BE903746A - COMPOUND WITH ANTIMICROBIAL ACTIVITY, ITS PREPARATION AND PHARMACEUTICAL FORMS CONTAINING THE SAME. - Google Patents
COMPOUND WITH ANTIMICROBIAL ACTIVITY, ITS PREPARATION AND PHARMACEUTICAL FORMS CONTAINING THE SAME. Download PDFInfo
- Publication number
- BE903746A BE903746A BE0/215934A BE215934A BE903746A BE 903746 A BE903746 A BE 903746A BE 0/215934 A BE0/215934 A BE 0/215934A BE 215934 A BE215934 A BE 215934A BE 903746 A BE903746 A BE 903746A
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- Belgium
- Prior art keywords
- oxy
- compound
- preparation
- emi
- antimicrobial activity
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Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 150000001875 compounds Chemical class 0.000 title claims description 11
- 230000000845 anti-microbial effect Effects 0.000 title claims description 4
- -1 1- (2,4-Dichloro-beta - ((2,4-dichlorobenzyl) oxy) phenethyl) -1- ((dihydrocinnamoyl) oxy) methylimidazolium chloride Chemical compound 0.000 claims abstract description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 4
- 230000000843 anti-fungal effect Effects 0.000 claims description 3
- 229940121375 antifungal agent Drugs 0.000 claims description 3
- WHOXQNQYEQVPEL-UHFFFAOYSA-N 2,4-dichloro-1-[[2-chloro-1-(2,4-dichlorophenyl)ethoxy]methyl]benzene Chemical compound C=1C=C(Cl)C=C(Cl)C=1C(CCl)OCC1=CC=C(Cl)C=C1Cl WHOXQNQYEQVPEL-UHFFFAOYSA-N 0.000 claims description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 2
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 abstract 1
- 208000035143 Bacterial infection Diseases 0.000 abstract 1
- 208000022362 bacterial infectious disease Diseases 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 230000002070 germicidal effect Effects 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- QLACLEPYLWLNTD-UHFFFAOYSA-N dihydrocinnamic acid Natural products COc1ccc(CCC(O)=O)c(O)c1OC QLACLEPYLWLNTD-UHFFFAOYSA-N 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000000050 nutritive effect Effects 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 206010040872 skin infection Diseases 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- JDIIGWSSTNUWGK-UHFFFAOYSA-N 1h-imidazol-3-ium;chloride Chemical compound [Cl-].[NH2+]1C=CN=C1 JDIIGWSSTNUWGK-UHFFFAOYSA-N 0.000 description 1
- KBMWRDHROVTFDI-UHFFFAOYSA-N 2,4-dichloro-1-(ethoxymethyl)benzene Chemical compound CCOCC1=CC=C(Cl)C=C1Cl KBMWRDHROVTFDI-UHFFFAOYSA-N 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 238000009631 Broth culture Methods 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000011872 intimate mixture Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 238000009629 microbiological culture Methods 0.000 description 1
- 238000012009 microbiological test Methods 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000012056 semi-solid material Substances 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Chlorure de 1-(2,4-Dichloro-beta-((2,4-dichlorobenzyl)oxy)phénéthyl) -1- ((dihydrocinnamoyl)oxy)méthylimidazolium de formule I:son procédé de préparation en faisant réagir le 1-((dihydrocinnamoyl)oxy) - methylimidazole avec le 1-chloro-2-(2,4-dichlorophényl) -2- ((2,4-dichlorobenzyl)oxy)ethone. Application dans le traitement des infections entanées mycotiques ou bactériennes, des maladies de la cavité oro-pharyngale et du tractus gastro-intestinal.1- (2,4-Dichloro-beta - ((2,4-dichlorobenzyl) oxy) phenethyl) -1- ((dihydrocinnamoyl) oxy) methylimidazolium chloride of formula I: its preparation process by reacting 1- ( (dihydrocinnamoyl) oxy) - methylimidazole with 1-chloro-2- (2,4-dichlorophenyl) -2- ((2,4-dichlorobenzyl) oxy) ethone. Application in the treatment of entrained mycotic or bacterial infections, diseases of the oropharyngeal cavity and the gastrointestinal tract.
Description
"Composé à activité antimicrobienne, sa préparation et formes pharmaceutiques en contenant" "Composé à activité antimicrobienne, sa préparation et formes pharmaceutiques en contenant".
La présente invention est relative au composé formé
<EMI ID=1.1>
à la formule :
<EMI ID=2.1>
Le composé ci-dessus se prépare en faisant réagir
<EMI ID=3.1>
de formule III, suivant le schéma ci-après :
<EMI ID=4.1>
<EMI ID=5.1>
A titre de variante, le composé (I) peut être préparé <EMI ID=6.1>
imidazole, de formule IV, avec l'ester chlorométhylique de l'acide dihydrocinnamique de formule V selon le schéma suivant :
<EMI ID=7.1>
Schéma II
Les exemples suivants sont donnés à titre d'illustration de l'invention.
