U.S. patent application number 13/934030 was filed with the patent office on 2013-11-07 for isoxazole derivatives for use as fungicides.
The applicant listed for this patent is Syngenta Crop Protection LLC. Invention is credited to Carla Bobbio, Camilla Corsi, Micah Gliedt, Valeria Grasso, Ulrich Johannes Haas, Jilali Kessabi, Shy-Fuh Lee, Peter Schneiter, Sebastian Volker Wendeborn.
Application Number | 20130296381 13/934030 |
Document ID | / |
Family ID | 40343739 |
Filed Date | 2013-11-07 |
United States Patent
Application |
20130296381 |
Kind Code |
A1 |
Corsi; Camilla ; et
al. |
November 7, 2013 |
ISOXAZOLE DERIVATIVES FOR USE AS FUNGICIDES
Abstract
The present invention relates to isoxazole compounds of formula
(I) having fungicidal activity, to agricultural compositions
comprising them, and to the use of said compounds and compositions
in agriculture for the control of microbial pests, particularly
fungal pests, on plants ##STR00001##
Inventors: |
Corsi; Camilla; (Basel,
CH) ; Wendeborn; Sebastian Volker; (Stein, CH)
; Bobbio; Carla; (Dresden, DE) ; Kessabi;
Jilali; (Stein, CH) ; Schneiter; Peter;
(Stein, CH) ; Grasso; Valeria; (Stein, CH)
; Haas; Ulrich Johannes; (Stein, CH) ; Lee;
Shy-Fuh; (Sunnyvale, CA) ; Gliedt; Micah;
(Sunnyvale, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Syngenta Crop Protection LLC |
Greensboro |
NC |
US |
|
|
Family ID: |
40343739 |
Appl. No.: |
13/934030 |
Filed: |
July 2, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13133708 |
Aug 26, 2011 |
8476446 |
|
|
PCT/EP2009/066966 |
Dec 11, 2009 |
|
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13934030 |
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Current U.S.
Class: |
514/340 ;
546/272.1 |
Current CPC
Class: |
A61P 31/10 20180101;
C07D 413/06 20130101; C07D 413/04 20130101; A61P 31/12 20180101;
A01N 43/80 20130101; A61P 17/00 20180101 |
Class at
Publication: |
514/340 ;
546/272.1 |
International
Class: |
A01N 43/80 20060101
A01N043/80; C07D 413/06 20060101 C07D413/06 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 17, 2008 |
GB |
0823002.1 |
Claims
1. A compound of the formula (I) ##STR00009## wherein R.sup.1 is H
or acyl; or an agrochemically acceptable salt thereof.
2. A compound according to claim 1 wherein R.sup.1 is H.
3. A compound according to claim 1 which is the (S)-enantiomer of
the compound of formula (I).
4. A compound according to claim 3 which is
(S)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)isoxazol-4-yl]pyri-
din-3-yl-methanol ##STR00010##
5. A compound according to claim 3 having an enantiomeric excess of
(S) to (R) of at least 80%.
6. A composition comprising a compound according to claim 1, or an
agrochemically acceptable salt thereof, and an agrochemically
acceptable diluent or carrier.
7. A composition according to claim 6 further comprising at least
one additional fungicide or systemically acquired resistance
inducer.
8. A method of controlling or preventing infestation of cultivated
plants, plant propagation material, or a technical material, by
pathogenic microorganisms, comprising applying a compound according
to claim 1, to said plants, parts thereof or the locus thereof,
plant propagation material, or technical material in an amount
effective to control said microorganisms.
9. A method according to claim 9, wherein said plant propagation
material comprises seeds.
10. A method according to claim 10 wherein the pathogenic
microorganism is a fungal organism.
11. A method according to claim 11 wherein the fungal organism is
selected from Septoria tritici, Stagonospora nodorum, Phytophthora
infestans, Botrytis cinerea, Sclerotinia homoeocarpa and Puccinia
recondite.
12. A method of treating a fungal infection in a subject in need
thereof comprising administering a compound according to claim 1 or
a pharmaceutically acceptable salt thereof to said subject in an
amount effective to treat said fungal infection.
Description
[0001] This application is a continuation of copending U.S.
application Ser. No. 13/133,708, filed on 9 Jun. 2011, herein
incorporated by reference in its entirety for all purposes.
[0002] The present invention relates to isoxazole compounds having
fungicidal activity, to agricultural compositions comprising them,
and to the use of said compounds and compositions in agriculture
for the control of microbial pests, particularly fungal pests, on
plants.
[0003] The incidence of serious fungal infections, either systemic
or topical, continues to increase for plants, animals, and humans.
Many fungi are common in the environment and not harmful to plants
or mammals. However, some fungi can produce disease in plants,
humans and/or animals.
[0004] Fungicides are compounds, of natural or synthetic origin,
which act to protect plants against damage caused by fungi,
including oomycetes. Current methods of agriculture rely heavily on
the use of fungicides. In fact, some crops cannot be grown usefully
without the use of fungicides. Using fungicides allows a grower to
increase the yield of the crop and consequently, increase the value
of the crop. Numerous fungicidal agents have been developed.
However, the treatment of fungal infestations and infections
continues to be a major problem. Furthermore, fungicide and
antifungal drug resistance has become a serious problem, rendering
these agents ineffective for some agricultural and therapeutic
uses. As such, a need exists for the development of new fungicidal
and antifungal compounds (see, e.g., U.S. Pat. No. 6,673,827; See
also U.S. Pat. No. 6,617,330 to Walter, which describes
pyrimidin-4-enamine as fungicides).
[0005] International patent application WO2006/031631 refers to a
series of isoxazole derivatives having fungicidal properties. There
exists a need therefore for alternative methods of control of
fungi. Preferably, new compounds may possess improved fungicidal
properties, such as improved efficacy, improved selectivity, lower
tendency to generate resistance or activity against a broader
spectrum of fungi. Compounds may be more advantageously formulated
or provide more efficient delivery and retention at sites of
action, or may be more readily biodegradable. Advantageous
compounds or their degradation components may generally be less
toxic.
