WO2006105056A2 - Insecticidal 2,4-diaminoquinazolines and related derivatives - Google Patents

Insecticidal 2,4-diaminoquinazolines and related derivatives Download PDF

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Publication number
WO2006105056A2
WO2006105056A2 PCT/US2006/011218 US2006011218W WO2006105056A2 WO 2006105056 A2 WO2006105056 A2 WO 2006105056A2 US 2006011218 W US2006011218 W US 2006011218W WO 2006105056 A2 WO2006105056 A2 WO 2006105056A2
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optionally substituted
compound
group
halogen
hydrogen
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PCT/US2006/011218
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French (fr)
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WO2006105056A3 (en
Inventor
John A. Dixson
Elizabeth G. Rowley
Saroj Sehgel
Thomas G. Cullen
Michael J. Wyle
Frank J. Zawacki
Louis V. Lafrance Iii
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Fmc Corporation
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Publication of WO2006105056A3 publication Critical patent/WO2006105056A3/en

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    • 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
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • 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
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/16—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof the nitrogen atom being part of a heterocyclic ring
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/38—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the group >N—CO—N< where at least one nitrogen atom is part of a heterocyclic ring; Thio analogues thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/48—Two nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/16—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • the present invention generally relates to pesticidal compounds and their use in controlling insects and acarids.
  • it pertains to compositions of insecticidal 2,4-diaminoquinazolines, related derivatives and agriculturally acceptable salts thereof, and methods for their use in controlling insects and acarids.
  • insects in general can cause significant damage, not only to crops grown in agriculture, but also, for example, to structures and turf where the damage is caused by soil-borne insects, such as termites and white grubs. Such damage may result in the loss of millions of dollars of value associated with a given crop, turf or structures.
  • Insecticides and acaricides are useful for controlling insects and acarids which may otherwise cause significant damage to crops such as wheat, corn, soybeans, potatoes, and cotton to name a few.
  • insecticides and acaricides are desired which can control the insects and acarids without damaging the crops, and which have no deleterious effects to mammals and other living organisms.
  • R is selected from the group consisting of hydrogen, haloalkyl, alkoxyalkyl, alkphenylalkyl, alkoxycarbonylalkyl, alkthioalkyl, alkoxycarbonylaminoalkyl, phenoxycarbonylaminoalkyl, phenylcarbonylalkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl and optionally substituted cycloalkalkyl, wherein the optional substituents are selected from the group consisting of halogen, alkyl, aryl, alkamino, dialkylamino, alkenylalkyl, alkynylalkyl, carbonylaryl, phenylalkyl, alkoxycarbonyl, haloalkcarbonyl, alkoxyalkyl, 3-pyridylcarbonyl, heterocyclyl, phenoxythionyl, phenylaminocarbonyl, pheny
  • R 6 and R 10 are independently selected from the group consisting of halogen, alkyl, alkoxy and cyano, and wherein * denotes a point of attachment;
  • R 2 and R 4 are independently selected from hydrogen or alkylcarbonyl;
  • R 5 is selected from the group consisting of optionally substituted aryloxy, optionally substituted cycloalkyl and
  • optional substituents are independently selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy and SF 5
  • R 7 , R 8 and R 9 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, SF 5 and either of R and
  • R 8 , or R 8 and R 9 taken together with -OCH 2 O-, -OC(CH 3 ) 2 CH 2 - or -OC(CH 3 ) 2 O-, forming a benzo-fused ring; and the corresponding agriculturally acceptably salts thereof.
  • the present invention is also directed to methods of controlling insects, where control is desired, which comprise applying an insecticidally effective amount of the above composition to the locus of crops, or other areas where insects are present or are expected to be present.
  • One aspect of the present invention relates to certain new and useful compounds, namely novel 2,4-diaminoquinazolines and related derivatives (hereinafter termed "compounds of formula I") as depicted in formula I:
  • R is selected from the group consisting of hydrogen, haloalkyl, alkoxyalkyl, alkphenylalkyl, alkoxycarbonylalkyl, alkthioalkyl, alkoxycarbonylarninoalkyl, phenoxycarbonylaminoalkyl, phenylcarbonylalkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl and optionally substituted cycloalkalkyl, wherein the optional substituents are selected from the group consisting of halogen, alkyl, aryl, alkamino, dialkylamino, alkenylalkyl, alkynylalkyl, carbonylaryl, phenylalkyl, alkoxycarbonyl, haloalkcarbonyl, alkoxyalkyl, 3-pyridylcarbonyl, heterocyclyl, phenoxythionyl, phenylaminocarbonyl, phen
  • A is selected from the group consisting of optionally substituted cycloalkyl, optionally substituted thiopheneyl,
  • R 2 and R 4 are independently selected from hydrogen or alkylcarbonyl
  • R 5 is selected from the group consisting of optionally substituted aryloxy, optionally substituted cycloalkyl and
  • optional substituents are independently selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy and SF 5
  • R 7 , R 8 and R 9 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, SF 5 and either of R 7 and R 8 , or R 8 and R 9 taken together with -OCH 2 O-, -OC(CH 3 ) 2 CH 2 - or -OC(CH 3 ) 2 O-, forming a benzo-fused ring; and the corresponding agriculturally acceptably salts thereof.
  • Preferred species of the present invention are those compounds of formula I where R 2 is hydrogen and A is
  • More preferred species of the present invention are those compounds of formula I where R 2 is hydrogen, A is
  • R 4 is hydrogen and R 5 is
  • R , R and R are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, SF 5 and either of R 7 and R 8 , or R 8 and R 9 taken together with -OCH 2 O-, -OC(CH 3 ) 2 CH 2 - or -OC(CH 3 ) 2 O-, forming a benzo-fused ring.
  • R 4 is hydrogen and R 5 is
  • R 8 is hydrogen
  • R and R 9 are independently selected from the group consisting of halogen, haloalkyl and haloalkoxy, and R is
  • Z 1 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl and haloalkoxy; more particularly wherein R 7 , R 9 and Z 1 are halogen.
  • R is selected from the group consisting of
  • R 14 , R 22 , R 26 and R 27 are independently selected from the group consisting of
  • R 5 is selected from the group consisting of
  • the compounds of the present invention may possess asymmetric centers, which can give rise to optical enantiomorphs and diastereomers.
  • the compounds may exist in two or more forms, i.e., polymorphs, which are significantly different in physical and chemical properties.
  • the compounds of the present invention may also exist as tautomers, in which migration of a hydrogen atom within the molecule results in two or more structures, which are in equilibrium.
  • the compounds of the present invention may also possess acidic or basic moieties, which may allow for the formation of agriculturally acceptable salts or agriculturally acceptable metal complexes.
  • Agriculturally acceptable salts and metal complexes include, without limitation, for example, ammonium salts, the salts of organic and inorganic acids, such as hydrochloric acid, sulfonic acid, ethanesulfonic acid, trifiuoroacetic acid, methylbenzenesulfonic acid, phosphoric acid, gluconic acid, pamoic acid, and other acid salts, and the alkali metal and alkaline earth metal complexes with, for example, sodium, potassium, lithium, magnesium, calcium, and other metals.
  • compositions containing an insecticidally effective amount of at least one compound of formula I with an insecticidally compatible carrier therefor Another aspect of the present invention relates to compositions containing an insecticidally effective amount of at least one compound of formula I, and an effective amount of at least one second compound, with an insecticidally compatible carrier therefor.
  • Another aspect of the present invention relates to methods of controlling insects by applying an insecticidally effective amount of a composition set forth above to a locus of crops such as, without limitation, cereals, cotton, vegetables, and fruits, or other areas where insects are present or are expected to be present.
  • the present invention also includes the use of the compounds and compositions set forth herein for control of non-agricultural insect species, for example, dry wood termites and subterranean termites; as well as for use as pharmaceutical agents and compositions thereof.
  • the present insecticidal compounds may be formulated as a granular of relatively large particle size (for example, 8/16 or 4/8 US Mesh), as water-soluble or water-dispersible granules, as powdery dusts, as wettable powders, as emulsifiable concentrates, as aqueous emulsions, as solutions, or as any of other known types of agriculturally-useful formulations, depending on the desired mode of application. It is to be understood that the amounts specified in this specification are intended to be approximate only, as if the word "about" were placed in front of the amounts specified.
  • insecticidal compositions may be applied either as water-diluted sprays, or dusts, or granules to the areas in which suppression of insects is desired. These formulations may contain as little as 0.1%, 0.2% or 0.5% to as much as 95% or more by weight of active ingredient.
  • Dusts are free flowing admixtures of the active ingredient with finely divided solids such as talc, natural clays, kieselguhr, flours such as walnut shell and cottonseed flours, and other organic and inorganic solids which act as dispersants and carriers for the toxicant; these finely divided solids have an average particle size of less than about 50 microns.
  • a typical dust formulation useful herein is one containing 1.0 part or less of the insecticidal compound and 99.0 parts of talc.
  • Wettable powders, also useful formulations for insecticides are in the form of finely divided particles that disperse readily in water or other dispersant.
  • wettable powder is ultimately applied to the locus where insect control is needed either as a dry dust or as an emulsion in water or other liquid.
  • Typical carriers for wettable powders include Fuller's earth, kaolin clays, silicas, and other highly absorbent, readily wet inorganic diluents. Wettable powders normally are prepared to contain about 5-80% of active ingredient, depending on the absorbency of the carrier, and usually also contain a small amount of a wetting, dispersing or emulsifying agent to facilitate dispersion.
  • a useful wettable powder formulation contains 80.0 parts of the insecticidal compound, 17.9 parts of Palmetto clay, and 1.0 part of sodium lignosulfonate and 0.3 part of sulfonated aliphatic polyester as wetting agents. Additional wetting agent and/or oil will frequently be added to a tank mix for to facilitate dispersion on the foliage of the plant.
  • ECs emulsif ⁇ able concentrates
  • ECs emulsif ⁇ able concentrates
  • ECs emulsif ⁇ able concentrates
  • these concentrates are dispersed in water or other liquid carrier and normally applied as a spray to the area to be treated.
  • the percentage by weight of the essential active ingredient may vary according to the manner in which the composition is to be applied, but in general comprises 0.5 to 95% of active ingredient by weight of the insecticidal composition.
  • Flowable formulations are similar to ECs, except that the active ingredient is suspended in a liquid carrier, generally water.
  • Flowables like ECs, may include a small amount of a surfactant, and will typically contain active ingredients in the range of 0.5 to 95%, frequently from 10 to 50%, by weight of the composition.
  • flowables may be diluted in water or other liquid vehicle, and are normally applied as a spray to the area to be treated.
  • Typical wetting, dispersing or emulsifying agents used in agricultural formulations include, but are not limited to, the alkyl and alkylaryl sulfonates and sulfates and their sodium salts; alkylaryl polyether alcohols; sulfated higher alcohols; polyethylene oxides; sulfonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of polyhydric alcohols and the ethylene oxide addition products of such esters; and the addition product of long-chain mercaptans and ethylene oxide.
  • Many other types of useful surface-active agents are available in commerce. Surface-active agents, when used, normally comprise 1 to 15% by weight of the composition.
