GB2175899A - Azole derivatives - Google Patents

Azole derivatives Download PDF

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Publication number
GB2175899A
GB2175899A GB08612161A GB8612161A GB2175899A GB 2175899 A GB2175899 A GB 2175899A GB 08612161 A GB08612161 A GB 08612161A GB 8612161 A GB8612161 A GB 8612161A GB 2175899 A GB2175899 A GB 2175899A
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Prior art keywords
halogen
formula
compound
alkyl
compound according
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GB8612161D0 (en
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Maximilian Grassberger
Fritz Schaub
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Sandoz AG
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Sandoz AG
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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
    • 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
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • 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

Abstract

Azole derivatives of the formula I, <IMAGE> wherein R1 and R2 represent independently hydrogen, nitro, halogen or lower alkenyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, lower alkyl or lower alkoxy each optionally mono- or poly-substituted by halogen, R3 represents lower alkyl, lower alkenyl or lower alkynyl each optionally mono- or poly-substituted by halogen, carboxy, lower alkoxycarbonyl, lower alkoxy, lower alkylthio, amino, lower alkanoylamino, lower alkoxycarbonylamino, lower alkylamino or lower dialkylamino; or phenyl optilkynyl contained in R3 may be mono- or poly-substituted by halogen. X represents N or CH and n represents a whole number from 2 to 5, in enantiomeric or racemic form, are indicated for use as pharmaceuticals and agrochemicals in particular as antimycotics and fungicides.