[0006] It has surprisingly been found that the isoxazole compounds
of the present invention exhibit unexpected fungicidal activity and
are therefore suitable for use in agriculture as crop protection
agents to combat or prevent fungal infestations, or to control
other pests such as weeds, insects, or acarids that are harmful to
crops.
[0007] Accordingly, in a first aspect, the present invention
provides a compound of formula (I)
##STR00002##
wherein R.sup.1 is H or acyl, preferably H; or an agrochemically
acceptable salt thereof.
[0008] Acyl includes any readily hydrolysable acyl groups, and
comprises, for example, C(O)R.sup.2, C(O)OR.sup.2, C(O)NHR.sup.2
and C(O)NR.sup.2R.sup.3, wherein R.sup.2 and R.sup.3 are each
independently selected from alkyl, alkenyl, akynyl, heterocyclyl,
aryl and heteroaryl. Acyl groups may be optionally substituted with
one or more, for example 1, 2, 3 or 4, halo or OR.sup.2 groups.
Preferred acyl groups are acetyl, benzoyl and phenylacetyl.
[0009] Alkyl groups may be straight, branched or cyclic and contain
1 to 24 carbon atoms. Preferred alkyl groups may contain 1 to 10
carbon atoms, more preferably 1 to 6 carbons, even more preferably
1 to 4 carbon atoms. Representative alkyl groups include, for
example, methyl, ethyl, isopropyl, n-propyl, n-butyl, t-butyl,
t-amyl, 2,5-dimethylhexyl, cyclobutyl, cyclopropyl, cyclopentyl and
cyclohexyl.
[0010] Heterocyclyl groups may contain from 3 to 10 ring-atoms up
to 4 of which may be hetero-atoms such as nitrogen, oxygen and
sulfur, and may be saturated or partially unsaturated. Examples of
heterocyclyl groups are oxiranyl, azetidinyl, tetrahydrofuranyl,
thiolanyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl,
sulfolanyl, dioxolanyl, dihydropyranyl, tetrahydropyranyl,
piperidinyl, pyrazolinyl, pyrazolidinyl, dioxanyl, morpholinyl,
dithianyl, thiomorpholinyl, piperazinyl, azepinyl, oxazepinyl,
thiazepinyl, thiazolinyl and diazapanyl.
[0011] Aryl includes phenyl, naphthyl, anthracenyl and
phenanthrenyl.
[0012] Heteroaryl groups may contain from 3 to 10 ring-atoms up to
4 of which may be hetero-atoms such as nitrogen, oxygen and sulfur.
Examples of heteroaryl groups are furyl, thienyl, pyrrolyl,
oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl,
isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridyl,
pyrimidinyl, pyrazinyl, pyridazinyl, tetrazolyl, triazinyl. In
addition, the term heteroaryl includes fused heteroaryl groups, for
example benzimidazolyl, benzoxazolyl, imidazopyridinyl,
benzoxazinyl, benzothiazinyl, oxazolopyridinyl, benzofuranyl,
quinolinyl, quinazolinyl, quinoxalinyl, benzothiazolyl,
phthalimido, benzofuranyl, benzodiazepinyl, indolyl and
isoindolyl.
[0013] Halo means fluoro, chloro, bromo or iodo.
[0014] The compounds of the invention include compounds of formula
(I) as hereinbefore defined, polymorphs, and isomers thereof,
including optical, geometric and tautomeric isomers, and
isotopically-labeled compounds of formula (I).
[0015] Agrochemically acceptable salts possess a cation, which is
known and accepted in the art for the formation of salts for
agricultural or horticultural use. Preferably the salts are
water-soluble.
[0016] Suitable salts of the compounds of formula (I) include acid
addition salts such as those with an inorganic acid such as
hydrochloric, hydrobromic, sulphuric, nitric or phosphoric acid, or
an organic carboxylic acid such as oxalic, tartaric, lactic,
butyric, toluic, hexanoic or phthalic acid, or a sulphonic acid
such as methane, benzene or toluene sulphonic acid. Other examples
of organic carboxylic acids include haloacids such as
trifluoroacetic acid.
[0017] N-oxides are oxidised forms of tertiary amines or oxidised
forms of nitrogen containing heteroaromatic compounds. They are
described in many books for example in "Heterocyclic N-oxides" by
Angelo Albini and Silvio Pietra, CRC Press, Boca Raton, Fla.,
1991.
[0018] In a preferred embodiment, the present invention provides a
composition comprising a compound of formula (I), or an
agrochemically acceptable salt thereof, and an agrochemically
acceptable diluent or carrier. References to compounds of the
invention herein shall be deemed to include both a compound of
formula (I) and agrochemically acceptable salts thereof.
[0019] The compound of formula (I) exists as a racemate comprising
(R) and (S)-enantiomers. The (S)-enantiomer has been found to have
significantly greater fungicidal activity compared to the
(R)-enantiomer.
[0020] Accordingly, in a preferred aspect, the present invention
additionally provides the (S)-enantiomers of the compound of
formula (I)
##STR00003##
wherein R.sup.1 is H or acyl, preferably H; or an agrochemically
acceptable salt thereof.
[0021] Accordingly, in a preferred aspect, there is provided a
composition comprising a compound of formula (S)-(I), or an
agrochemically acceptable salt thereof, and an agrochemically
acceptable diluent or carrier.
[0022] Preferably, the compound of formula (S)-(I) is provided as a
single enantiomer having an enantiomeric excess (e.e.) of at least
40%, for example, at least 50%, 60%, 70% or 80%, preferably at
least 90%, more preferably at least 95%, yet more preferably at
least 98% and most preferably at least 99%.
[0023] Most preferably, the compound of formula (I) is
(S)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)isoxazol-4-yl]pyri-
din-3-yl-methanol (Example 2)
##STR00004##
Example 2
[0024] or an agrochemically acceptable salt thereof.
[0025] Preferably, the compound of Example 2 is provided as a
single enantiomer having an enantiomeric excess (e.e.) of at least
40%, for example, at least 50%, 60%, 70% or 80%, preferably at
least 90%, more preferably at least 95%, yet more preferably at
least 98% and most preferably at least 99%.
