US3775422A - Unsymmetrical 1,4-dihydro-4-aryl-nicotinate esters - Google Patents

Unsymmetrical 1,4-dihydro-4-aryl-nicotinate esters Download PDF

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US3775422A
US3775422A US00107849A US3775422DA US3775422A US 3775422 A US3775422 A US 3775422A US 00107849 A US00107849 A US 00107849A US 3775422D A US3775422D A US 3775422DA US 3775422 A US3775422 A US 3775422A
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carbon atoms
straight
alkyl
branched chain
moieties
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F Bossert
W Vater
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Bayer AG
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Bayer AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
    • C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Definitions

  • R is hydrogen, straight, branched or cyclic lower alkyl
  • R is straight or branched chain alkyl of 1 to 4 carbon atoms
  • R is straight or branched chain alkyl of 1 to 6 carbon atoms, straight or branched chain dialkyl of 1 to 6 carbon atoms, straight or branched chain alkenyl of 2 6 carbon atoms, straight or branched chain alkinyl of 2 to 6vcarbon atoms, cyclic alkyl of 3 to 6 carbon atoms, cyclic alkenyl of 3 to 6 carbon atoms, straight or branched chain alkyl or alkenyl of 2 to 6 carbon atoms interrupted by 1 or 2 oxygen atoms, straight or branched chain alkyl of 1 to 6 carbon atoms substituted by hydroxyl, or straight or branched chain alkenyl of 2 to 6 carbon atoms substituted by hydroxyl;
  • R is aryl, unsubstituted or substituted by 1 to 3 members selected from the group consisting of 1 to 3 nitro moieties, 1 or 2 cyano moieties, 1 to 3 halogen atoms, 1 or 2 hydroxyl moieties, 1 or 2 acyloxy moieties of 1 or 2 carbon atoms in the acyl portion, 1 to 3 alkoxy moieties of 1 to 4 carbon atoms, a dioxymethylene moiety of the formula:
  • alkylmercapto moiety of 1 to 4 carbon atoms in the alkyl portion trifluoromethyl, carboxyl, carbalkoxy of 1 to 4 carbon atoms in the alkoxy portion and an alkylsulphonyl moiety of 1 to 4 carbon atoms in the alkyl portion; benzyl; styryl; pyridyl; pyrimidyl; furyl;
  • pyrrolyl pyridyl, pyrrolyl, thienyl or furyl substituted by alkyl of 1 or 2 carbon atoms
  • pyrimidyl substituted by at least one member selected from the group consisting of alkyl of 1 or 2 carbon atoms, 1 or 2 methoxy moieties and 1 or 2 ethoxy moieties;
  • R is straight or branched chain alkyl of 1 to 4 carbon atoms.
  • R200 C CO-Rt wherein R is hydrogen, straight, branched or cyclic lower alkyl
  • R is straight or branched chain alkyl of 1 to 4 carbon atoms
  • R i straight or branched chain alkyl of 1 to 6 carbon atoms, straight or branched chain dialkyl of l to 6 carbon atoms, straight or branched chain alkenyl of 2 to 6 carbon atoms, straight or branched chain alkinyl of 2 to 6 carbon atoms, cyclic alkyl of 3 to 6 carbon atoms, cyclic alkenyl of 3 to 6 carbon atoms, straight or branched chain alkyl or alkenyl of 2 to 6 carbon atoms interrupted by 1 or 2 oxygen atoms, straight or branched chain alkyl of 1 to 6 carbon atoms substituted by hydroxyl, or straight or branched chain alkenyl of 2 to 6 carbon atoms substituted by hydroxyl;
  • R is aryl, unsubstituted or substituted by l to 3 members selected from the group consisting of 1 to 3 nitro moieties, 1 or 2 cyano moieties, l to 3 halogen atoms, 1 or 2 hydroxyl moieties, 1 or 2 acyloxy moieties of 1 or 2 carbon atoms in the acyl portion, 1 to 3 alkoxy moieties of 1 to 4 carbon atoms, a dioxymethylene moiety of the formula:
  • alkylmercapto moiety of 1 to 4 carbon atoms in the alkyl portion trifluoromethyl, carboxyl, carbalkoxy of 1 to 4 carbon atoms in the alkoxy portion and an alkylsulphonyl moiety of 1to 4 carbon atoms in the alkyl portion; benzyl, styryl; pyridyl; pyrimidyl; furyl; thienyl; pyrrolyl; pyridyl, pyrrolyl, thienl or furyl substituted by alkyl of l or 2 carbon atoms; or pyrimidyl substituted by at least one member selected from the group consisting of alkyl of 1 or 2 carbon atoms, 1 or 2 methoxy moieties and 1 or 2 ethoxy moieties; and
  • R is straight or branched chain alkyl of l to 4 carbon atoms
  • the compounds of the present invention may be produced by reacting a xylidene derivative of the formula:
  • R and R are as above defined, and ammonia or an amine of the formula HzN-R wherein R is as above defined, or a salt thereof, or
  • an elevated temperature preferably from about 70 C. to about 120 C. in the presence of at least one organic solvent, such as an alcohol, glacial acetic acid, pyridine, dioxane, dimethylformamide, dimethylsulphoxide or a halogenated hydrocarbon.
