DK163058B - TRIAZOLETHANOL DERIVATIVE, PHARMACEUTICAL PREPARATIONS CONTAINING THE COMPOUND, THE COMPOUND FOR USE AS A MEDICINE, AND PROCEDURE FOR THE PREPARATION OF THE COMPOUND - Google Patents
TRIAZOLETHANOL DERIVATIVE, PHARMACEUTICAL PREPARATIONS CONTAINING THE COMPOUND, THE COMPOUND FOR USE AS A MEDICINE, AND PROCEDURE FOR THE PREPARATION OF THE COMPOUND Download PDFInfo
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- DK163058B DK163058B DK318185A DK318185A DK163058B DK 163058 B DK163058 B DK 163058B DK 318185 A DK318185 A DK 318185A DK 318185 A DK318185 A DK 318185A DK 163058 B DK163058 B DK 163058B
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/08—Compounds containing oxirane rings with hydrocarbon radicals, substituted by halogen atoms, nitro radicals or nitroso radicals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
iin
DK 163058 BDK 163058 B
Den foreliggende opfindelse angår et hidtil ukendt triazolethanol-derivat, nemlig R(-) -a- (4-chlorphenyl) -a-(1-cyclopropyl-l-methyleth-yl)-1H-1,2,4-triazol-l-ethanol, dvs. den venstredrej ende enantiomer af forbindelsen med formlen IThe present invention relates to a novel triazolethanol derivative, namely R (-) -a- (4-chlorophenyl) -a- (1-cyclopropyl-1-methylethyl) -1H-1,2,4-triazole-1 -ethanol, i.e. the left-hand end enantiomer of the compound of formula I
OH CH, 5 M-f<iOH CH, 5 M-f <i
Cl eller salte eller metalcomplexer heraf, samt en fremgangsmåde til fremstilling deraf, farmaceutiske præparater indeholdende forbindelsen og forbindelsen til anvendelse som lægemiddel, især som anti-mycotisk middel. Betegnelsen "vens tredrej ende" kan erstattes af 10 præfixetCl or salts or metal complexes thereof, and a process for their preparation, pharmaceutical compositions containing the compound and the compound for use as a drug, especially as an anti-mycotic agent. The term "friend's triple end" can be replaced by the prefix
Britisk patentskrift nr. 2.136.423-A og 2.064.520-A beskriver hver især en lang række triazol- og imidazolderivater, men nævner ikke specifikt (-)-enantiomeren ifølge opfindelsen eller dens fordelagtige antimycotiske egenskaber.British Patent Nos. 2,136,423-A and 2,064,520-A each disclose a wide variety of triazole and imidazole derivatives, but do not specifically mention the (-) enantiomer of the invention or its beneficial antimycotic properties.
15 Forbindelsen ifølge opfindelsen i fri form eller i salt- eller metal-complexform kan ifølge opfindelsen fås ved, at en forbindelse med den almene formel 11 {»—nThe compound of the invention in free form or in salt or metal complex form can be obtained according to the invention by a compound of the general formula 11
IIII
MM
hvor M er hydrogen, et metal eller en trialkylsilylgruppe, omsættes 20 med den venstredrej ende enantiomer af en forbindelse med formlen IIIwherein M is hydrogen, a metal or a trialkylsilyl group, 20 is reacted with the left-handed enantiomer of a compound of formula III
0 CH30 CH3
OL —C-C—AOL-C-C-A
2 I . N III2 I. N III
x CH3x CH3
DK 163058 BDK 163058 B
2 eller et reaktivt funktionelt derivat deraf, og den således vundne forbindelse udvindes i fri form eller i salt- eller metalcomplexform.2 or a reactive functional derivative thereof, and the compound thus obtained is recovered in free form or in salt or metal complex form.
Fremgangsmåden kan udføres på konventionel måde, fx som beskrevet i britisk patentskrift nr, 2.136.423-A eller i de nedenstående eksem-5 pier.The process can be carried out in a conventional manner, for example as described in British Patent Specification No. 2,136,423-A or in the examples below.