[0026] The compounds and compositions of the present invention are
useful for protecting plants against diseases that are caused by
fungi, including oomycetes. The compounds of the invention can be
used in the agricultural sector and related fields as active
ingredients for controlling plant pests. The compounds of the
invention can be used to inhibit or destroy the pests that occur on
plants or parts of plants (fruit, blossoms, leaves, stems, tubers,
roots) of different crops of useful plants, optionally while at the
same time protecting also those parts of the plants that grow later
e.g. from phytopathogenic micro-organisms.
[0027] The compounds and compositions of the present invention may
be used as dressing agents for the treatment of plant propagation
material, in particular of seeds (fruit, tubers, grains) and plant
cuttings (e.g. rice), for the protection against fungal infections
as well as against phytopathogenic fungi occurring in the soil.
[0028] In an additional aspect, the present invention provides a
method of controlling or preventing infestation of cultivated
plants by pathogenic microorganisms, comprising applying a compound
of formula (I) or composition thereof to said plants, parts thereof
or the locus thereof in an amount effective to control said
microorganisms.
[0029] The compounds and compositions of the present invention may
be used against phytopathogenic fungi, for example, those of the
following classes: Fungi imperfecti (e.g. Botrytis, Pyricularia,
Heiminthosporium, Fusarium, Septoria, Cercospora and Alternaria)
and Basidiomycetes (e.g. Rhizoctonia, Hemileia, Puccinia).
Additionally, they may also be used against the Ascomycetes classes
(e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and
of the Oomycetes classes (e.g. Phytophthora, Pythium, Plasmopara).
Specific examples of fungi that may be treated include, but are not
limited to, Septoria tritici, Stagonospora nodorum, Phytophthora
infestans, Botrytis cinerea, Sclerotinia homoeocarpa and Puccinia
recondita.
[0030] In a preferred embodiment of the invention, the compounds
and compositions of the present invention are used against the
fungal organism Septoria tritici.
[0031] The crops of useful plants to be protected typically
comprise, for example, the following species of plants: cereals
(wheat, barley, rye, oats, maize (including field corn, pop corn
and sweet corn), rice, sorghum and related crops); beet (sugar beet
and fodder beet); leguminous plants (beans, lentils, peas,
soybeans); oil plants (rape, mustard, sunflowers); cucumber plants
(marrows, cucumbers, melons); fibre plants (cotton, flax, hemp,
jute); vegetables (spinach, lettuce, asparagus, cabbages, carrots,
eggplants, onions, pepper, tomatoes, potatoes, paprika, okra);
plantation crops (bananas, fruit trees, rubber trees, tree
nurseries), ornamentals (flowers, shrubs, broad-leaved trees and
evergreens, such as conifers); as well as other plants such as
vines, bushberries (such as blueberries), caneberries, cranberries,
peppermint, rhubarb, spearmint, sugar cane and turf grasses
including, for example, cool-season turf grasses (for example,
bluegrasses (Poa L.), such as Kentucky bluegrass (Poa pratensis
L.), rough bluegrass (Poa trivialis L.), Canada bluegrass (Poa
compressa L.) and annual bluegrass (Poa annua L.); bentgrasses
(Agrostis L.), such as creeping bentgrass (Agrostis palustris
Huds.), colonial bentgrass (Agrostis tenius Sibth.), velvet
bentgrass (Agrostis canina L.) and redtop (Agrostis alba L.);
fescues (Festuca L.), such as tall fescue (Festuca arundinacea
Schreb.), meadow fescue (Festuca elatior L.) and fine fescues such
as creeping red fescue (Festuca rubra L.), chewings fescue (Festuca
rubra var. commutate Gaud.), sheep fescue (Festuca ovina L.) and
hard fescue (Festuca longifolia); and ryegrasses (Lolium L.), such
as perennial ryegrass (Lolium perenne L.) and annual (Italian)
ryegrass (Lolium multiflorum Lam.)) and warm-season turf grasses
(for example, Bermudagrasses (Cynodon L. C. Rich), including hybrid
and common Bermudagrass; Zoysiagrasses (Zoysia Willd.), St.
Augustinegrass (Stenotaphrum secundatum (Walt.) Kuntze); and
centipedegrass (Eremochloa ophiuroides (Munro.) Hack.)).
[0032] The crops of useful plants also includes plants that have
been rendered tolerant to herbicides like bromoxynil or classes of
herbicides (such as HPPD inhibitors, ALS inhibitors; for example
primisulfuron, prosulfuron and trifloxysulfuron, EPSPS
(5-enol-pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS
(glutamine synthetase) inhibitors or PPO
(protoporphyrinogen-oxidase) inhibitors) as a result of
conventional methods of breeding or genetic engineering. An example
of a crop that has been rendered tolerant to imidazolinones (e.g.
imazamox) by conventional methods of breeding (mutagenesis) is
Clearfield.RTM. summer rape (Canola). Examples of crops that have
been rendered tolerant to herbicides or classes of herbicides by
genetic engineering methods include glyphosate- and
glufosinate-resistant maize varieties commercially available under
the trade names RoundupReady.RTM., Herculex I.RTM. and
LibertyLink.RTM..
[0033] The crops of useful plants also includes plants which have
been so transformed by the use of recombinant DNA techniques that
they are capable of synthesising one or more selectively acting
toxins, such as are known from toxin-producing bacteria, especially
those of the genus Bacillus.
[0034] The crops of useful plants also includes plants which have
been so transformed by the use of recombinant DNA techniques that
they are capable of synthesising antipathogenic substances having a
selective action, such as the so-called "pathogenesis-related
proteins" (PRPs, see e.g. European patent application EP
0,392,225). Examples of such antipathogenic substances and
transgenic plants capable of synthesising such antipathogenic
substances are known, for example, from European patent
applications EP 0,392,225 and EP 0,353,191, and International
patent application WO 95/33818. The methods of producing such
transgenic plants are generally known to the person skilled in the
art and are described, for example, in the publications mentioned
above.
[0035] In a preferred embodiment of the invention, the crops of
useful plants are selected from cereals, rice, beets, leguminous
plants, oil plants, cucumber plants, fibre plants, vegetables,
plantation crops, ornamentals, vines, bushberries, caneberries,
cranberries, peppermint, rhubarb, spearmint, sugar cane and turf
grasses.