  • organic solvent such as an alcohol, glacial acetic acid, pyridine, dioxane, dimethylformamide, dimethylsulphoxide or a halogenated hydrocarbon.
  • the xylidene derivatives of the Formula 2 above are produced by condensing an aldehyde with an 0:,[3-dik6't0116.
  • the compounds of the present invention may also be produced by reacting a xylidene derivative of the formula:
  • RLC CHCRI NH-R (8) wherein R and R are as above defined under the re action conditions above set forth.
  • xylidene derivatives of Formula 6 above can be produced by condensing an aldehyde with an acyl-fatty acid ester.
  • R in Formula 1 above is other than hydrogen
  • the compounds of the present invention may be produced according to a process carried out in the presence of pyridine, which process is set forth in co-pending application Le A 12 217-A U.S. Ser. No. 35,574, filed May 7, 1970.
  • Suitable reactants for use in the process of the present invention and for the production of the compounds of the present invention include as illustrative examples the following:
  • Aldehydes Benzaldehyde, 2-, 3-, or 4 hydroxy- 'benzaldehyde, 2,4- or 2,6 dihydroxybenzaldehyde, 2-, 3-, or 4 methoxybenzaldehyde, 2 isopropoxybenzaldehyde, 3 butoxybeu zaldehyde, 3,4,5 trimeth- 4 oxybenzaldehyde, 2-, 3-, or 4 chloro or bromo or fluorobenzaldehyde, 2,4 or 2,6 dichlorobenzaldehyde, 2-methylbenzaldehyde, 2,4-dimethylbenzaldehyde, 3,5-dlisopropyl 4 hydroxybenzaldehyde, 2-, 3- or 4-nitrobenzaldehyde, 2,4- or 2,6-dinitrobenzaldehyde, 2-nitro-6- bromobenzaldehyde, 2-nitro-3-methoxy-6-chlorobenzaldehyde, 2-nitro-3-hydroxy-4-chlor
  • Acyl-fatty acid esters Formylacetic acid ethyl ester, formylacetic acid butyl ester, acetoacetic acid methyl ester, acetoacetic acid ethyl ester, acetoacetic acid propyl ester, acetoacetic acid isopropyl ester, acetoacetic acid- (on or 3-) hydroxyethyl ester, acetoacetic acid (aor 8-) methoxyethyl ester, acetoacetic acid (01- or ,8)-ethoxyethyl ester, acetoacetic acid(aor 13-) propoxyethyl ester, acetoacetic acid furfuryl ester, acetoacetic acid tetrahydrofurfuryl ester, acetoacetic acid allyl ester, acetoacetic acid propargyl ester, acetoacetic acid cyclohexyl ester, propionylacetic acid ethy
  • Amines Methylamine, ethylamine, propylarnine, isopropylamine, butylamine, allylamine, propargylamine, 1- hydroxyethylamine-2, l,3-dihydroxyisopropylamine, cyclohexylamine, benzylamine, 4-chlorobenzylamine, 3,4- dimethoxybenzylamine and phenethylamine.