  • compositions include suspensions of the active ingredient in a relatively non-volatile solvent such as water, corn oil, kerosene, propylene glycol, or other suitable solvents.
  • Still other useful formulations for insecticidal 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, or other organic solvents.
  • Granular formulations, wherein the toxicant is carried on relative coarse particles, are of particular utility for aerial distribution or for penetration of cover crop canopy.
  • Pressurized sprays, typically aerosols wherein the active ingredient is dispersed in finely divided form as a result of vaporization of a low- boiling dispersant solvent carrier may also be used.
  • Water-soluble or water- dispersible granules are free flowing, non-dusty, and readily water-soluble or water- miscible.
  • the granular formulations, emulsifiable concentrates, flowable concentrates, aqueous emulsions, solutions, etc. may be diluted with water to give a concentration of active ingredient in the range of say 0.1% or 0.2% to 1.5% or 2%.
  • the active insecticidal compounds of this invention may be formulated and/or applied with one or more second compounds.
  • Such combinations may provide certain advantages, such as, without limitation, exhibiting synergistic effects for greater control of insect pests, reducing rates of application of insecticide thereby minimizing any impact to the environment and to worker safety, controlling a broader spectrum of insect pests, safening of crop plants to phytotoxicity, and improving tolerance by non-pest species, such as mammals and fish.
  • Second compounds include, without limitation, other pesticides, plant growth regulators, fertilizers, soil conditioners, or other agricultural chemicals.
  • an effective amount and concentration of the active compound is of course employed; the amount may vary in the range of, e.g. about 0.001 to about 3 kg/ha, preferably about 0.03 to about 1 kg/ha.
  • higher application rates e.g., four times the rates mentioned above may be employed.
  • the herbicides include, without limitation, for example: N- (phosphonomethyl)glycines such as glyphosate; aryloxyalkanoic acids such as 2,4- D, MCPA, and MCPP; ureas such as isoproturon; imidazolinones such as imazapyr, imazamethabenz, imazethapyr, and imazaquin; diphenyl ethers such as acifluorfen, bifenox, and fomasafen; hydroxybenzonitriles such as ioxynil and bromoxynil; sulfonylureas such as chlorimuron, achlorsulfuron, bensulfuron, pyrazosulfuron, thifensulfuron, and triasulfuron; 2-(4-aryloxymethyl)glycines such as glyphosate; aryloxyalkanoic acids such as 2,4- D, MCPA, and MCPP;
  • the other insecticides include, for example: organophosphate insecticides, such as chlorpyrifos, diazinon, dimethoate, malathion, parathion- methyl, and terbufos; pyrethroid insecticides, such as fenvalerate, deltamethrin, fenpropathrin, cyfluthrin, flucythrinate, permethrin, ⁇ / ⁇ -cypermethrin, beta- cypermethrin, zet ⁇ -cypermethrin, bifenthrin, cypermethrin, resolved cyhalothrin, etofenprox, esfenvalerate, tralomethrin, tefluthrin, cycloprothrin, bet
  • organophosphate insecticides such as chlorpyrifos, diazinon, dimethoate, malathion, parathion- methyl,
  • the fungicides include, for example: benzimidazole fungicides, such as benomyl, carbendazim, thiabendazole, and thiophanate-methyl; 1,2,4-triazole fungicides, such as epoxyconazole, cyproconazole, flusilazole, flutriafol, propiconazole, tebuconazole, triadimefon, and triadimenol; substituted anilide fungicides, such as metalaxyl, oxadixyl, procymidone, and vinclozolin; organophosphoras fungicides, such as fosetyl, iprobenfos, pyrazophos, edifenphos, and tolclofos-methyl; morpholine
  • the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other pesticides such as nematicides
  • the nematicides include, for example: carbofuran, carbosulfan, turbufos, aldecarb, ethoprop, fenamphos, oxamyl, isazofos, cadusafos, and other nematicides.
  • the plant growth regulators include, for example: maleic hydrazide, chlormequat, ethephon, gibberellin, mepiquat, thidiazon, inabenf ⁇ de, triaphenthenol, paclobutrazol, unaconazol, DCPA, prohexadione, trinexapac-ethyl, and other plant growth regulators.
  • Soil conditioners are materials which, when added to the soil, promote a variety of benefits for the efficacious growth of plants.
  • Soil conditioners are used to reduce soil compaction, promote and increase effectiveness of drainage, improve soil permeability, promote optimum plant nutrient content in the soil, and promote better pesticide and fertilizer incorporation.
  • the soil conditioners include organic matter, such as humus, which promotes retention of cation plant nutrients in the soil; mixtures of cation nutrients, such as calcium, magnesium, potash, sodium, and hydrogen complexes; or microorganism compositions which promote conditions in the soil favorable to plant growth.
  • microorganism compositions include, for example, bacillus, pseudomonas, azotobacter, azospirillum, rhizobium, and soil-borne cyanobacteria.
  • Fertilizers are plant food supplements, which commonly contain nitrogen, phosphorus, and potassium.
  • the fertilizers include nitrogen fertilizers, such as ammonium sulfate, ammonium nitrate, and bone meal; phosphate fertilizers, such as superphosphate, triple superphosphate, ammonium sulfate, and dianimonium sulfate; and potassium fertilizers, such as muriate of potash, potassium sulfate, and potassium nitrate, and other fertilizers.
  • nitrogen fertilizers such as ammonium sulfate, ammonium nitrate, and bone meal
  • phosphate fertilizers such as superphosphate, triple superphosphate, ammonium sulfate, and dianimonium sulfate
  • potassium fertilizers such as muriate of potash, potassium sulfate, and potassium nitrate, and other fertilizers.
  • alkyl and “alkoxy”, used alone or as part of a larger moiety, includes straight or branched chains of at least one or two carbon atoms, as appropriate to the substituent, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms.
  • haloalkyl and haloalkoxy alone or as part of a larger moiety, include straight or branched chain alkyls of 1 to 14 carbon atoms, preferably lower straight or branched chain alkyls of 1 to 6 carbon atoms, wherein one or more hydrogen atoms have been replaced with halogen atoms, as, for example, trifluoromethyl or 2,2,2-trifluoroethoxy, respectively.
  • alkenyl and “alkynyl” used alone or as part of a larger moiety includes straight or branched chains of at least two carbon atoms containing at least one carbon-carbon double bond or triple bond, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms.
  • heterocyclic refers to a non-aromatic ring structure of four to eight atoms consisting of carbon and nitrogen, and may include oxygen or sulfur.
  • Five member rings include, without limitation, for example, pyrrolidine.
  • Six member rings include, without limitation, for example, piperazine, piperidine, morpholine and thiomorpholine.
  • aryl refers to an aromatic ring structure, including fused rings, having four to ten carbon atoms, for example, phenyl or naphthyl.
  • heteroaryl and heterocyclyl refer to an aromatic ring structure, including fused rings, in which at least one of the atoms is other than carbon, for example, without limitation, sulfur, oxygen, or nitrogen.
  • polycyclyl refers to a non-aromatic fused ring structure.
  • Ammonio refers to compounds of nitrogen that may be considered derived from ammonia and includes primary, secondary and tertiary amines wherein one or more of the hydrogen atoms is replaced with alkyl groups.
  • GC analysis refers to gas chromatographic analysis of, for example, a chemical reaction mixture.
  • DMF refers to N,N-dimethylformamide.
  • THF tetrahydrofuran.
  • TEA triethylamine.
  • ambient temperature or “room temperature” often abbreviated as "RT”, for example, in reference to a chemical reaction mixture temperature, refers to a temperature in the range of 20 0 C to 30 0 C.
  • insecticidal or "acaricidal”
  • insecticide or “acaricide” refers to a compound of the present invention, either alone or in admixture with at least one of a second compound, or with at least one compatible carrier, which causes the destruction or the inhibition of action of insects or acarids.
  • Cyclohexylamine 2 (5.7 mL, 50 mmol) was added to dichloroquinazoline 1 (5.0 g, 25 mmol) dissolved in 100 mL of tetrahydrofuran at 0 0 C. The mixture was stirred at ambient temperature under a nitrogen atmosphere for about 18 hours. The resulting solids were filtered off and washed with ethyl ether. The filtrate was evaporated to give 7.5 g of quinazoline 3 in tetrahydrofuran. This intermediate 3 was used in the next reaction without further purification.
  • the test was established as described above using sub-multiples of the standard 50 millimolar DMSO solution of candidate insecticide.
  • the standard 50 millimolar solution was diluted by the robot with DMSO to give 5, 0.5, 0.05, 0.005, 0.0005 millimolar, or more dilute solutions of the candidate insecticide.
  • each well of the test plate was placed one second instar tobacco budworm larvea, each weighing approximately five milligrams. After the larvae were placed in each well, the plate was sealed with clear polyfilm adhesive tape. The tape over each well was perforated to ensure an adequate air supply. The plates were then held in a growth chamber at 25 0 C and 60% relative humidity for five days (light 14 hours/day).
  • insecticidal activity for each rate of application of compound was assessed as percent inhibition of insect weight relative to the weight of insects from untreated controls, and percent mortality when compared to the total number of insects infested.

Abstract

Certain novel 2,4-diaminoquinazolines, related derivatives and agriculturally acceptable salts thereof have provided unexpected pesticidal activity. These compounds are represented by formula (I): wherein R, R2, R4, R5 and A are fully described herein. In addition, compositions comprising an insecticidally effective amount of at least one compound of formula (I), and optionally, an effective amount of at least one of a second compound are also disclosed; along with methods of controlling insects comprising applying said compositions to a locus where insects are present or are expected to be present.

Description

INSECTICIDAL 2.4-DTAMINOOUINAZOLINES AND RELATED DERIVATIVES
This application claims the benefit of U.S. Provisional Application No. 60/665,701 , filed March 28, 2005.
FIELD OF THE INVENTION
The present invention generally relates to pesticidal compounds and their use in controlling insects and acarids. In particular, it pertains to compositions of insecticidal 2,4-diaminoquinazolines, related derivatives and agriculturally acceptable salts thereof, and methods for their use in controlling insects and acarids.
BACKGROUND OF THE INVENTION
It is well known that insects in general can cause significant damage, not only to crops grown in agriculture, but also, for example, to structures and turf where the damage is caused by soil-borne insects, such as termites and white grubs. Such damage may result in the loss of millions of dollars of value associated with a given crop, turf or structures. Thus, there is a continuing demand for new insecticides, and for new acaricides that are safer, more effective, and less costly. Insecticides and acaricides are useful for controlling insects and acarids which may otherwise cause significant damage to crops such as wheat, corn, soybeans, potatoes, and cotton to name a few. For crop protection, insecticides and acaricides are desired which can control the insects and acarids without damaging the crops, and which have no deleterious effects to mammals and other living organisms.
