DE2949491A1 - 1,4-DIHYDROPYRIDINE, THEIR PRODUCTION AND USE - Google Patents

1,4-DIHYDROPYRIDINE, THEIR PRODUCTION AND USE

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Publication number
DE2949491A1
DE2949491A1 DE19792949491 DE2949491A DE2949491A1 DE 2949491 A1 DE2949491 A1 DE 2949491A1 DE 19792949491 DE19792949491 DE 19792949491 DE 2949491 A DE2949491 A DE 2949491A DE 2949491 A1 DE2949491 A1 DE 2949491A1
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formula
group
compounds
compound
iii
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DE2949491C2 (en
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Peter Dr Neumann
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Novartis AG
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Sandoz AG
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Priority to CH548480A priority Critical patent/CH654836A5/en
Priority to PH24383A priority patent/PH19536A/en
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Publication of DE2949491C2 publication Critical patent/DE2949491C2/de
Priority to MX9203580A priority patent/MX9203580A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Heart & Thoracic Surgery (AREA)
  • General Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Cardiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)

Description

2949Α9Ί2949Α9Ί

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Die vorliegende Erfindung betrifft 1,4-Dihydropyridine der Formel I,The present invention relates to 1,4-dihydropyridines of formula I,

R2OOCR 2 OOC

worin R,, R-, R, und X folgende Bedeutungen haben und y die Stellung des Dihydropyridinrestes angibt:where R ,, R-, R, and X have the following meanings and y indicates the position of the dihydropyridine radical:

Verb.Verb. 55 Rl ' R l ' 22 R2 R 2 (CH3 (CH 3 >2> 2 R3 R 3 yy XX 11 66th CH3 CH 3 22 CH2CHCH 2 CH HH 44th 00 22 77th CH3 CH 3 CH3 CH 3 HH 44th OO 33 88th C2H5 C 2 H 5 22 C2H5 C 2 H 5 HH 55 00 44th 99 CH2CH(CH3)CH 2 CH (CH 3 ) 55 C2H5 C 2 H 5 HH 44th SS. 1010 CH2CH(CH3)CH 2 CH (CH 3 ) 55 C2H5 C 2 H 5 >3> 3 HH 44th 00 1111 C(CU3) 3 C (CU 3 ) 3 55 C(CH3 C (CH 3 (CU3 (CU 3 HH 44th 00 1212th CII CH(CH )CII CH (CH) CH CIICH CII HH 44th 00 (CH2)2OC2H (CH 2 ) 2 OC 2 H C2H5 C 2 H 5 HH 44th 00 (CH2J2OC2H(CH 2 J 2 OC 2 H C2H5 C 2 H 5 HH 44th SS. (CH2J2OC2H(CH 2 J 2 OC 2 H C2H5 C 2 H 5 HH 55 SS. CH(ClI3) 2 CH (ClI 3 ) 2 CH3 CH 3 HH 44th OO (CH2J2OCH3 (CH 2 J 2 OCH 3 CH3 CH 3 HH 44th 00

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Verb.Verb. Rl R l R2 R 2 R3 R 3 yy XX 1313th I CH3 I CH 3 HH 44th 00 1414th (CH.)o0CH(CH_)
2 2 3 <(CH.) O 0CH (CH_)
2 2 3 < CH3 CH 3 HH 44th 00 1515th (CH2J2OC2H5 (CH 2 J 2 OC 2 H 5 CH3 CH 3 HH 44th 00 1616 <^<^ CH(CH )CH (CH) HH 44th 00 1717th C2H5 C 2 H 5 HH 44th 00 1818th (CH ) OCH(CH) OCH C2H5 C 2 H 5 CH3 CH 3 44th 00 1919th CH3 CH 3 C2H5 C 2 H 5 H-C3H7 HC 3 H 7 44th 00 C2K5 C 2 K 5 C2H5 C 2 H 5

Die Verbindungen der Formel I fallen unter den Schutzumfang der Europäischen Patentanmeldung Nr. 78100165.6, sie werden jedoch darin nicht spezifisch genannt. Es wurde nunmehr gefunden, dass die Verbindungen der Formel I besonders wertvolle pharmakologische Eigenschaften besitzen. Sie bewirken insbesondere eine starke und langanhaltende Erweiterung der Koronargefässe.The compounds of the formula I fall under the scope of protection of European Patent Application No. 78100165.6, but they are not specifically mentioned therein. It it has now been found that the compounds of the formula I have particularly valuable pharmacological properties own. In particular, they cause a strong and long-lasting expansion of the coronary vessels.

