EP0000336B1 - N-benzylpyrimidinyl-amidines, procédé pour leur préparation et médicaments les contenant - Google Patents

N-benzylpyrimidinyl-amidines, procédé pour leur préparation et médicaments les contenant Download PDF

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Publication number
EP0000336B1
EP0000336B1 EP78100184A EP78100184A EP0000336B1 EP 0000336 B1 EP0000336 B1 EP 0000336B1 EP 78100184 A EP78100184 A EP 78100184A EP 78100184 A EP78100184 A EP 78100184A EP 0000336 B1 EP0000336 B1 EP 0000336B1
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EP
European Patent Office
Prior art keywords
pyrimidin
trimethoxybenzyl
amino
sulfanilamido
methyl
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Expired
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EP78100184A
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German (de)
English (en)
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EP0000336A1 (fr
Inventor
Peter Dr. Scharwaechter
Klaus Dr. Gutsche
Wilhelm Dr. Kohlmann
Gerd Dr. Kroemer
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BASF SE
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BASF SE
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Publication date
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Publication of EP0000336A1 publication Critical patent/EP0000336A1/fr
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Classifications

    • 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
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim

Definitions

  • the invention relates to amidino-benzylpyrimidines of the general formula I.
  • R 1 , R 2 and R 3 which may be the same or different from one another, are hydrogen, methyl, methoxy or chlorine
  • R 4 is alkyl having 1 to 6 carbon atoms or benzyl
  • R 5 and R 6 are the same or can be different from one another, hydrogen, lower alkyl having 1 to 4 carbon atoms, trimethoxybenzyl, benzyl or phenyl, cyclohexyl, adamantyl or furfuryl or one of the radicals R 5 or R 6 the grouping ⁇ C 6 H 4 ⁇ SO 4 ⁇ NH ⁇ R 7 means, where R 7 represents the rest or the pyrimidin-2-yl-, 4-methyl-pyrimidin-2-yl, 5-methyt-pyrimidin-2-yl, 5-isopropyl-pyrimidin-2-yl, -5-methoxy-pyrimidin-2-yl, 6-me
  • Suitable acids for the formation of pharmacologically acceptable salts are hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, acetic acid, lactic acid, citric acid and salicylic acid.
  • R 1 , R 2 and R 3 are preferably in the 3, 4 and 5 positions of the benzene ring.
  • R 4 is a lower alkyl radical having 1 to 4 carbon atoms or the benzyl radical.
  • R 1 , R 2 and R 3 are hydrogen, methyl or methoxy are further preferred, and of these particularly preferred are those in which R 1 , R 2 and R 3 are in the Positions 3, 4 and 5 of the benzyl radical are located and are methoxy groups.
  • the compounds of the general formula I are antimicrobially active in diseases caused by bacteria and protozoa and, combined with sulfonamides, potentiate their antibacterial action. They can therefore be used, for example, for bacterial diseases of the respiratory organs, digestive organs and urinary tract as well as for throat, nose and ear infections and in general for systemic infectious diseases and malaria.
  • the compounds of the general formula and their salts can be combined with the sulfonamides mentioned by way of example in various mixing ratios, the ratio of compound general formula I to sulfonamide being able to vary from 1:10 to 5: 1. However, preferred mixing ratios are 1: 1 to 1: 5. As a rule, 20 to 550 mg of an active ingredient of the general formula I are suitable as doses.
  • These compounds can be prepared with or without a solvent.
  • suitable solvents are pyridine, ethanol or water or mixtures of these solvents.
  • the reaction temperatures are between 0 and 150 ° C, preferably between 20 and 120 ° C or at temperatures up to the boiling point of the solvent used.
  • the invention accordingly also relates to chemotherapeutic agents which, in addition to conventional carriers and diluents, contain a compound of the general formula I, in particular in combination with a sulfonamide, as active ingredients, and the use of the compounds of the general formula I as sulfonamide potentiators.
  • chemotherapeutic agents or preparations are produced in a known manner with the usual carriers or diluents and the commonly used pharmaceutical-technical auxiliaries in accordance with the desired type of application.
  • the preferred preparations are in a dosage form which is suitable for oral administration.
  • Dosage forms of this type are, for example, tablets, film-coated tablets, dragees, capsules, pills, powders, solutions or suspensions.
  • the active ingredients are mixed with corn starch and granulated with an aqueous gelatin solution.
  • the dry granulate is sieved and mixed with the aggregates. Tablets are pressed from this mixture in the usual way.
  • the active ingredients are granulated with aqueous gelatin solution and, after drying, are mixed with corn starch, talc and magnesium stearate. Tablets are pressed from this mixture in the usual way.
  • the active ingredient is mixed with corn starch and granulated with aqueous gelatin solution.
  • the dry granulate is sieved and mixed with the aggregates. Tablets are pressed from this mixture in the usual way.
  • the active ingredient is granulated with aqueous gelatin solution and, after drying, mixed with IV starch, talc and magnesium stearate. Tablets are pressed from this mixture in the usual way.
  • the finely ground active ingredients are suspended in the aqueous tylose mucus. Then all other ingredients are added in succession with stirring. Finally, make up to 100.0 with water.
  • the finely ground active ingredient is suspended in the aqueous tylose mucus. Then all other ingredients are added in succession with stirring. Finally, make up to 100.0 with water.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Claims (7)