SUMMARY OF THE INVENTION
In accordance with the present invention, it has now been found that certain novel 2,4-diaminoquinazolines and related derivatives of formula I are surprisingly active in the control of insects and acarids when used in the insecticidal and acaricidal compositions and methods of this invention. The compounds of formula I are represented by the following general formula:
Figure imgf000003_0001
I wherein:
R is selected from the group consisting of hydrogen, haloalkyl, alkoxyalkyl, alkphenylalkyl, alkoxycarbonylalkyl, alkthioalkyl, alkoxycarbonylaminoalkyl, phenoxycarbonylaminoalkyl, phenylcarbonylalkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl and optionally substituted cycloalkalkyl, wherein the optional substituents are selected from the group consisting of halogen, alkyl, aryl, alkamino, dialkylamino, alkenylalkyl, alkynylalkyl, carbonylaryl, phenylalkyl, alkoxycarbonyl, haloalkcarbonyl, alkoxyalkyl, 3-pyridylcarbonyl, heterocyclyl, phenoxythionyl, phenylaminocarbonyl, phenylalkcarbonyl, phenylaminothioalkyl, phenylalkcarbonyl, halophenylalkcarbonyl, phenylalkoxycarbonyl, cycloalkcarbonyl, alkaminocarbonyl, cycloalkcarbonyl, phenylaminocarbonyl, phenylalkcarbonyl, optionally substituted aryl, optionally substituted phenylcarbonyl, optionally substituted phenylalkoxycarbonyl and optionally substituted phenylaminocarbonyl, wherein the optional substituents are selected from the group consisting of halogen, alkyl, alkoxy, alkaminothionyl, haloalkyl, haloalkoxy and SF5; A is selected from the group consisting of optionally substituted cycloalkyl, optionally substituted thiopheneyl,
Figure imgf000003_0002
wherein the optional substitutents, R6 and R10 are independently selected from the group consisting of halogen, alkyl, alkoxy and cyano, and wherein * denotes a point of attachment; R2 and R4 are independently selected from hydrogen or alkylcarbonyl; R5 is selected from the group consisting of optionally substituted aryloxy, optionally substituted cycloalkyl and
Figure imgf000004_0001
wherein the optional substituents are independently selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy and SF5, and wherein R7, R8 and R9 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, SF5 and either of R and
R8, or R8 and R9 taken together with -OCH2O-, -OC(CH3)2CH2- or -OC(CH3)2O-, forming a benzo-fused ring; and the corresponding agriculturally acceptably salts thereof.
The present invention is also directed to methods of controlling insects, where control is desired, which comprise applying an insecticidally effective amount of the above composition to the locus of crops, or other areas where insects are present or are expected to be present.
DETAILED DESCRIPTION OF THE INVENTION
One aspect of the present invention relates to certain new and useful compounds, namely novel 2,4-diaminoquinazolines and related derivatives (hereinafter termed "compounds of formula I") as depicted in formula I:
Figure imgf000004_0002
I wherein:
R is selected from the group consisting of hydrogen, haloalkyl, alkoxyalkyl, alkphenylalkyl, alkoxycarbonylalkyl, alkthioalkyl, alkoxycarbonylarninoalkyl, phenoxycarbonylaminoalkyl, phenylcarbonylalkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl and optionally substituted cycloalkalkyl, wherein the optional substituents are selected from the group consisting of halogen, alkyl, aryl, alkamino, dialkylamino, alkenylalkyl, alkynylalkyl, carbonylaryl, phenylalkyl, alkoxycarbonyl, haloalkcarbonyl, alkoxyalkyl, 3-pyridylcarbonyl, heterocyclyl, phenoxythionyl, phenylaminocarbonyl, phenylalkcarbonyl, phenylaminothioalkyl, phenylalkcarbonyl, halophenylalkcarbonyl, phenylalkoxycarbonyl, cycloalkcarbonyl, alkaminocarbonyl, cycloalkcarbonyl, phenylaminocarbonyl, phenylalkcarbonyl, optionally substituted aryl, optionally substituted phenylcarbonyl, optionally substituted phenylalkoxycarbonyl and optionally substituted phenylaminocarbonyl, wherein the optional substituents are selected from the group consisting of halogen, alkyl, alkoxy, alkaminothionyl, haloalkyl, haloalkoxy and SF5;
A is selected from the group consisting of optionally substituted cycloalkyl, optionally substituted thiopheneyl,
Figure imgf000005_0001
wherein the optional substitutents, R6 and R10 are independently selected from the group consisting of halogen, alkyl, alkoxy and cyano, and wherein * denotes a point of attachment;
R2 and R4 are independently selected from hydrogen or alkylcarbonyl;
R5 is selected from the group consisting of optionally substituted aryloxy, optionally substituted cycloalkyl and
Figure imgf000005_0002
wherein the optional substituents are independently selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy and SF5, and wherein R7, R8 and R9 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, SF5 and either of R7 and R8, or R8 and R9 taken together with -OCH2O-, -OC(CH3)2CH2- or -OC(CH3)2O-, forming a benzo-fused ring; and the corresponding agriculturally acceptably salts thereof.
Preferred species of the present invention are those compounds of formula I where R2 is hydrogen and A is
Figure imgf000006_0001
More preferred species of the present invention are those compounds of formula I where R2 is hydrogen, A is
Figure imgf000006_0002
R4 is hydrogen and R5 is
Figure imgf000006_0003
wherein R , R and R are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, SF5 and either of R7 and R8, or R8 and R9 taken together with -OCH2O-, -OC(CH3)2CH2- or -OC(CH3)2O-, forming a benzo-fused ring.
Even more preferred species of the present invention are those compounds of formula I where R is hydrogen, A is
Figure imgf000006_0004
R4 is hydrogen and R5 is
Figure imgf000006_0005
wherein R8 is hydrogen, R and R9 are independently selected from the group consisting of halogen, haloalkyl and haloalkoxy, and R is
Figure imgf000007_0001
wherein Z1 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl and haloalkoxy; more particularly wherein R7, R9 and Z1 are halogen.
Other preferred compounds of the present invention include compounds of formula I- A:
Figure imgf000007_0002
I - A, formula I-B:
Figure imgf000007_0003
I-B, formula I-C:
Figure imgf000007_0004
I-C, and formula I-D:
Figure imgf000008_0001
I-D, wherein
R is selected from the group consisting of
Figure imgf000008_0002
Figure imgf000008_0003
wherein R14, R22, R26 and R27 are independently selected from the group consisting
Figure imgf000008_0004
and R5 is selected from the group consisting of
Figure imgf000009_0001
In addition, in certain cases the compounds of the present invention may possess asymmetric centers, which can give rise to optical enantiomorphs and diastereomers. The compounds may exist in two or more forms, i.e., polymorphs, which are significantly different in physical and chemical properties. The compounds of the present invention may also exist as tautomers, in which migration of a hydrogen atom within the molecule results in two or more structures, which are in equilibrium. The compounds of the present invention may also possess acidic or basic moieties, which may allow for the formation of agriculturally acceptable salts or agriculturally acceptable metal complexes.
This invention includes the use of such enantiomorphs, polymorphs, tautomers, salts and metal complexes. Agriculturally acceptable salts and metal complexes include, without limitation, for example, ammonium salts, the salts of organic and inorganic acids, such as hydrochloric acid, sulfonic acid, ethanesulfonic acid, trifiuoroacetic acid, methylbenzenesulfonic acid, phosphoric acid, gluconic acid, pamoic acid, and other acid salts, and the alkali metal and alkaline earth metal complexes with, for example, sodium, potassium, lithium, magnesium, calcium, and other metals.
Another aspect of the present invention relates to compositions containing an insecticidally effective amount of at least one compound of formula I with an insecticidally compatible carrier therefor. Another aspect of the present invention relates to compositions containing an insecticidally effective amount of at least one compound of formula I, and an effective amount of at least one second compound, with an insecticidally compatible carrier therefor. Another aspect of the present invention relates to methods of controlling insects by applying an insecticidally effective amount of a composition set forth above to a locus of crops such as, without limitation, cereals, cotton, vegetables, and fruits, or other areas where insects are present or are expected to be present.
The present invention also includes the use of the compounds and compositions set forth herein for control of non-agricultural insect species, for example, dry wood termites and subterranean termites; as well as for use as pharmaceutical agents and compositions thereof.
One skilled in the art will, of course, recognize that the formulation and mode of application of a toxicant may affect the activity of the material in a given application. Thus, for agricultural use the present insecticidal compounds may be formulated as a granular of relatively large particle size (for example, 8/16 or 4/8 US Mesh), as water-soluble or water-dispersible granules, as powdery dusts, as wettable powders, as emulsifiable concentrates, as aqueous emulsions, as solutions, or as any of other known types of agriculturally-useful formulations, depending on the desired mode of application. It is to be understood that the amounts specified in this specification are intended to be approximate only, as if the word "about" were placed in front of the amounts specified.
These insecticidal compositions may be applied either as water-diluted sprays, or dusts, or granules to the areas in which suppression of insects is desired. These formulations may contain as little as 0.1%, 0.2% or 0.5% to as much as 95% or more by weight of active ingredient.
Dusts are free flowing admixtures of the active ingredient with finely divided solids such as talc, natural clays, kieselguhr, flours such as walnut shell and cottonseed flours, and other organic and inorganic solids which act as dispersants and carriers for the toxicant; these finely divided solids have an average particle size of less than about 50 microns. A typical dust formulation useful herein is one containing 1.0 part or less of the insecticidal compound and 99.0 parts of talc. Wettable powders, also useful formulations for insecticides, are in the form of finely divided particles that disperse readily in water or other dispersant. The wettable powder is ultimately applied to the locus where insect control is needed either as a dry dust or as an emulsion in water or other liquid. Typical carriers for wettable powders include Fuller's earth, kaolin clays, silicas, and other highly absorbent, readily wet inorganic diluents. Wettable powders normally are prepared to contain about 5-80% of active ingredient, depending on the absorbency of the carrier, and usually also contain a small amount of a wetting, dispersing or emulsifying agent to facilitate dispersion. For example, a useful wettable powder formulation contains 80.0 parts of the insecticidal compound, 17.9 parts of Palmetto clay, and 1.0 part of sodium lignosulfonate and 0.3 part of sulfonated aliphatic polyester as wetting agents. Additional wetting agent and/or oil will frequently be added to a tank mix for to facilitate dispersion on the foliage of the plant.
Other useful formulations for insecticidal applications are emulsifϊable concentrates (ECs) which are homogeneous liquid compositions dispersible in water or other dispersant, and may consist entirely of the insecticidal compound and a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone, or other non-volatile organic solvents. For insecticidal application these concentrates are dispersed in water or other liquid carrier and normally applied as a spray to the area to be treated. The percentage by weight of the essential active ingredient may vary according to the manner in which the composition is to be applied, but in general comprises 0.5 to 95% of active ingredient by weight of the insecticidal composition.
Flowable formulations are similar to ECs, except that the active ingredient is suspended in a liquid carrier, generally water. Flowables, like ECs, may include a small amount of a surfactant, and will typically contain active ingredients in the range of 0.5 to 95%, frequently from 10 to 50%, by weight of the composition. For application, flowables may be diluted in water or other liquid vehicle, and are normally applied as a spray to the area to be treated. Typical wetting, dispersing or emulsifying agents used in agricultural formulations include, but are not limited to, the alkyl and alkylaryl sulfonates and sulfates and their sodium salts; alkylaryl polyether alcohols; sulfated higher alcohols; polyethylene oxides; sulfonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of polyhydric alcohols and the ethylene oxide addition products of such esters; and the addition product of long-chain mercaptans and ethylene oxide. Many other types of useful surface-active agents are available in commerce. Surface-active agents, when used, normally comprise 1 to 15% by weight of the composition.
