DE1080266B - X-ray contrast media - Google Patents

X-ray contrast media

Info

Publication number
DE1080266B
DE1080266B DESCH24639A DESC024639A DE1080266B DE 1080266 B DE1080266 B DE 1080266B DE SCH24639 A DESCH24639 A DE SCH24639A DE SC024639 A DESC024639 A DE SC024639A DE 1080266 B DE1080266 B DE 1080266B
Authority
DE
Germany
Prior art keywords
ray contrast
contrast media
dimethylaminomethyleneamino
triiodophenyl
propionic acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
DESCH24639A
Other languages
German (de)
Inventor
Dr Hans Priewe
Dr Alexander Poljak
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Schering AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from DESCH24255A external-priority patent/DE1076894B/en
Application filed by Schering AG filed Critical Schering AG
Priority to DESCH24639A priority Critical patent/DE1080266B/en
Priority to GB7421/59A priority patent/GB884623A/en
Priority to CH7064459A priority patent/CH381806A/en
Priority to AT238759A priority patent/AT210991B/en
Priority to DK114759A priority patent/DK90336C/en
Priority to BE577346A priority patent/BE577346A/en
Priority to NL237800A priority patent/NL121190C/xx
Priority to NL237800D priority patent/NL237800A/xx
Priority to DESCH26697A priority patent/DE1094931B/en
Priority to DESCH26755A priority patent/DE1099696B/en
Publication of DE1080266B publication Critical patent/DE1080266B/en
Priority to GB2248860A priority patent/GB950321A/en
Priority to FR835872A priority patent/FR195M/en
Priority to DK360060A priority patent/DK93696C/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C07D285/135—Nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/04—X-ray contrast preparations
    • A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
    • A61K49/0447—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
    • A61K49/0495—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound intended for oral administration
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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
    • C07D239/69—Benzenesulfonamido-pyrimidines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/195—Radicals derived from nitrogen analogues of carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32—Nitrogen atom
    • C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
    • C09B23/16—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing hetero atoms
    • C09B23/162—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing hetero atoms only nitrogen atoms
    • C09B23/166—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing hetero atoms only nitrogen atoms containing two or more nitrogen atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)

Description

Röntgenkontrastmittel Zusatz zur Patentanmeldung Sch 24255IVa/30h (Auslegeschrift 1076 894) In der Hauptpatentanmeldung Sch 24255 IVa/30h ist vorgeschlagen worden, in kernjodierten a-Alkyl-ß-(aminophenyl)-propionsäuren die Aminogruppe durch die Dimethylaminomethylenaminogruppe zu ersetzen und die so erhaltenen Verbindungen bzw. deren nichttoxische Salze mit organischen und/oder anorganischen Basen als schattengebende Substanzen in peroral applizierbaren Röntgenkontrastmitteln zur Abbildung des Gallensystems zu verwenden, da gezeigt werden konnte, daß diese Verbindungen im Vergleich mit den bekannten kernjodierten a-Alkyl-ß-(aminophenyl)-propionsäuren erhebliche Vorteile besitzen.X-ray contrast agent addendum to patent application Sch 24255IVa / 30h (Auslegeschrift 1076 894) In the main patent application Sch 24255 IVa / 30h it has been proposed to replace the amino group in nuclear iodized α-alkyl-β- (aminophenyl) propionic acids with the dimethylaminomethyleneamino group and the compounds obtained in this way or their non-toxic salts with organic and / or inorganic bases as shading substances in orally administered X-ray contrast media for imaging the biliary system, since it could be shown that these compounds in comparison with the known nucleus-iodinated α-alkyl-ß- (aminophenyl) - propionic acids have considerable advantages.

Diese Vorteile bestehen vor allem in einer vergleichsweise sehr niedrigen Toxizität, einer ausgezeichneten Resorbierbarkeit bei peroraler Applikation und einer wesentlich besseren Gallenverteilung bei gleichzeitig kräftiger Schattengebung.These advantages consist primarily in a comparatively very low one Toxicity, excellent absorbability when administered orally and a much better bile distribution with strong shading at the same time.