  • R is hydrogen, alkyl of 1 to 6 carbon atoms, benzyl or phenethyl, R is straight or branched chain alkyl 1 to 4 carbon atoms, R is monoor dialkyl of 1 to 6 carbon atoms, alkinyl of 2 to 6 carbon atoms, cyclic alkyl of 3 to 6 carbon atoms, alkyl of 2 to 6 carbon atoms interrupted by oxygen, or cyclic alkyl of 3 to 6 carbon atoms wherein the ring contains oxygen as a heteroatom, R is benzyl; phenyl unsubstituted or substituted by 1 or 2 nitro moieties, cyano moieties, halogen atoms especially fluorine, chlorine or bromine, alkoxy moieties of 1 to 3 carbon atoms or trifiuoromethyl; pyridyl, pyrrolyl, furyl or thienyl unsubstituted or substituted by alkyl of
  • the 1,4-dihydropyridines of the present invention have a broad range of utility as indicated above and the following effects have been exhibited in animal experiments:
  • the compounds produce a distinct and long-lasting dilation of the coronary vessels on parenteral, oral and perlingual administration. This action on the coronary vessels is intensified by a simultaneous, nitrite-like, effect of reducing the load on the heart.
  • the tonus of the smooth muscles of the vessels is greatly reduced under the action of the compounds.
  • This vascular-spasmolytic action can occur in the total vascular system or can manifest itself to a more or less isolated extent in circumscribed vascular regions (such as for example the central-nervous system).
  • the compounds reduce the blood pressure of normal tonic and hypertonic animals and can thus be used as anti-hypertensive agents.
  • the compounds have strong muscular-spasmolytic actions, which manifest themselves on the smooth muscle of the gastro-intestinal tract, the urogenital tract, and the respiratory system.
  • compositions are produced which comprise a compound of the present invention or more than one compound of the present invention in combination with a pharmaceutically acceptable non-toxic inert diluent or carrier.
  • the present invention further includes a medicament in unit dosage form which comprises a compound of the present invention or more than one compound of the present invention per se or in combination with a pharmaceutically acceptable non-toxic inert diluent or carrier.
  • the medicament may include a protective envelope containing the active compound or compounds, and if present, the pharmaceutically acceptable non-toxic inert diluent or carrier.
  • medicament in unit dosage form means a medicament as defined above in the form of discrete portions each containing a unit dosage, or a multiple or sub-multiple of a unit dose of the active compound or compounds, for example two, three or four unit doses or a half, a third or a fourth of a unit dose.
  • Such portions may, for example, be in monolithic coherent form, such as tablets, suppositories, pills or dragees; in wrapped or concealed form, such a wrapped powders, cachets, sachets or capsules; in ampoules, either free or as a sterile solution suitable for parenteral injection; or in any other form known to the art.
  • the 1,4-dihydropyridines of the Formula 1 can be administered orally or parenterally.
  • the compounds of Formula 1 can be administered as such or as pharmaceutical compositions as described above.
  • suitable forms of application in combination with various inert carriers are: tablets, capsules, dragees, ampoules, powders, sprays, aqueous suspensions, injectable solutions, elixirs, syrups and the like.
  • Such carriers comprise solid diluents or fillers, a sterile aqueous medium as well as various non-toxic organic solvents and the like. Tablets and the like intended or oral application may, of course, be provided with sweetening additives and similar substances.
  • the therapeutically active compound should be present at a concentration of about 0.5 to 90 percent by weight of the total mixture, in quantities which are sufiicient to achieve the range of dosage, mentioned above.
  • the tablets or capsules may also contain additives, such as sodium citrate, calcium carbonate and dicalcium phosphate together with various other additives, such as starch, preferably potato starch, and the like, and binding agents, such as polyvinylpyrrolidone, gelatin and the like.
  • additives such as sodium citrate, calcium carbonate and dicalcium phosphate together with various other additives, such as starch, preferably potato starch, and the like, and binding agents, such as polyvinylpyrrolidone, gelatin and the like.
  • Lubricants such as magnesium stearate, sodium lauryl sulphate and talc may also be added for the production of tablets.
  • the active substance may be used with various flavouring agents, coloring substances, emulsifiers and/or together with diluents, such as water, ethanol, propylene glycol, glycerol and similar compounds or combinations of this type.