<EMI ID=8.1>
[(2,4-dichlorobenzyl)oxy]-éthane.
Un mélange intime de l-[(dihydrocinnamoyl)oxy]méthylimidazole (1,61 g; 7,0 mmoles) et de 1-chloro-2-(2,4-dichlorophényl)-2[(2,4-dichlorobenzyl)oxy]éthane (2,69 g; 7,0 mmoles) est chauffé
à 70[deg.]C pendant 1-2 heures. Il se forme une masse dense vitreuse qui est dissoute dans un mélange d'éthanol et d'éther diéthylique 1/2, à partir duquel, par évaporation, le chlorure d'imidazolium cristallise. On recueille le produit sur buchner, on le lave sur filtre avec un mélange d'éther diéthylique et d'acétate d'éthyle 2/1 et on dessèche. Le produit pur obtenu présente les caractéristiques suivantes :
Aspect : poudre microcristalline blanche
Point de fusion : 129-133[deg.]C(non corrigé).
Solubilité: soluble dans l'éthanol, le méthanol, les solvants chlorurés; peu soluble dans l'eau.
<EMI ID=9.1>
C H N
Calculé % 54,70 4,10 4,55 Trouvé % 54,62 4,15 4,52
<EMI ID=10.1>
7,1-7,6 (m, 13H: aromatiques).
Exemple 2.
<EMI ID=11.1>
lique de l'acide dihydrocinnamique.
En opérant de façon analogue à l'Exemple
<EMI ID=12.1>
benzyl)oxy]phénéthyl]imidazole (3,0 g; 7,21 mmoles) et l'ester chlorométhylique de l'acide dihydrocinnamique (1,42 g; 7,21 mmoles), on obtient le produit ayant les mêmes caractéristiques chimiques et physico-chimiques que celle obtenues dans l'Exemple 1 (point de fusion, point de fusion mixte, spectre IR).
Le composé de la formule I, qui ci-après est désigné pour la brièveté par le sigle de laboratoire PU 062, montre une activité antifongique et germicide évidente à large spectre, en agissant soit sur les levures et les moisissures, soit sur les bactéries gram-positives ou gram-négatives, en égalant ou surpassant l'activité du miconazol pris comme témoin de comparaison.
Les essais microbiologiques qui sont présentées ci-après démontrent une telle activité.
Détermination de la concentration inhibitrice minimale (C.I.M.).
On a déterminé la concentration minimale
à laquelle une substance germicide inhibe la croissance ou est mortelle pour les micro-organismes pris en considération. On a préparé un nombre approprié de dilutions du produit germicide, ces dilutions étant ensuite inoculées avec les micro-organismes préalablement choisis. Après une période d'incubation, on calcule la valeur C.I.M.On a utilisé les terrains de culture suivants : Mueller et Hinton Agar (Merck). On a utilisé des souches microbiennes provenant de diverses collections nationales et internationales. Les souches ont été conservées au réfrigérateur sur des cultures inclinées d'agar nutritif à la température d'environ 5[deg.]C.
Deux jours avant l'expérience, les cultures microbiennes ont été inoculées dans un terrain liquide de bouillon nutritif ou dans un autre terrain lorsque la souche l'exige; après incubation on les a transplantées dans de nouvelles éprouvettes de bouillon nutritif et on les alaissées se développer jusqu'à la première phase stationnaire de croissance. Les cultures en bouillon sont ensuite diluées avec une solution physiologique jusqu'à un trouble standard correspondant à environ 10 cellules par ml. Pour la préparation des plaques d'agar médicamentaire, on a utilisé une solutionmère contenant 1 mg de la substance à l'examen par ml de solvant. A partir de la solution-mère, on a effectué des dilutions dans de l'agar Mueller-Hinton et on a obtenu les concentrations suivantes
<EMI ID=13.1>
tions ont été effectuées grâce à un inoculateur multiple "Multipoint inoculator". Des plaques garnies des échantillons de bactéries ont été incubées à 35[deg.]C pendant 48 heures; les plaques essayées avec les champignons ont été incubées à 22[deg.]C pendant 5 jours. Pendant la période prescrite d'incubation, on a examiné les plaques en enregistrant, pour chaque micro-organisme, la concentration minimale de l'antiseptique capable d'en inhiber la croissance.
Les résultats obtenus sont présentés dans le tableau suivant.
TABLEAU A.