[0036] The compounds and compositions of the present invention can
be applied to the crop area or plant to be treated, simultaneously
or in succession with further compounds. These further compounds
can be, for example, fertilizers or micronutrient donors or other
preparations which influence the growth of plants. They can also be
selective herbicides as well as insecticides, fungicides,
bactericides, nematicides, molluscicides, plant growth regulators,
plant activators or mixtures of several of these preparations, if
desired together with further carriers, surfactants or application
promoting adjuvants customarily employed in the art of
formulation.
[0037] The compounds of the present invention can be mixed with
other fungicides, resulting in some cases in unexpected synergistic
activities.
[0038] Mixing components which are particularly preferred are
azoles such as azaconazole, bitertanol, propiconazole,
difenoconazole, diniconazole, cyproconazole, epoxiconazole,
fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil,
imibenconazole, ipconazole, tebuconazole, tetraconazole,
fenbuconazole, metconazole, myclobutanil, perfurazoate,
penconazole, bromuconazole, pyrifenox, prochloraz, triadimefon,
triadimenol, triflumizole or triticonazole; pyrimidinyl carbinoles
such as ancymidol, fenarimol or nuarimol; 2-amino-pyrimidine such
as bupirimate, dimethirimol or ethirimol; morpholines such as
dodemorph, fenpropidin, fenpropimorph, spiroxamin or tridemorph;
anilinopyrimidines such as cyprodinil, pyrimethanil or mepanipyrim;
pyrroles such as fenpiclonil or fludioxonil; phenylamides such as
benalaxyl, furalaxyl, metalaxyl, R-metalaxyl, ofurace or oxadixyl;
benzimidazoles such as benomyl, carbendazim, debacarb, fuberidazole
or thiabendazole; dicarboximides such as chlozolinate,
dichlozoline, iprodine, myclozoline, procymidone or vinclozolin;
carboxamides such as carboxin, fenfuram, flutolanil, mepronil,
oxycarboxin or thifluzamide; guanidines such as guazatine, dodine
or iminoctadine; strobilurines such as azoxystrobin,
kresoxim-methyl, metominostrobin, pyraclostrobin, picoxystrobin,
SSF-129, methyl
2[(2-trifluoromethyl)-pyrid-6-yloxymethyl]-3-methoxy-acrylate or
2-[{.alpha.
[(.alpha.-methyl-3-trifluoromethyl-benzyl)imino]-oxy}-o-tolyl]-glyoxylic
acid-methylester-O-methyloxime (trifloxystrobin); dithiocarbamates
such as ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb
or ziram; N-halomethylthio-dicarboximides such as captafol, captan,
dichlofluanid, fluoromide, folpet or tolyfluanid; copper compounds
such as Bordeaux mixture, copper hydroxide, copper oxychloride,
copper sulfate, cuprous oxide, mancopper or oxine-copper;
nitrophenol derivatives such as dinocap or nitrothal-isopropyl;
organo phosphorous derivatives such as edifenphos, iprobenphos,
isoprothiolane, phosdiphen, pyrazophos or toclofos-methyl; and
other compounds of diverse structures such as acibenzolar-S-methyl,
harpin, anilazine, blasticidin-S, chinomethionat, chloroneb,
chlorothalonil, cymoxanil, dichlone, diclomezine, dicloran,
diethofencarb, dimethomorph, dithianon, etridiazole, famoxadone,
fenamidone, fentin, ferimzone, fluazinam, flusulfamide, fenhexamid,
fosetyl-aluminium, hymexazol, kasugamycin, methasulfocarb,
pencycuron, phthalide, polyoxins, probenazole, propamocarb,
pyroquilon, quinoxyfen, quintozene, sulfur, triazoxide,
tricyclazole, triforine, validamycin,
(S)-5-methyl-2-methylthio-5-phenyl-3-phenylamino-3,5-di-hydroimidazol-4-o-
ne (RPA 407213),
3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2-oxopropyl)-4-methylbenzamide
(RH-7281),
N-allyl-4,5-dimethyl-2-trimethylsilylthiophene-3-carboxamide (MON
65500),
4-chloro-4-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfon-amide (1
KF-916),
N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)-propionam-
ide (AC 382042) or iprovalicarb (SZX 722).
[0039] The compounds of the present invention can be mixed with one
or more systemically acquired resistance inducer ("SAR" inducer),
alone or in combination with a fungicide as above. SAR inducers are
known and described in, for example, U.S. Pat. No. 6,919,298. In
general, a SAR inducer is any compound which has the ability to
turn on resistance in a plant to a disease-causing agent,
including, but not limited to a virus, a bacterium, a fungus, or
combinations of these agents. In addition, an SAR inducer may
induce resistance to insect feeding in a plant, as defined by
Enyedi et al. (1992; Cell 70: 879-886). Exemplary SAR inducers
cover many structural families of compounds, but are united by
their ability to induce a resistance to plant diseases and/or pest
feeding. One class of SAR inducers is the salicylates. The
commercial SAR inducers acibenzolar-s-methyl (available as
Actigard.RTM. from Syngenta), harpin protein (available as
Messenger.TM. from Eden Biosciences), yeast extract hydrolysate
from Saccharomyces cerevisiae (available as Keyplex.RTM.
350-DP.RTM. from Morse Enterprises Limited, Inc. of Miami, Fla.),
and Oryzemate are useful in the present invention. Elicitors,
including the Goemar products are another class of SAR inducers
that can also be used. In addition, ethylene, its biosynthetic
precursors, or ethylene releasing compounds such as Ethrel are
considered SAR inducers of utility in this context.
[0040] Suitable carriers and adjuvants can be solid or liquid and
are substances useful in formulation technology, e.g. natural or
regenerated mineral substances, solvents, dispersants, wetting
agents, tackifiers, thickeners, binders or fertilizers.
[0041] A preferred method of application of the compounds and
compositions of the present invention is foliar application. The
frequency of application and the rate of application will depend on
the risk of infestation by the corresponding pathogen. However, the
compounds of the present invention can also penetrate the plant
through the roots via the soil (systemic action) by drenching the
locus of the plant with a liquid formulation, or by applying the
compounds in solid form to the soil, e.g. in granular form (soil
application). In crops of water such as rice, such granulates can
be applied to the flooded rice field. The compounds and
compositions of the present invention may also be applied to seeds
(coating) by impregnating the seeds or tubers either with a liquid
formulation of the fungicide or coating them with a solid
formulation.
