro. Also shown are: the use of said 2-[R.sub.1 NN(R)]-3-Q'-5-PY-6-Q-pyridines as cardiotonic agents; and, the intermediates, 2,3-dihalo-5-PY-6-Q-pyridines, and their preparation from 3-nitro-5-PY-6-Q-2(1H)-pyridinones.
    Type: Grant
    Filed: November 2, 1981
    Date of Patent: September 28, 1982
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
  • Patent number: 4331672
    Abstract: 2-[R.sub.1 NHN(R)]-3-Q'-5-Py-6-Q-pyridines or pharmaceutically-acceptable acid-addition salts thereof are useful as cardiotonic agents, where Q is hydrogen or lower-alkyl, PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, Q' is hydrogen or halo, R is hydrogen, lower-alkyl or lower-hydroxyalkyl, and R.sub.1 is hydrogen or when R is other than hydrogen R.sub.1 is the same as R. These compounds are prepared by reacting a 2-halo-3-Q'-5-PY-6-Q-pyridine with R.sub.1 NHNHR where 2-halo is bromo or chloro. Also shown are: the use of said 2-[R.sub.1 NN(R)]-3-Q'-5-PY-6-Q-pyridines as cardiotonic agents; and, the intermediates, 2,3-dihalo-5-PY-6-Q-pyridines, and their preparation from 3-nitro-5-PY-6-Q-2(1H)-pyridinones.
    Type: Grant
    Filed: February 4, 1981
    Date of Patent: May 25, 1982
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
  • Patent number: 4313951
    Abstract: 1-R.sub.1 -3-[amino, cyano, carbamyl, halo, lower-alkylamino, di-(lower-alkyl)amino or lower-acylamino]-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones or pharmaceutically-acceptable acid-addition or cationic salts thereof are useful as cardiotonic agents, where R.sub.1 is hydrogen, lower-alkyl or lower-hydroxyalkyl. 1-R.sub.1 -3-amino-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones are prepared by hydrolyzing the corresponding 3-cyano compounds to produce the corresponding 3-carbamyl compounds and reacting the latter with a reagent capable of converting carbamyl to amino. The 1-R.sub.1 -3-cyano-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones are prepared by reacting (pyridinylmethyl) lower-alkyl ketones with dimethylformamide di-(lower-alkyl) acetal to produce 1-(pyridinyl)-2-(dimethylamino)ethenyl lower-alkyl ketone and reacting said ketones with N-R.sub.1 -.alpha.-cyanoacetamide to produce the 1-R.sub.1 -3-cyano-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones.
    Type: Grant
    Filed: October 20, 1980
    Date of Patent: February 2, 1982
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Richard E. Philion
  • Patent number: 4310670
    Abstract: The process which comprises reacting 4-picoline below about 30.degree. C. with at least three mole equivalents of an inorganic acid halide, preferably phosphorus oxychloride, per mole of 4-picoline and excess dimethylformamide, reacting in solution the unisolated resulting N-[3-dimethylamino-2-(4-pyridinyl)-2-propenylidene]-N-methylmethaniminium salt (after adding the reaction mixture to cold water, adjusting the pH to about 8.0 and filtering off the precipitated inorganic cationic salts) with excess .alpha.-cyanoacetamide and at least three mole equivalents of base, and then isolating 5-cyano-[3,4'-bipyridin]-6(1H)-one in free base form (after neutralization) or in the form of its inorganic cationic salt. Said 5-cyano-[3,4'-bipyridin]-6(1H)-one is an intermediate for preparing the cardiotonic amrinone.
    Type: Grant
    Filed: February 26, 1980
    Date of Patent: January 12, 1982
    Assignee: Sterling Drug Inc.
    Inventors: Karl O. Gelotte, Edward D. Parady
  • Patent number: 4302591
    Abstract: Iminobenzyl dihydropyridines of the formula ##STR1## wherein, each R is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, sulfonamido, halogen, alkoxy, alkenyloxy, alkynyloxy, cyano, hydroxy, acyloxy, nitro, amino, alkylmercapto, alkylamino, alkanoylamino, carbalkoxyamino, carboxy, methanesulfonyl, carbalkoxy or trifluoromethyl;each R.sub.4 is lower alkoxy;each R.sub.2 is lower alkyl;and R.sub.3 is alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclic or ##STR2## wherein R is as previously defined; have anti-hypertensive activity.