Ferner besitzen sie eine starke calciumantagonistische Wirkung und zeichnen sich durch eine gute Verträglichkeit aus.They also have a strong calcium antagonist Effect and are characterized by a good tolerance.

Erfindungsgemäss gelangt man zu Verbindungen der Formel I, indem man in Verbindungen der Formel II,According to the invention, compounds of the formula are obtained I, in that in compounds of the formula II,

IIII

HC=YHC = Y

worin X obige Bedeutung besitzt, und -HC=Y i) Formyl,wherein X has the above meaning, and -HC = Y i) formyl,

ii) eine Gruppe der Formel -HC=C-C(=Z)CHii) a group of the formula -HC = C-C (= Z) CH

COOR,COOR,

oderor

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COOR1 COOR 1

.HC-Ci=Z)CH3 iii) eine Gruppe der Formel -HC.HC-Ci = Z) CH 3 iii) a group of the formula -HC

HC-CC-Z )CH3 COOR2 HC-CC-Z) CH 3 COOR 2

bedeutet, worin Z und Z1 unabhängig voneinander für Sauerstoff oder NR stehen und R1 -R3 obige Bedeutung besitzen, die Gruppe -HC=Y durch die Gruppe der Formel III,denotes in which Z and Z 1 independently of one another represent oxygen or NR and R 1 - R 3 have the above meaning, the group -HC = Y by the group of the formula III,

R3OOCR 3 OOC

Ύ Ύ '■Ύ Ύ '■

IIIIII

3
worin R-i~R^ obige Bedeutung besitzen, ersetzt.3
where Ri ~ R ^ have the above meaning, replaced.

Das Verfahren kann in einer für analoge Dihydropyridin-Synthesen bekannten Weise, z.B. nach Hantzsch, durchgeführt werden. Falls die Gruppe -HC=Y für Forinyl steht, und falls Verbindungen der Formel I, worin R, die gleiche Bedeutung wie R„ hat, hergestellt werden sollen, so ist es zweckmässig, eine Verbindung der Formel II mit einer Verbindung der Formel IV,The process can be carried out in a manner known for analogous dihydropyridine syntheses, for example according to Hantzsch will. If the group -HC = Y is forinyl, and if compounds of the formula I in which R are the same Meaning as R "has to be produced, it is expedient to use a compound of the formula II with a compound of the formula IV,

CH3-CO-CH2-COOR2 IVCH 3 -CO-CH 2 -COOR 2 IV

worin R- obige Bedeutung besitzt, in Gegenwart einer Verbindung der Formel V,wherein R- has the above meaning, in the presence of a compound of the formula V,

H2NR3 H 2 NR 3

worin R_ obige Bedeutung besitzt, umzusetzenwhere R_ has the above meaning to implement

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Vorzugsv/eise verwendet man mindestens 2 Mol einer Verbindung der Formel IV pro Mol einer Verbindung der Formel Wahlweise kann eine Verbindung der Formel II mit einer Verbindung der Formel VI,Preference is given to using at least 2 moles of a compound of the formula IV per mole of a compound of the formula Optionally, a compound of the formula II with a compound of the formula VI,

CH -C(NK-R )=CH-COOR VICH -C (NK-R) = CH-COOR VI

worin R_ und R obige Bedeutung besitzen, umgesetzt werden.wherein R_ and R have the above meaning, implemented will.

