Halogen Containing Or Process Utilizing Halogen Or Halogen Containing Compound Patents (Class 546/258)
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Patent number: 4787931Abstract: N-phenyl-N'-(pyridinyl-N-oxide)ureas of the formula ##STR1## and their use as plant regulators are disclosed and exemplified.Type: GrantFiled: June 17, 1986Date of Patent: November 29, 1988Assignee: FMC CorporationInventors: Robert Henrie, II, Christine M. Green, Robert E. Sticker
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Patent number: 4786641Abstract: 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: GrantFiled: August 20, 1987Date of Patent: November 22, 1988Assignee: Bayer AktiengesellschaftInventors: Siegfried Goldmann, Hans-Jurgen Ahr, Walter Puls, Hilmar Bischoff, Dieter Petzinna, Klaus Schlossmann, Joachim Bender
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Patent number: 4764516Abstract: 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: GrantFiled: December 6, 1985Date of Patent: August 16, 1988Assignee: Bayer AktiengesellschaftInventors: Gerhard Franckowiak, Rolf Grosser, Gunter Thomas, Matthias Schramm, Rainer Gross
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Patent number: 4737506Abstract: 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: GrantFiled: April 7, 1986Date of Patent: April 12, 1988Assignee: Kowa Co., Ltd.Inventors: Noboru Shimizu, Hiroyuki Ishiwata, Tomio Ohta, Hiroshi Ishihama, Yasumi Uchida
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Patent number: 4705794Abstract: 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: GrantFiled: February 28, 1983Date of Patent: November 10, 1987Assignee: Bayer AktiengesellschaftInventors: Egbert Wehinger, Horst Meyer, Ulrich Benz
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Patent number: 4698352Abstract: 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: GrantFiled: October 27, 1983Date of Patent: October 6, 1987Assignee: 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
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Patent number: 4686217Abstract: 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: GrantFiled: April 17, 1984Date of Patent: August 11, 1987Assignee: Fisons plcInventors: Andrew J. G. Baxter, John Dixon, Kenneth J. Gould, Alan C. Tinker
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Patent number: 4672118Abstract: 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: GrantFiled: January 9, 1984Date of Patent: June 9, 1987Assignee: The Dow Chemical CompanyInventors: Thomas E. Fisk, Christopher J. Tucker
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Patent number: 4654353Abstract: 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: GrantFiled: April 26, 1985Date of Patent: March 31, 1987Assignee: Pfizer Inc.Inventors: David Alker, Simon F. Campbell, Peter E. Cross
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Patent number: 4618607Abstract: 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: GrantFiled: December 10, 1982Date of Patent: October 21, 1986Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Kazuhiko Araki, Hideki Ao, Jun Inui, Kenichi Aihara
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Patent number: 4579859Abstract: 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: GrantFiled: May 17, 1984Date of Patent: April 1, 1986Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Ikuo Ueda, Daizo Morino, Koichi Takimoto
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Patent number: 4558058Abstract: 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: GrantFiled: December 9, 1983Date of Patent: December 10, 1985Assignee: Cassella AktiengesellschaftInventors: Karl Schonafinger, Helmut Bohn, Melitta Just, Piero Martorana
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Patent number: 4551467Abstract: 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: GrantFiled: October 11, 1979Date of Patent: November 5, 1985Assignee: Bayer AktiengesellschaftInventors: Egbert Wehinger, Friedrich Bossert, Wulf Vater, Kurt Stoepel
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Patent number: 4549022Abstract: 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: GrantFiled: November 2, 1984Date of Patent: October 22, 1985Assignee: Hoffmann-La Roche Inc.Inventor: Alexander E. Wick
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Patent number: 4532342Abstract: 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: GrantFiled: June 8, 1982Date of Patent: July 30, 1985Assignee: Warner-Lambert CompanyInventors: Milton L. Hoefle, Sylvestor Klutchko
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Patent number: 4520131Abstract: 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: GrantFiled: March 3, 1983Date of Patent: May 28, 1985Assignee: USV PharmaceuticalInventors: Bernard Loev, Howard Jones, John T. Suh
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Patent number: 4483985Abstract: 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: GrantFiled: January 19, 1981Date of Patent: November 20, 1984Assignee: Bayer AktiengesellschaftInventors: Egbert Wehinger, Friedrich Bossert
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Patent number: 4472584Abstract: 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: GrantFiled: March 3, 1983Date of Patent: September 18, 1984Assignee: USV Pharmaceutical CorporationInventors: Bernard Loev, Howard Jones, John T. Suh
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Patent number: 4463008Abstract: 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: GrantFiled: November 10, 1982Date of Patent: July 31, 1984Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr., Baldev Singh
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Patent number: 4362734Abstract: 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: GrantFiled: August 26, 1981Date of Patent: December 7, 1982Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
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Patent number: 4351941Abstract: 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: GrantFiled: November 2, 1981Date of Patent: September 28, 1982Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
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Patent number: 4331672Abstract: 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: GrantFiled: February 4, 1981Date of Patent: May 25, 1982Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
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Patent number: 4313951Abstract: 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: GrantFiled: October 20, 1980Date of Patent: February 2, 1982Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Richard E. Philion
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Patent number: 4310670Abstract: 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: GrantFiled: February 26, 1980Date of Patent: January 12, 1982Assignee: Sterling Drug Inc.Inventors: Karl O. Gelotte, Edward D. Parady
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Patent number: 4302591Abstract: 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: GrantFiled: September 2, 1980Date of Patent: November 24, 1981Assignee: USV Pharmaceutical CorporationInventors: James R. Shroff, Bernard Loev
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Patent number: 4297360Abstract: 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: GrantFiled: March 28, 1980Date of Patent: October 27, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr., Donald F. Page
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Patent number: 4285955Abstract: 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: GrantFiled: October 12, 1979Date of Patent: August 25, 1981Assignee: Bayer AktiengesellschaftInventors: Egbert Wehinger, Friedrich Bossert
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Patent number: 4265895Abstract: 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: GrantFiled: March 17, 1980Date of Patent: May 5, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Monte D. Gruett
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Patent number: 4264612Abstract: 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: GrantFiled: March 17, 1980Date of Patent: April 28, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Monte D. Gruett
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Patent number: 4264603Abstract: 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: GrantFiled: March 17, 1980Date of Patent: April 28, 1981Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Monte D. Gruett
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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: 4248873Abstract: 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: GrantFiled: November 6, 1978Date of Patent: February 3, 1981Assignee: Bayer AktiengesellschaftInventors: Friedrich Bossert, Gerhard Franckowiak, Arend Heise, Stanislav Kazda, Horst Meyer, Kurt Stoepel, Robertson Towart, Egbert Wehinger
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Patent number: 4225601Abstract: 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: GrantFiled: September 10, 1979Date of Patent: September 30, 1980Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr.