Forbindelsen ifølge opfindelsen fås i fri baseform eller i syreadditionssalt- eller metalcomplexform. Saltet eller metalcomplexerne kan på konventionel måde fås ud fra den tilsvarende frie form og omvendt.The compound of the invention is obtained in free base form or in acid addition salt or metal complex form. The salt or metal complexes can be obtained in the conventional manner from the corresponding free form and vice versa.
Forbindelserne ifølge opfindelsen kan isoleres fra reaktionsblandin-10 gen og oprenses ved i og for sig kendte metoder.The compounds of the invention can be isolated from the reaction mixture and purified by methods known per se.
For så vidt fremstillingen af udgangsmaterialerae ikke er beskrevet, . er de enten kendte eller kan fås analogt med fremgangsmåder beskrevet heri eller analogt med kendte fremgangsmåder.Insofar as the preparation of starting materials is not described,. are they known or can be obtained by analogy to methods described herein or analogous to known methods.
Forbindelserne ifølge opfindelsen har interessante biologiske, især 15 antimycotiske egenskaber og er derfor indiceret til anvendelse som lægemidler, især som antimycotiske midler. Den antimycotiske virkning kan fastslås ved tests in vitro, fx den serielle fortyndingstest in vitro på forskellige familier og arter af myceter såsom gærsvampe, skimmelsvampe og dermatophyter ved koncentrationer på fra ca. 0,4 20 Mg/ml til ca. 100 jig/ml samt ved tests in vivo, fx ved systemisk, peroral indgivelse af doser på fra ca. 0,4 mg/kg legemsvægt til 100 mg/kg legemsvægt til mus, der er blevet inficeret intravaginalt med Candida albicans.The compounds of the invention have interesting biological, especially 15 antimycotic properties and are therefore indicated for use as drugs, especially as antimycotic agents. The antimycotic effect can be ascertained by in vitro tests, for example, the in vitro serial dilution test on various families and species of mycets such as yeast fungi, molds and dermatophytes at concentrations of from ca. 0.4 mg / ml to approx. 100 µg / ml as well as in vivo tests, for example by systemic oral administration of doses of from ca. 0.4 mg / kg body weight to 100 mg / kg body weight in mice that have been intravaginally infected with Candida albicans.
En indiceret egnet daglig dosis er fx i området fra 70 til 2000 mg 25 indgivet fx i delte doser 1-4 gange daglig eller i retardform; doseringsformer, der er egnede til fx oral indgivelse, omfatter da fra 17,5 til 2000 mg, fortrinsvis 17,5-500 mg aktiv bestanddel.An indicated suitable daily dose is, for example, in the range of 70 to 2000 mg 25 administered, for example, in divided doses 1-4 times daily or in retarded form; dosage forms suitable for, for example, oral administration then comprise from 17.5 to 2000 mg, preferably 17.5 to 500 mg of active ingredient.
Det er ved sådanne tests blevet fastslået, at den venstredrej ende enantiomer ifølge opfindelsen udviser en betydeligt bedre aktivitet 30 end det tilsvarende racemat eller den højredrejende (+)-enantiomer.It has been established in such tests that the left-handed enantiomer of the invention exhibits a significantly better activity than the corresponding racemate or right-handed (+) enantiomer.
Ved en sammenligningstests under anvendelse af Candida vaginitismo-In a comparison test using Candida vaginitismo
DK 163058 BDK 163058 B
3 dellen i rotter blev der observeret følgende helbredelsesprocenter efter 2 perorale indgivelser.In the 3 subgroup in rats, the following healing percentages were observed after 2 oral administrations.
Dosis (mg/kg) Racemat (-)-enantiomer (+)-enantiomer 5 1,6 93% 93% 2% 0,8 73% 84% 3% 0,4 41% 72% 0%Dose (mg / kg) Racemate (-) - Enantiomer (+) - Enantiomer 5 1.6 93% 93% 2% 0.8 73% 84% 3% 0.4 41% 72% 0%
Forbindelsen ifølge opfindelsen kan fremstilles og anvendes i fri 10 baseform eller i form af farmaceutisk acceptable salte (syreadditionssalte eller alkoholater). I almindelighed udviser saltformerne den samme grad af aktivitet som de fri baseformer. Syrer, der kan anvendes ved fremstilling af syreadditionssaltformer, omfatter eksempelvis saltsyre, brombrintesyre, svovlsyre, salpetersyre, fumarsyre 15 og naphthalen-1,5-disulfonsyrer.The compound of the invention can be prepared and used in free base form or in the form of pharmaceutically acceptable salts (acid addition salts or alcoholates). In general, the salt forms exhibit the same degree of activity as the free base forms. Acids which can be used in the preparation of acid addition salt forms include, for example, hydrochloric, hydrobromic, sulfuric, nitric, fumaric and naphthalene-1,5-disulfonic acids.