Other useful formulations include suspensions of the active ingredient in a relatively non-volatile solvent such as water, corn oil, kerosene, propylene glycol, or other suitable solvents.
Still other useful formulations for insecticidal 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, or other organic solvents. Granular formulations, wherein the toxicant is carried on relative coarse particles, are of particular utility for aerial distribution or for penetration of cover crop canopy. Pressurized sprays, typically aerosols wherein the active ingredient is dispersed in finely divided form as a result of vaporization of a low- boiling dispersant solvent carrier may also be used. Water-soluble or water- dispersible granules are free flowing, non-dusty, and readily water-soluble or water- miscible. In use by the farmer on the field, the granular formulations, emulsifiable concentrates, flowable concentrates, aqueous emulsions, solutions, etc., may be diluted with water to give a concentration of active ingredient in the range of say 0.1% or 0.2% to 1.5% or 2%.
The active insecticidal compounds of this invention may be formulated and/or applied with one or more second compounds. Such combinations may provide certain advantages, such as, without limitation, exhibiting synergistic effects for greater control of insect pests, reducing rates of application of insecticide thereby minimizing any impact to the environment and to worker safety, controlling a broader spectrum of insect pests, safening of crop plants to phytotoxicity, and improving tolerance by non-pest species, such as mammals and fish.
Second compounds include, without limitation, other pesticides, plant growth regulators, fertilizers, soil conditioners, or other agricultural chemicals. In applying an active compound of this invention, whether formulated alone or with other agricultural chemicals, an effective amount and concentration of the active compound is of course employed; the amount may vary in the range of, e.g. about 0.001 to about 3 kg/ha, preferably about 0.03 to about 1 kg/ha. For field use, where there are losses of insecticide, higher application rates (e.g., four times the rates mentioned above) may be employed.
When the active insecticidal compounds of the present invention are used in combination with at least one additional compound, e.g., with other pesticides such as herbicides, the herbicides include, without limitation, for example: N- (phosphonomethyl)glycines such as glyphosate; aryloxyalkanoic acids such as 2,4- D, MCPA, and MCPP; ureas such as isoproturon; imidazolinones such as imazapyr, imazamethabenz, imazethapyr, and imazaquin; diphenyl ethers such as acifluorfen, bifenox, and fomasafen; hydroxybenzonitriles such as ioxynil and bromoxynil; sulfonylureas such as chlorimuron, achlorsulfuron, bensulfuron, pyrazosulfuron, thifensulfuron, and triasulfuron; 2-(4-aryloxyphenoxy)alkanoic acids such as fenoxaprop, fluazifop, quizalofop, and diclofop; benzothiadiazinones such as bentazone; 2-chloroacetanilides such as butachlor, metolachlor, acetochlor, and dimethenamide; arenecarboxylic acids such as dicamba; pyridyloxyacetic acids such as fluroxypyr, aryl triazolinones such as sulfentrazone and carfentrazone-ethyl; isoxazolidinones such as clomazone; and other herbicides.
When the active insecticidal compounds of the present invention are used in combination with at least one additional compound, e.g., with other pesticides such as other insecticides, the other insecticides include, for example: organophosphate insecticides, such as chlorpyrifos, diazinon, dimethoate, malathion, parathion- methyl, and terbufos; pyrethroid insecticides, such as fenvalerate, deltamethrin, fenpropathrin, cyfluthrin, flucythrinate, permethrin, α/^α-cypermethrin, beta- cypermethrin, zetø-cypermethrin, bifenthrin, cypermethrin, resolved cyhalothrin, etofenprox, esfenvalerate, tralomethrin, tefluthrin, cycloprothrin, betacyfluthrin, and acrinathrin; carbamate insecticides, such as aldecarb, carbaryl, carbofuran, and methomyl; organochlorine insecticides, such as endosulfan, endrin, heptachlor, and lindane; benzoylurea insecticides, such as diflubenuron, triflumuron, teflubenzuron, chlorfluazuron, flucycloxuron, hexaflumuron, flufenoxuron, and lufenuron; and other insecticides, such as amitraz, clofentezine, fenpyroximate, hexythiazox, spinosad, and imidacloprid.
When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other pesticides such as fungicides, the fungicides include, for example: benzimidazole fungicides, such as benomyl, carbendazim, thiabendazole, and thiophanate-methyl; 1,2,4-triazole fungicides, such as epoxyconazole, cyproconazole, flusilazole, flutriafol, propiconazole, tebuconazole, triadimefon, and triadimenol; substituted anilide fungicides, such as metalaxyl, oxadixyl, procymidone, and vinclozolin; organophosphoras fungicides, such as fosetyl, iprobenfos, pyrazophos, edifenphos, and tolclofos-methyl; morpholine fungicides, such as fenpropimorph, tridemoφh, and dodemorph; other systemic fungicides, such as fenarimol, imazalil, prochloraz, tricyclazole, and triforine; dithiocarbamate fungicides, such as mancozeb, maneb, propineb, zineb, and ziram; non-systemic fungicides, such as chlorothalonil, dichlofluanid, dithianon, and iprodione, captan, dinocap, dodine, fluazinam, gluazatine, PCNB, pencycuron, quintozene, tricylamide, and validamycin; inorganic fungicides, such as copper and sulphur products, and other fungicides.
When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other pesticides such as nematicides, the nematicides include, for example: carbofuran, carbosulfan, turbufos, aldecarb, ethoprop, fenamphos, oxamyl, isazofos, cadusafos, and other nematicides.
When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as plant growth regulators, the plant growth regulators include, for example: maleic hydrazide, chlormequat, ethephon, gibberellin, mepiquat, thidiazon, inabenfϊde, triaphenthenol, paclobutrazol, unaconazol, DCPA, prohexadione, trinexapac-ethyl, and other plant growth regulators. Soil conditioners are materials which, when added to the soil, promote a variety of benefits for the efficacious growth of plants. Soil conditioners are used to reduce soil compaction, promote and increase effectiveness of drainage, improve soil permeability, promote optimum plant nutrient content in the soil, and promote better pesticide and fertilizer incorporation. When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as soil conditioners, the soil conditioners include organic matter, such as humus, which promotes retention of cation plant nutrients in the soil; mixtures of cation nutrients, such as calcium, magnesium, potash, sodium, and hydrogen complexes; or microorganism compositions which promote conditions in the soil favorable to plant growth. Such microorganism compositions include, for example, bacillus, pseudomonas, azotobacter, azospirillum, rhizobium, and soil-borne cyanobacteria. Fertilizers are plant food supplements, which commonly contain nitrogen, phosphorus, and potassium. When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as fertilizers, the fertilizers include nitrogen fertilizers, such as ammonium sulfate, ammonium nitrate, and bone meal; phosphate fertilizers, such as superphosphate, triple superphosphate, ammonium sulfate, and dianimonium sulfate; and potassium fertilizers, such as muriate of potash, potassium sulfate, and potassium nitrate, and other fertilizers.
As used in this specification and unless otherwise indicated the substituent terms "alkyl" and "alkoxy", used alone or as part of a larger moiety, includes straight or branched chains of at least one or two carbon atoms, as appropriate to the substituent, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms. The terms "haloalkyl" and "haloalkoxy", alone or as part of a larger moiety, include straight or branched chain alkyls of 1 to 14 carbon atoms, preferably lower straight or branched chain alkyls of 1 to 6 carbon atoms, wherein one or more hydrogen atoms have been replaced with halogen atoms, as, for example, trifluoromethyl or 2,2,2-trifluoroethoxy, respectively. The term "alkenyl" and "alkynyl" used alone or as part of a larger moiety, includes straight or branched chains of at least two carbon atoms containing at least one carbon-carbon double bond or triple bond, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms. The term "heterocyclic" refers to a non-aromatic ring structure of four to eight atoms consisting of carbon and nitrogen, and may include oxygen or sulfur. Five member rings include, without limitation, for example, pyrrolidine. Six member rings include, without limitation, for example, piperazine, piperidine, morpholine and thiomorpholine. The term "aryl" refers to an aromatic ring structure, including fused rings, having four to ten carbon atoms, for example, phenyl or naphthyl. The terms "heteroaryl" and "heterocyclyl" refer to an aromatic ring structure, including fused rings, in which at least one of the atoms is other than carbon, for example, without limitation, sulfur, oxygen, or nitrogen. The term "polycyclyl" refers to a non-aromatic fused ring structure. "Amino" refers to compounds of nitrogen that may be considered derived from ammonia and includes primary, secondary and tertiary amines wherein one or more of the hydrogen atoms is replaced with alkyl groups. The term "GC analysis" refers to gas chromatographic analysis of, for example, a chemical reaction mixture. The term "DMF" refers to N,N-dimethylformamide. The term "THF" refers to tetrahydrofuran. The term "TEA" refers to triethylamine. The term "halogen" or "halo" refers to fluorine, bromine, iodine, or chlorine. The term "ambient temperature" or "room temperature" often abbreviated as "RT", for example, in reference to a chemical reaction mixture temperature, refers to a temperature in the range of 20 0C to 30 0C. The term "insecticidal" or "acaricidal", "insecticide" or "acaricide" refers to a compound of the present invention, either alone or in admixture with at least one of a second compound, or with at least one compatible carrier, which causes the destruction or the inhibition of action of insects or acarids.
The following examples further illustrate the present invention, but, of course, should not be construed as in any way limiting its scope. The examples are organized to present protocols for the synthesis of the compounds of formula I of the present invention, set forth a list of such synthesized species, and set forth certain biological data indicating the efficacy of such compounds.
The 2,4-diaminoquinazolines and related derivatives of formula I can be synthesized by methods that are individually known to one skilled in the art from intermediate compounds readily available in commerce, for example, as set forth in Example 1 and Example 2 below. Example 1
Synthesis of (3,5-dichlorophenyl)[4-(cyclohexylamino)quinazolin-2-yl]amine
(Compound 22)
Figure imgf000016_0001
Cyclohexylamine 2 (5.7 mL, 50 mmol) was added to dichloroquinazoline 1 (5.0 g, 25 mmol) dissolved in 100 mL of tetrahydrofuran at 0 0C. The mixture was stirred at ambient temperature under a nitrogen atmosphere for about 18 hours. The resulting solids were filtered off and washed with ethyl ether. The filtrate was evaporated to give 7.5 g of quinazoline 3 in tetrahydrofuran. This intermediate 3 was used in the next reaction without further purification.