Vorzugsweise werden mindestens 2 Mol einer Verbindung der Formel VI pro Mol einer Verbindung der Formel II eingesetzt.Preferably, at least 2 moles of a compound of the formula VI per mole of a compound of the formula II used.

Falls die Gruppe -HC=Y für Formyl steht, und besonders wenn Verbindungen der Formel I hergestellt werden sollen, worin R, verschieden von R„ ist, kann man auch eine Verbindung der Formel II mit einer Verbindung der Formel IV und einer Verbindung der Formel VII; If the group -HC = Y stands for formyl, and especially if compounds of the formula I are to be prepared in which R is different from R ", one can also use a compound of the formula II with a compound of the formula IV and a compound of the formula VII ;

CH -C(NH-R )=CH-COOR VIICH -C (NH-R) = CH-COOR VII

worin R, und R^ obige Bedeutung besitzen, umsetzen.wherein R, and R ^ have the above meaning, implement.

Eine Verbindung der Formel VI kann als Zv/ischenprodukt während der Reaktion einer Verbindung der Formel IV mit einer Verbindung der Formel V entstehen. Eine Verbindung der Formel II, worin die Gruppe -HC=Y für eine Gruppe ü) oder iii) steht, kann als Zwischenprodukt in den obigen Reaktionen entstehen. Sie können aber auch nach anderen Verfahren hergestellt werden.A compound of the formula VI can be used as an intermediate product during the reaction of a compound of the formula IV with a compound of the formula V arise. A compound of the formula II in which the group -HC = Y represents a group ü) or iii) can be formed as an intermediate in the above reactions. But you can also after other processes.

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Wahlweise oder insbesondere für die Herstellung von Verbindungen der Formel I, worin R, eine andere Bedeutung als R_ hat, ist es zweckmässig, eine Verbindung der Formel II, v/orin -HC=Y für eine Gruppe ii) steht, mit einer Verbindung der Formel IV oder VI, und, wo erforderlich, mit einer Verbindung der Formel V umzusetzen. Eine Verbindung der Formel II, worin -HC=Y für eine Gruppe iii) steht, kann als Zwischenprodukt gebildet werden.Optionally or in particular for the preparation of compounds of the formula I in which R has a different meaning as R_, it is expedient to use a compound of the formula II, v / orin -HC = Y for a group ii) is, with a compound of the formula IV or VI, and, where necessary, with a compound of the formula V to react. A compound of the formula II in which -HC = Y is a group iii) can be used as an intermediate are formed.

In den obigen Reaktionen ist es möglich, dass in gewissen Fällen, wenn R, und R„ nicht gleich sind, dass mehr als ein Isomeres der Formel I entsteht. Diese können in an sich bekannter Weise, z.B. säulen- oder dünnschichtchromatographisch, getrennt werden.In the above reactions it is possible that, in certain cases, when R 1 and R "are not the same, that more than one isomer of formula I is formed. These can be in a manner known per se, e.g. columnar or be separated by thin layer chromatography.

Geht man von einer Verbindung der Formel II aus, v/orin -HC=Y für eine Gruppe iii) steht, so handelt es sich um eine Cyclisierungsreaktion. Stehen Z und Z1 jeweils für Sauerstoff, dann sollte ein Amin der Formel V anwesend sein.If one starts from a compound of the formula II in which v / orin -HC = Y stands for a group iii), then it is a cyclization reaction. If Z and Z 1 each stand for oxygen, then an amine of the formula V should be present.

Die obigen Reaktionen können alle unter denselben Bedingungen durchgeführt werden.The above reactions can all under the same conditions be performed.

Das Verfahren wird zweckmässigerweise in Lösung durchgeführt. Geeignete Lösungsmittel sind Wasser, Aethanol, Dioxan, Dimethylformamid, Dimethylsulfoxid, Pyridin oder Eisessig. Die Reaktionstemperaturen liegen zwischen 20 und 160° C, vorzugsweise zwischen 60 und 12Ό° C.The process is expediently carried out in solution. Suitable solvents are water, ethanol, dioxane, dimethylformamide, dimethyl sulfoxide, pyridine or glacial acetic acid. The reaction temperatures are between 20 and 160 ° C, preferably between 60 and 12Ό ° C.