Forbindelserne kan blandes med konventionelle farmaceutisk acceptable diluenter og bærere og eventuelt andre excipienser og administreres oralt, topisk, intravenøst eller parenteralt i former såsom tabletter, kapsler, cremer, tinkturer eller injicerbare præparater.The compounds can be mixed with conventional pharmaceutically acceptable diluents and carriers and optionally other excipients and administered orally, topically, intravenously or parenterally in forms such as tablets, capsules, creams, tinctures or injectable preparations.
2Q Sådanne præparater udgør også en del af opfindelsen.Such compositions also form part of the invention.
Forbindelserne ifølge opfindelsen i fri form eller i landbrugsmæssig acceptabel salt- eller metalcomplexform er også egnede til bekæmpelse af phytopatogene svampe. Denne fungicide virkning kan bl.a. påvises ved tests in vivo mod Uromyces appendicula tus (bønnerust) på pral-25 bønner samt mod andre rustsvampe (fx Hemileia, Puccinia) på kaffe, hvede, hør og prydplanter (fx pelargonie, løvemund); og mod iKry siphe cichoracearum på agurker samt mod andre pulver-meldugarter (fx E. graminis f. sp. tritici., E. gram. f. sp. hordei, Podosphaera leu-cotricha, Uncinula recator) på hvede, byg, æble og vinstokke. 1The compounds of the invention in free form or in agricultural acceptable salt or metal complex form are also suitable for the control of phytopathogenic fungi. This fungicidal effect may include is demonstrated by tests in vivo against Uromyces appendicula tus (bean roast) on barley beans and against other rust fungi (e.g. Hemileia, Puccinia) on coffee, wheat, flax and ornamental plants (e.g. geranium, lioness); and against iKry siphe cichoracearum on cucumbers and against other powdery mildew species (e.g. E. graminis f. sp. tritici., E. gram. f. sp. hordei, Podosphaera leu-cotricha, Uncinula recator) on wheat, barley, apple and vines. 1
Opfindelsen illustreres ved følgende eksempel.The invention is illustrated by the following example.
EKSEMPEL 1 4EXAMPLE 1 4
DK 163058 BDK 163058 B
(-)-a-(4-Chlorphenyl)-a-(1-cyclopropyl-l-methylethyl)-lH-l,2,4-tria-zol-1-ethanol 0(5 g (-)-2 - (4- chlorphenyl) -2-(1- cyclopropyl -1 -methylethyl) - oxiran 5 omrores ved stuetemperatur i 2 dage med triazolnatrium (fremstillet ud fra 0,29 g 1,2,4-triazol og 0,1 g NaH) i 5 ml tørt dimethylformamid. Den resulterende blanding inddampes i vakuum, og remanensen opløses i vand/dichlormethan. Den organiske fase isoleres, vaskes med vand, tørres over MgSO^ og koncentreres ved inddampning. Det således 10 vundne rå produkt kan oprenses ved omkrystallisation af n-hexan eller ved chromatografi på silicagel med ethylacetat. Der fås hvide kry- 20 staller, smeltepunkt 104-105°C, [ce] jj = -87,5°.(-) - α- (4-Chlorophenyl) -a- (1-cyclopropyl-1-methylethyl) -1H-1,2,4-triazol-1-ethanol O (5 g (-) - 2 - ( 4-Chlorophenyl) -2- (1-cyclopropyl-1-methylethyl) oxirane is stirred at room temperature for 2 days with triazole sodium (prepared from 0.29 g of 1,2,4-triazole and 0.1 g of NaH) in The resulting mixture is evaporated in vacuo and the residue is dissolved in water / dichloromethane, the organic phase is isolated, washed with water, dried over MgSO4 and concentrated by evaporation. The crude product thus obtained can be purified by recrystallization from n. -hexane or by chromatography on silica gel with ethyl acetate to give white crystals, mp 104-105 ° C, [ce] j = -87.5 °.