Figure imgf000017_0001
Intermediate 3 and dichloroaniline 4 (12.2 g, 75.3 mmol) were mixed without additional solvent, and heated at 100 0C for 3 hours. The resulting black solid was cooled and then taken up in 150 mL dichloromethane. The solids were filtered off and washed with more dichloromethane. The solids were then dissolved in ethyl acetate and washed with aqueous sodium bicarbonate and brine. The organic layer was dried with magnesium sulfate and concentrated under reduced pressure to give Compound 22 and an excess of aniline 4. Compound 22 was purified by column chromatography on silica gel. Elution was accomplished with 1 L of dichloromethane followed by 2 L of 10% ethyl acetate in dichloromethane. The appropriate fractions were combined and concentrated under reduced pressure to give 10.0 g of residue, which was Compound 22 and about 20 percent by weight of ethyl acetate. The ethyl acetate was removed by drying in a vacuum oven. The NMR spectrum was consistent with the proposed structure.
Example 2 Synthesis of Compound 191
Figure imgf000018_0001
A solution of 5.8 g (0.31 mol) of N-t-Boc-piperidone in 80 ml of ethanol was cooled to O0C on an ice bath. To this was added 5.2 ml (0.04 mol) of TEA then 2.6 g (0.37 mol) of solid hydroxylamine HCl. The mixture was warmed to room temperature and then heated to reflux temperature for 6 h. The solvent was removed and the solid was partitioned between saturated aqueous ammonium chloride and ethyl acetate (100 ml each). The aqueous layer was extracted with a second portion of ethyl acetate (100 ml) and the combined extract was dried over sodium sulfate. The solvent was removed at reduced pressure to afford 6.0 g of a white solid. The solid was dissolved in 60 ml of methanol and then hydrogenated over 5% Rhodium on Alumina (0.6 g) at 5O0C. After the uptake of hydrogen ceased, the catalyst was filtered and the solvent removed to afford 5.5 g (98%) of reactant 5. The NMR spectrum was consistent with the proposed structure.
A solution of 5.9 g (0.0296 mol) of dichloroquinazoline 1 in 150 ml of THF was stirred at 0-50C (ice bath) and then 6.5 g (0.032 mol) of reactant 5 was added followed by 8.2 ml (0.592 mol) of TEA and 5 mg of DMAP (catalyst). The mixture was warmed to room temperature and stirred for 2Oh. The mixture was poured onto a column of 200 ml silica gel and the product eluted with ethyl acetate (500 ml). The residue obtained after evaporation of the solvent was triturated in 25 ml dichloromethane/50 ml hexane while cooling on an ice bath. The solid was filtered and dried to afford 7.9 g (74%) of compound 6. The NMR spectrum was consistent with the proposed structure.
A mixture of 7.9 g (0.022 mol) of intermediate 6 and 8.9 g (0.055 mol) of 3,5-dichloroaniline in 20 ml of 1,4-dioxane was heated to a pot temperature of 12O0C for 10 h and then cooled to room temperature. The solid was stirred vigorously with 200 ml of diethyl ether for 2 h and then filtered. The solid was washed with an additional 200 ml of diethyl ether. The solid was added to 500 ml of 5% aqueous potassium carbonate with stirring and then extracted with 400 ml of ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and then passed through a small bed of silica gel eluding with ethyl acetate to remove base line material. The solvent was concentrated at reduced pressure to afford 10.4 g (97%) of intermediate 7. The NMR spectrum was consistent with the proposed structure.
Figure imgf000019_0001
Cmpdl91
A mixture of 9.0 g (0.018 mol) of intermediate 7 and 50 ml of dichloromethane was stirred while cooling in an ice bath. The slurry was treated dropwise with 9 ml of trifluoroacetic acid and then allowed to warm to room temperature. After stirring for 20 h, the solvents were removed and the residue was dissolved in a minimum of dichloromethane. The dichloromethane solution was added dropwise to 500 ml of cold 5% potassium carbonate solution with stirring. The resulting solid was filtered and dried to afford 6.4 g (92%) of intermediate 8. The NMR spectrum was consistent with the proposed structure.
A solution of 0.35 g (0.0009 mol) of intermediate 8 in 20 ml of THF was treated with 0.5 ml (excess) TEA. The mixture was cooled briefly on a dry ice- acetone bath while 0.1 ml (0.0009 mol) of 4-fluorophenylisocyanate was added. The mixture was allowed to warm to room temperature and then stirred for 1 h. The reaction mixture was poured onto a column of 50 ml of silica gel and eluted with 150 ml of ethyl acetate. The solvent was removed and the residue was triturated with 20 mis of 20% dichloromethane in hexane. The solid was filtered and dried to afford 0.47 g (100%) of Compound 191. The NMR spectrum was consistent with the proposed structure. It is well known to one of ordinary skill in the art that compounds like the compounds of formula I of the present invention can contain optically active and racemic forms. It is also well known in the art that compounds like the compounds of formula I may contain stereoisomeric forms, tautomeric forms and/or exhibit polymorphism. It is to be understood that the present invention encompasses any racemic, optically active, polymorphic, tautomeric, or stereoisomeric form, or mixtures thereof. It should be noted that it is well known in the art how to prepare optically active forms, for example by resolution of a racemic mixture, or by synthesis from optically active intermediates.
The following table sets forth some additional examples of compounds of formula I useful in the present invention:
Table 1
Figure imgf000020_0001
I-E
Compound Number
1 H 2 2-Cl 3 3-Cl 4 4-Cl 5 3,5-Cl2 6 2-Me 7 3-Me
4-Me
10 3-OMe 11 4-OMe
Figure imgf000021_0001
I-F
Compound Number Z Compound Number Z
12 H 23 3,5-F2
14 3-Cl 24 3,4-F2
15 4-Cl 25 3,5-Me2
16 2,3-Cl2 26 3,4-Me2
19 3,4-Cl2 27 3,5-OMe2
20 2,6-Cl2 28 3,4-OMe2
21 2,4,6-Cl3 29 4-F
22 3,5-Cl2 30 3-F
31 2,3,4,5,6-F5
32 3,4,5-Cl3
33 3-Cl, 4-F
Figure imgf000021_0002
Compound Number R' Compound Number R'
34 t-Bu 43 NHCONHEt
35 Me 44 OEt
36 CO2 t-Bu 45 OCF3
38 H 46 OSO2CH3
39 CF3 47 Cl
40 NH2 48 Br Compound Number R7 Compound Number R7
42 NO2 49 i-Pr 50 CO2Me
Figure imgf000022_0001
£H
Compound Number R0 Compound Number R°
51 H 56 Me
52 Cl 57 Br
53 F 58 I
54 MeO 59 SCF3
55 CN
Figure imgf000022_0002
H
Compound Number R9 R7 61 F I 62 F CF3 63 CF3 Br 64 Cl F 65 Cl Cl
Figure imgf000023_0001
I-K
Compound No. X Y Ry
66 C-H N H
67 C-H N Cl
68 N C-H H
69 N C-Cl Cl
70 C-Cl N H
Figure imgf000023_0002
I-L
Compound No. R11
71 H 72 Me
Figure imgf000024_0001
I-M
Compounds 73-94 are HCl salts
Compound Z R1Z Compound Z R"
No. No.
73 H H 84 4-Cl H
74 2-F H 92 2-CF3 H
79 2,4-F2 H 93 3-CF3 H
80 3,4-F2 H
82 H Me
83 2-Cl H
Compounds 95-118 are Free Bases
Compound Compound
No. Z R12 No. Z R12
95 H H 107 4-Cl H
96 2-F H 108 3,4-Cl2 H
99 2,5-F2 H 110 2-Me H
100 2,6-F2 H 111 3-Me H
101 2,4-F2 H 115 2-CF3 H
102 3,4-F2 H 116 3-CF3 H
104 H Me 117 4-CF3 H
105 2-Cl H 118 4-F Me
106 3-Cl H
Figure imgf000025_0001
I-N
Compound No. Position of Chlorine or Other Moiety
120 121 7 123 6,7-OMe
Figure imgf000025_0002
I O
Compound No. R
124 cyclohexyl
Figure imgf000025_0003
127 cyclopentyl
128 α-methylbenzyl
129 t-butyl
130 H
131 cycloheptyl
134 cyclohexanone ethylene ketal
Figure imgf000026_0001
i-p
Compound No. R1
136 C=O(C6H5)
Figure imgf000026_0002
146 C4H9
147 Cyclohexyl
148 CH2-cyclohexyl
149 CH2OCH3
151 CH2NHCO2-t-Bu
152 CH2NHCO2Ph
Figure imgf000026_0003
I-Q
Compound No. R 14
153 C6H5 154 COC6H5 Compound No. R] 14
155 CH2C6H5 156 CO2-t-Bu 157 CH2CH2OCH3 158 CH3 159 CO2C6H5 160 CO2CH3 161 SO2C6H5 162 CO2Et 163 H 164 CONHPh 165 COCH2Ph 166 CO2CH2Ph 167 COCH2C6H4-4-F 168 CSNHPh
Figure imgf000027_0001
I-R
Compound No. R1 15
169 C6H4-P-SO2NPr2
170 C6H5
171 Cyclopropyl
172 NHC4H9
173 OC6H13
174 OC6H3-2-OMe-4-Cl
175 OC6H4-4-F
176 OCH2C6H5
177 octyl
178 3-ρyridyl
179 2,3-Cl2-phenyl
180 C2F5
181 O-t-Bu
182 OPh
183 OMe
184 OEt
185 NHPh
186 CH2Ph
187 CH2-4F-Ph Compound No. R 15
188 OC6H4-4-Cl 189 OC6H4-4-OMe 190 OC6H4-4-Br 191 NHC6H4-4F 192 NHC6H4-4-OCF3 193 NHC6H4-4-Cl 194 NHC6H4-2-F 195 NHC6H4-3-F 196 NMe(Ph)
Figure imgf000028_0001
I-S
Compound No. B D
198 NH NMe H
199 O NH 3,5 Cl
200 S NH 3,5 Cl
201 NMe NH 3,5 Cl
202 NAc NAc 3,5 Cl
203 NH NAc 3,5 Cl
Figure imgf000028_0002
I-T
Compound No. 16
R-
204 Et
205 Bu
208 CF3
209 EtO2C(CH2)2
210 (CHs)2C=CH
211 CH2=CH
212 cycohexyl
213 Me
214 MeO
216 MeNH
217 PhNH
218 4-F-PhNH
Quinazoline Replacements I; Cmpds 219-226 below:
Figure imgf000029_0001
Cmpd 219 Cmpd 220 Cmpd 221
Figure imgf000029_0002
Figure imgf000030_0001
Cmpd 225
Figure imgf000030_0002
I-U
Compound No. R 17 R18
228 Me H 229 H Me 230 Me Me 231 Cl H 232 H Cl 233 Cl Cl 234 Me Cl
Figure imgf000031_0001
Figure imgf000031_0003
Fenazaquin Hybrids I; (Compound 256 below)
Figure imgf000031_0002
Figure imgf000032_0001
I-W
Compound No. Z1
257 H 258 2-F 259 3-F 260 4-F 261 2,4-F2 262 2,5- F2 263 2,6- F2 264 2-Cl 265 3-Cl 266 4-Cl 267 2,3-Cl2 268 2,4-Cl2 269 2,5-Cl2 270 2,6-Cl2 271 3,4-Cl2 272 3,5-Cl2 273 2-Me 274 3-Me 275 4-Me 276 2-OMe 277 3-OMe 278 4-OMe 279 4-CF3 280 3-Cl,4-F 281 4-C3F7 282 2-Cl, 4-F, 5-Me
Figure imgf000033_0001
I-X
Compound No. R 20 G Z1
283 O NH H 284 O NCH3 H 285 S NH H
Figure imgf000033_0002
I-Y
Compound No. G R21
286 O CH2OH2CH=CH2 287 O cyclohexyl 288 O CH2CH=CH2 289 O CH2C≡CH 290 NH cyclohexyl 291 NH i-Pr
Figure imgf000034_0001
I-Z
Compound No. R- 22
292 BOC 293 H 294 CONH-4-FPh 293 CONH-2-FPh 296 CONH-3-FPh 297 CONH-2,4-F2Ph 298 CONH-2,5F2Ph 299 CONH-2,6F2Ph 300 CO2Ph 301 CO2-4-FPh 302 CO2-4-ClPh 303 CO2-4-MePh 304 CO2-4-MeOPh
Figure imgf000034_0002
I-AA
Compound No. R 15
305 3-pyridyl 306 2,3-Cl2-Ph 307 C2F5 308 OH2CH2CF3
Figure imgf000034_0003
Compound No. R1:
310 CH2SO2Ph 311 CF3 312 4-CF3O-Ph 313 4-CF3PhCH2 314 3-CF3Ph 315 4-0H-Ph 316 trans-CH=CHPh-4-Cl 317 4-pyridyl 318 3-pyridyl-N-oxide
Figure imgf000035_0001
I-BB
CompoundNo. R
319 4-OCF3-Ph 320 4-t-Bu-Ph-(CH2)2 321 4-cyclohexanone, ethylene ketal 322 4-cyclohexanone 324 PhNHCO 326 N-phenylpiperidinyl 327 4-CF3O-phenylsulfonylpiperidinyl 328 CF3SO2-piperidinyl 329 (CH2)3NHBOC
Figure imgf000035_0002
331 (CH2)3NH2-TFΛ 332 (CH2)3NHCONHPh-4-F
Figure imgf000035_0003
I-CC
Compound No. A R 14 Compound No. R 14
Figure imgf000036_0001
337 cyclohexane CO2Ph 338 cyclohexane CONHPh-4-F 339 cyclohexane CONHPh-3-F 340 cyclohexane CONHPh-4-CF3 342 cyclohexane CONHPh-4-OCF3
Figure imgf000036_0002
I-DD
Compound No.
