WO2021001825A1 - Methionine metabolic pathway inhibitors - Google Patents
Methionine metabolic pathway inhibitors Download PDFInfo
- Publication number
- WO2021001825A1 WO2021001825A1 PCT/IL2020/050732 IL2020050732W WO2021001825A1 WO 2021001825 A1 WO2021001825 A1 WO 2021001825A1 IL 2020050732 W IL2020050732 W IL 2020050732W WO 2021001825 A1 WO2021001825 A1 WO 2021001825A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- alkyl
- group
- haloalkyl
- alkoxy
- hydrogen
- Prior art date
Links
- 0 *c(cc1)ccc1[Re] Chemical compound *c(cc1)ccc1[Re] 0.000 description 7
- ZFPRRNNRUVHJRM-UHFFFAOYSA-N CC(Nc1cc(NC(CNC(C2=CC=C3N=NNC3C2)=O)=O)ccc1)=O Chemical compound CC(Nc1cc(NC(CNC(C2=CC=C3N=NNC3C2)=O)=O)ccc1)=O ZFPRRNNRUVHJRM-UHFFFAOYSA-N 0.000 description 1
- SOZWZSJXFAHYDK-UHFFFAOYSA-N CCc(cccc1)c1NC(CNC(c(cc1NN)ccc1N=C)=O)=O Chemical compound CCc(cccc1)c1NC(CNC(c(cc1NN)ccc1N=C)=O)=O SOZWZSJXFAHYDK-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/50—1,3-Diazoles; Hydrogenated 1,3-diazoles
- A01N43/52—1,3-Diazoles; Hydrogenated 1,3-diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
- A01N43/647—Triazoles; Hydrogenated triazoles
-
- 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
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
- A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
-
- 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
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/06—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D249/18—Benzotriazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/26—Radicals substituted by sulfur atoms
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Definitions
- the present application relates to the field of methionine metabolic pathway inhibition.
- the present application relates to novel inhibitors of cystathionin gamma synthase (CGS), the method for their molecular design and identification based on structural information obtained, and use thereof in various agricultural and non-agricultural applications.
- CGS cystathionin gamma synthase
- Cystathionine g-synthase is the first enzyme of the trans-sulphuration pathway in bacteria and plants.
- sulphide is derived from the reduction of sulphate and is incorporated into L-cysteine (L-Cys), which is subsequently converted to L-homocysteine (L-Hcys), the immediate precursor of L-methionine (L-Met).
- L-Cys L-cysteine
- L-Hcys L-homocysteine
- L-Met L-methionine
- the CGS catalyses the committed step of methionine biosynthesis. Encoded by the metB gene in Escherichia coli ( E . coli ), the CGS catalyses a pyridoxal phosphate-dependent, a,g- replacement reaction in which L-Cys and (9-succinyl-L-homoserine are condensed to produce L- cystathionine (L-Cth) and succinate.
- L-Cys and (9-succinyl-L-homoserine are condensed to produce L- cystathionine (L-Cth) and succinate.
- the present application relates to inhibitors of methionine metabolic pathway having Formula (I):
- T is a sulphonyl radical or carbonyl radical:
- Ri is a radical of Formulae (A), (B), (C) or (D):
- R 4 is a five-membered heteroaromatic ring having one to three heteroatoms selected from N, O and S, and optionally substituted with (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (Ci-C 3 )-alkoxy or hydroxy group, or halogen atom;
- R 5 is hydrogen, or (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl or (Ci-C 3 )-alkoxy group;
- R 6 , R S and R 9 are independently selected from hydrogen, halogen, amino, cyano, (C 1 -C 3 )- alkyl, (Ci-C 3 )-haloalkyl, hydroxy, (Ci-C 3 )-alkoxy, (Ci-C 3 )-haloalkoxy, mono-(Ci-C 3 )-alkylamino, di-(Ci-C 3 )-alkylamino, amino-(Ci-C 3 )-alkyl, mono-(Ci-C 3 )-alkylamino-(Ci-C 3 )-alkyl, di-(Ci-C 3 )- alkylamino-(Ci-C 3 )-alkyl and nitro group;
- R 7 is hydrogen, halogen, cyano, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (Ci-C 3 )-alkoxy, hydroxy, (Ci-C 3 )-haloalkoxy, amino, mono-(Ci-C 3 )-alkylamino, di-(Ci-C 3 )-alkylamino, amino-(Ci-C 3 )-alkyl, mono-(Ci-C 3 )-alkylamino-(Ci-C 3 )-alkyl, di-(Ci-C 3 )-alkylamino-(Ci-C 3 )-alkyl, nitro or 3,5- dimethyl- 1 //-pyrazol- 1 -yl group;