Den absolutte konfiguration af den venstredrej ende eller (-)-enantio-meren ifølge opfindelsen er "R", og forbindelsen kan derfor betegnes 15 R-(-)-a-(4-chlorphenyl)-a-(1-cyclopropyl-l-methylethyl)-1H-1,2,4-triazol-1-ethanol pThe absolute configuration of the left-hand or (-) enantiomer of the invention is "R", and the compound can therefore be designated R - (-) - α- (4-chlorophenyl) -α- (1-cyclopropyl-1) -methylethyl) -1H-1,2,4-triazole-1-ethanol p
ClCl
Udgangsmaterialet kan fremstilles på følgende måde: 20 a) 4-Chlor-a-(1-cyclopropyl-l-methylethyl) -a- (4-methylbenzosulfinyl) -methylbenzylalkohol 3,1 g R(+)-methyl-p-tolylsulfoxid i 75 ml tetrahydrofuran sættes ved-5°C dråbevis til en opløsning af lithiumdiisopropylamin i tetrahydrofuran (fremstillet ud fra 2,37 g diisopropylamin og 14,4 ml 1,6N 25 BuLi (hexan) i 120 ml tørt tetrahydrofuran) og blandingen omrøres i 1 time ved -5°C. Der tilsættes derefter 4,6 g 1-(4-chlorphenyl)-2-The starting material can be prepared as follows: a) 4-Chloro-α- (1-cyclopropyl-1-methylethyl) -α- (4-methylbenzosulfinyl) methylbenzyl alcohol 3.1 g of R (+) - methyl-p-tolylsulfoxide in 75 ml of tetrahydrofuran are added dropwise to a solution of lithium diisopropylamine in tetrahydrofuran (prepared from 2.37 g of diisopropylamine and 14.4 ml of 1.6N 25 BuLi (hexane) in 120 ml of dry tetrahydrofuran) dropwise at 1 ° C. hour at -5 ° C. 4.6 g of 1- (4-chlorophenyl) -2-
DK 163058 BDK 163058 B
5 cyclopropyl-2-methyl-propan-1-on, hvorefter temperaturen stiger til 0eC, og blandingen får lov at stige til stuetemperatur og behandles med 40 ml mættet vandigt NH4CI. Den organiske fase skilles fra, og den vandige fase ekstraheres med ethylacetat. De forenede organiske 5 faser tørres over MgS04 og koncentreres ved inddampning. Remanensen skilles fra ved chromatografi på silicagel med n-hexan/ethylacetat, hvilket giver de to diastereoisomerer A-l og A-2.5 cyclopropyl-2-methyl-propan-1-one, after which the temperature rises to 0 ° C and the mixture is allowed to rise to room temperature and treated with 40 ml of saturated aqueous NH 4 Cl. The organic phase is separated and the aqueous phase is extracted with ethyl acetate. The combined organic phases are dried over MgSO 4 and concentrated by evaporation. The residue is separated by chromatography on silica gel with n-hexane / ethyl acetate to give the two diastereoisomers A-1 and A-2.