Soweit die Herstellung der Ausgangsverbindungen nicht beschrieben wird, sind diese bekannt oder analog zu bekannten Verbindungen herstellbar.If the preparation of the starting compounds is not described, these are known or analogous to known ones Connections can be established.

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Die Verbindungen der Forir.el I zeichnen sich durch günstige pharmakodynamische Eigenschaften aus. Insbesondere bewirken sie eine Erweiterung der Herzkranzgefässe und besitzen eine günstige Wirkung gegen Angina pectoris. Sie steigern ferner die Durchblutung des Gehirns und der Beinmuskulatur. Sie besitzen ausserdem calciumantagonistische und antihypertensive Wirkungen.The connections of the Forir.el I are characterized by favorable pharmacodynamic properties. In particular, they cause the coronary arteries to expand and have a beneficial effect against angina pectoris. They also increase blood flow to the brain and the leg muscles. They also have calcium antagonistic and antihypertensive effects.

Von den Verbindungen der Formel I sind die Verbindungen 1, 5, 11, 12, 13, 14, 15, 16, 17, 18 und 19 bevorzugt. Of the compounds of the formula I, compounds 1, 5, 11, 12, 13, 14, 15, 16, 17, 18 and 19 are preferred.

Ganz besonders wertvoll sind die Verbindungen 1 undThe compounds 1 and are particularly valuable

Die Erfindung umfasst pharmazeutische Zubereitungen, die Verbindungen der Formel I zusammen mit pharmazeutisch verwendbaren Träger- oder Verdünnungsmitteln enthalten. Sie können in an sich bekannter Weise hergestellt werden und liegen z.B. als Tabletten, Dragees oder Kapseln vor.The invention encompasses pharmaceutical preparations, the compounds of the formula I together with pharmaceutical contain usable carriers or diluents. They can be produced in a manner known per se are and are available, for example, as tablets, coated tablets or capsules.

In den nachfolgenden Beispielen sind die Temperaturen in Grad-Celsius angegeben und sind unkorrigiert.In the following examples, the temperatures are given in degrees Celsius and are uncorrected.

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Beispiel 1;Example 1;

4- (2,1,3-Benzoxadiazolyl-4)-3-methoxycarbonyl-1,4-dihydro-2,6-dinethylpyridin-5-carbonsäure-isobutylester 4- (2,1,3-Benzoxadiazoly 1- 4) -3-methoxycarbonyl-1,4-dihydro-2,6-dinethylpyridine-5-carboxylic acid isobutyl ester

3 g 2,1,3-Benzoxadiazol-4-aldehyd, 3,2 g Acetessigsäureisobutylester, 2,3 g ß-Aminocrotonsäuremethylester und 10 ml Aethanol werden zusammen unter Rühren 3 Stunden zum Rückfluss erhitzt. Das Reaktionsgemisch wird anschliessend eingedampft und der Rückstand über Silicagel mit Chloroform/Essigester (8:1) chromatographiert, wobei man die Titelverbindung, die aus Diisopropyläther und Methylcyclohexan umkristallisiert bei 148-158° schmilzt, erhält.3 g 2,1,3-benzoxadiazole-4-aldehyde, 3.2 g isobutyl acetoacetate, 2.3 g of ß-aminocrotonic acid methyl ester and 10 ml of ethanol are stirred together for 3 hours heated to reflux. The reaction mixture is then evaporated and the residue over silica gel chromatographed with chloroform / ethyl acetate (8: 1), the title compound being obtained from diisopropyl ether and methylcyclohexane, recrystallized at 148-158 °, is obtained.