Description

SPECIFICATION New azole derivatives, processes for their production and their use The present invention concerns azole derivatives of the formula I,
wherein R1 and R2 represent independently hydrogen, nitro, halogen or lower alkenyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, lower alkyl or lower alkoxy each optionally mono- or polysubstituted by halogen, R3 represents lower alkyl, lower alkenyl or lower alkynyl each optionally mono- or polysubstituted by halogen, carboxy, lower alkoxycarbonyl, lower alkoxy, lower alkylthio, amino, lower alkanoylamino, lower alkoxycarbonylamino, lower alkylamino or lower dialkylamino; or phenyl optionally substituted by halogen, lower alkyl, lower alkoxy, amino, lower alkanoylamino, lower alkoxycarbonylamino, lower alkylamino, lower dialkylamino, 1-piperazinyl or 4-lower alkanoyl-1-piperazinyl; whereby each alkyl, alkenyl or alkynyl contained in R3 may be mono- or polysubstituted by halogen.
X represents N or CH and n represents a whole number from 2 to 5, in enantiomeric or racemic form, processes for their production and their use as pharmaceuticals e.g. antimycotics or as agrochemicals e.g. fungicides.
Lower alkyl groups contain in particular 1 to 5 preferably 1 to 4 e.g. 1 or 2 carbon atoms.
This applies also to lower alkyl moieties contained in other groups. Lower alkenyl and lower alkynyl contain particularly 3 to 6 especially 3 or 4 carbon atoms. Halogen represents in particular F, Cl, Br or I preferably F or CI. Cycloalkyl groups contained in the compounds according to the invention are conveniently 3 to 6-membered, preferably 3-membered (n=2).
The compounds of formula I according to the invention may exist in free form or in the form of a salt e.g. in the form of an addition salt with an organic or inorganic acid, in the form of an ethanolate salt or in the form of a metal complex for example with a metal of groups Ib, Ia, llb, Vlb, Vllb or VIII of the periodic table such as copper or zinc with an anion such as chloride, sulfate or nitrate. Salt forms and metal complexes can be prepared in conventional manner from the corresponding free forms and vice-versa.
According to the invention the compounds of formula I may be prepared by a) reacting a compound of formula II
or a compound of formula Ia
wherein R1, R2, R3 and n have the above meanings and R4 represents a leaving group, with a compound of formula lil
wherein X has the above meanings and M stands for hydrogen or a metal equivalent or b) reacting a compound of formula IV
wherein R1, R2, R3 and n have the above meanings, with a compound of formula Ill as defined above and dimethylsulfoniummethylide or dimethyloxosulfoniummethylide or a precursor thereof, whereby any amino groups present may be protected by corresponding protecting groups which are removed following completion of the reaction, and recovering the compounds thus obtained in free form or in salt form.
Process a) can be carried out for example by reacting a compound of formula II or Ila with an azole of formula III as such (M=H) or in the form of its metal compound (M=metal) especially in the form of the alkalimetal compound e.g. the sodium salt, in an inert solvent such as dirnethyl- formamide between room temperature and boiling point of the reaction mixture.
Process b) can be carried out in conventional manner, for example as described in JACS 84/3782 (1982), Heterocycles 8/397 (1977) and JACS 87/1353 (1965).
Protecting groups and leaving groups are those conventionally employed in these types of reaction. Protectings groups may be introduced and removed in conventional manner.
The compounds of formula I contain an assymetric carbon atom and can therefore exist in the form of enantiomers or mixtures thereof which can be separated in conventional manner. Use of optically active starting materials yields corresponding end products. The invention concerns both substantially pure enantiomers as well as mixtures thereof whereby when Rl=CI or Br, R2=H, R3=CH3 and n=2 the (+)-enantiomer is preferred.
Preferred substituent meanings are For Rl and R2 a) hydrogen b) halogen For R3 lower alkyl especially methyl For X a) N b) CH and For n=2.
Preferred compounds of Formula I contain combinations of these substituent meanings.
The compounds of Formula II are new and can be prepared from compounds of Formula IV analogously to process b). Compounds of Formula Ia can be prepared for example from compounds of Formula II in conventional manner.
The compounds of Formula IV are in part new and can be prepared in conventional manner, for example a) by reacting a compound of Formula V
wherein Rl, R2 and n have the above meanings and Hal stands for halogen with a thiol of the Formula VI HS-R3 (VI) wherein R3 has the above meanings, in free form, conveniently in the presence at a base or in salt form or b) by reacting a compound of formula IX
wherein R1, R2, n and Hal have the above meanings with halogen e.g. Br2 in a mixture of ether/dioxane to give a compound of Formula VIII