20 A-l - farveløs olie, [a] D = +115’ (acetone) 20 A-2 - farveløs olie, [e] p = +48” (acetone) 10 b) (-)-4-Chlor-a-(1-cyclopropyl-1-methylethyl)-a-(4-methylphenyl)-thiomethylbenzylalkohol 0,75 g NaBIfy sættes langsomt portionsvis til 2,8 g af forbindelse A-l (jfr. a)) og 1,77 g C0CI2.6H2O i 120 ml tørt ethanol ved -10eC. Omrøringen fortsættes i 2 timer ved stuetemperatur, og der tilsættes 15 derefter 3N HCl, indtil den vandige fase bliver lyserød. Ekstraktion udføres ved hjælp af diethylether, og etherfasen vaskes med mættet vandigt NaCl, tørres over MgS04 og koncentreres ved inddampning. Det således vundne rå produkt kan oprenses ved chromatografi på silicagel 20 med toluen. Farveløs olie, [a] p - -15,7° (acetone).20 Al - colorless oil, [a] D = + 115 '(acetone) 20 A-2 - colorless oil, [e] p = +48' (acetone) 10 b) (-) - 4-Chloro-a- ( 1-Cyclopropyl-1-methylethyl) -a- (4-methylphenyl) -thiomethylbenzyl alcohol 0.75 g NaBIfy is slowly added portionwise to 2.8 g of compound Al (cf. a) and 1.77 g of COCl 2 ml of dry ethanol at -10 ° C. Stirring is continued for 2 hours at room temperature and then 3N HCl is added until the aqueous phase turns pink. Extraction is carried out by diethyl ether and the ether phase is washed with saturated aqueous NaCl, dried over MgSO 4 and concentrated by evaporation. The crude product thus obtained can be purified by chromatography on silica gel 20 with toluene. Colorless oil, [a] p - -15.7 ° (acetone).
20 c) (-)-2- (4-Chlorphenyl) -2- (1-cyclopropyl-1-methylethyl)oxiran 1,37 g triethyloxoniumtetrafluorborat sættes ved 0°C til 1 g (-)-4-chlor-α-(1-cyclopropyl-l-me thylethyl) -a- (4-methylphenyl) - thiomethylbenzylalkohol i 10 ml tørt dichlormethan, og blandingen omrøres i 2,5 time ved stuetemperatur. Efter tilsætning af 5 ml 10%'s vandig NaOH 25 omrøres der i 2,5 time ved stuetemperatur, og den organiske fase skilles fra. Denne vaskes med vand, tørres over MgS04 og koncentreres ved inddampning. Det således vundne rå produkt kan oprenses ved chromatografi på silicagel med toluen/n-hexan (1/1), hvilket giver 25 hvide krystaller, smeltepunkt 57-58°C, [a] p - -44° (acetone).C) (-) - 2- (4-Chlorophenyl) -2- (1-cyclopropyl-1-methylethyl) oxirane 1.37 g of triethyloxonium tetrafluoroborate are added at 0 ° C to 1 g of (-) - 4-chloro-α- (1-Cyclopropyl-1-methylethyl) -α- (4-methylphenyl) -thiomethylbenzyl alcohol in 10 ml of dry dichloromethane and the mixture is stirred for 2.5 hours at room temperature. After adding 5 ml of 10% aqueous NaOH 25, stir for 2.5 hours at room temperature and the organic phase is separated. This is washed with water, dried over MgSO 4 and concentrated by evaporation. The crude product thus obtained can be purified by chromatography on silica gel with toluene / n-hexane (1/1) to give 25 white crystals, mp 57-58 ° C, [α] p - -44 ° (acetone).
Claims (6)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3425848 | 1984-07-13 | ||
| DE3425848 | 1984-07-13 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK318185D0 DK318185D0 (en) | 1985-07-11 |
| DK318185A DK318185A (en) | 1986-01-14 |
| DK163058B true DK163058B (en) | 1992-01-13 |
| DK163058C DK163058C (en) | 1992-06-09 |
Family
ID=6240558
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK318185A DK163058C (en) | 1984-07-13 | 1985-07-11 | TRIAZOLETHANOL DERIVATIVE, PHARMACEUTICAL PREPARATIONS CONTAINING THE COMPOUND, THE COMPOUND FOR USE AS A MEDICINE AND PROCEDURE FOR THE PREPARATION OF THE COMPOUND |