1. Amidino-benzylpyrimidines de formule générale I
Figure imgb0022
dans laquelle
R1, R2 et R3, qui peuvent être identiques ou différents, représentent de l'hydrogène, un groupe méthyle ou méthoxy ou du chlore, R4 est un reste alkyle en C1 à C6 ou un reste benzyle et R5 et R6, qui peuvent être identiques ou différents, représentent de l'hydrogène, un reste alkyle infer- ieur en C1 à C4, un reste triméthoxybenzyle, benzyle ou phényle, un reste cyclohexyle, adaman- tyle ou furfuryle, ou l'un des restes R5 et R6 représente le groupement ―C6H4―SO2―NH―R7 dans lequel R7 désigne le reste
Figure imgb0023
ou le reste pyrimidine-2-yle, 4-méthyl-pyrimidine-2-yle, 5-méthyl-pyrimidine-2-yle, 5-isopropyl- pyrimidine-2-yle, 5-méthoxy-pyrimidine-2-yle, 6-méthoxy-pyridazine-3-yle, 3-méthoxy-pyrazine-2-yle, 5-méthyl-isoxazol-3-yle ou 2-pyridinyle, ou R5 et R6 forment, simultanément avec l'azote sur lequel ils sont fixés, un hétérocycle saturé de 5 à 7 chaînons pouvant contenir, le cas échéant, un atome d'oxygène ou le groupe N-Y dans lequel Y représente un reste méthyle, benzyle ou phényle,

ainsi que leurs sels pharmacologiquement sans inconvénients pour l'individu, obtenus par réaction avec des acides couramment utilisés à cette fin.
2. N - [4 - Amino - 5 - (3,4,5 - triméthoxybenzyl) - pyrimidine - 2 - yl] - N',N' - (3 - aza - 3 - phényl - pentaméthylène) - acétamidine, ainsi que ses sels pharmacologique ment sans inconvénients pour l'individu, obtenus par réaction avec des acides couramment utilisés à cette fin.
3. N - [4 - Amino - 5 - (3,4,5 - triméthoxybenzyl) - pyrimidine - 2 - yl] - N' - [4 - (5 - méthoxypyrimidine - 2 - yl) - sulfamido] - phényl - acétamidine, ainsi que ses sels pharmacologiquement sans inconvénients pour l'individu, obtenus par réaction avec des acides couramment utilisés à cette fin.
4. N - [4 - Amino - 5 - (3,4,5 - triméthoxybenzyl) - pyrimidine - 2 - yl] - N' - [4 - (5 - méthyl - pyrimidine - 2 - yl) - sulfamido] - phényl - acétamidine, ainsi que ses sels pharmacologiquement sans inconvénients pour l'individu, obtenus par réaction avec des acides couramment utilisés à cette fin.
5. N - [4 - Amino - 5 - (3,4,5 - triméthoxybenzyl) - pyrimidine - 2 - yl] - N' - [4 - pyrimidine - 2 - yl) - sulfamido] - phényl - acétamidine, ainsi que ses sels pharmacologiquement sans inconvénients pour l'individu, obtenus par réaction avec des acides couramment utilisés à cette fin.
6. Procédé de préparation des composés selon l'une des revendications 1 à 5, caractérisé par le fait qu'on fait réagir, le cas échéant en présence d'un solvant, un composé de formule générale Il
Figure imgb0024
dans laquelle R1, R2, R3 et R4 ont la même signification que dans la formule générale I, R8 représentant un reste alkyle inférieur en C1 à C4 ou un reste benzyle, avec une amine de formule générale III
Figure imgb0025
dans laquelle R5 et R6 ont la même signification que dans la formule générale 1 et, si désiré, on transforme le composé ainsi obtenu en un sel pharmacologiquement sans inconvénients pour l'individu, obtenu par réaction avec des acides couramment utilisés à cette fin.
7. Produits pharmaceutiques contenant un composé selon les revendications 1 à 5, le cas échéant en association avec un sulfamide à effet anti-bactérien, et des supports solides ou liquides non toxiques, thérapeutiquement sans inconvénients pour lesdits produits et l'individu, ainsi que des produits auxiliaires galéniques.
EP78100184A 1977-07-15 1978-06-19 N-benzylpyrimidinyl-amidines, procédé pour leur préparation et médicaments les contenant Expired EP0000336B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE2732029 1977-07-15
DE19772732029 DE2732029A1 (de) 1977-07-15 1977-07-15 Neue amidino-benzylpyrimidine, verfahren zu ihrer herstellung und diese enthaltende arzneimittel