[0042] The term locus as used herein is intended to embrace the
fields on which the treated crop plants are growing, or where the
seeds of cultivated plants are sown, or the place where the seed
will be placed into the soil. The term seed is intended to embrace
plant propagating material such as cuttings, seedlings, seeds, and
germinated or soaked seeds.
[0043] The term plant propagation material means the generative
parts of a plant including seeds of all kinds (fruit, tubers,
bulbs, grains etc), roots, rhizomes, cuttings, cut shoots and the
like. Plant propagation material may also include plants and young
plants which are to be transplanted after germination or after
emergence from the soil.
[0044] The compounds of the present invention may be used in
unmodified form or, preferably, together with the adjuvants
conventionally employed in the art of formulation. To this end they
are conveniently formulated in known manner to as granules,
wettable or soluble powders, emulsifiable concentrates, coatable
pastes, dusts, flowables, directly sprayable or dilutable
solutions, suspensions or emulsions, or as controlled release forms
such as microcapsules. As with the type of the compositions, the
methods of application, such as spraying, atomizing, dusting,
scattering, coating or pouring, are chosen in accordance with the
intended objectives and the prevailing circumstances.
[0045] The compositions of the present invention and, if desired, a
solid or liquid adjuvant, are prepared in known manner, typically
by intimately mixing and/or grinding the compound with extenders,
e.g. solvents, solid carriers and, optionally, surface active
compounds (surfactants).
[0046] Suitable carriers and adjuvants may be solid or liquid and
correspond to the substances ordinarily employed in formulation
technology, such as, e.g. natural or regenerated mineral
substances, solvents, dispersants, wetting agents, tackifiers,
thickeners binding agents or fertilizers. Such carriers are for
example described in WO 97/33890.
[0047] The agrochemical compositions will usually contain from 0.1
to 99% by weight, preferably from 0.1 to 95% by weight, of the
compound of formula (I), 99.9 to 1% by weight, preferably 99.8 to
5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by
weight, preferably from 0.1 to 25% by weight, of a surfactant.
[0048] Whereas it is preferred to formulate commercial products as
concentrates, the end user will normally use dilute
formulations.
[0049] The compositions may also contain further adjuvants such as
stabilizers, antifoams, viscosity regulators, binders or tackifiers
as well as fertilizers, micronutrient donors or other formulations
for obtaining special effects.
[0050] Suitably, the agrochemical compositions of the present
invention are applied prior to disease development. Rates and
frequency of use of the formulations are those conventionally used
in the art and will depend on the risk of infestation by the fungal
pathogen, the developmental stage of the plant and on the location,
timing and application method. Advantageous rates of application
are normally from 5 g to 2 kg of active ingredient (a.i.) per
hectare (ha), preferably from 10 g to 1 kg a.i./ha, most preferably
from 20 g to 600 g a.i./ha. When used as seed drenching agent,
convenient rates of application are from 10 mg to 1 g of active
substance per kg of seeds.
[0051] Suspension concentrates are aqueous formulations in which
finely divided solid particles of the active compound are
suspended. Such formulations include anti-settling agents and
dispersing agents and may further include a wetting agent to
enhance activity as well an anti-foam and a crystal growth
inhibitor. In use, these concentrates are diluted in water and
normally applied as a spray to the area to be treated. The amount
of active ingredient may range from 0.5% to 95% of the
concentrate.
[0052] Wettable powders are in the form of finely divided particles
which disperse readily in water or other liquid carriers. The
particles contain the active ingredient retained in a solid matrix.
Typical solid matrices include fuller's earth, kaolin clays,
silicas and other readily wet organic or inorganic solids. Wettable
powders normally contain from 5% to 95% of the active ingredient
plus a small amount of wetting, dispersing or emulsifying
agent.
[0053] Emulsifiable concentrates are homogeneous liquid
compositions dispersible in water or other liquid and may consist
entirely of the active compound with a liquid or solid emulsifying
agent, or may also contain a liquid carrier, such as xylene, heavy
aromatic naphthas, isophorone and other non-volatile organic
solvents. In use, these concentrates are dispersed in water or
other liquid and normally applied as a spray to the area to be
treated. The amount of active ingredient may range from 0.5% to 95%
of the concentrate.
[0054] Granular formulations include both extrudates and relatively
coarse particles and are usually applied without dilution to the
area in which control of plant pathogenic fungi is required.
Typical carriers for granular formulations include sand, fuller's
earth, attapulgite clay, bentonite clays, montmorillonite clay,
vermiculite, perlite, calcium carbonate, brick, pumice,
pyrophyllite, kaolin, dolomite, plaster, wood flour, ground corn
cobs, ground peanut hulls, sugars, sodium chloride, sodium
sulphate, sodium silicate, sodium borate, magnesia, mica, iron
oxide, zinc oxide, titanium oxide, antimony oxide, cryolite,
gypsum, diatomaceous earth, calcium sulphate and other organic or
inorganic materials which absorb or which can be coated with the
active compound. Granular formulations normally contain 5% to 25%
of active ingredients which may include surface-active agents such
as heavy aromatic naphthas, kerosene and other petroleum fractions,
or vegetable oils; and/or stickers such as dextrins, glue or
synthetic resins.
[0055] Dusts are free-flowing admixtures of the active ingredient
with finely divided solids such as talc, clays, flours and other
organic and inorganic solids which act as dispersants and
carriers.
[0056] Microcapsules are typically droplets or granules of the
active ingredient enclosed in an inert porous shell which allows
escape of the enclosed material to the surroundings at controlled
rates. Encapsulated droplets are typically 1 to 50 microns in
diameter. The enclosed liquid typically constitutes 50 to 95% of
the weight of the capsule and may include solvent in addition to
the active compound. Encapsulated granules are generally porous
granules with porous membranes sealing the granule pore openings,
retaining the active species in liquid form inside the granule
pores. Granules typically range from 1 millimetre to 1 centimetre
and preferably 1 to 2 millimetres in diameter. Granules are formed
by extrusion, agglomeration or prilling, or are naturally
occurring. Examples of such materials are vermiculite, sintered
clay, kaolin, attapulgite clay, sawdust and granular carbon. Shell
or membrane materials include natural and synthetic rubbers,
cellulosic materials, styrene-butadiene copolymers,
polyacrylonitriles, polyacrylates, polyesters, polyamides,
polyureas, polyurethanes and starch xanthates.