343 5-Me 344 6-Me 345 7-Me 347 5-F 348 6-F 349 7-F 350 8-F 351 perfluoro 352 H 354 6-Cl 355 7-Cl 357 6,7-MeO
Figure imgf000037_0001
I-EE
Compound No. n
358 1 H 359 2 H
Figure imgf000037_0002
I-FF
Compound No. R9 R'
360 Cl Cl 361 I Br 362 Br Br
Figure imgf000037_0003
Compound No. R 364 cyclohexyl
Figure imgf000038_0001
366
— boc
Figure imgf000038_0002
I-JJ
Compound No. R' 24
368 CF3 369 CH3 370 NHPh
Figure imgf000038_0003
I-KK
Compound No. R' 24
371 CF3 372 cyclohexyl 373 CH3
Figure imgf000039_0001
I-MM
CompoundNo. R3
378 cyclohexyl-NH 379 3 -Me-cyclohexyl-NH 382 ethoxypropylamino 385 1 -naphthyl-NHCH2CH2NH
Figure imgf000039_0002
Figure imgf000039_0003
I-NN
Compound No. R 15
389 7-Me NHPh-4-F 390 7-Me OPh-4-F 391 6-Me NHPh 392 7-Me NHPh-4-CF3 393 6-Me NHPh-4-F 394 6-Me NHPh-4-Cl 395 7-Me NHPh-4-Cl 396 6-Me NHPh 397 6-F O-t-Bu 398 6-F NHPh-4-F 399 7-Me O-t-Bu 400 6-Me O-t-Bu Compound No. R 15
401 7-F O-t-Bu
Figure imgf000040_0001
I-OO
Compound No. 1 15
]
402 2-thienyl
403 4-Et-Ph
404 2-CH2-thienyl
405 4-MeO-Ph
406 3-MeO-Ph
407 4-Ph-Ph
408 2-furanyl
409 4-Me-Ph
410 2,3-Cl2-5-piperidinyl
411 2-Cl-3-piperidinyl
412 3-furanyl
413 1-imidazolyl
414 9-xanthenyl
415 9-fluorene
416 2-naphthalenyl
417 5-Br-2-fiiranyl
418 3-methyl-2-thienyl
419 5-methyl-2-thienyl
420 . 5-Br-2-thienyl
422 1-naρhthalenyl
423 4-i-Pr-Phenyl
424 4-EtO-phenyl
425 3-Bz-phenyl
426 CH=CH-2,4-Cl2-phenyl
The following table sets forth physical characterizing data for certain compounds of formula I of the present invention:
Table 2 2,4-Diaminoquinazolines Compound Characterization
Melting Point
(0C) of Solids or
Cmpd. Molecular Formula Physical State
1 C24H31N5 Thick Oil
2 C24H30ClN5 Glass
3 C24H30ClN5 Glass
4 C24H30ClN5 Glass
5 C24H29Cl2N3 Glass
6 C25H33N5 Solid
7 C25H33N5 Solid
8 C25H33N5 Solid
10 C25H33N5O Glassy Solid
11 C25H33N5O Glassy Solid
12 C20H22N4 Foam
14 C20H21ClN4 75-79
15 C20H21ClN4 158-160
16 C20H20Cl2N4 192-194
19 C20H20Cl2N4 108-110
22 C20H20Cl2N4 165-166
23 C20H20F2N4 164-167
24 C2OH20F2N4 148-151
25 C22H26N4 82-85
26 C22H26N4 146-148
27 C22H26N4O2 81-85
28 C22H26N4O2 93-96
Figure imgf000041_0001
30 C20H21FN4 150-152
31 C20H17F5N4 205-210
32 C20H19Cl3N4 143-146
33 C20H20ClFN4 Solid
34 C24H30N4 66-72
38 C24H27Cl2N5O2 183-185
Figure imgf000041_0002
40 C20H23N5 Oil
42 C20H21N5O2 78-81
44 C22H25N4O 69-71
45 C21H21F3N4O 104-106
48 C20H21BrN4 128.5-130
49 C23H28N4 60-65
50 C22H24N4O2 75-80
54 C2IH23ClN4O 76-80
55 C21H20ClN5 199-201
57 C20H20BrClN4 141-143.5
Figure imgf000041_0003
60 C21H20F2N4O2 180-182
61 C20H20FIN4 80-83
62 C21H20F4N4 132-134.5 Melting Point (0C) of Solids or
Cmpd. Molecular Formula Physical State
Figure imgf000042_0001
70 Ci9H20CINs Solid
Figure imgf000042_0002
72 C21H30N4 66-70
73 C2IH24N4CIH Solid
74 C2IH23FN4ClH Solid
79 C2IH22F2N4ClH Solid
80 C2IH22F2N4CiH Solid
82 C22H26N4ClH Solid
83 C2IH23ClN34ClH Solid
92 C22H23F3N4ClH Solid
93 C22H23F3N4ClH Solid
Figure imgf000042_0003
96 C2IH23FN4 Solid
99 C2IH22F2N4 Solid
Figure imgf000042_0004
101 C2iHj2F2N4 Solid
102 C21H22F2N4 Solid
104 C22H26N4 Solid
105 C21H23ClN4 Solid
106 C2)H23ClN4 Solid
108 CaH22Cl2N4 Solid
111 C22H26N4 Solid
115 C22H23F3N4 Solid
116 C22H23F3N4 Solid
117 C22H23F3N4 Solid
118 C22H25FN4 Solid
120 C20Hi9Cl3N4 185-186
121 C20H19Cl3N4 165-167
123 C24H30N4O2 Solid
124 C20H20CI2N4 165-166
125 CwH20Cl2N4 Thick Oil
126 CIjH20CI2N4 118-120
127 C19Hi8Cl2N4 115-117
128 C22H18Cl2N4 53-56
Figure imgf000042_0005
130 C14H10Cl2N4 199-201
131 CaH22Cl2N4 155-157
134 C22H22Cl2N4O2 Foam
137 C25H23Cl2N5O2S 250
138 C22H18Cl2N4 48-50
139 C19H20Cl2N4 173-175
140 C20H20Cl2N4O2 174-176
141 C18Hi8CI2N4S 125-127
142 C17Hi6Cl2N4S 122-124 Melting Point
(0C) of Solids or
Cmpd. Molecular Formula Physical State
145 Ci9H20Cl2N4 47-50
146 C19H20Cl2N4 110-113
147 C21H22Cl2N4 59-62
148 C22H24Cl2N4 144-146
149 C17H16Cl2N4O 147-149
151 C21H23Cl2N5O2 152-155
152 C23H19Cl2N5O2 250
154 C26H23Cl2N5O 190-192
155 C26H25Cl2N5 65-69
156 C24H27Cl2N5O2 183-185
157 C22H25Cl2N5O Glassy Oil
158 C20H21Cl2N5 98-101
159 C26H23Cl2N5O2 200-201
160 C21H21Cl2N5O2 210-212
Figure imgf000043_0001
162 C22H23Cl2N5O2 Solid
163 C19Hi9Cl2N5 Solid
164 C26H24Cl2N6O 208-211
165 C27H25Cl2N5O 240-242
166 C27H25Cl2N5O2 215-217
167 C27H24Cl2FN5O 246-248
168 C26H24Cl2N6S 237-239
169 C32H36Cl2N6O3S 95
171 C23H23Cl2N5O 233-235
172 C24H28Cl2N6O 224-225
173 C26H3ICl2N5O2 167-169
174 C27H24Cl3N5O3 125
175 C26H22Cl2FN5O2 194-196
177 C28H35Cl2N5O 168-170
178 C25H22Cl2N6O 135
179 C26H2ICl4N5O 160
180 C22Hj8Cl2F5N5O 202-205
188 C26H22Cl3N5O2 137-141
189 C27H25Cl2N5O3 189-191
190 C26H22BrCl2N5O2 160
191 C26H23Cl2FN6O 231-233
192 C27H23Cl2F3N6O2 130-132
193 C27H26Cl2N6O 129-132
194 C26H23Cl2FN6O 250
195 C26H23Cl2FN6O 201-203
196 C27H26Cl2N6O 250
198 C21H24N4 150-152
201 C2IH22Cl2N4 82-84
203 C22H22Cl2N4O 210-215
204 C23H24Cl2N4O 187-189
205 C25H28Cl2N4O 190-192 Melting Point
(0C) of Solids or
Cmpd. Molecular Formula Physical State
208 C22Hi9Cl2F3N4O 237-239
209 C26H28Cl2N4O3 164-165
210 2C25H26Cl2N4O Solid
211 C23H22Cl2N4O 145-150
212 C27H30Cl2N4O 188-190
216 C22H23Cl2N5O 180-185
217 C27H25Cl2N3O 170-173
218 C22H22Cl2N4O2 Foam
219 C18H18Cl2N4S 99-102
220 C20H24Cl2N4 140.5-141.5
221 C19H22Cl2N4 182-183
222 C18H20Cl2N6 190.5-192.5
225 C24H31Cl2N3O2 195-196
228 C17H20Cl2N4 212-215
229 C17H20Cl2N4 45-48
230 C18H22Cl2N4 145-148
235 C20H20Cl2N4 165-166
238 C17H16Cl2N4O 147-149
239 C22H18Cl2N4 48-50
244 C24H28N4O2 Oil
256 C26H26Cl2N4 Foam
257 C26H24Cl2N6O 208-211
258 C26H23Cl2FN6O 250
259 C26H23Cl2N6O 201-203
2δO C26H23Cl2FN6O 231-233
261 C26H22Cl2F2N6O 250
262 C26H22Cl2F2N6O Solid
263 C26H22Cl2F2N6O Solid
264 C26H23Cl3N6O Solid
265 C26H23Cl3N6O Solid
266 C26H23Cl3N6O Solid
267 C26H22Cl4N6O Solid
268 C26H22Cl4N6O Solid
269 C26H22Cl4N6O Solid
270 C26H22Cl4N6O Solid
271 C26H22Cl4N6O Solid
272 C26H22Cl4N6O Solid
273 C27H26Cl2N6O 141-142
274 C27H26Cl2N6O 138-139
275 C27H26Cl2N6O 129-132
276 C27H26Cl2N6O2 189-190
277 C27H26Cl2N6O2 220-223
278 C27H26Cl2N6O2 128-130
279 C27H23Cl2F3N6O 156-159
280 C26H22Cl3FN6O Solid
281 C29H23Cl2F7N6O Solid Melting Point