- R is CH or N
- A is CH-R10 or N-Rn; E is C-R12 or N;
- J is C-R 13 or N;
- Rio, R 11 , R 12 and R 13 are independently selected from hydrogen, (Ci-C 3 )-alkyl and (C 1 -C 3 )- haloalkyl;
- X and Y are independently CH or N;
- Z is C-R14 or N
- Ri 4 is hydrogen, halogen, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, hydroxy, (Ci-C 3 )-alkoxy, carboxylate, (Ci-C 3 )-alkylcarboxylate, carboxylic acid, (Ci-C 3 )-alkylcarboxylic acid, carboxamide, (Ci-C 3 )-alkylcarboxamide, cyano, nitro, phenyl, benzyl, pyridinyl or phenylamino, wherein said phenyl, benzyl, pyridinyl or phenylamino are optionally substituted with one to three same or different substituents independently selected from halogen, (Ci-C 3 )-alkyl, (C 3 -C 6 )-cycloalkyl, (Ci- C 3 )-haloalkyl, hydroxy, (Ci-C 3 )-alk
- L is N-R 15 , O or S
- Ri5 is hydrogen, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, benzyl, pyridinyl or phenyl, wherein said benzyl, pyridinyl or phenyl are optionally substituted with one to three same or different substituents independently selected from halogen, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, hydroxy, (Ci-C 3 )-alkoxy, cyano, amino and nitro group;
- R 2 is a hydrogen atom
- R 3 is a phenyl group optionally substituted with one to three same or different substituents independently selected from a halogen atom, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (Ci-C 3 )-alkoxy, amino, cyano, hydroxy, nitro, carboxylic acid, (Ci-C 3 )-alkylcarboxylic acid, carboxylate, carboxamide, (Ci-C 3 )-alkylcarboxylate and (Ci-C 3 )-alkylcarboxamide group; and
- R 2 is a hydrogen atom
- R 3 is a phenyl or pyridinyl group substituted with the radical of the Formula (E) and optionally substituted at any available carbon atom of the phenyl or pyridinyl ring with (C 1 -C 3 )- alkyl, (Ci-C 3 )-haloalkyl, (Ci-C 3 )-alkoxy, carboxylic acid, carboxylate, (Ci-C 3 )-alkylcarboxylic acid, (Ci-C 3 )-alkylcarboxylate, (Ci-C 3 )-alkylcarboxamide, carboxamide, halogen, cyano, hydroxy or nitro group; (iii) provided that when Ri is a radical of Formula (C), then
- the pyrrolidinyl ring of said indolinyl radical is substituted with one R 16 group attached to any available pyrrolidinyl ring carbon atom, and selected from hydrogen, halogen, nitro, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (Ci-C 3 )-alkoxy, hydroxy, cyano, carboxylic acid, carboxylate, (Ci- C 3 )-alkylcarboxylate, carboxamide, (Ci-C 3 )-alkylcarboxylic acid, (Ci-C 3 )-alkylcarboxamide, or amino group; and the phenyl aromatic ring of said radical is optionally substituted with one to three substituents Rn attached to any available phenyl ring carbon atom and independently selected from halogen, nitro, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (Ci-C
- R 2 is hydrogen or (Ci-C 3 )-alkyl
- R 3 is a radical of the formula:
- Ris is one to three same or different substituents attached to any available carbon atom of the phenyl ring and independently selected from hydrogen, amino, (Ci-C 3 )-alkyl, (C 1 -C 3 )- haloalkyl, (Ci-C 3 )-alkoxy, (Ci-C 3 )-alkylcarboxylic acid, carboxylic acid, (Ci-C 3 )-alkylcarboxylate, carboxylate, (Ci-C 3 )-alkylcarboxamide, carboxamide, halogen, cyano, hydroxy, nitro and acetylamino group; and either:
- the compounds of the Formula (I), capable of inhibiting methionine metabolic pathway, can be used in inhibiting cystathionin g-synthase (CGS) in general, and in plants, fungi and bacteria, in particular. These compounds can be used as herbicides, pesticides, fungicides, agricultural plant stimulants or antimicrobial agents.
- the compounds of the present invention can be used for seed treatment.
- the compounds of the present invention are used as selective herbicides, non-selective herbicides, agricultural herbicides, non- agricultural herbicides or weed killers, herbicides in integrated pest management, herbicides in gardening, herbicides in clearing waste ground, herbicides in clearing industrial or constructions sites, or herbicides in clearing railways and railway embankments.