Unter Verwendung des im Beispiel 1 beschriebenen Verfahrens und entsprechender Ausgangsverbindungen, z.B.Using the procedure described in Example 1 and appropriate starting compounds, e.g.

einer Verbindung der Formel II, worin -HC=Y für die Gruppe i) steht, und Verbindungen der Formeln IV und V, und für die Beispiele 4, 5 und 8-17 ζweckmässigerweise eine Verbindung der Formel II, worin -HC=Y für eine Gruppe ii) steht, sowie eine Verbindung der Formel VI, gelangt man zu folgenden Verbindungen der Formel I, worin y die Stellung des Dihydropyridinrestes angibt:a compound of the formula II in which -HC = Y is the group i), and compounds of the formulas IV and V, and for Examples 4, 5 and 8-17 by default a compound of the formula II in which -HC = Y is a group ii), and a compound of formula VI, the following compounds of formula I are obtained, in which y is the position of the dihydropyridine radical indicates:

Verb.Verb. Rl R l R2 R 2 R3 R 3 yy XX Smp.M.p. 22 CH3 CH 3 CH3 CH 3 HH 44th OO 215-221215-221 33 C2H5 C 2 H 5 C2H5 C 2 H 5 HH 55 OO 173-174173-174 44th CH2CH(CH3J2 CH 2 CH (CH 3 J 2 C2H5 C 2 H 5 HH 44th SS. 85-9585-95 55 CH2CH(CH3)2 CH 2 CH (CH 3 ) 2 C2H5 C 2 H 5 HH 44th OO 145-146.5145-146.5

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Verb.Verb. Rl R l R2 R 2 R3 R 3 yy XX Snip.Snip. 66th C(CH,) -
■J -5C (CH,) -
■ J -5 HH 44th 00 207-210207-210 77th C(CH3J3 C (CH 3 J 3 2 H 2 H 44th 00 135.5-137135.5-137 88th CH2CH(CH3J2 CH 2 CH (CH 3 J 2 C2H5 C 2 H 5 HH 44th 00 126-128126-128 99 (CH2J2OC2H5 (CH 2 J 2 OC 2 H 5 C2H5 C 2 H 5 HH 44th SS. OeIOeI 1010 (CH2J2OC2H5 (CH 2 J 2 OC 2 H 5 C2H5 C 2 H 5 HH 55 SS. 72-7872-78 1111 (CH2J2OC2H5 (CH 2 J 2 OC 2 H 5 CH3 CH 3 HH 44th 00 131-153131-153 1212th CH(CH JCH (CH J CH3 CH 3 HH 44th 00 151-153151-153 1313th (CH2J2OCH3 (CH 2 J 2 OCH 3 CH3 CH 3 HH 44th 00 114-120114-120 1414th (CH2) 2OCH (CH3J2 (CH 2 ) 2 OCH (CH 3 J 2 CH3 CH 3 HH 44th 00 140-147140-147 1515th (CH2J2OC2H5 (CH 2 J 2 OC 2 H 5 CH3 CH 3 HH 44th 00 156-163156-163 1616 CH(CH3J2 CH (CH 3 J 2 HH 44th 00 119119 1717th C2H5 C 2 H 5 HH 44th OO 159159 1818th (CH2J2OCH3 (CH 2 J 2 OCH 3 C2H5 C 2 H 5 CH3 CH 3 44th CC. 106106 1919th CH3 CH 3 C2H5 n C 2 H 5 n -CH-CH 44th 00 9999 C2H5 C 2 H 5 C2H5 C 2 H 5

3700/IG/SE3700 / IG / SE

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Claims (3)