    Type: Grant
    Filed: September 2, 1980
    Date of Patent: November 24, 1981
    Assignee: USV Pharmaceutical Corporation
    Inventors: James R. Shroff, Bernard Loev
  • Patent number: 4297360
    Abstract: 2-R.sub.3 RN-3-R.sub.1 R'N-5-PY-6-Q-pyridines (I) or pharmaceutically-acceptable acid-addition salts thereof are useful as intermediates in the preparation of 1- or 3-substituted-1,3-dihydro-5-Q-6-PY-2H-imidazo[4,5-b]pyridin-2-ones or -2-thiones and also as intermediates for preparing 1- or 3-substituted-5-Q-6-PY-3H(or 1H)-imidazo[4,5-b]pyridines, where R.sub.1, R.sub.3, R, R', PY and Q are defined hereinbelow. Also shown are processes for preparing I and the following intermediates used therein: 2-halo-3-nitro-5-PY-6-Q-pyridines (III), 2-R.sub.3 RN-3-nitro-5-PY-6-Q-pyridines (V), 2-halo-5-PY-6-Q-pyridines (VII), 2-R.sub.3 RN-5-PY-6-Q-pyridines (VIII) and 2-R.sub.3 RN-3-halo-5-PY-6-Q-pyridines (IX) or salts thereof. Certain embodiments of II and VIII also are useful as cardiotonics and are shown as active components of cardiac compositions and methods for increasing cardiac contractility.
    Type: Grant
    Filed: March 28, 1980
    Date of Patent: October 27, 1981
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
  • Patent number: 4285955
    Abstract: The invention relates to a process for the production of 1,4-dihydropyridinecarboxylic acid compounds which involves hydrolysis, under alkaline conditions and in a temperature range from 10.degree. to 100.degree. C., of an ester group which contains an electron-attracting group. The invention also includes novel compounds made according to the invention as well as compositions containing said novel compounds. Also included in the invention are methods for the use of said compounds and compositions. The compounds obtained according to the process of the invention are useful because of their circulation-influencing action and are also useful as intermediates for the preparation of compounds having circulation-influencing action.
    Type: Grant
    Filed: October 12, 1979
    Date of Patent: August 25, 1981
    Assignee: Bayer Aktiengesellschaft
    Inventors: Egbert Wehinger, Friedrich Bossert
  • Patent number: 4265895
    Abstract: 1,2-Dihydro-1-R-5-PY-6-Q-3H-pyrazolo[3,4-b]pyridin-3-ones or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonic agents, are prepared by reacting lower-alkyl 2-halo-5-PY-6-Q-nicotinate with 1-R-hydrazine. Also disclosed are cardiotonic compositions and method for increasing cardiotonic contractility using said compounds or salts.
    Type: Grant
    Filed: March 17, 1980
    Date of Patent: May 5, 1981
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Monte D. Gruett
  • Patent number: 4264612
    Abstract: Cardiotonic composition and method for increasing cardiac contractility using an effective amount of a cardiotonic lower-alkyl 2-halo-5-PY-6-Q'-nicotinate or pharmaceutically-acceptable acid-addition salt thereof, where halo is chloro or bromo, Q' is hydrogen or lower-alkyl and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. Also shown are novel lower-alkyl 2-halo-5-PY-6-(lower-alkyl)nicotinates or pharmaceutically-acceptable acid-addition salt thereof, useful as intermediates or cardiotonics and preparation thereof.
    Type: Grant
    Filed: March 17, 1980
    Date of Patent: April 28, 1981
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Monte D. Gruett
  • Patent number: 4264603
    Abstract: 1-R-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridin-3-amines or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonics, are prepared by reacting a 2-halo-5-PY-6-Q-nicotinonitrile with 1-R-hydrazine, where R is hydrogen, lower-alkyl, lower-hydroxyalkyl, 2,3-dihydroxypropyl or lower-alkoxyalkyl, Q is hydrogen or lower-alkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. Also shown are cardiotonic compositions and method for increasing cardiac contractility using said compounds or salts.