<EMI ID=14.1>
<EMI ID=15.1>
<EMI ID=16.1>
que l'on a obtenues avec le composé PU 062 sont plus favorables ou égales à celles du miconazol pour tous les micro-organismes pris en considération, de sorte que l'on peut conclure en affirmant que le PU 062 a démontré qu'il présente une activité antifongique/germicide élevée, supérieure à celle manifestée par le miconazol.
Font également partie de la présente invention, les formes pharmaceutiques contenant, comme principe actif, le composant répondant à la formule I. Il peut s'agir de matières solides, de matières semi-solides ou de liquides, destinés à une administration par voie orale, par exemple des capsules, des comprimés, des dragées, des sirops, des gels pour voie buccale, que l'on prépare avec des excipients, des agents aromatisants, des solvants, etc., d'une utilisation habituelle dans la technique pharmaceutique;
ou bien ces mêmes matières ou liquides peuvent être destinées à des applications topiques, par exemple sous forme de poudres, de lotions, de pommades, d'onguents, de laits, de gels, de teintures dermatologiques ou de tablettes, d'ovules, de pommades vaginales et aussi de savons médicaux, toutes ces formes posologiques étant réalisées avec les procédés et les composants habituels d'un usage courant dans la technique pharmaceutique.
De telles formes pharmaceutiques trouvent une application dans toutes les formes morbides entretenues par des infections cutanées mycotiques, simples ou mixtes, par des infections cutanées bactériennes primitives et secondaires, dans le traitement curatif et prophylactique des maladies de la cavité oro-pharyngale et du tractus gastro-intestinal, ainsi que dans les infections vulvo-vaginales.
REVENDICATIONS.
1. Chlorure de 1-[ 2,4-Dichloro-�-[(2,4-dichloro-
<EMI ID=17.1>
de formule I :
<EMI ID=18.1>
2. Procédé de préparation du composé suivant
"Compound with antimicrobial activity, its preparation and pharmaceutical forms containing it" "Compound with antimicrobial activity, its preparation and pharmaceutical forms containing it".
The present invention relates to the compound formed
<EMI ID = 1.1>
to the formula:
<EMI ID = 2.1>
The above compound is prepared by reacting
<EMI ID = 3.1>
of formula III, according to the diagram below:
<EMI ID = 4.1>
<EMI ID = 5.1>
Alternatively, compound (I) can be prepared <EMI ID = 6.1>
imidazole, of formula IV, with the chloromethyl ester of dihydrocinnamic acid of formula V according to the following scheme:
<EMI ID = 7.1>
Diagram II
The following examples are given by way of illustration of the invention.
<EMI ID = 8.1>
[(2,4-dichlorobenzyl) oxy] -ethane.
An intimate mixture of l - [(dihydrocinnamoyl) oxy] methylimidazole (1.61 g; 7.0 mmol) and 1-chloro-2- (2,4-dichlorophenyl) -2 [(2,4-dichlorobenzyl) oxy ] ethane (2.69 g; 7.0 mmol) is heated
at 70 [deg.] C for 1-2 hours. A dense glassy mass is formed which is dissolved in a mixture of ethanol and 1/2 diethyl ether, from which, by evaporation, the imidazolium chloride crystallizes. The product is collected on a buchner, washed on a filter with a mixture of diethyl ether and ethyl acetate 2/1 and dried. The pure product obtained has the following characteristics:
Appearance: white microcrystalline powder
Melting point: 129-133 [deg.] C (not corrected).
Solubility: soluble in ethanol, methanol, chlorinated solvents; poorly soluble in water.
<EMI ID = 9.1>
C H N
Calculated% 54.70 4.10 4.55 Found% 54.62 4.15 4.52
<EMI ID = 10.1>
7.1-7.6 (m, 13H: aromatic).
Example 2.
<EMI ID = 11.1>
dihydrocinnamic acid.
By operating in a manner analogous to the Example
<EMI ID = 12.1>
benzyl) oxy] phenethyl] imidazole (3.0 g; 7.21 mmol) and the chloromethyl ester of dihydrocinnamic acid (1.42 g; 7.21 mmol), the product having the same chemical characteristics is obtained and physicochemical than that obtained in Example 1 (melting point, mixed melting point, IR spectrum).
The compound of formula I, which hereinafter is designated for brevity by the laboratory acronym PU 062, shows obvious broad spectrum antifungal and germicidal activity, acting either on yeasts and molds, or on gram bacteria. -positive or gram-negative, equaling or surpassing the activity of miconazol taken as a comparison control.
The microbiological tests which are presented below demonstrate such activity.
Determination of the minimum inhibitory concentration (C.I.M.).