  • solutions of the active substances in sesame or peanut oil or in aqueous propylene glycol or N,N-dimethyl formamide can be used, as can sterile aqueous solutions in the case of the water-soluble compounds.
  • Aqueous solutions of this type should be buffered in the usual way, when required, and the liquid diluent should previously be rendered isotonic by the addition of the necessary amount of salt or glucose.
  • These aqueous solutions are particularly suitable for intravenous and intraperitoneal injections.
  • Sterile aqueous media of this type may be prepared in a manner per se known.
  • compositions in orally administrable form are the preferred embodiment of the pharmaceutical compositions.
  • Table sets forth a range of viable dosages for compounds representative of those of the present invention:
  • the compound of Example 1 has exhibited good activity when administered orally at a dosage range of from 1 to about 50 mg./kg.
  • EXAMPLE 1 4- (2-pyridyl -2, 6-dimethyl-3-aceto-1,4-dihydropyridine-S-carboxylic acid ethyl ester After stirring a solution of 21.4 g. of pyridin-2-aldehyde and 20 g. of acetylacetone in 250 ccs. of benzene, with the addition of 2 ccs. of piperidine for approx. 12 hours at room temperature, the water is separated off, the solution is dried and the solvent is distilled off in vacuo.
  • EXAMPLE 3 4 phenyl 2,6 dimethyl-3-aceto-1,4-dihydropyridine-5- carboxylic acid ethyl ester (identical to Example 1(b) 0.1 mol of benzalacetic acid ethyl ester (obtained from 10.6 g. of benzaldehyde and 13 g. of acetoacetic acid ethyl ester in benzene with the addition of piperidine) is heated for 3-4 hours with g. of Z-aminopenten-(2)-one-(4) to 90-100, after cooling the solid reaction product is taken up in a little ether, and after filtering off and recrystallizing, yellow crystals of melting point 167 C. (alcohol) are obtained.
  • EXAMPLE 4 (2' methylphenyl) 2,6 dimethyl 3 aceto-1,4- dihydropyridine-S-carboxylic acid ethyl ester (melting point 155 (C.) was prepared by a method analogous to that described in Example 3 from 2-methyl-benzal-acetylacetone and fl-aminocrotonic acid ethylester.
  • EXAMPLE 5 4-(4'-pyrimidyl -2,6-dimethyl-3-aceto-1,4-dihydropyridine-S-carboxylic acid ethyl ester 1 cc. of piperidine is added to a solution of 10 g. of pyrimidine-4aldehyde and 10 g. of acetylacetone in 150 ccs. of benzene, the mixture is stirred for 48 hours at room temperature, the Water is then separated 01f, the solution is dried and evaporated, and the residue (pyrimid- 4-al-acetylacetone) is heated with 13 g. of B-aminocrotonic acid ethyl ester for 5 hours on a water-bath.
  • R is straight chain alkyl of 1 to 4 carbon atoms.
  • R is hydrogen or methyl
  • R is methyl
  • R is methyl, ethyl, diethyl, B-methoxyethyl, propargyl or furfuryl
  • R is phenyl, nitrophenyl, cyanophenyl, fluorophenyl, trifluoromethylphenyl, benzyl, or nitrochlorophenyl
  • R is methyl.