    Type: Grant
    Filed: March 17, 1980
    Date of Patent: April 28, 1981
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Monte D. Gruett
  • Patent number: 4264609
    Abstract: 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: Grant
    Filed: February 26, 1980
    Date of Patent: April 28, 1981
    Assignee: Sterling Drug Inc.
    Inventors: Karl O. Gelotte, Chester J. Opalka, Jr.
  • Patent number: 4248873
    Abstract: The invention includes novel nitro-substituted 1,4-dihydropyridines useful because of their influence on the circulation. Also included in the invention are methods for the preparation of said novel nitro-substituted 1,4-dihydropyridines, compositions containing them and methods for the use of said compounds and compositions.
    Type: Grant
    Filed: November 6, 1978
    Date of Patent: February 3, 1981
    Assignee: Bayer Aktiengesellschaft
    Inventors: Friedrich Bossert, Gerhard Franckowiak, Arend Heise, Stanislav Kazda, Horst Meyer, Kurt Stoepel, Robertson Towart, Egbert Wehinger
  • Patent number: 4225601
    Abstract: 3-(Hydroxy or hydroxymethyl)-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof is useful as a cardiotonic agent. 3-Hydroxy-5-(4-pyridinyl)-2(1H)-pyridinone is prepared by autoclaving a mixture of an alkali lower-alkoxide, loweralkanol and 3-halo-5-(4-pyridinyl)-2(1H)-pyridinone and acidifying the cooled reaction mixture. 3-Hydroxymethyl-5-(4-pyridinyl)-2(1H)-pyridinone is prepared by reacting 5-(4-pyridinyl)-2(1H)-pyridinone with excess formaldehyde at an acidic pH. Said 3-(hydroxy or hydroxymethyl)-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically-acceptable acid-addition salt thereof is disclosed as the active ingredient in cardiotonic compositions for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment.
    Type: Grant
    Filed: September 10, 1979
    Date of Patent: September 30, 1980
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Chester J. Opalka, Jr.
  • Patent number: 4225715
    Abstract: Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.
    Type: Grant
    Filed: June 20, 1979
    Date of Patent: September 30, 1980
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Chester J. Opalka, Jr.
  • Patent number: 4223150
    Abstract: 1,1' dialkyl -4,4'-bipyridylium dihalide is prepared by heating 4,4'-bipyridyl with an .alpha.-halogen substituted organic acid of formula X R.sub.1 COOH where X is Cl or Br, R is C.sub.1-3, preferably monochloroacetic acid alkyl group in the presence of water until the pH is below 4.0.
    Type: Grant
    Filed: October 10, 1978
    Date of Patent: September 16, 1980
    Assignee: Cheng Hong Chemical Co., Ltd.
    Inventor: Ming F. Chen
  • Patent number: 4220781
    Abstract: The invention relates to 2-alkyl nicotinoids and improved methods for producing them.
    Type: Grant
    Filed: December 21, 1978
    Date of Patent: September 2, 1980
    Assignee: Philip Morris, Inc.
    Inventors: Edward B. Sanders, Henry V. Secor, Jeffrey I. Seeman
  • Patent number: 4177278
    Abstract: The invention includes the provision of 2-alkyleneaminodihydropyridines and salts thereof and are useful, inter alia, as coronary dilators and antihypertensive agents. Also included in the invention are pharmaceutical compositions containing said 2-alkyleneaminodihydropyridines and methods of treatment involving the use of said compounds or compositions.
    Type: Grant
    Filed: March 15, 1978
    Date of Patent: December 4, 1979
    Assignee: Bayer Aktiengesellschaft
    Inventors: Friedrich Bossert, Egbert Wehinger, Arend Heise, Stanislav Kazda, Kurt Stoepel, Robertson Towart, Wulf Vater, Klaus Schlossmann
  • Patent number: 4158093
    Abstract: A process for dequaternizing a 2-(2-pyridyl)ethyl or 2-(4-pyridyl)ethyl quaternary salt of a pyridine or bipyridine base comprising the step of heating or reacting the pyridylethyl quaternary salt with a caustic material such as sodium hydroxide. Also included is a process for preparing a second pyridine base (or a bipyridine base) in which a first pyridine base is initially selected and its 2-(2-pyridyl)ethyl or 2-(4-pyridyl)ethyl quaternary salt or its acid salt prepared. An electrophilic, nucleophilic or coupling reaction can then be performed on the quaternary salt to change the substituent or to form the bipyridyl coupling and the resultant salt dequaternized with a caustic material, such as sodium hydroxide, to produce a second pyridine or a bipyridine base.