wherein R1, R2, n and Hal have the above meanings and reacting this with a thiol of Formula VI, in free form conveniently in the presence of a base or in salt form to give a compound of Formula VII
and cyclisation of this.
Insofar as the preparation of starting materials is not described they are either known or may be prepared analogously to known processes or processes herein described.
End products and starting materials may be isolated and purified in conventional manner.
The compounds of the invention possesses interesting biological, particularly antimycotic properties and are therefore indicated for use as pharmaceuticals in particular as antimycotics. The antimycotic activity can be established by in vitro tests, e.g. in vitro series dilution test on various families and species of mycetes, such as yeasts, mold fungi and dermatophytes at concentrations of about 0.6 to about 50 ,ug/ml and also by in vivo tests, e.g. by systemic, p.o.
application of dosages of ca. 0.1 to 10 mg/kg body weight (2x/day) to rats which have been intra-vaginally infected with Candida albicans.
An indicated suitable daily dosage is for example in the range of from 40 to 700 mg; administered e.g. in divided doses 1 to 4 times a day or in controlled release form; dosage forms suitable for e.g. oral administration comprise from 10 to 700 mg of active ingredient.
The compounds of the invention may be employed in the free base form or in the form of pharmaceutically acceptable salts (acid addition salts or ethanolates). In general the salt forms exhibit the same order or activity as the free base forms. Examples of such acid addition salts include the hydrochloride, hydrogenfumarate and naphthaline-1 ,5-disulfonate.
The compounds may be admixed with conventional pharmaceutically acceptable diluents and carriers, and, optionally other excipients and administered orally, topically, i.v. or parenterally in such forms as tablets, capsules, creams, tinctures or injectable preparations.
Such compositions also form part of the invention. The invention therefore also concerns a method of combatting infections and diseases caused by mycetes comprising administering to a subject in need of such treatment an effective amount of a compound of formula I in free base form or in the form of a pharmaceutically acceptable salt thereof and such compounds for use as pharmaceuticals, in particular as antimycotic agents.
The compounds of the invention in free form or in agriculturally acceptable salt or metal complex form are also suitable for combatting phytopathogenic fungi. This fungicidal activity can be demonstrated i.a. in in vivo tests against Uromyces appendiculatus (bean rust) on runner beans as well as against other rust fungi (e.g. Hemileia, Puccinia) on coffee, wheat, flax and ornamentals (e.g. pelargonium, snapdragon); and against Erysiphe cichoracearum on cucumber as well as against other powdery mildews (e.g. E. graminis f. sp. tritici. E. gram. f. sp. hordei, Podosphaera leucotricha, Unicinula recator) on wheat, barley, apple and vines.
The following examples illustrate the invention. All temperatures are given in degrees centigrade.
EXAMPLE 1: a-(4-Chloropheny!)-a-( 1 -methylthio)cyclopropyl- lH- 1,2,4-triazole- methanol (proc. b)J: To a suspension of 3.2 g of sodium hydride (50%) in 120 ml abs. dimethylformamide are added in portions 14.8 g of trimethylsulfoxonium iodide and stirring continued for 45 minutes. A solution of 3.2 g of sodium hydride (50%), 120 ml of abs. dimethylformamide and 4.6 g of 1,2,4-triazole added in portions is prepared simultaneously, also stirred for 45 minutes and combined with the above mentioned suspension. To this mixture is then added dropwise at room temperature a solution of 10.6 g of 4-chlorophenyl-1-methylthiocycloprnpylketone in 50 ml of absolute dimethylformamide.The reaction mixture is stirred for 7 days at room temperature and the soluent removed under vacuum of 1 Tory/500. The oily residue is partitioned between chloroform and water, the combined organic phases washed with water and saturated aqueous NaCI, dried over sodium sulfate and concentrated. The title compound is obtained following column chromatography on silica gel (ethylacetate) as colourless crystals. m.p. 131-133 .
EXAMPLE 2: a-(4-Bromophenyl)-a-( 1-methylthioJcyclopropyl- lH- 1,2,4-triazole- 1-ethanol (proc. b): Obtained analogously to example 1. m.p. 125-127".
EXAMPLE 3: (+)-a-(4-chlorophenyl)-a-( 1 -methylthio)cyclopropyl- 1 H- 1,2, 4-triazole- 1-ethanol (proc.
aJ) A mixture of 129 mg of (+)-4-chloro-a-(1-methylthio)cyclopropyl-a-methyloxymethyl-benzylalco- hol, 53 mg of 1,2,4-triazol, 105 mg of potassiumcarbonate and 10 ml of'dry dimethylformamide is stirred for 4 hrs. at 70 . The mixture is then poured onto water, extracted with ethyl acetate and the organic phase dried over MgSO4 and concentrated by evaporation. The residue is chromatographed over silica gel with ethylacetate. Colourless crystals m.p. 112-114"; [aj200 (acetate)=+40.20 are obtained.