  • R is monoalkyl of l to 6 Colunm 6, line 69 should read as follows:

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
US00107849A 1970-01-24 1971-01-19 Unsymmetrical 1,4-dihydro-4-aryl-nicotinate esters Expired - Lifetime US3775422A (en)

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DE19702003146 DE2003146A1 (de) 1970-01-24 1970-01-24 Neue 1,4-Dihydropyridinderivate

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US (1) US3775422A (en:Method)
AT (2) AT304552B (en:Method)
BE (1) BE761929A (en:Method)
CA (1) CA945167A (en:Method)
CH (1) CH586200A5 (en:Method)
CS (2) CS163748B2 (en:Method)
DE (1) DE2003146A1 (en:Method)
ES (1) ES387562A1 (en:Method)
FR (1) FR2081452B1 (en:Method)
GB (1) GB1317425A (en:Method)
HU (1) HU162199B (en:Method)
IE (1) IE34890B1 (en:Method)
IL (1) IL35924A (en:Method)
NL (1) NL7100816A (en:Method)
ZA (1) ZA7152B (en:Method)

Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3857849A (en) * 1973-02-28 1974-12-31 Bayer Ag 2-amino-1,4-dihydropyridine derivatives
US3860601A (en) * 1972-03-06 1975-01-14 Horst Meyer 2,6-diamino-1,4-dihydropyridine derivatives
US3862162A (en) * 1972-08-31 1975-01-21 Bayer Ag Certain-2-amino-1,4-dihydro-4-phenyl-6-lower alkyl (or phenyl)-3-pyridinecarboxylates
US3867393A (en) * 1972-03-06 1975-02-18 Horst Meyer 2-Amino-1,4-dihydropyridine derivatives
US3876646A (en) * 1972-03-06 1975-04-08 Bayer Ag 2-amino-4,5-dihydropyridine derivatives
US3917620A (en) * 1972-03-06 1975-11-04 Bayer Ag 2-Amino-4,5-dihydropyridine derivatives
US3917619A (en) * 1972-03-06 1975-11-04 Bayer Ag 2-Amino-4,5-dihydropyridine derivatives
US3917622A (en) * 1972-03-06 1975-11-04 Bayer Ag 2-Amino-1,4-dihydropyridine derivatives
US3923818A (en) * 1972-06-10 1975-12-02 Bayer Ag 1,4-Dihydropyridines
US3925395A (en) * 1972-08-31 1975-12-09 Bayer Ag 4-Aryl-6-amino-3,4-dihydropyrid-2-one-3,5-dicarboxylic acid ester
US3935223A (en) * 1972-03-06 1976-01-27 Bayer Aktiengesellschaft 2-Amino-1,4-dihydropyridine derivatives
US3939171A (en) * 1972-03-06 1976-02-17 Bayer Aktiengesellschaft 2-Amino-1,4-dihydropyridine derivatives
US3959474A (en) * 1972-03-06 1976-05-25 Bayer Aktiengesellschaft 2,6-Diamino-1,4-dihydropyridine-3,5-dicarboxylic acid esters used as coronary vessel dilators and anti-hypertensive agents
US3968117A (en) * 1972-06-10 1976-07-06 Bayer Aktiengesellschaft 1,4-Dihydropyridines
US3985886A (en) * 1972-03-06 1976-10-12 Bayer Aktiengesellschaft 2-Amino-4,5-dihydropyridine derivatives and process for their preparation
US3988458A (en) * 1972-03-06 1976-10-26 Bayer Aktiengesellschaft Bicyclic derivatives of 1,4-dihydropyridine 3,5-carboxylic acid esters
US3989708A (en) * 1972-08-31 1976-11-02 Bayer Aktiengesellschaft 2-Amino-1,4-dihydropyridine derivatives
US3992545A (en) * 1972-03-06 1976-11-16 Bayer Aktiengesellschaft 2-Amino-4,5-dihydropyridine derivatives in pharmaceutical compositions
US4001258A (en) * 1972-03-06 1977-01-04 Bayer Aktiengesellschaft 2-amino-1,4-dihydropyridine derivatives
US4002762A (en) * 1973-03-03 1977-01-11 Bayer Aktiengesellschaft 2-Amino-3,4-dihydropyridines used to effect coronary vessel dilation and treat hypertension
US4497808A (en) * 1981-12-30 1985-02-05 Ciba-Geigy Corporation N-Oxide compounds useful in the treatment of cardiovascular ailments