- Fig. 1 shows the coomassie-stained 12% SDS gel electrophoresis of the proteins eluted from the nickel column:
- Lane 1 is a marker band
- Lane 10 the band showing the protein expressed from the first colony after it was eluted from the nickel column.
- Figs. 2a-2b show the assay development for monitoring CGS activity.
- the bar plots in Fig. 2a show the light absorbance at 360 nm following the incubation of CGS, cysteine and phospho-serine ester together with 7-methyl-6-thioguanosine (MESG) and purine nucleoside phosphorylase (PNP).
- the MESG is a chromophoric substrate used for the quantitation of inorganic phosphate in the PNP assay.
- the increased absorbance indicates phosphate release.
- Fig. 2b presents a table showing the corresponding initial components used in the reaction. DETAILED DESCRIPTION
- the term “about” is understood as within a range of normal tolerance in the art, for example within two standard deviations of the mean. In one embodiment, the term “about” means within 10% of the reported numerical value of the number with which it is being used, preferably within 5% of the reported numerical value. For example, the term “about” can be immediately understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. In other embodiments, the term “about” can mean a higher tolerance of variation depending on for instance the experimental technique used.
- CGS cystathionin g-synthase
- the present embodiments are related to small organic compounds capable of binding to and hence, selectively inhibiting the enzyme cystathionin g-synthase (CGS). These organic compounds may potentially be developed into the CGS-based herbicides, which would be non-toxic to humans since CGS is absent in mammalians.
- alkyl refers to a saturated monovalent hydrocarbon radical.
- exemplary alkyl groups include methyl, ethyl and propyl.
- (Ci-C3)-alkyl refers to an alkyl containing from one to three carbon atoms.
- haloalkyl this is intended to refer to an alkyl having bonded thereto one, two or three of the other, specifically-named groups, such as halogen, at any point of attachment on either the straight or branched chain of the alkyl.
- aryl refers to a monovalent unsaturated aromatic hydrocarbon radical of six to eighteen ring atoms having a single ring or multiple condensed rings.
- exemplary aryl groups are phenyl, biphenyl, benzyl, naphthyl, anthryl, pyrenyl and the like.
- substituted is used with such groups, as in “optionally substituted with one to three substituents independently selected from”, it should be understood that the aryl moiety may be optionally substituted with the same or different groups independently selected from those recited above and hereinafter as appropriate.
- cycloalkyl refers to a fully saturated and partially unsaturated cyclic monovalent hydrocarbon radical having three to six carbon atoms in a ring.
- exemplary cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl and cyclohexanyl.
- heterocyclic and “heterocyclyl” refer to fully saturated or partially unsaturated non-aromatic cyclic radicals of three to eight ring atoms in each cycle (in each monocyclic group, six to twelve atoms in a bicyclic group, and ten to eighteen atoms in a tricyclic group), which have at least one heteroatom (nitrogen, oxygen or sulphur) and at least one carbon atom in a ring.
- Each ring of the heterocyclic group containing a heteroatom may have from one to three heteroatoms, where the nitrogen and/or sulphur heteroatoms may optionally be oxidised and the nitrogen heteroatoms may optionally be quatemised.
- a heterocyclyl group may have a carbon ring atom replaced with a carbonyl group.
- the heterocyclyl group may be attached to the remainder of the molecule at any nitrogen atom or carbon atom of the ring or ring system.
- the heterocyclo group may have a second or third ring attached thereto in a spiro or fused fashion, provided the point of attachment is to the heterocyclyl group.
- An attached spiro ring may be a carbocyclic or heterocyclic ring and the second and/or third fused ring may be a cycloalkyl, aryl or heteroaryl ring.
- Exemplary monocyclic heterocyclic groups include azetidinyl, oxiranyl, pyrrolidinyl, pyrazolinyl, imidazolidinyl, dioxanyl, dioxolanyl, oxazolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahyrdofuryl, tetrahydropyranyl, thiamorpholinyl, and the like.
- bicyclic heterocyclic groups include indolinyl, isoindolinyl, quinuclidinyl, benzopyrrolidinyl, benzopyrazolinyl, benzoimidazolidinyl, benzopiperidinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, dihydroisoindolyl and the like.