    Type: Grant
    Filed: December 15, 1977
    Date of Patent: June 12, 1979
    Assignee: Reilly Tar & Chemical Corporation
    Inventors: Thomas D. Bailey, Charles K. McGill
  • Patent number: 4155909
    Abstract: The invention relates to 2-alkyl nicotinoids and improved methods for producing them.
    Type: Grant
    Filed: June 13, 1977
    Date of Patent: May 22, 1979
    Assignee: Philip Morris Incorporated
    Inventors: Edward B. Sanders, Henry V. Secor, Jeffrey I. Seeman
  • Patent number: 4154926
    Abstract: The present invention relates to inter-phenylene-PG 3,4-didehydropiperidylamides. These compounds are pharmacological agents, being prolonged orally active platelet aggregation inhibitors in mammalian species. These compounds are accordingly useful for antithrombotic applications.
    Type: Grant
    Filed: April 20, 1978
    Date of Patent: May 15, 1979
    Assignee: The Upjohn Company
    Inventor: Walter Morozowich
  • Patent number: 4151165
    Abstract: A novel process for the preparation of an N,N'-disubstitued-4,4'-bipyridylium salt, characterized in that an N,N'-disubstitued tetrahydro-4,4'-bipyridyl corresponding to the desired salt is treated with at least one aromatic nitro compound in the presence of water. The process of the present invention is more advantageously effected further in the presence of a water-immiscible organic solvent. According to the present invention, the desired product can be obtained with high purity and in high yield.
    Type: Grant
    Filed: March 23, 1978
    Date of Patent: April 24, 1979
    Assignee: Asahi Kasei Kogyo Kabushiki Kaisha
    Inventors: Masaaki Shiga, Teruyuki Misumi, Takashi Tanaka
  • Patent number: 4147697
    Abstract: A process is disclosed for quaternarizing 4,4'-dipyridyl diacetate to N,N'-dimethyl-4,4'-dipyridylium dihalide by reaction with an alkyl halide, preferably a lower alkyl halide such as methyl chloride, the reaction being carried out by:Using acetic acid as solvent for the 4,4'-dipyridyl diacetate in amounts of at least 1:1 by weight in respect of the diacetate subjected to reaction; andHeating the reactants at temperatures ranging from 60.degree. to 150.degree. C. and at pressures ranging from 2 to 10 kg/cm.sup.2. The acetic acid used as a solvent may be utilized for further quaternarizations of 4,4'-dipyridyl diacetate. Preferably the acetic acid is recycled to the zone of oxidation of diacetyl-tetrahydrodipyridyl, the resulting product being quaternarized in the same recycled acetic acid.
    Type: Grant
    Filed: January 10, 1978
    Date of Patent: April 3, 1979
    Assignee: Montedison S.p.A.
    Inventors: Mario Bornengo, Sergio Bacciarelli
  • Patent number: 4146627
    Abstract: The circulation provides new aminoalkylidene-amino-1,4-dihydropyridines which influence the circulatory system and are useful, for instance, as antihypertensive agents. Also included in the invention are methods for the preparation of said dihydropyridines, compositions containing them and methods for their use.
    Type: Grant
    Filed: August 26, 1977
    Date of Patent: March 27, 1979
    Assignee: Bayer Aktiengesellschaft
    Inventors: Egbert Wehinger, Friedrich Bossert, Horst Meyer, Wulf Vater, Arend Heise, Stanislav Kaada, Kurt Stoepel
  • Patent number: 4145432
    Abstract: This invention relates to 1,4-dihydropyridine derivatives. More particularly, it relates to new 1,4-dihydropyridine derivatives thereof which have vasodilating and anti-hypertensive activity, to processes for the preparation thereof, and to pharmaceutical composition comprising the same for therapeutical treatment in cardiovascular diseases and hypertension in human being.
    Type: Grant
    Filed: July 1, 1976
    Date of Patent: March 20, 1979
    Assignee: Fujisawa Pharmaceutical Co., Ltd.