Es wurde nun gefunden, daß die in der Seitenkette unsubstituierten kernjodierten ß-(Dimethylaminomethylenaminophenyl)-propionsäuren im Vergleich mit den in a-Stellung alkyl- bzw. cycloalkylsubstituierten Verbindungen in ihrer Wirkung und ihren Eigenschaften keineswegs beeinträchtigt, sondern teilweise sogar verstärkt bzw. verbessert sind.It has now been found that those in the side chain are unsubstituted Nuclear iodinated ß- (dimethylaminomethyleneaminophenyl) propionic acids in comparison with the effect of the compounds substituted by alkyl or cycloalkyl substituted in the a-position and their properties are in no way impaired, but in some cases even reinforced or are improved.

Die Vorteile der neuen Verbindungen ergeben sich deutlich beim Vergleich mit schon bekannten Verbindungen im Tierversuch. Bei Gegenüberstellung der erfindungsgemäßen ß - (3 - Dimethylaminomethylenamino-2,4,6-trijodphenyl)-propionsäure (I) mit der in der Hauptpatentanmeldung Sch 24255 IVa/30h beschriebenen a-Äthyl ß-(3-dimethylaminomethylenamino-2,4,6-trijodphenyl)-propionsäure (II) wie auch mit der bekannten ß - (3 - Amino - 2,4,6 - trijodphenyl) - propionsäure (III) wurden folgende Werte erhalten: Gallenverteilung in % nach 100 mg/kg LDGo intraduodenal Ratte nach i. v. mg/kg 1 g Stunden (I) 440 16,7 69,4 81,9 (1I) 490 13,4 63,1 73;6 (11I) 375 6,6 13,5 20,9 Die Herstellung der erfindungsgemäßen Verbindungen geschieht z. B. über die bekannten j odierten Aminoverbindungen, indem man diese bzw. ihre Säureadditionssalze mit N-Dimethylformamid in Gegenwart eines sauren Reaktionsvermittlers wie Phosphoroxychlorid reagieren läßt. Selbstverständlich sind auch andere allgemeine Methoden verwendbar. Diese Herstellungsverfahren gehören nicht zum Schutzrecht. Beispiel 1 1,25 kg ß-(3-Dimethylaminomethylenamino-2,4,6-trijodphenyl)-propionsäure werden mit 0,51 Stärkekleister, der 25 g Maisstärke enthält, in einer Knetmaschine angeteigt. Die feuchte Masse wird wie üblich in einer Granuliermaschine granuliert und im Vakuum getrocknet. Das fertige Granulat wird dann mit 0,125 kg- Maisstärke und 6 g Magnesiumsteaxat vermischt und zu Tabletten mit einem Wirkstoffgehalt von 500 mg verpreßt.The advantages of the new compounds emerge clearly when compared with compounds already known in animal experiments. When comparing the ß- (3-dimethylaminomethyleneamino-2,4,6-triiodophenyl) propionic acid (I) according to the invention with the a-ethyl ß- (3-dimethylaminomethyleneamino-2,4,6 described in the main patent application Sch 24255 IVa / 30h) -triiodophenyl) -propionic acid (II) as well as with the known ß - (3 - amino - 2,4,6 - triiodophenyl) - propionic acid (III) the following values were obtained: Bile distribution in % after 100 mg / kg LDGo intraduodenal rat after iv mg / kg 1 g hours (I) 440 16.7 69.4 81.9 (1I) 490 13.4 63.1 73; 6 (11I) 375 6.6 13.5 20.9 The compounds according to the invention are prepared, for. B. via the known iodized amino compounds by allowing them or their acid addition salts to react with N-dimethylformamide in the presence of an acidic reaction mediator such as phosphorus oxychloride. Of course, other general methods can also be used. These manufacturing processes do not belong to the property right. Example 1 1.25 kg of β- (3-dimethylaminomethyleneamino-2,4,6-triiodophenyl) propionic acid are made into a paste with 0.51 of starch paste containing 25 g of corn starch in a kneading machine. The moist mass is granulated as usual in a granulating machine and dried in vacuo. The finished granules are then mixed with 0.125 kg corn starch and 6 g magnesium steaxate and compressed into tablets with an active ingredient content of 500 mg.

Beispiel 2 Das gut wasserlösliche Natriumsalz der ß-(3-Dimethylaminomethylenamino -2,4,6 - trij odphenyl) - propionsäure wird in Gelatinekapseln abgefüllt. Jede Kapsel enthält 750 mg Wirkstoff. Zur maschinellen Kapselherstellung kann das Natriumsalz mit 40 °/o Paraffinöl zu einer fließfähigen Paste verarbeitet werden.Example 2 The readily water-soluble sodium salt of β- (3-dimethylaminomethyleneamino -2,4,6-trijodphenyl) -propionic acid is filled into gelatine capsules. Any capsule contains 750 mg of active ingredient. The sodium salt can be used for mechanical capsule production processed with 40% paraffin oil to a flowable paste.