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Patent number: 4225715Abstract: 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: GrantFiled: June 20, 1979Date of Patent: September 30, 1980Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr.
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Patent number: 4223150Abstract: 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: GrantFiled: October 10, 1978Date of Patent: September 16, 1980Assignee: Cheng Hong Chemical Co., Ltd.Inventor: Ming F. Chen
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Patent number: 4220781Abstract: The invention relates to 2-alkyl nicotinoids and improved methods for producing them.Type: GrantFiled: December 21, 1978Date of Patent: September 2, 1980Assignee: Philip Morris, Inc.Inventors: Edward B. Sanders, Henry V. Secor, Jeffrey I. Seeman
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Patent number: 4177278Abstract: 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: GrantFiled: March 15, 1978Date of Patent: December 4, 1979Assignee: Bayer AktiengesellschaftInventors: Friedrich Bossert, Egbert Wehinger, Arend Heise, Stanislav Kazda, Kurt Stoepel, Robertson Towart, Wulf Vater, Klaus Schlossmann
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Patent number: 4158093Abstract: 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: GrantFiled: December 15, 1977Date of Patent: June 12, 1979Assignee: Reilly Tar & Chemical CorporationInventors: Thomas D. Bailey, Charles K. McGill
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Patent number: 4155909Abstract: The invention relates to 2-alkyl nicotinoids and improved methods for producing them.Type: GrantFiled: June 13, 1977Date of Patent: May 22, 1979Assignee: Philip Morris IncorporatedInventors: Edward B. Sanders, Henry V. Secor, Jeffrey I. Seeman
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Patent number: 4154926Abstract: 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: GrantFiled: April 20, 1978Date of Patent: May 15, 1979Assignee: The Upjohn CompanyInventor: Walter Morozowich
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Patent number: 4151165Abstract: 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: GrantFiled: March 23, 1978Date of Patent: April 24, 1979Assignee: Asahi Kasei Kogyo Kabushiki KaishaInventors: Masaaki Shiga, Teruyuki Misumi, Takashi Tanaka
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Patent number: 4147697Abstract: 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: GrantFiled: January 10, 1978Date of Patent: April 3, 1979Assignee: Montedison S.p.A.Inventors: Mario Bornengo, Sergio Bacciarelli
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Patent number: 4146627Abstract: 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: GrantFiled: August 26, 1977Date of Patent: March 27, 1979Assignee: Bayer AktiengesellschaftInventors: Egbert Wehinger, Friedrich Bossert, Horst Meyer, Wulf Vater, Arend Heise, Stanislav Kaada, Kurt Stoepel
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Patent number: 4145432Abstract: 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: GrantFiled: July 1, 1976Date of Patent: March 20, 1979Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventor: Yoshinari Sato
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Patent number: 4140684Abstract: 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: GrantFiled: April 3, 1975Date of Patent: February 20, 1979Assignee: Fidelity Union Trust Company, Executive Trustee under the Sandoz TrustInventors: Hermann Burkhard, Roland Entschel, Willy Steinemann
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Patent number: 4137233Abstract: 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: GrantFiled: February 10, 1978Date of Patent: January 30, 1979Assignee: Sterling Drug Inc.Inventors: George Y. Lesher, Chester J. Opalka, Jr.
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Patent number: 4136033Abstract: 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: GrantFiled: June 25, 1974Date of Patent: January 23, 1979Assignee: Sandoz Ltd.Inventor: Willy Steinemann
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Patent number: 4131738Abstract: 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: GrantFiled: July 5, 1977Date of Patent: December 26, 1978Assignee: The Upjohn CompanyInventor: Herman W. Smith
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Patent number: 4124714Abstract: 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: GrantFiled: August 5, 1977Date of Patent: November 7, 1978Assignee: Sandoz, Inc.Inventor: Jeffrey Nadelson