We determined the minimum concentration
to which a germicidal substance inhibits growth or is fatal for the microorganisms under consideration. An appropriate number of dilutions of the germicidal product were prepared, these dilutions then being inoculated with the microorganisms previously chosen. After an incubation period, the C.I.M. value is calculated. The following culture grounds were used: Mueller and Hinton Agar (Merck). Microbial strains from various national and international collections have been used. The strains were stored in the refrigerator on tilted cultures of nutritive agar at a temperature of about 5 [deg.] C.
Two days before the experiment, the microbial cultures were inoculated in a liquid soil of nutritive broth or in another ground when the strain requires it; after incubation they were transplanted into new test tubes of nutritive broth and they were left to develop until the first stationary phase of growth. The broth cultures are then diluted with physiological solution to a standard cloudiness corresponding to about 10 cells per ml. For the preparation of the medicinal agar plates, a stock solution containing 1 mg of the test substance per ml of solvent was used. From the stock solution, dilutions were made in Mueller-Hinton agar and the following concentrations were obtained
<EMI ID = 13.1>
tions were carried out using a "Multipoint inoculator" multiple inoculator. Plates filled with bacteria samples were incubated at 35 [deg.] C for 48 hours; the plates tested with the mushrooms were incubated at 22 [deg.] C for 5 days. During the prescribed incubation period, the plates were examined by recording, for each microorganism, the minimum concentration of antiseptic capable of inhibiting its growth.
The results obtained are presented in the following table.
TABLE A.
<EMI ID = 14.1>
<EMI ID = 15.1>
<EMI ID = 16.1>
that have been obtained with the compound PU 062 are more favorable or equal to those of miconazol for all the microorganisms taken into account, so that it can be concluded by affirming that the PU 062 has demonstrated that it has a high antifungal / germicidal activity, higher than that manifested by miconazol.
Also forming part of the present invention, the pharmaceutical forms containing, as active principle, the component corresponding to formula I. It can be solid materials, semi-solid materials or liquids, intended for oral administration. , for example capsules, tablets, dragees, syrups, gels for the oral route, which are prepared with excipients, flavoring agents, solvents, etc., of usual use in the pharmaceutical technique;
or these same materials or liquids can be intended for topical applications, for example in the form of powders, lotions, ointments, ointments, milks, gels, dermatological tinctures or tablets, ova, vaginal ointments and also medical soaps, all these dosage forms being produced with the usual methods and components commonly used in pharmaceutical technology.
Such pharmaceutical forms find application in all the morbid forms maintained by mycotic skin infections, single or mixed, by primary and secondary bacterial skin infections, in the curative and prophylactic treatment of diseases of the oropharyngeal cavity and of the gastrointestinal tract -intestinal, as well as in vulvovaginal infections.
CLAIMS.
1. 1- [2,4-Dichloro chloride - & - [(2,4-dichloro
<EMI ID = 17.1>
of formula I:
<EMI ID = 18.1>
2. Process for the preparation of the following compound
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT8423796A IT1213251B (en) | 1984-11-29 | 1984-11-29 | Antimicrobial quat chloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BE903746A true BE903746A (en) | 1986-03-14 |
Family
ID=11210066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BE0/215934A BE903746A (en) | 1984-11-29 | 1985-11-29 | COMPOUND WITH ANTIMICROBIAL ACTIVITY, ITS PREPARATION AND PHARMACEUTICAL FORMS CONTAINING THE SAME. |
Country Status (2)
| Country | Link |
|---|---|
| BE (1) | BE903746A (en) |
| IT (1) | IT1213251B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0195116A2 (en) * | 1985-03-19 | 1986-09-24 | ISTITUTO FARMACO BIOLOGICO RIPARI GERO S.r.l. | Compound having antibacterial and antimycotic activities, preparation thereof and pharmaceutical compositions containing it |
-
1984
- 1984-11-29 IT IT8423796A patent/IT1213251B/en active
-
1985
- 1985-11-29 BE BE0/215934A patent/BE903746A/en not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0195116A2 (en) * | 1985-03-19 | 1986-09-24 | ISTITUTO FARMACO BIOLOGICO RIPARI GERO S.r.l. | Compound having antibacterial and antimycotic activities, preparation thereof and pharmaceutical compositions containing it |
| EP0195116A3 (en) * | 1985-03-19 | 1987-06-03 | Ripari Gero Ist Farm Biolog | Compound having antibacterial and antimycotic activities, preparation thereof and pharmaceutical compositions containing it |
Also Published As
| Publication number | Publication date |
|---|---|
| IT1213251B (en) | 1989-12-14 |
| IT8423796A0 (en) | 1984-11-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RE | Patent lapsed |
Owner name: PULITZER ITALIANA S.P.A. Effective date: 19931130 |