Country Status (17)
| Country | Link |
|---|---|
| JP (1) | JPS6144878A (en) |
| AU (1) | AU582761B2 (en) |
| BE (1) | BE902837A (en) |
| CH (1) | CH668772A5 (en) |
| DE (1) | DE3524296C2 (en) |
| DK (1) | DK163058C (en) |
| FR (1) | FR2567515B1 (en) |
| GB (1) | GB2161483B (en) |
| IE (1) | IE58516B1 (en) |
| IL (1) | IL75774A (en) |
| IT (1) | IT1200087B (en) |
| LU (1) | LU86001A1 (en) |
| NL (1) | NL8501962A (en) |
| NZ (1) | NZ212718A (en) |
| PH (1) | PH23287A (en) |
| SE (1) | SE456679B (en) |
| ZA (1) | ZA855286B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH647513A5 (en) * | 1979-11-13 | 1985-01-31 | Sandoz Ag | TRIAZOLE DERIVATIVES, THEIR PRODUCTION AND USE. |
| JPS5697276A (en) * | 1979-11-13 | 1981-08-05 | Sandoz Ag | Alphaaaryll1hh1*2*44triazolee11ethanols |
| ZA817473B (en) * | 1980-11-19 | 1982-10-27 | Ici Plc | Triazole and imidazole compounds |
| CH658654A5 (en) * | 1983-03-04 | 1986-11-28 | Sandoz Ag | AZOLE DERIVATIVES, METHOD FOR THEIR PRODUCTION AND MEANS THAT CONTAIN THESE COMPOUNDS. |
-
1985
- 1985-07-04 CH CH2871/85A patent/CH668772A5/en not_active IP Right Cessation
- 1985-07-06 DE DE3524296A patent/DE3524296C2/en not_active Expired - Lifetime
- 1985-07-08 FR FR8510531A patent/FR2567515B1/en not_active Expired
- 1985-07-09 NL NL8501962A patent/NL8501962A/en active Search and Examination
- 1985-07-09 IT IT48324/85A patent/IT1200087B/en active
- 1985-07-09 BE BE1/011292A patent/BE902837A/en not_active IP Right Cessation
- 1985-07-11 IL IL75774A patent/IL75774A/en not_active IP Right Cessation
- 1985-07-11 PH PH32517A patent/PH23287A/en unknown
- 1985-07-11 AU AU44779/85A patent/AU582761B2/en not_active Expired
- 1985-07-11 SE SE8503443A patent/SE456679B/en not_active IP Right Cessation
- 1985-07-11 NZ NZ212718A patent/NZ212718A/en unknown
- 1985-07-11 IE IE174785A patent/IE58516B1/en not_active IP Right Cessation
- 1985-07-11 DK DK318185A patent/DK163058C/en not_active IP Right Cessation
- 1985-07-11 GB GB08517526A patent/GB2161483B/en not_active Expired
- 1985-07-12 JP JP60155017A patent/JPS6144878A/en not_active Expired - Lifetime
- 1985-07-12 ZA ZA855286A patent/ZA855286B/en unknown
- 1985-07-12 LU LU86001A patent/LU86001A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU582761B2 (en) | 1989-04-13 |
| IL75774A0 (en) | 1985-11-29 |
| FR2567515B1 (en) | 1988-09-09 |
| CH668772A5 (en) | 1989-01-31 |
| DK318185A (en) | 1986-01-14 |
| NZ212718A (en) | 1989-01-27 |
| DE3524296C2 (en) | 1994-08-25 |
| IE851747L (en) | 1986-01-13 |
| IL75774A (en) | 1989-12-15 |
| DK318185D0 (en) | 1985-07-11 |
| BE902837A (en) | 1986-01-09 |
| SE8503443D0 (en) | 1985-07-11 |
| DK163058C (en) | 1992-06-09 |
| DE3524296A1 (en) | 1986-01-16 |
| SE8503443L (en) | 1986-01-14 |
| PH23287A (en) | 1989-06-30 |
| LU86001A1 (en) | 1986-02-12 |
| IT1200087B (en) | 1989-01-05 |
| ZA855286B (en) | 1987-02-25 |
| GB8517526D0 (en) | 1985-08-14 |
| GB2161483B (en) | 1988-07-13 |
| AU4477985A (en) | 1986-01-16 |
| IT8548324A0 (en) | 1985-07-09 |
| SE456679B (en) | 1988-10-24 |
| NL8501962A (en) | 1986-02-03 |
| FR2567515A1 (en) | 1986-01-17 |
| IE58516B1 (en) | 1993-10-06 |
| GB2161483A (en) | 1986-01-15 |
| JPS6144878A (en) | 1986-03-04 |
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