Publications (2)

Publication Number Publication Date
EP0000336A1 EP0000336A1 (fr) 1979-01-24
EP0000336B1 true EP0000336B1 (fr) 1981-04-15

Family

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Family Applications (1)

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EP78100184A Expired EP0000336B1 (fr) 1977-07-15 1978-06-19 N-benzylpyrimidinyl-amidines, procédé pour leur préparation et médicaments les contenant

Country Status (15)

Country Link
EP (1) EP0000336B1 (fr)
JP (1) JPS5419986A (fr)
AR (1) AR227759A1 (fr)
AT (1) AT360999B (fr)
AU (1) AU520820B2 (fr)
CA (1) CA1129410A (fr)
DE (2) DE2732029A1 (fr)
DK (1) DK143273C (fr)
FI (1) FI782221A (fr)
HU (1) HU179408B (fr)
IE (1) IE47022B1 (fr)
IL (1) IL55063A0 (fr)
IT (1) IT1096976B (fr)
NO (1) NO782455L (fr)
ZA (1) ZA784012B (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2730468A1 (de) * 1977-07-06 1979-01-18 Basf Ag Neue n-pyrimidinyl-imidsaeureester, verfahren zu ihrer herstellung und diese enthaltende arzneimittel
US4333936A (en) * 1978-07-03 1982-06-08 Basf Aktiengesellschaft Novel amidino-benzylpyrimidines, processes for their manufacture and antibacterial and antiprotozoal use thereof
DE3045720A1 (de) * 1980-12-04 1982-07-08 Basf Ag, 6700 Ludwigshafen N-pyrimidinyl-carbaminsaeureester, verfahren zu ihrer herstellung und diese enthaltende arzneimittel
JPS5915110U (ja) * 1982-07-22 1984-01-30 クラリオン株式会社 定電圧回路
JPH0618012B2 (ja) * 1983-01-25 1994-03-09 セイコーエプソン株式会社 定電圧回路

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4849791A (fr) * 1971-10-26 1973-07-13

Also Published As

Publication number Publication date
AT360999B (de) 1981-02-10
ATA513078A (de) 1980-07-15
IE47022B1 (en) 1983-11-30
IT7825382A0 (it) 1978-07-05
AU3790378A (en) 1980-01-17
IE781354L (en) 1979-01-15
FI782221A (fi) 1979-01-16
IL55063A0 (en) 1978-09-29
ZA784012B (en) 1979-08-29
DK143273B (da) 1981-08-03
DE2732029A1 (de) 1979-02-01
IT1096976B (it) 1985-08-26
HU179408B (en) 1982-10-28
EP0000336A1 (fr) 1979-01-24
DE2860614D1 (en) 1981-05-07
AR227759A1 (es) 1982-12-15
NO782455L (no) 1979-01-16
CA1129410A (fr) 1982-08-10
JPS5419986A (en) 1979-02-15
DK315878A (da) 1979-01-16
AU520820B2 (en) 1982-03-04
DK143273C (da) 1981-11-30

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