[0057] Other useful formulations for agrochemical applications
include simple solutions of the active ingredient in a solvent in
which it is completely soluble at the desired concentration, such
as acetone, alkylated naphthalenes, xylene and other organic
solvents. Pressurised sprayers, wherein the active ingredient is
dispersed in finely-divided form as a result of vaporisation of a
low boiling dispersant solvent carrier, may also be used.
[0058] Suitable agricultural adjuvants and carriers that are useful
in formulating the compositions of the invention in the formulation
types described above are well known to those skilled in the
art.
[0059] Liquid carriers that can be employed include, for example,
water, toluene, xylene, petroleum naphtha, crop oil, acetone,
methyl ethyl ketone, cyclohexanone, acetic anhydride, acetonitrile,
acetophenone, amyl acetate, 2-butanone, chlorobenzene, cyclohexane,
cyclohexanol, alkyl acetates, diacetonalcohol, 1,2-dichloropropane,
diethanolamine, p-diethylbenzene, diethylene glycol, diethylene
glycol abietate, diethylene glycol butyl ether, diethylene glycol
ethyl ether, diethylene glycol methyl ether, N,N-dimethyl
formamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol,
dipropylene glycol methyl ether, dipropylene glycol dibenzoate,
diproxitol, alkyl pyrrolidinone, ethyl acetate, 2-ethyl hexanol,
ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha
pinene, d-limonene, ethylene glycol, ethylene glycol butyl ether,
ethylene glycol methyl ether, gamma-butyrolactone, glycerol,
glycerol diacetate, glycerol monoacetate, glycerol triacetate,
hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate,
isooctane, isophorone, isopropyl benzene, isopropyl myristate,
lactic acid, laurylamine, mesityl oxide, methoxy-propanol, methyl
isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl
octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane,
n-octylamine, octadecanoic acid, octyl amine acetate, oleic acid,
oleylamine, o-xylene, phenol, polyethylene glycol (PEG400),
propionic acid, propylene glycol, propylene glycol monomethyl
ether, p-xylene, toluene, triethyl phosphate, triethylene glycol,
xylene sulfonic acid, paraffin, mineral oil, trichloroethylene,
perchloroethylene, ethyl acetate, amyl acetate, butyl acetate,
methanol, ethanol, isopropanol, and higher molecular weight
alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol,
octanol, etc., ethylene glycol, propylene glycol, glycerine and
N-methyl-2-pyrrolidinone. Water is generally the carrier of choice
for the dilution of concentrates.
[0060] Suitable solid carriers include, for example, talc, titanium
dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr,
chalk, diatomaxeous earth, lime, calcium carbonate, bentonite clay,
fuller's earth, cotton seed hulls, wheat flour, soybean flour,
pumice, wood flour, walnut shell flour and lignin.
[0061] A broad range of surface-active agents are advantageously
employed in both said liquid and solid compositions, especially
those designed to be diluted with carrier before application. These
agents, when used, normally comprise from 0.1% to 15% by weight of
the formulation. They can be anionic, cationic, non-ionic or
polymeric in character and can be employed as emulsifying agents,
wetting agents, suspending agents or for other purposes. Typical
surface active agents include salts of alkyl sulfates, such as
diethanolammonium lauryl sulphate; alkylarylsulfonate salts, such
as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide
addition products, such as nonylphenol-C.sub. 18 ethoxylate;
alcohol-alkylene oxide addition products, such as tridecyl
alcohol-C.sub. 16 ethoxylate; soaps, such as sodium stearate;
alkylnaphthalenesulfonate salts, such as sodium
dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate
salts, such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol
esters, such as sorbitol oleate; quaternary amines, such as lauryl
trimethylammonium chloride; polyethylene glycol esters of fatty
acids, such as polyethylene glycol stearate; block copolymers of
ethylene oxide and propylene oxide; and salts of mono and dialkyl
phosphate esters.
[0062] Other adjuvants commonly utilized in agricultural
compositions include crystallisation inhibitors, viscosity
modifiers, suspending agents, spray droplet modifiers, pigments,
antioxidants, foaming agents, anti-foaming agents, light-blocking
agents, compatibilizing agents, antifoam agents, sequestering
agents, neutralising agents and buffers, corrosion inhibitors,
dyes, odorants, spreading agents, penetration aids, micronutrients,
emollients, lubricants and sticking agents.
[0063] In addition, further, other biocidally active ingredients or
compositions may be combined with the compound of formula (I) and
used in the methods of the invention and applied simultaneously or
sequentially with the compound of formula (I). When applied
simultaneously, these further active ingredients may be formulated
together with the compound of formula (I) or mixed in, for example,
the spray tank. These further biocidally active ingredients may be
fungicides, herbicides, insecticides, bactericides, acaricides,
nematicides and/or plant growth regulators.
[0064] Accordingly, the present invention provides a composition
comprising a compound of formula (I) and (i) a fungicide, (ii) a
herbicide, (iii) an insecticide, (iv) a bactericide, (v) an
acaricide, (vi) a nematicide and/or (vii) a plant growth
regulator.
[0065] Additionally, the present invention provides for the use of
a composition in the methods of the present invention, said
composition comprising a compound of formula (I) and (i) a
fungicide, (ii) a herbicide, (iii) an insecticide, (iv) a
bactericide, (v) an acaricide, (vi) a nematicide and/or (vii) a
plant growth regulator.
[0066] The compounds and combinations of the present invention may
also be used for controlling fungal infection (particularly by mold
and mildew) of technical materials, including protecting technical
material against attack of fungi and reducing or eradicating fungal
infection of technical materials after such infection has occurred.