EXAMPLE 4: (-)-(4-chlorophenyl)-a-(1-methylthio)cyclopropyl- 1H- 1,2,4-triazole- 1-ethanol (proc. a)) Obtained analogously to example 3 [a]20 (acetone)= -40 .
The starting materials may be obtained for example as follows: A) 4-chlorophenyl- l-methylthiocyclopropylketone (for example 1) a) 4-chlorophenyl-3-chloro- 1 -bromopropylketone 65.1 g of 4-chlorophenyl-3-chloropropylketone are dissolved in a mixture of 120 ml of abs ether and 60 ml of abs. dioxane, heated to boiling and treated with 48 g of bromine. Following stirring for 30 minutes at RT the reaction mixture is poured onto 300 ml of ice and then extracted with ether. The combined organic phases are dried over sodium sulfate, concentrated and the solid residue crystallised from petroleum ether m.p. 67-69".
b) 4-chlorophenyl-3-chloro- 1 -methylthiopropylketone To a suspension of 10.6 g of sodium methanethiolate in 200 ml of abs. 1,2-dimethoxyethane are added dropwise with stirring 45.25 g of 4-chlorophenyl-3-chloro-1-bromopropylketone in 100 ml abs. 1,2-dimethoxyethane whilst maintaining the temperature below 30o. The reaction mixture is stirred for 2 hrs. at RT and carefully diluted with 150 ml of water and 250 ml of ether. The organic phase is washed with water, dried and concentrated. The title substance is purified by column chromatography over silica gel (n-hexane/ethylacetate =98/2). Colourless oil.
Rf=0. 12 (n-hexane/ethylacetate=98/2).
c) 4-chlorophenyl- 1 -methylthiocyclopropylketone A solution of 10.86 g of potassium hydroxide in 45 ml of methanol is reacted dropwise with a solution of 24.3 g of 4-chlorophenyl-3-chloro-1-methylthiopropylketone in 45 ml of methanol.
The reaction mixture is stirred for 1 hr. at RT concentrated on a rotary evaporator, partitioned between toluene and water, the combined organic phases washed with water, dried and concentrated by evaporation. The oily residue is crystallised from petroleum ether. Colourless crystals.
m.p. 30-32".
B) 4-bromophenyl- 1 -methylthiocyclopropylketone (for example 2) Analogous to A).
a) 4-bromophenyl-3-chloro-1-bromopropylketone m.p. 92-94" b) 4-bromophenyl-3-chloro- 1 -methylthiopropylketone Rf= 0.13 (n-hexane/ethylacetate = 98/2) c) 4-bromophenyl- 1 -methylthiocyclopropylketone m.p. 43-45" C) 4-chloro-a-(1-methylthio)cyclopropyl-a-mesyloxymethyl-benzZlalcohol (for examples 3 and 4) a) 1 -(4-chlorophen vl)-l -(1 -methylthio)cyclopropyl-oxfrane To a suspension of 0.73 g of sodium hydride (80%) in 50 ml of dry dimethylformamide are added in portions 5.34 g of trimethylsulfoxoniumiodide and the mixture stirred for 45 mins.
A solution of 5 g of 4-chlorophenyl- 1 -methylthiocyclopropylketone in 25 ml of dimethylformamide is then added dropwise and the mixture stirred for 18 hrs. at RT. The mixture is concentrated in vacuum (1 Torr) and the residue taken up in ethylacetate/water. The organic phase is separated, dried (MgSO4) and concentrated by evaporation.
A colourless oil is obtained.
1H-NMR: 7.1-7.6 (m,4H); 2.76-3.0 (AB-System, 2H); 1.98 (s, 3H); 0.7-1.3 (m, 4H).
b) 4-chloro-a-hydroxymethyl-a-( 1 -methylthio)cyclopropyl-benzylalcohol 0.2 g of 1-(4-chlorophenyl)-1-(1-methylthio)cyclopropyl-oxirane are stirred with 0.3 molar KOH solution in dimethylsulfoxide/water (4/1) for 20 hrs. at 60 . The mixture is then diluted with 50 ml of water and extracted with ethyl acetate. The extract-solution is dried (NaSO4) and concentrated by evaporation. The crude product can be purified by chromatography over silica gel with a mixture of hexane/ethylacetate (4/1).
Colourless crystals are obtained. m.p. 86-91".
c) Separation of optical antipodes To 2.65 g of racemic product in 50 ml pyridine are added in portions with ice-water cooling 2.67 g of campharic acid chloride and the mixture stirred for 20 hrs. at RT. The mixture is poured onto ice-cooled dilute sulfuric acid, extracted with ethylacetate, the organic phase dried (MgSO4) and concentrated by evaporation. The mixture of diastereomeric esters is separated by chromatography on silica gel with hexane/ethyl acetate (4/1) Diastereomer A: m.p. 122-124", [a]2g (acetone)=+28'.
Diastereomer B: m.p. 125-127", [a]20 (acetone)=-43.6'.
2 g of diastereomer A are stirred with 3 g of strongly basic ion exchanger in a mixture of methanol and water for 15 hrs. at reflux temperature. After filtration and concentration by evaporation the dextrorotatory enantiomer is obtained as colourless crystals.
m.p. 60-62".
[a]2g (acetone)= +79.7" d) (+)-4-chloro-a-(1-methylthio)cyclopropyl-a-mesyloxymethyl-benzZlalcohol To 1.27 g of (+)-4-chloro-a-hydroxymethyl-a-(1-methylthio)cyclopropylbenzylalcohol in 20 ml of dry pyridine are added dropwise with ice-water cooling 0.68 of mesylchloride. The mixture is stirred for 2.5 hrs. at 0-5" and poured onto ice-cold dilute sulfuric acid, extracted with ethylacetate and the organic phase dried (MgSO4) and concentrated by evaporation to obtain a colourless oil.
1H-NMR: 7.2-7.65 (m, 4H); 4.5-5.22 (AB-System, 2H); 3.0 (s, 3H); 1.52 (s, 3H); 0.5-1.4 (m, 4H).
[a]2g= +57.4 .
The (-)-antipode may be obtained analogously.