(0C) of Solids or
Cmpd. Molecular Formula Physical State
282 C27H24Cl3FN6O Solid
283 C26H24Cl2N6O 208-211
284 C27H26Cl2N6O 250
28S C26H24Cl2N6S 237-239
286 C24H25Cl2N5O2 189-192
287 C26H29Cl2N5O2 234-236
288 C23H23Cl2N5O2 182-184
289 C23H21Cl2N5O2 219-221
290 C26H30Cl2N6O 250
291 C23H26Cl2N6O 218-220
292 C24H27Cl2N5O2 166-168
294 C26H23Cl2FN6O 115-120
295 C26H23Cl2FN6O 120-125
296 C26H23Cl2FN6O 125-129
297 C26H22Cl2F2N6O Solid
298 C26H22Cl2F2N6O Solid
299 C26H22Cl2F2N6O Solid
300 C26H23Cl2N5O2 100-117
301 C26H22Cl2FN5O2 Solid
302 C26H22Cl3N5O2 Solid
303 C27H25Cl2N5O2 150-222
304 C27H25Cl2N5O3 165-175
305 C25H22Cl2N6O 135
Figure imgf000045_0001
307 C22Hi8Cl2F5N5O 202-205
308 C23H22Cl2F3N5O 105
309 C28H27Cl3F3N5O 120-130
310 C27H25Cl2N5O3S 220-224
311 C21H18Cl2F3N5O 193-195
312 C27H22Cl2F3N5O2 173.5-175.5
313 C28H24Cl2F3N5O 227-230
314 C27H22Cl2F3N5O 150-153
315 C26H23Cl2N5O2 141-143
316 C28H24Cl3N5O 145-147
317 C25H22Cl2N6O 143-146
318 C25H22Cl2N6O2 142-144
319 C21H13Cl2F3N4O 189-190.5
320 C26H26Cl2N4 Foam
321 C22H22Cl2N4O2 Foam
322 C20H18Cl2N4O Oil
324 C21H15Cl2N5O 203-206
326 C25H23Cl2N5 125-130
327 C26H22Cl2F3N5O3S Solid
328 C20Hi8Cl2F3N5O2S 225-227
329 C22H25Cl2N5O2 65-70
330 C25H21Cl2FN6O 200 Melting Point
(0C) of Solids or
Cmpd. Molecular Formula Physical State
331 CI7HI9C12N5-2 C2F3O2 250
332 C24H2ICl2FN6O 180-186
335 C25H27Cl2N5S 75-82
337 C26H27Cl2N5O2 218-223
338 C26H27Cl2FN6O 240-245
339 C26H27Cl2FN6O 225-230
340 C27H27Cl2F3N6O 200-201
342 C27H27Cl2F3N6O2 177-180
344 C2IH22Cl2N4 165-166.5
Figure imgf000046_0001
347 C20H19Cl2FN4 130-132
348 C20Hi9Cl2FN4 193-195
349 C20Hi9Cl2FN4 159-160.5
352 C20H20Cl2N4 165-166
354 C20Hi9Cl3N4 185-186
355 C20Hi9Cl3N4 165-167
357 C24H30N4O2 Solid
360 C20H20Cl2N4 165-166
361 C20H20BrIN4 Oil
362 C20H20Br2N4 Oil
364 C2,H2iCl2N3 172-174
365 C27H24Cl2FN5O 179-185
366 C25H28Cl2N4O2 168-170
368 C28H22Cl2F4N6O2 244-246
369 C28H25Cl2FN6O2 169-172
370 C33H28Cl2FN7O2 214-215
371 C22Hi9Cl2F3N4O 237-239
372 C27H30Cl2N4O 188-190
373 C22H22Cl2N4O 210-215
378 C20H28N4 155-158
379 C2[H30N4 66-70
Figure imgf000046_0002
385 C26H29N5 Oil
387 C20H28N4O2 Oil
388 C25H28F3N5 Oil
389 C27H25Cl2FN6O 124-126
390 C27H24Cl2FN5O2 114-115.5
391 C27H26Cl2N6O 120-126
392 C28H25Cl2F3N6O 142-145
393 C27H25Cl2FN6O 221-223
394 C27H25Cl3N6O 234-236
395 C27H25Cl3N6O 220-222
396 C24H26Cl2FN5O2 206-210
397 C24H26Cl2FN5O2 206-210
398 C26H22Cl2F2N6O 230-235
399 C25H29Cl2N5O2 143-145 Melting Point
(0C) of Solids or
Cmpd. Molecular Formula Physical State
400 C25H29CI2N5O2 160-165
401 C24H26Cl2FN5O2 210-215
402 C24H2ICl2N5OS Solid
403 C28H27Cl2N5O Solid
404 C25H23Cl2N5OS Solid
4OS C27H25Cl2N5O2 Solid
406 C27H25Cl2N5O2 Solid
407 C32H27Cl2N5O Solid
408 C24H21Cl2N5O2 SoHd
409 C27H25Cl2N5O Solid
410 C25H20Cl4N6O 215-220
411 C25H2ICl3N6O 200-205
412 C24H21Cl2N5O2 203-205
413 C23H2ICl2N7O 235-237
414 C33H27Cl2N5O2 181-183
415 C33H27Cl2N5O 181-183
416 C30H25Cl2N5O 145-149
417 C24H20BiCl2N5O2 225-228
418 C25H23Cl2N5OS 201-204
419 C25H23Cl2N5OS 180-185
420 C24H20BrCl2N5OS 138-141
422 C30H25Cl2N5O 168-170
423 C29H29Cl2N5O 168-170
424 C28H27Cl2N5O2 210-218
425 C33H27Cl2N5O2 203-210
426 C28H23Cl4N5O 205-208
Compounds were evaluated for activity against the tobacco budworm (Heliothis virescens [Fabricius]) in a surface-treated diet test.
In this test one mL of molten (65-700C) wheat germ-based artificial diet was pipetted into each well of a four by six (24 well) multi-well plate (ID# 430345-15.5 mm dia. x 17.6 mm deep; Corning Costar Corp., One Alewife Center, Cambridge, MA 02140). The diet was allowed to cool to ambient temperature before treatment with candidate insecticide.
For a determination of insecticidal activity, solutions of the compounds were
® prepared for testing using a Packard 204DT Multiprobe Robotic System (Packard
Instrument Company, 800 Research Parkway, Meriden, CT 06450), in which the robot first diluted a standard 50 miHimolar DMSO solution of compound with a 1:1 water/acetone solution (VfV) in a ratio of 1 :7 stock solution to water/acetone. The robot subsequently pipetted 40 microliters of the so-prepared solution onto the surface of the diet in each of three wells in the 24 multi-well plate. The process was repeated with solutions of seven other compounds. Once treated, the contents of the multi-well plate were allowed to dry, leaving 0.25 millimoles of compound on the surface of the diet, or a concentration of 0.25 millimolar. Appropriate untreated controls containing only DMSO on the diet surface were also included in this test.
For evaluations of the insecticidal activity of a compound at varying rates of application, the test was established as described above using sub-multiples of the standard 50 millimolar DMSO solution of candidate insecticide. For example, the standard 50 millimolar solution was diluted by the robot with DMSO to give 5, 0.5, 0.05, 0.005, 0.0005 millimolar, or more dilute solutions of the candidate insecticide. In these evaluations there were six replicates of each rate of application placed on the surface of the diet in the 24 multi-well plate, for a total of four rates of application of compound in each plate.
In each well of the test plate was placed one second instar tobacco budworm larvea, each weighing approximately five milligrams. After the larvae were placed in each well, the plate was sealed with clear polyfilm adhesive tape. The tape over each well was perforated to ensure an adequate air supply. The plates were then held in a growth chamber at 25 0C and 60% relative humidity for five days (light 14 hours/day).
After the five-day exposure period insecticidal activity for each rate of application of compound was assessed as percent inhibition of insect weight relative to the weight of insects from untreated controls, and percent mortality when compared to the total number of insects infested.
Insecticidal activity data at selected rates of application from this test are provided in Table 3. Compounds of formula I are identified by numbers that correspond to those in Table 1.