    Inventor: Yoshinari Sato
  • Patent number: 4140684
    Abstract: Dyes of the formula ##STR1## wherein R.sub.1 is a carbocyclic or heterocyclic diazo component radical,R.sub.2 is cyano or acyl,R.sub.3 is alkyl, carbocyclic aryl or heterocyclyl, or a substituted deriive thereof, andR.sub.4 is hydrocarbyl or substituted hydrocarbyl, with the proviso that R.sub.4 is free of sulfo groups and protonizable groups, are useful as disperse dyes for the dyeing and printing of fibres and textiles of synthetic and semi-synthetic, hydrophobic organic substances of high molecular weight. These dyes build up excellently and yield dyeings which are fast to thermofixation, sublimation, pleating, ozone, rubbing, gas fumes, water, sea water, perspiration, alkali and washing.
    Type: Grant
    Filed: April 3, 1975
    Date of Patent: February 20, 1979
    Assignee: Fidelity Union Trust Company, Executive Trustee under the Sandoz Trust
    Inventors: Hermann Burkhard, Roland Entschel, Willy Steinemann
  • Patent number: 4137233
    Abstract: Compounds useful as cardiotonic agents are 1-R-3-Q-5-PY-2(1H)-pyridinones (I) where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, Q is amino (preferred), lower-alkylamino, di-(lower-alkyl)amino or NHAc, Ac is lower-alkanoyl or lower-carbalkoxy, and PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The corresponding compounds where Q is nitro, carbamyl, cyano, halo or hydrogen are useful as intermediates and those where Q is hydrogen or cyano also are useful as cardiotonic agents. Said compounds are prepared: by reacting .alpha.-PY-.beta.-(R.sub.1 R.sub.2 N)acrolein (II) with malonamide to produce 1,2-dihydro-2-oxo-5-PY-nicotinamide (Ia) and reacting Ia with a reagent capable of converting carbamyl to amino to produce 3-amino-5-PY-2(1H)-pyridinone (Ib); by reacting II or .alpha.-PY-malonaldehyde (II') with .alpha.
    Type: Grant
    Filed: February 10, 1978
    Date of Patent: January 30, 1979
    Assignee: Sterling Drug Inc.
    Inventors: George Y. Lesher, Chester J. Opalka, Jr.
  • Patent number: 4136033
    Abstract: Compounds of the formula ##STR1## wherein K.sup..sym. is a cationic group, preferably heterocyclic,R is hydrogen or an organic radical, preferably alkyl, phenyl or acyl,R.sub.1 is hydrogen, hydrocarbyl, substituted hydrocarbyl, heterocyclyl, substituted heterocyclyl, amino or substituted amino, andA.sup..crclbar. is an anion,Are useful as intermediates in the synthesis of azo dyes of the formula ##STR2## wherein D is an aromatic carbocyclic or heterocyclic diazo component radical, andK.sup..sym., r, r.sub.1 and A.sup..crclbar. are as defined above.
    Type: Grant
    Filed: June 25, 1974
    Date of Patent: January 23, 1979
    Assignee: Sandoz Ltd.
    Inventor: Willy Steinemann
  • Patent number: 4131738
    Abstract: This invention relates to certain structural analogs of the prostaglandins which have been unexpectedly discovered to be pharmacological analogs of prostacyclin (PGI.sub.2), i.e., they exhibit the characteristic prostacyclin-type biological responses. These novel compounds are all 6-hydroxy-PGE-type compounds. They are useful for the pharmacological purposes for which prostacyclin is used, e.g., a antithromboti agents, smooth muscle stimulators, gastric antisecretory agents, antihypertensive agents, antiasthma agents, nasal decongestants, or regulators or fertility and procreation.
    Type: Grant
    Filed: July 5, 1977
    Date of Patent: December 26, 1978
    Assignee: The Upjohn Company
    Inventor: Herman W. Smith
  • Patent number: 4124714
    Abstract: This disclosure describes novel compounds of the formula: ##STR1## where R.sub.3 is hydrogen or halo having an atomic weight of about 19 to 36, which are useful as minor tranquilizers, sleep inducers, muscle relaxants, neuroleptics and anti-ulcer agents.
    Type: Grant
    Filed: August 5, 1977
    Date of Patent: November 7, 1978
    Assignee: Sandoz, Inc.
    Inventor: Jeffrey Nadelson