Claims (10)

1. Azole derivatives of the formula I,
wherein R1 and R2 represent independently hydrogen, nitro, halogen or lower alkenyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, lower alkyl or lower alkoxy each optionally mono- or polysubstituted by halogen, R3 represents lower alkyl, lower alkenyl or lower alkynyl each optionally mono- or polysubstituted by halogen, carboxy, lower alkoxycarbonyl, lower alkoxy, lower alkylthio, amino, lower alkanoylamino, lower alkoxycarbonylamino, lower alkylamino or lower dialkylamino; or phenyl optionally substituted by halogen, lower alkyl, lower alkoxy, amino, lower alkanoylamino, lower alkoxycarbonylamino, lower alkylamino, lower dialkylamino, 1-piperazinyl or 4-lower alkanoyl-1-piperazinyl; whereby each alkyl, alkenyl or alkynyl contained in R3 may be mono- or polysubstituted by halogen.
X represents N or CH and n represents a whole number from 2 to 5 in enantiomeric or racemic form.
2. A compound according to claim 1 wherein R, and R2 represent independently hydrogen or halogen, R3 represents lower alkyl and n stands for 2.
3. Azole derivatives of the formula I,
wherein R, and R2 represent independently hydrogen, nitro, halogen or lower alkenyl, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, lower alkyl or lower alkoxy each optionally mono- or polysubstituted by halogen, R3 represents lower alkyl, lower alkenyl or lower alkynyl each optionally mono- or polysubstituted by halogen, carboxy, lower alkoxycarbonyl, lower alkoxy, lower alkylthio, amino, lower alkanoylamino, lower alkoxycarbonylamino, lower alkylamino or lower dialkylamino; or phenyl optionally substituted by halogen, lower alkyl, lower alkoxy, amino, lower alkanoylamino, lower alkoxycarbonylamino, lower alkylamino, lower dialkylamino, 1-piperazinyl or 4-lower alka noyl- 1 -piperazinyl; X represents N or CH and n represents a whole number from 2 to 5 in enantiomeric or racemic form,
4. A compound according to claim 1, 2 or 3 in free form.
5. A compound according to claim 1, 2 or 3 in salt form.
6. (+ )-a-(4-chlorophenyl)-a-[( 1 -methylthio)cyclopropyl]- 1H-1,2,4-triazole-l -ethanol in free form or in salt form.
7. A pharmaceutical composition comprising a compound according anyone of claims 1 to 6 in free form or in the form of a pharmaceutically acceptable salt, together with a pharmaceutically acceptable diluent or carrier.
8. A compound according to anyone of claims 1 to 6 in free form or in the form of a pharmaceutically acceptable salt for use as a pharmaceutical.
9. A compound according to anyone of claims 1 to 6 in free form or in the form of a pharmaceutically acceptable salt for use as an antimycotic.
10. A process for preparing a compound according to claim 1 in free form or a salt form which comprises, a) reacting a compound of formula II
or a compound of formula lia
wherein R,, R2, R3 and n have the above meanings and R4 represents a leaving group, with a compound of formula Ill
wherein X has the above meanings and M stands for hydrogen or a metal equivalent or b) reacting a compound of formula IV
wherein R,, R2, R3 and n have the above meanings, with a compound of formula Ill as defined above and dimethylsulfoniummethylide or dimethyloxosulfoniummethylide or a precursor thereof, whereby any amino groups present may be protected by corresponding protecting groups which are removed following completion of the reaction, and recovering the compounds thus obtained in free form or in salt form.
GB08612161A 1985-05-23 1986-05-19 Azole derivatives Withdrawn GB2175899A (en)

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CH220485 1985-05-23
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KR (1) KR860008990A (en)
AU (1) AU5765386A (en)
BE (1) BE904802A (en)
DK (1) DK237686A (en)
ES (1) ES8802573A1 (en)
FI (1) FI862123A (en)
FR (1) FR2582305A1 (en)
GB (1) GB2175899A (en)
GR (1) GR861317B (en)
IL (1) IL78870A0 (en)
IT (1) IT1203790B (en)
LU (1) LU86443A1 (en)
NL (1) NL8601189A (en)
PT (1) PT82624B (en)
SE (1) SE8602309L (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4812465A (en) * 1986-12-29 1989-03-14 Cl Pharma Aktiengesellschaft Triazole derivatives for use as antimycotic agents

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GR852627B (en) * 1984-11-02 1986-03-03 Bayer Ag

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3365739D1 (en) * 1982-01-15 1986-10-09 Ciba Geigy Ag Fungicidal and plant-growth regulating tri-azolcarbinol derivatives
CN1008735B (en) * 1984-11-02 1990-07-11 拜尔公司 Pyrrole ylmethyl-cyclopropyl-carbinol derivatives with replacement is a composition of active components

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4812465A (en) * 1986-12-29 1989-03-14 Cl Pharma Aktiengesellschaft Triazole derivatives for use as antimycotic agents

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BE904802A (en) 1986-11-24
SE8602309L (en) 1986-11-24
IT1203790B (en) 1989-02-23
PT82624B (en) 1988-08-17
SE8602309D0 (en) 1986-05-21
DK237686A (en) 1986-11-24
LU86443A1 (en) 1986-12-05
IL78870A0 (en) 1986-09-30
IT8648049A0 (en) 1986-05-23
AU5765386A (en) 1986-11-27
GB8612161D0 (en) 1986-06-25
GR861317B (en) 1986-09-19
ES555201A0 (en) 1987-07-16
ES8802573A1 (en) 1987-07-16
NL8601189A (en) 1986-12-16
FI862123A (en) 1986-11-24
DK237686D0 (en) 1986-05-21
PT82624A (en) 1986-06-01
KR860008990A (en) 1986-12-19
FI862123A0 (en) 1986-05-21

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