Table 3
Insecticidal Activity of 2,4-Diaminoquinazolines
When Applied to the Surface of the Diet of Tobacco Budworm (Heliothis virescens
[Fabricius]) Percent
Percent Growth
Cmpd No. Mortality Inhibition
1 0 92
2 0 79
3 0 76
4 50 100
5 33 98
6 0 80
7 0 97
8 0 98
10 0 93
11 33 100
12 0 83
14 33 100
I5 17 95
19 33 100
22 100 100
23 33 100
24 50 100
25 0 93
26 0 95
28 0 91
29 33 99
30 0 83
31 0 70
32 100 100
33 83 100
34 0 94
38 83 100
39 67 100
40 0 52
42 100 100
45 50 100
48 6 100
49 0 94 so 0 96
55 50 100
57 67 10
59 67 100
60 33 98
61 100 100
62 67 100
63 83 100
65 100 100
70 17 95
71 0 90
72 33 81
73 0 81
74 0 86
79 0 93
80 0 76
83 0 94
93 0 83
95 0 83
100 33 97
101 17 86
104 0 92
106 0 89
108 0 91
111 0 69
115 17 100
116 17 95
117 0 73
120 33 98
121 33 99
123 33 98
124 100 100
125 50 98
126 17 93
127 67 98 Percent
Percent Growth
CmpdNo. Mortality Inhibition
130 0 93
131 83 100
134 100 100
137 50 99
138 83 100
139 50 100
140 17 79
141 17 94
145 67 100
146 83 100
147 67 100
148 100 100
151 67 100
152 67 100
154 83 100
155 50 100
156 83 100
157 33 100
158 0 85
159 100 100
160 83 100
162 83 100
163 17 100
164 100 100
165 67 100
166 50 100
167 100 100
168 100 100
169 83 99
170 83 100
171 100 100
172 100 100
173 33 100
174 50 100
175 100 100
176 50 100
177 67 99
178 83 100
179 50 100
180 83 100
181 83 100
182 100 100
184 83 100
185 100 100
186 67 100
187 100 100
188 67 100
189 67 100
190 100 99
191 100 100
192 67 100
193 100 100
194 67 100
195 100 100
196 50 99
201 17 74
203 67 100
205 17 92
208 100 100
209 100 100
210 50 100
211 67 100
212 100 100
213 67 100
216 100 100
217 100 100
218 100 100
219 33 99 Percent
Percent Growth
CmpdNo. Mortality Inhibition
220 67 98
221 0 88
222 0 34
225 83 100
228 17 74
229 0 84
230 17 98
235 100 100
239 83 100
256 83 100
257 100 100
258 67 100
259 100 100
260 100 100
261 83 100
262 100 100
263 17 97
. 264 100 100
265 83 100
266 100 100
267 67 100
268 100 100
269 50 99
270 83 100
271 67 99
272 83 99
273 100 100
274 100 100
275 100 100
276 100 100
277 100 100
278 100 100
279 100 100
280 17 66
281 33 96
282 50 100
283 100 100
284 50 99
285 100 100
286 83 100
287 50 100
288 100 100
289 100 100
290 0 92
291 100 100
292 67 100
294 67 99
295 0 94
296 33 100
297 50 100
298 0 99
299 33 100
300 50 100
301 50 100
302 50 100
303 33 100
304 17 100
305 83 100
306 50 100
307 83 100
308 100 100
309 100 100
310 0 100
311 100 100
312 83 100
313 100 100
314 100 100
315 100 100 Percent
Percent Growth
CmpdNo. Mortality Inhibition
316 100 100
317 100 100
318 100 100
319 100 100
320 83 100
321 100 100
322 33 100
324 0 66
326 50 100
327 100 96
328 100 100
329 100 100
330 83 100
331 100 100
332 100 100
335 33 70
337 83 100
338 100 100
339 17 100
340 33 100
342 100 100
344 83 100
345 100 99
348 67 100
349 83 100
352 100 100
354 33 98
355 33 99
357 33 98
360 100 100
361 67 100
362 67 100
364 33 50
365 0 97
368 100 100
369 100 100
370 100 100
371 100 100
372 100 100
373 67 100
378 0 90
379 33 81
387 0 80
388 0 75
389 100 100
390 100 100
391 100 100
392 67 98
393 50 100
394 100 100
395 83 100
396 100 100
397 67 100
398 100 100
399 33 99
400 67 98
401 83 100
402 100 100
403 100 100
404 67 100
405 100 100
406 33 100
407 50 82
408 100 100
409 100 100
410 100 100
411 100 100
412 100 100 Percent
Percent Growth
Cmpd No. Mortality Inhibition
413 100 100
414 50 99
415 83 100
416 100 100
417 50 100
418 100 100
419 100 100
420 83 100
422 83 100
423 50 100
424 100 100
425 50 100
426 50 100
While this invention has been described with an emphasis upon preferred embodiments, it will be understood by those of ordinary skill in the art that variations of the preferred embodiments may be used and that it is intended that the invention may be practiced otherwise than as specifically described herein.

Claims

WHAT IS CLAIMED IS:
1. A compound of formula I :
Figure imgf000054_0001
wherein:
R is selected from the group consisting of hydrogen, haloalkyl, alkoxyalkyl, alkphenylalkyl, alkoxycarbonylalkyl, alkthioalkyl, alkoxycarbonylaminoalkyl, phenoxycarbonylaminoalkyl, phenylcarbonylalkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl and optionally substituted cycloalkalkyl, wherein the optional substituents are selected from the group consisting of halogen, alkyl, aryl, alkamino, dialkylamino, alkenylalkyl, alkynylalkyl, carbonylaryl, phenylalkyl, alkoxycarbonyl, haloalkcarbonyl, alkoxyalkyl, 3-pyridylcarbonyl, heterocyclyl, phenoxythionyl, phenylaminocarbonyl, phenylalkcarbonyl, phenylaminothioalkyl, phenylalkcarbonyl, halophenylalkcarbonyl, phenylalkoxycarbonyl, cycloalkcarbonyl, alkaminocarbonyl, cycloalkcarbonyl, phenylaminocarbonyl, phenylalkcarbonyl, optionally substituted aryl, optionally substituted phenylcarbonyl, optionally substituted phenylalkoxycarbonyl and optionally substituted phenylaminocarbonyl, wherein the optional substituents are selected from the group consisting of halogen, alkyl, alkoxy, alkaminothionyl, haloalkyl, haloalkoxy and SF5;
A is selected from the group consisting of optionally substituted cycloalkyl, optionally substituted thiopheneyl,
Figure imgf000054_0002
wherein the optional substitutents, R6 and R10 are independently selected from the group consisting of halogen, alkyl, alkoxy and cyano, and wherein * denotes a point of attachment;
R2 and R4 are independently selected from hydrogen or alkylcarbonyl;
R5 is selected from the group consisting of optionally substituted aryloxy, optionally substituted cycloalkyl and
Figure imgf000055_0001
wherein the optional substituents are independently selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, haloalkoxy and SF5, and wherein R7, R8 and R9 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, SF5 and either of R7 and
R8, or R8 and R9 taken together with -OCH2O-, -OC(CH3)2CH2- or -OC(CH3)2O-, forming a benzo-fused ring; and the corresponding agriculturally acceptably salts thereof.
2. The compound of claim 1 , wherein R2 is hydrogen and A is
Figure imgf000055_0002
3. The compound of claim 2, wherein R is hydrogen and R5 is
Figure imgf000055_0003
wherein R7, R8 and R9 are independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, SF5 and either of R7 and R8, or R8 and R9 taken together with -OCH2O-, -OC(CH3)2CH2- or -OC(CH3)2O-, forming a benzo-fused ring.
4. The compound of claim 3, wherein R8 is hydrogen, R7 and R9 are independently selected from the group consisting of halogen, haloalkyl and haloalkoxy, and R is
Figure imgf000056_0001
wherein Z1 is selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl and haloalkoxy.
5. The compound of claim 4, wherein R , R and Z are halogen.
6. A composition comprising an insecticidally effective amount of a compound of claim 1 and an agriculturally acceptable extender or adjuvant.
7. The insecticidal composition of claim 6, further comprising one or more second compounds selected from the group consisting of pesticides, plant growth regulators, fertilizers and soil conditioners.
8. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 6 to a locus where insects are present or are expected to be present.
9. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 7 to a locus where insects are present or are expected to be present.
PCT/US2006/011218 2005-03-28 2006-03-28 Insecticidal 2,4-diaminoquinazolines and related derivatives WO2006105056A2 (en)

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Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009084695A1 (en) * 2007-12-28 2009-07-09 Carna Biosciences Inc. 2-aminoquinazoline derivative
WO2009143058A1 (en) * 2008-05-22 2009-11-26 Allergan, Inc. Bicyclic compounds having activity at the cxcr4 receptor
WO2011140527A3 (en) * 2010-05-07 2012-03-29 California Institute Of Technology And The University Of Kansas Methods and compositions for inhibition of the transitional endoplasmic reticulum atpase
JP2014500235A (en) * 2010-09-29 2014-01-09 インターベツト・インターナシヨナル・ベー・ベー N-heteroaryl compounds
US20160024116A1 (en) * 2005-12-15 2016-01-28 Rigel Pharmaceuticals, Inc. Kinase Inhibitors And Their Uses
CN105367555A (en) * 2014-08-07 2016-03-02 广东东阳光药业有限公司 Substituted heteroaryl compound and composition and application thereof
CN106413715A (en) * 2014-04-22 2017-02-15 林伯士艾瑞斯公司 IRAK inhibitors and uses thereof
CN107531725A (en) * 2015-08-13 2018-01-02 北京韩美药品有限公司 IRAK4 inhibitor and its application
WO2018233648A1 (en) * 2017-06-21 2018-12-27 南京明德新药研发股份有限公司 Isothiazolo[4,3-d]pyrimidine-5,7-diamine derivative as tlr8 agonist
JP2019524790A (en) * 2016-08-09 2019-09-05 ホンユン バイオテック カンパニー リミテッド Thienopyrimidine compound, method for producing the same, pharmaceutical composition and application thereof
CN111423384A (en) * 2019-07-04 2020-07-17 沈阳药科大学 2-aminopyrimidine compounds and application thereof
US11084807B2 (en) 2016-08-18 2021-08-10 Vidac Pharama Ltd. Piperazine derivatives, pharmaceutical compositions and methods of use thereof
WO2021155426A1 (en) * 2020-02-04 2021-08-12 TroBio Therapeutics Pty Ltd Quinazoline compounds and the use thereof in the treatment of cancer

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989005297A1 (en) * 1987-12-03 1989-06-15 Smithkline Beckman Intercredit B.V. Compounds
US5064833A (en) * 1989-05-10 1991-11-12 Smithkline Beecham Intercredit B.V. Substituted quinazoline derivatives for use in gastrointestinal diseases
WO1997020822A1 (en) * 1995-12-01 1997-06-12 Novartis Ag Quinazolin-2,4-diazirines as npy receptor antagonist
US6339089B2 (en) * 1997-08-13 2002-01-15 Fujirebio Inc. Pyrimidine nucleus-containing compound and a medicament containing the same for a blood oxygen partial pressure amelioration, and a method for preparing the same

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989005297A1 (en) * 1987-12-03 1989-06-15 Smithkline Beckman Intercredit B.V. Compounds
US5064833A (en) * 1989-05-10 1991-11-12 Smithkline Beecham Intercredit B.V. Substituted quinazoline derivatives for use in gastrointestinal diseases
WO1997020822A1 (en) * 1995-12-01 1997-06-12 Novartis Ag Quinazolin-2,4-diazirines as npy receptor antagonist
US6339089B2 (en) * 1997-08-13 2002-01-15 Fujirebio Inc. Pyrimidine nucleus-containing compound and a medicament containing the same for a blood oxygen partial pressure amelioration, and a method for preparing the same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GIARDINA D. ET AL.: 'Structure-Activity Relationships in Prazosin-Related Compounds. 2. Role of the Piperazine Ring on alpha-Blocking Activity' J. MED. CHEM. vol. 36, no. 6, 1993, pages 690 - 698, XP000652149 *

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WO2009143058A1 (en) * 2008-05-22 2009-11-26 Allergan, Inc. Bicyclic compounds having activity at the cxcr4 receptor
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US11078213B2 (en) 2016-08-09 2021-08-03 Hongyun Biotech Co., Ltd. Thienopyrimidine compound, preparation method thereof, pharmaceutical composition and application thereof
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