Sandoz-Patent-GmbH LörrachSandoz-Patent-GmbH Loerrach Case 5G0-549€Case 5G0-549 € 1,4-Dihydropyridine, ihre Herstellung und Verwendung1,4-Dihydropyridines, their preparation and use PatentansprücheClaims 1,4-Oihydropyridine der Formel I,1,4-Oihydropyridines of the formula I, R2OOCR 2 OOC worin R,, R~, R3 und X folgende Bedeutungen haben und y die Stellung des Dihydropyridinrestes angibt: where R ,, R ~ , R 3 and X have the following meanings and y indicates the position of the dihydropyridine residue: Verb. 1 2 3 4Verb. 1 2 3 4 "1 CH."1 CH. CH,CH, C2H5 CH2CH(CK3)C 2 H 5 CH 2 CH (CK 3 ) R2 R 2 R3 R 3 yy XX CH2CH(CH3)2 CH 2 CH (CH 3 ) 2 HH 44th OO CH3 CH 3 HH 44th OO C2H5 C 2 H 5 HH 55 OO C2H5 C 2 H 5 HH 44th SS.
030026/0729030026/0729 ORIGINAL INSPECTEDORIGINAL INSPECTED 500-5496500-5496 Verb.Verb. Rl R l R2 R 2 R3 R 3 yy XX 55 C2H5 C 2 H 5 HH 44th 00 66th CH-CH(CH-).CH-CH (CH-).
2 3 22 3 2 C(CH3J3 C (CH 3 J 3 HH 44th 00 77th C(CH3) jC (CH 3 ) j CH2CH(CH3)CH 2 CH (CH 3 ) 2 H 2 H 44th 00 88th CIl2ClHCH3) 2 CIl 2 ClHCH 3 ) 2 C2H5 C 2 H 5 HH 44th 00 99 (CH2J2OC2H5 (CH 2 J 2 OC 2 H 5 C2H5 C 2 H 5 HH 44th SS. 1010 (CH2J2OC2H5 (CH 2 J 2 OC 2 H 5 C2Il5 C 2 Il 5 HH 55 SS. 1111 (CH2J2OC2H5 (CH 2 J 2 OC 2 H 5 CH3 CH 3 HH 44th 00 1212th CH(CH3J2 CH (CH 3 J 2 CH3 CH 3 HH 44th 00 1313th (CH2) 2OCII3 (CH 2 ) 2 OCII 3 I CH3 I CH 3 HH 44th OO 1414th (CH2)20CH(CH3)(CH 2 ) 2 0CH (CH 3 ) CH3 CH 3 HH 44th 00 1515th (CH2) 2OC2H5 (CH 2 ) 2 OC 2 H 5 CH3 CH 3 HH 44th 00 1616 HH 44th 00 1717th C2H5 C 2 H 5 HH 44th 00 1818th (CH2J2OCH3 (CH 2 J 2 OCH 3 C2H5 C 2 H 5 CH3 CH 3 44th OO 1919th CH3 CH 3 C2H5 C 2 H 5 H-C3HHC 3 H 44th 00 C2H5 C 2 H 5 C2H5 C 2 H 5
2. Verfahren zur Herstellung von Verbindungen der Formel I dadurch gekennzeichnet, dass man in Verbindungen der Formel II,2. Process for the preparation of compounds of the formula I, characterized in that compounds of formula II, HC=YHC = Y worin X obige Bedeutung besitzt, und -HC=Y i) Formyl, wherein X has the above meaning, and -HC = Y i) formyl, ii) eine Gruppe der Formel -HC=C-C(=Z)CH- ii) a group of the formula -HC = CC (= Z) CH- 1 COOR,1 COOR, oderor 030026/0729030026/0729 500-5496500-5496 iii) eine Gruppe der Formel -KCiii) a group of the formula -KC CCOR1 HC-Ci=Z)CH.CCOR 1 HC-Ci = Z) CH. HC-C(=Z*)CK.HC-C (= Z *) CK. OOR,OOR, bedeutet, worin Z und Z1 unabhängig voneinander für Sauerstoff oder NR3 stehen und R1-R3 obige Bedeutung besitzen, die Gruppe -HC=Y durch die Gruppe der Formel III,denotes in which Z and Z 1 independently of one another represent oxygen or NR 3 and R 1 -R 3 have the above meaning, the group -HC = Y by the group of the formula III, R2OOCR 2 OOC COOR-COOR- IIIIII obige Bedeutung besitzen, ersetzt.have the above meaning, replaced. 3. Heilmittel, gekennzeichnet durch einen Gehalt an Verbindungen der Formel I.3. Medicinal products, characterized by a content of compounds of the formula I. 030026/0729030026/0729
DE19792949491 1977-06-20 1979-12-08 1,4-DIHYDROPYRIDINE, THEIR PRODUCTION AND USE Granted DE2949491A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CH548480A CH654836A5 (en) 1979-12-08 1980-07-17 Heterocyclic organic compounds and therapeutic agents containing them
PH24383A PH19536A (en) 1977-06-20 1980-08-01 Benzoxadiazoles and benzothiadiazoles and pharmaceutical composition containing them
MX9203580A MX9203580A (en) 1979-12-08 1992-06-26 1,4-DIHYDROPIRIDINES AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM.