US4529733A (en) * 1983-04-06 1985-07-16 Merrell Dow Pharmaceuticals Inc. Antihypertensive 3-furoyl-1,4-dihydropyridines
WO1986002640A1 (en) * 1984-10-31 1986-05-09 Bristol-Myers Company Dihydropyridin-3,5-dicarboxylates incorporating aryloxypropanolamine moieties
US4722931A (en) * 1984-03-27 1988-02-02 Laboratorios Delagrange Calcium antagonist
US4772596A (en) * 1986-10-09 1988-09-20 Sankyo Company Limited Dihydropyridine derivatives, their preparation and their use
US4992451A (en) * 1985-06-14 1991-02-12 Sankyo Company, Limited 1,4-dihydropyridine derivatives
US5420142A (en) * 1991-06-07 1995-05-30 Bayer Aktiengesellschaft Certain 3-formyl-1, 4-dihydropyridines and their pharmaceutical composition and use
US20090214675A1 (en) * 2005-07-22 2009-08-27 Bayer Healthcare Ag 4-Chromenonyl-1,4-dihydropyridinecarbonitriles and the use thereof
US20100022484A1 (en) * 2005-07-22 2010-01-28 Alexander Kuhl 4-Chromenonyl-1,4-dihydropyridines and their use
US9828344B2 (en) 2012-06-01 2017-11-28 LEIBNIZ-INSTITUT FÜR ALTERSFORSCHUNG FRITZ-LIPMANN-INSTITUT e.V. (FLI) Inhibitors of the notch signaling pathway and secretion for use in medicine

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1430961A (en) * 1972-01-22 1976-04-07 Yamanouchi Pharma Co Ltd 1-substituted-1,4-dihyddrypyridine derivatives
GB1409865A (en) * 1973-02-13 1975-10-15 Science Union & Cie Dihydropyridines derivatives their preparation and pharmaceu tical compositions containing them
FR2320750A1 (fr) * 1975-08-12 1977-03-11 Hexachimie Dihydro-1,4 pyridines et leur application therapeutique
DE3021958A1 (de) * 1980-06-12 1981-12-24 Bayer Ag, 5090 Leverkusen 1,4-dihydropyridine, verfahren zu deren herstellung sowie diese enthaltende arzneimittel

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US3455939A (en) * 1967-06-07 1969-07-15 Smithkline Corp 4-(4-chloro-3-sulfamoylphenyl)-1,4-dihydropyridines

Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3988458A (en) * 1972-03-06 1976-10-26 Bayer Aktiengesellschaft Bicyclic derivatives of 1,4-dihydropyridine 3,5-carboxylic acid esters
US3917619A (en) * 1972-03-06 1975-11-04 Bayer Ag 2-Amino-4,5-dihydropyridine derivatives
US4001258A (en) * 1972-03-06 1977-01-04 Bayer Aktiengesellschaft 2-amino-1,4-dihydropyridine derivatives
US3867393A (en) * 1972-03-06 1975-02-18 Horst Meyer 2-Amino-1,4-dihydropyridine derivatives
US3876646A (en) * 1972-03-06 1975-04-08 Bayer Ag 2-amino-4,5-dihydropyridine derivatives
US3887558A (en) * 1972-03-06 1975-06-03 Bayer Ag Process for producing 2,6-diamino -1,4- dihydro-3,5-pyridine-dicarboxylates and derivatives thereof
US3917620A (en) * 1972-03-06 1975-11-04 Bayer Ag 2-Amino-4,5-dihydropyridine derivatives
US3860601A (en) * 1972-03-06 1975-01-14 Horst Meyer 2,6-diamino-1,4-dihydropyridine derivatives
US3917622A (en) * 1972-03-06 1975-11-04 Bayer Ag 2-Amino-1,4-dihydropyridine derivatives
US3985886A (en) * 1972-03-06 1976-10-12 Bayer Aktiengesellschaft 2-Amino-4,5-dihydropyridine derivatives and process for their preparation
US3992545A (en) * 1972-03-06 1976-11-16 Bayer Aktiengesellschaft 2-Amino-4,5-dihydropyridine derivatives in pharmaceutical compositions
US3935223A (en) * 1972-03-06 1976-01-27 Bayer Aktiengesellschaft 2-Amino-1,4-dihydropyridine derivatives