Beispiel 3 Das gemäß Beispiel 1 erhaltene Granulat wird durch Auftragen von 20 % des Eigengewichtes Zuckersyrup im Dragierkessel dragiert und anschließend gewachst.Example 3 The granules obtained according to Example 1 are applied by applying Sugar syrup coated with 20% of its own weight in a coating pan and then waxed.

Claims (3)

PATENTANSPRÜCHE: 1. Abgeänderte Röntgenkontrastmittel gemäß Hauptpatentanmeldung Sch 24255 IVa/30h, insbesondere zur peroralen Applikation für die Cholecystographie,enthaltend als schattengebende Substanz kernjodierte ß - (Dimethylaminomethylenaminophenyl)-propionsäuren der allgemeinen Formel worin n die Zahlen 2 bis 3 bedeutet. PATENT CLAIMS: 1. Modified X-ray contrast media according to the main patent application Sch 24255 IVa / 30h, in particular for oral application for cholecystography, containing ß- (dimethylaminomethyleneaminophenyl) propionic acids of the general formula with nuclear iodine as a shading substance where n is the numbers 2 to 3. 2. Röntgenkontrastmittel gemäß Anspruch 1, dadurch gekennzeichnet, daß es als schattengebende Substanz ß-(Dimethylaminomethylenamino-2;4,6-trijodphenyl)-propionsäure enthält. 2. X-ray contrast medium according to claim 1, characterized in that it is ß- (dimethylaminomethyleneamino-2; 4,6-triiodophenyl) propionic acid as the shading substance contains. 3. Röntgenkontrastmittel gemäß Anspruch 1 und 2, dadurch gekennzeichnet, daß es die nichttoxischen Salze mit anorganischen und/oder organischen Basen enthält.3. X-ray contrast medium according to claim 1 and 2, characterized in that that it contains the non-toxic salts with inorganic and / or organic bases.
DESCH24639A 1958-04-05 1958-08-29 X-ray contrast media Pending DE1080266B (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
DESCH24639A DE1080266B (en) 1958-06-20 1958-08-29 X-ray contrast media
GB7421/59A GB884623A (en) 1958-04-05 1959-03-03 New triiodophenyl-propionic acids and x-ray contrast media comprising the same
CH7064459A CH381806A (en) 1958-04-05 1959-03-11 X-ray contrast media
AT238759A AT210991B (en) 1958-06-20 1959-03-26 X-ray contrast media
DK114759A DK90336C (en) 1958-08-29 1959-04-02 X-ray contrast agent.
BE577346A BE577346A (en) 1958-04-05 1959-04-03 Process for the preparation of N, N'-trisubstituted formamidines.
NL237800D NL237800A (en) 1958-04-05 1959-04-04
NL237800A NL121190C (en) 1958-06-20 1959-04-04
DESCH26697A DE1094931B (en) 1958-06-20 1959-09-16 X-ray contrast media
DESCH26755A DE1099696B (en) 1958-06-20 1959-09-30 X-ray contrast media
GB2248860A GB950321A (en) 1958-04-05 1960-06-27 Derivatives of iodophenyl-propionic acids and improvements in and relating to x-ray contrast media
FR835872A FR195M (en) 1958-04-05 1960-08-12 X-ray contrast agent.
DK360060A DK93696C (en) 1958-08-29 1960-09-10 X-ray contrast agent.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DESCH24255A DE1076894B (en) 1958-06-20 1958-06-20 X-ray contrast media
DESCH24639A DE1080266B (en) 1958-06-20 1958-08-29 X-ray contrast media

Publications (1)

Publication Number Publication Date
DE1080266B true DE1080266B (en) 1960-04-21

Family

ID=25992751

Family Applications (1)

Application Number Title Priority Date Filing Date
DESCH24639A Pending DE1080266B (en) 1958-04-05 1958-08-29 X-ray contrast media

Country Status (3)

Country Link
AT (1) AT210991B (en)
DE (1) DE1080266B (en)
NL (1) NL121190C (en)

Also Published As

Publication number Publication date
NL121190C (en) 1966-09-15
AT210991B (en) 1960-09-10

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