Technical materials include, for example, organic and inorganic
materials wood, paper, leather, natural and synthetic fibers,
composites thereof such as particle board, plywood, wall-board and
the like, woven and non-woven fabrics, construction surfaces and
materials, cooling and heating system surfaces and materials,
ventilation and air conditioning system surfaces and materials, and
the like. The compounds and combinations according to the present
invention can be applied to such materials or surfaces in an amount
effective to inhibit or prevent disadvantageous effects such as
decay, discoloration or mold in like manner as described above.
Structures and dwellings constructed using or incorporating
technical materials in which such compounds or combinations have
been applied are likewise protected against attack by fungi.
[0067] Accordingly, in a further aspect, the present invention
provides a method of controlling or preventing infestation of
technical materials by pathogenic microorganisms, comprising
applying a compound of formula (I) or composition thereof said
technical materials, parts thereof or the locus thereof in an
amount effective to control said microorganisms.
[0068] The compounds and combinations of the present invention may
also be used in the treatment of fungal infections of human and
animal subjects, such as horses, cattle, sheep, dogs, cats) for
medical and veterinary purposes. Examples of such infections
include Onychomycosis, sporotichosis, hoof rot, jungle rot,
Pseudallescheria boydii, scopulariopsis or athletes foot, sometimes
generally referred to as "white-line" disease, as well as fungal
infections in immunocomprised patients such as AIDS patients and
transplant patients. Thus, fungal infections may be of skin or of
keratinaceous material such as hair, hooves, or nails, as well as
systemic infections such as those caused by Candida spp.,
Cryptococcus neoformans, and Aspergillus spp., such as as in
pulmonary aspergillosis and Pneumocystis carinii pneumonia. The
compounds and combinations of the present invention may be combined
with a pharmaceutically acceptable carrier and administered or
applied to such subjects or infections (e.g., topically,
parenterally) in an amount effective to treat the infection in
accordance with known techniques.
[0069] Accordingly, in a further aspect, the present invention
provides a method of treating a fungal infection in a subject in
need thereof, comprising administering a compound of formula (I) or
composition thereof to said subject in an amount effective to treat
said fungal infection.
[0070] Compounds of formula (I) may be prepared using the methods
below.
[0071] Isoxazoles in which R.sup.1.noteq.H may be prepared from (I)
(R.sup.1=H) using standard acylation or carbamoylation conditions.
For example, the acetate derivative of (I) (R.sup.1=COCH.sub.3) may
be synthesised from the alcohol (I) (R.sup.1=H) by reaction with
acetic anhydride and pyridine in ether solvent at room temperature
overnight. Acylations may be carried out using either acid
anhydrides (e.g. acetic anhydride, propionic anhydride) or acid
chlorides (e.g. benzoyl chloride) in the presence of an organic
base in an inert solvent (e.g. ether, dichloromethane).
Carbamoylations are effected by treating alcohols (I) with a strong
base such as sodium hydride followed by a carbamoyl chloride (e.g.
N,N-dimethylcarbamoyl chloride) in an inert solvent such as DMF
(dimethylformamide).
Example 1
[3-(4-Chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)isoxazol-4-yl]pyridin-3-
-yl-methanol
(i) Preparation of 3-(2,4-difluorophenyl)-1-pyridin-3-yl-propynone
(3)
##STR00005##
[0073] 1-Ethynyl-2,4-difluorobenzene (24 g, 0.17 mol) was dissolved
in THF (350 ml) and the reaction mixture was cooled at -78.degree.
C. A solution of n-BuLi, 2.5 M in hexane, (76.5 ml, 0.19 mol) was
added dropwise over 70 minutes maintaining the temperature below
-70.degree. C. The mixture was stirred at this temperature for a
further 10 minutes after the addition was finished. A solution of
the Weinreb amide 2 (prepared according to WO 05/097760, Letters in
Organic Chemistry, 4, 20, 2007) (28.9 g, 0.17 mol) in THF (100 ml)
was added dropwise over 20 minutes to the solution above keeping
the temperature below -70.degree. C. The mixture was now warmed to
-50.degree. C. obtaining a solution that was further stirred for 1
hour at this temperature. The reaction mixture was quenched with a
saturated solution of ammonium chloride (100 ml) and allowed to
warm to room temperature. The reaction was then poured into a
mixture of ethyl acetate/water. Successively, the aqueous phase was
washed twice with ethyl acetate. The combined organic layers were
washed with brine, dried over sodium sulphate, filtered and
concentrated. The crude was recrystallised from diethyl ether
obtaining 28 g of the desired product. The mother liquors were
concentrated and the residue was purified by column chromatography
on alumina using a mixture of cyclohexane/ethyl acetate 3:1.
Totally, 29.8 g (70%) of brown compound were obtained.
[0074] .sup.1H NMR (CDCl.sub.3): .delta. 7.02 (m, 1), 7.58 (m, 1),
7.71 (m, 1), 8.56 (m, 1) 8.90 (m, 1) and 9.48 ppm (m, 1). MS m/z:
244.0 (M+H).
(ii) Preparation of
[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)isoxazol-4-yl]pyridin--
3-yl-methanone (5)
##STR00006##
[0076] To a solution of 121 g (697 mmol) of
2-fluoro-4-chloromethylbenzaldehyde oxime in 500 ml of dimethyl
formamide was added 93 g (697 mmol) of N-chlorosuccinimide (see K.
C. Liu, B. R. Shelton, and R. K. Howe, J. Org. Chem. 1980, 45,
3916). The reaction mixture was stirred at room temperature for two
hours and then diluted with ethyl acetate. The ethyl acetate
solution was washed with water, saturated sodium chloride and dried
over magnesium sulfate. The drying agent was filtered off and
solvent removed by rotoevaporation to give 130 g (90%) of yellow
crystalline 2-fluoro-4-chloro-N-hydroxybenzenecarboximidoyl
chloride.
[0077] A mixture of 46.7 g (0.22 mol) of
2-fluoro-4-chloro-N-hydroxybenzenecarboximidoyl chloride, 42 g
(0.17 mol) of 3-(2,4-difluorophenyl)-1-pyridin-3-yl-propynone (3),
and 21.76 g (0.26 mol) of sodium bicarbonate in 500 mL of isopropyl
alcohol was heated at 85.degree. C. for 21 hours. The reaction
mixture was diluted with ethyl acetate and washed successively with
saturated ammonium chloride, water, and saturate sodium chloride
solution, and was dried over magnesium sulfate. The drying agent
was filtered off and the ethyl acetate was removed by
rotoevaporation. The crude was recrystallised from diethyl ether
obtaining the desired product as a yellowish solid (50.28 g,
70.2%).