US3939171A (en) * 1972-03-06 1976-02-17 Bayer Aktiengesellschaft 2-Amino-1,4-dihydropyridine derivatives
US3959474A (en) * 1972-03-06 1976-05-25 Bayer Aktiengesellschaft 2,6-Diamino-1,4-dihydropyridine-3,5-dicarboxylic acid esters used as coronary vessel dilators and anti-hypertensive agents
US3968117A (en) * 1972-06-10 1976-07-06 Bayer Aktiengesellschaft 1,4-Dihydropyridines
US3923818A (en) * 1972-06-10 1975-12-02 Bayer Ag 1,4-Dihydropyridines
US3989708A (en) * 1972-08-31 1976-11-02 Bayer Aktiengesellschaft 2-Amino-1,4-dihydropyridine derivatives
US3862162A (en) * 1972-08-31 1975-01-21 Bayer Ag Certain-2-amino-1,4-dihydro-4-phenyl-6-lower alkyl (or phenyl)-3-pyridinecarboxylates
US3925395A (en) * 1972-08-31 1975-12-09 Bayer Ag 4-Aryl-6-amino-3,4-dihydropyrid-2-one-3,5-dicarboxylic acid ester
US3857849A (en) * 1973-02-28 1974-12-31 Bayer Ag 2-amino-1,4-dihydropyridine derivatives
US4002762A (en) * 1973-03-03 1977-01-11 Bayer Aktiengesellschaft 2-Amino-3,4-dihydropyridines used to effect coronary vessel dilation and treat hypertension
US4497808A (en) * 1981-12-30 1985-02-05 Ciba-Geigy Corporation N-Oxide compounds useful in the treatment of cardiovascular ailments
US4529733A (en) * 1983-04-06 1985-07-16 Merrell Dow Pharmaceuticals Inc. Antihypertensive 3-furoyl-1,4-dihydropyridines
US4722931A (en) * 1984-03-27 1988-02-02 Laboratorios Delagrange Calcium antagonist
WO1986002640A1 (en) * 1984-10-31 1986-05-09 Bristol-Myers Company Dihydropyridin-3,5-dicarboxylates incorporating aryloxypropanolamine moieties
US4992451A (en) * 1985-06-14 1991-02-12 Sankyo Company, Limited 1,4-dihydropyridine derivatives
US4772596A (en) * 1986-10-09 1988-09-20 Sankyo Company Limited Dihydropyridine derivatives, their preparation and their use
US5420142A (en) * 1991-06-07 1995-05-30 Bayer Aktiengesellschaft Certain 3-formyl-1, 4-dihydropyridines and their pharmaceutical composition and use
US20090214675A1 (en) * 2005-07-22 2009-08-27 Bayer Healthcare Ag 4-Chromenonyl-1,4-dihydropyridinecarbonitriles and the use thereof
US20100022484A1 (en) * 2005-07-22 2010-01-28 Alexander Kuhl 4-Chromenonyl-1,4-dihydropyridines and their use
US7989633B2 (en) 2005-07-22 2011-08-02 Bayer Schering Pharma Aktiengesellschaft 4-Chromenonyl-1,4-dihydropyridines and their use
US8058447B2 (en) 2005-07-22 2011-11-15 Bayer Pharma Aktiengesellschaft 4-Chromenonyl-1,4-dihydropyridinecarbonitriles and the use thereof
US9828344B2 (en) 2012-06-01 2017-11-28 LEIBNIZ-INSTITUT FÜR ALTERSFORSCHUNG FRITZ-LIPMANN-INSTITUT e.V. (FLI) Inhibitors of the notch signaling pathway and secretion for use in medicine

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SU379091A3 (en:Method) 1973-04-18
IL35924A0 (en) 1971-02-25
ES387562A1 (es) 1974-01-01
CS163747B2 (en:Method) 1975-11-07
AT304552B (de) 1973-01-10
NL7100816A (en:Method) 1971-07-27
SU383290A3 (en:Method) 1973-05-25
GB1317425A (en) 1973-05-16
ZA7152B (en) 1971-10-27
DE2003146A1 (de) 1971-07-29
FR2081452A1 (en:Method) 1971-12-03
AT306720B (de) 1973-04-25
IE34890L (en) 1971-07-24
IE34890B1 (en) 1975-09-17
HU162199B (en:Method) 1973-01-29
IL35924A (en) 1974-09-10
CS163748B2 (en:Method) 1975-11-07
FR2081452B1 (en:Method) 1974-08-23
CA945167A (en) 1974-04-09
CH586200A5 (en:Method) 1977-03-31
BE761929A (en:Method) 1971-07-22

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