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH1283578A CH639659A5 (en) 1978-12-18 1978-12-18 NEW 1,4-DIHYDROPYRIDINE DERIVATIVES, THEIR PRODUCTION AND USE.

Publications (2)

Publication Number Publication Date
DE2949491A1 true DE2949491A1 (en) 1980-06-26
DE2949491C2 DE2949491C2 (en) 1988-10-27

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DE19792949491 Granted DE2949491A1 (en) 1977-06-20 1979-12-08 1,4-DIHYDROPYRIDINE, THEIR PRODUCTION AND USE

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EP0042089A2 (en) * 1980-06-12 1981-12-23 Bayer Ag 4-Heterocylic substituted dihydropyridines, processes for preparing them, their therapeutical use and their preparation
DE3136031A1 (en) * 1980-09-18 1982-04-08 Sandoz-Patent-GmbH, 7850 Lörrach PHARMACEUTICAL COMPOSITIONS, EFFECTIVE AGAINST CORONARY HEART DISEASES AND HIGH BLOOD PRESSURE
FR2528431A1 (en) * 1982-06-15 1983-12-16 Sandoz Sa NOVEL 1,4-DIHYDROPYRIDINE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS
AT384219B (en) * 1982-06-15 1987-10-12 Sandoz Ag Preparation of novel 1,4-dihydropyridine derivatives in optically active or racemate form
WO1994001405A1 (en) * 1992-07-10 1994-01-20 Siegfried Goldmann Light-activable 1-(2-nitrobenzyl)-substituted 1,4-dihydropyridines

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DE3269219D1 (en) * 1981-11-17 1986-03-27 Fisons Plc Dihydropyridines, methods for their production and their formulation and use as pharmaceuticals
ZA83959B (en) * 1982-03-10 1984-09-26 Sandoz Ltd 1,4-dihydropyridine derivatives,their preparation and pharmaceutical compositions containing them
US4414213A (en) * 1982-03-22 1983-11-08 Mead Johnson & Company Dihydropyridyl cyclic imidate esters and their pharmaceutical use
JPS5978186A (en) * 1982-10-27 1984-05-04 Yoshitomi Pharmaceut Ind Ltd 1,4-dihydropyridine-3,5-dicarboxylic acid ester derivative
US4794111A (en) * 1984-05-23 1988-12-27 Bayer Aktiengesellschaft Dihydropyridine preparations containing β-blockers
NL194389C (en) * 1984-06-14 2002-03-04 Novartis Ag Process for preparing a solid dispersion of a pharmaceutically active agent that has low water solubility in a solid matrix of a water-soluble polyalkylene glycol as a carrier.
US5260321A (en) * 1984-11-12 1993-11-09 Sandoz Ltd. Use of 1,4-dihydropyridine derivatives and combinations thereof with calcitonins
HU197201B (en) * 1985-10-01 1989-03-28 Sandoz Ag Process for producing oral pharmaceutical compositions of controlled solubility of the active components
DE3542794A1 (en) * 1985-12-04 1987-06-11 Bayer Ag ANTI-HYPERTENSIVE COMBINATION PREPARATION
GB8626217D0 (en) * 1986-11-03 1986-12-03 Sandoz Ltd Pharmaceutical compositions
US4816263A (en) * 1987-10-02 1989-03-28 Alza Corporation Dosage form for treating cardiovascular diseases comprising isradipine
KR940003492B1 (en) * 1988-10-27 1994-04-23 주식회사 유한양행 Process for preparation of 1,4 dihydropyridine derivatives
AU2003217676B2 (en) 2002-02-22 2009-06-11 Takeda Pharmaceutical Company Limited Active agent delivery systems and methods for protecting and administering active agents
WO2005023787A1 (en) * 2003-09-10 2005-03-17 Shasun Chemicals And Drugs Limited Process for the manufacture of 2,1,3-benzoxadiazole-4-carboxaldehyde
CN103613584B (en) * 2013-11-27 2016-04-27 沈阳药科大学 The method of a kind of Isrodipine synthetic product aftertreatment