[0078] .sup.1H NMR (CDCl.sub.3): .delta. 6.75 (m, 1), 7.05 (m, 2),
7.27 (m, 2), 7.67 (t, 1), 7.80 (m, 1), 8.03 (m, 1), 8.66 (m, 1) and
8.82 ppm (d, 1). MS m/z: 415 (M+H).
(iii) Preparation of
[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)isoxazol-4-yl]pyridin--
3-yl-methanol (6)
##STR00007##
[0080] To a solution of 5 (26.5 g, 63.9 mmol) in a mixture of
THF/methanol (400 ml/40 ml) at 0.degree. C. was added 2.42 g (63.7
mmol) of sodium borohydride. The mixture was stirred for 1.5 hours
and then diluted with ethyl acetate. The ethyl acetate solution was
washed with saturated sodium chloride solution and dried over
magnesium sulfate. The drying agent was filtered off and the ethyl
acetate was removed by rotoevaporation. The reaction mixture was
purified by column chromatography using a mixture of heptane/ethyl
acetate 1:1. The desired compound was obtained as white crystals
(17.5 g, 66%). mp=138-140.degree. C.
[0081] .sup.1H NMR (CDCl.sub.3): .delta. 4.19 (bs, 1), 5.89 (s, 1),
6.99 (m, 5), 7.28 (t, 1), 7.43 (d, 1), 7.59 (q, 1), and 8.19 (d, 1)
and 8.23 ppm (d, 1). MS m/z: 417 (M+H).
Example 2
(S)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenl)isoxazol-4-yl]pyridi-
n-3-yl-methanol
##STR00008##
[0083] Each enantiomer was isolated by preparative chromatography
using the racemic mixture 6 as starting material.
Preparative Method:
Column: 250.times.76 mm CHIRALPAK.RTM. AD 20 .mu.m;
[0084] Mobil phase: n-heptane/ethanol 70/30 (v/v) Flow rate: 270
ml/min
Detection: UV 280 nm
Temperature: 25.degree. C.
Analytical Method:
Column: 250.times.4.6 mm CHIRALPAK.RTM. AD-H 5 .mu.m;
[0085] Mobil phase: n-heptane/ethanol/diethylamine 70/30/0.1
(v/v/v) Flow rate: 1 ml/min
Detection: UV 230 nm
Temperature: 25.degree. C.
[0086] The first eluting enantiomer had a retention time of 7.6 min
([.alpha.]=+58.07, C=0.025 M, THF) while the second enantiomer had
a retention time of 9.9 min ([.alpha.]=-57.59, C=0.025 M, THF). The
second eluting enantiomer is the (S)-enantiomer.
BIOLOGICAL EXAMPLES
[0087] The fungicidal properties of Example 2 were demonstrated in
the following examples.
[0088] Botrytis cinerea (Gray mould): Conidia of the fungus from
cryogenic storage were directly mixed into nutrient broth (PDB
potato dextrose broth). After placing a (DMSO) solution of the test
compounds into a microtiter plate (96-well format) the nutrient
broth containing the fungal spores was added. The test plates were
incubated at 24.degree. C. and the inhibition of growth was
determined photometrically after 72 hours. Example 2 gave at least
80% control of Botrytis cinerea at 200 ppm.
[0089] Mycosphaerella arachidis (syn. Cercospora arachidicola),
Brown leaf spot of groundnut (peanut): Conidia of the fungus from
cryogenic storage were directly mixed into nutrient broth (PDB
potato dextrose broth). After placing a (DMSO) solution of the test
compounds into a microtiter plate (96-well format) the nutrient
broth containing the fungal spores was added. The test plates were
incubated at 24.degree. C. and the inhibition of growth was
determined photometrically after 72 hours at 620 nm. Example 2 gave
at least 80% control of Mycosphaerella arachidis at 200 ppm.
[0090] Septoria tritici (leaf blotch): Conidia of the fungus from
cryogenic storage were directly mixed into nutrient broth (PDB
potato dextrose broth). After placing a (DMSO) solution of the test
compounds into a microtiter plate (96-well format) the nutrient
broth containing the fungal spores was added. The test plates were
incubated at 24.degree. C. and the inhibition of growth was
determined photometrically after 72 hours. Example 2 gave at least
80% control of Septoria tritici at 200 ppm.
[0091] Monographella nivalis (syn. Microdochium nivale, Fusarium
nivale), snow mould, foot rot of cereals: Conidia of the fungus
from cryogenic storage were directly mixed into nutrient broth (PDB
potato dextrose broth). After placing a (DMSO) solution of the test
compounds into a microtiter plate (96-well format) the nutrient
broth containing the fungal spores was added. The test plates were
incubated at 24.degree. C. and the inhibition of growth was
determined photometrically after 72 hours at 620 nm. Example 2 gave
at least 80% control of Monographella nivalis at 200 ppm.
[0092] Fusarium culmorum (root rot): Conidia of the fungus from
cryogenic storage were directly mixed into nutrient broth (PDB
potato dextrose broth). After placing a (DMSO) solution of the test
compounds into a microtiter plate (96-well format) the nutrient
broth containing the fungal spores was added. The test plates were
incubated at 24.degree. C. and the inhibition of growth was
determined photometrically after 48 hours. Example 2 gave at least
80% control of Fusarium culmorum at 200 ppm.
[0093] Rhizoctonia solani (foot rot, damping-off): Mycelial
fragments of the fungus, prepared from a fresh liquid culture, were
directly mixed into nutrient broth (PDB potato dextrose broth).
After placing a (DMSO) solution of the test compounds into a
microtiter plate (96-well format) the nutrient broth containing the
fungal mycelium was added. The test plates were incubated at
24.degree. C. and the inhibition of growth was determined
photometrically after 48 h. Example 2 gave at least 80% control of
Rhizoctonia solani at 200 ppm.
* * * * *