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DE2635916A1 (en) * 1975-08-12 1977-02-24 Hexachimie DIHYDRO-1,4-PYRIDINE AND MEDICINAL PRODUCTS CONTAINING THESE
DE2616991A1 (en) * 1976-04-17 1977-10-27 Bayer Ag Thio-substd. dihydro-pyridine derivs. - coronary vasodilators and antihypertensives prepd. e.g. by reacting dicarbonyl cpds. with amines and thio-substd. ketones

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0042089A2 (en) * 1980-06-12 1981-12-23 Bayer Ag 4-Heterocylic substituted dihydropyridines, processes for preparing them, their therapeutical use and their preparation
EP0042089A3 (en) * 1980-06-12 1982-09-22 Bayer Ag 4-heterocylic substituted dihydropyridines, processes for preparing them, their therapeutical use and their preparation
DE3136031A1 (en) * 1980-09-18 1982-04-08 Sandoz-Patent-GmbH, 7850 Lörrach PHARMACEUTICAL COMPOSITIONS, EFFECTIVE AGAINST CORONARY HEART DISEASES AND HIGH BLOOD PRESSURE
FR2528431A1 (en) * 1982-06-15 1983-12-16 Sandoz Sa NOVEL 1,4-DIHYDROPYRIDINE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS MEDICAMENTS
WO1984000033A1 (en) * 1982-06-15 1984-01-05 Sandoz Ag 1,4-dihydro-pyridine derivatives, preparation thereof and pharmaceutical compositions containing them
AT384219B (en) * 1982-06-15 1987-10-12 Sandoz Ag Preparation of novel 1,4-dihydropyridine derivatives in optically active or racemate form
WO1994001405A1 (en) * 1992-07-10 1994-01-20 Siegfried Goldmann Light-activable 1-(2-nitrobenzyl)-substituted 1,4-dihydropyridines
US5606066A (en) * 1992-07-10 1997-02-25 Goldmann; Siegfried Light activable "caged" 1-(2-nitrobenzyl)-substituted 1,4-dihydropyridines

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GB2037766B (en) 1983-02-16
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HK16086A (en) 1986-03-14
GB2103203A (en) 1983-02-16
CY1321A (en) 1986-06-27
BE880591A (en) 1980-06-13
NZ192422A (en) 1982-09-14
NL7909024A (en) 1980-06-20
MY8500130A (en) 1985-12-31
FR2444681B1 (en) 1982-10-29
GB2037766A (en) 1980-07-16
AU5389679A (en) 1980-06-26
ZA796842B (en) 1981-07-29
SE7910188L (en) 1980-06-19
IT1164097B (en) 1987-04-08
CH639659A5 (en) 1983-11-30
FR2444681A1 (en) 1980-07-18
SE445219B (en) 1986-06-09
JPS5583783A (en) 1980-06-24
GB2103203B (en) 1983-06-08
IT7951095A0 (en) 1979-12-14
NL990014I1 (en) 1999-07-01
IE792445L (en) 1980-06-18
JPH0369910B2 (en) 1991-11-05
IE49496B1 (en) 1985-10-16
DE2949491C2 (en) 1988-10-27
NL193066B (en) 1998-05-06
KE3593A (en) 1986-02-07

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