- heteroaryl refers to aromatic monocyclic, bicyclic or tricyclic radicals of three to eight ring atoms in each cycle (for example, three to eight atoms in a monocyclic group, six to twelve atoms in a bicyclic group, and to to eigtheen atoms in a tricyclic group), which have at least one heteroatom (nitrogen, oxygen or sulphur) and at least one carbon atom in a ring.
- Each ring of the heteroaryl group may have one to four heteroatoms, wherein nitrogen and/or sulphur may optionally be oxidised, and the nitrogen heteroatoms may optionally be quatemised.
- the heteroaryl group may be attached to the remainder of the molecule at any nitrogen atom or carbon atom of the ring or ring system. Additionally, the heteroaryl group may have a second or third carbocyclic (cycloalkyl or aryl) or heterocyclic ring fused thereto provided the point of attachment is to the heteroaryl group.
- heteroaryl groups are pyrrolyl, thienyl, thiazolyl, imidazolyl, furanyl, indolyl, isoindolyl, oxazolyl, isoxazolyl, benzothiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl, tetrazolyl and so on.
- Exemplary bicyclic heteroaryl groups include benzothiazolyl, benzoxazolyl, quinolinyl, benzoxadiazolyl, benzothienyl, chromenyl, indolyl, indazolyl, isoquinolinyl, benzimidazolyl, benzopyranyl, benzofuryl, benzofurazanyl, benzopyranyl, cinnolinyl, quinoxalinyl, pyrrolopyridyl, furopyridinyl (such as furo[2,3-c]pyridinyl, furo[3,2-b]pyridinyl] or furo[2,3-b]pyridinyl), triazinylazepinyl, and the like.
- the heterocyclyl ring may optionally be fused to a (one) aryl or heteroaryl ring as defined herein provided the aryl and heteroaryl rings are monocyclic. Additionally, one or two ring carbon atoms in the heterocyclyl ring can optionally be replaced with a carbonyl group. When the heterocyclyl ring is partially saturated it can contain one to three ring double bonds provided that the ring is not aromatic.
- alkoxy refers to the groups of the stmcture -OR and wherein the group R is independently selected from the alkyl or cycloalkyl groups defined and recited above and hereinafter as appropriate.
- alkylamino or "dialkylamino” refers to an amino group wherein one or both of the hydrogen atoms are replaced with a group selected from the alkyl or cycloalkyl groups defined and recited above and hereinafter as appropriate.
- halo and halogen refers to fluoro/fluorine, chloro/chlorine, bromo/bromine, or iod/iodine radicals/atoms, relatively.
- haloalkyl refers to alkyl and cycloalkyl radicals as defined above, substituted with one or more halogen atoms, including those substituted with different halogens. Exemplary groups are chloromethyl, trifluoromethyl, perfluoropropyl, trichloroethylenyl, chloroacetylenyl, and the like.
- the present invention provides inhibitors of methionine metabolic pathway having the following Formula (I):
- T is a sulphonyl radical or carbonyl radical:
- Ri is a radical of Formulae (A), (B), (C) or (D):
- R 4 is a five-membered heteroaromatic ring having one to three heteroatoms selected from N, O and S, and optionally substituted with (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (Ci-C 3 )-alkoxy or hydroxy group, or halogen atom;
- R 5 is hydrogen, or (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl or (Ci-C 3 )-alkoxy group;
- R 6 , R S and R 9 are independently selected from hydrogen, halogen, amino, cyano, (C 1 -C 3 )- alkyl, (Ci-C 3 )-haloalkyl, hydroxy, (Ci-C 3 )-alkoxy, (Ci-C 3 )-haloalkoxy, mono-(Ci-C 3 )-alkylamino, di-(Ci-C 3 )-alkylamino, amino-(Ci-C 3 )-alkyl, mono-(Ci-C 3 )-alkylamino-(Ci-C 3 )-alkyl, di-(Ci-C 3 )- alkylamino-(Ci-C 3 )-alkyl and nitro group;
- R 7 is hydrogen, halogen, cyano, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (Ci-C 3 )-alkoxy, hydroxy, (Ci-C 3 )-haloalkoxy, amino, mono-(Ci-C 3 )-alkylamino, di-(Ci-C 3 )-alkylamino, amino-(Ci-C 3 )-alkyl, mono-(Ci-C 3 )-alkylamino-(Ci-C 3 )-alkyl, di-(Ci-C 3 )-alkylamino-(Ci-C 3 )-alkyl, nitro or 3,5- di ethyl- 1 //-pyrazol- 1 -yl group;
- R is CH or N
- A is CH-R10 or N-Rn
- E is C-R12 or N
- J is C-R13 or N
- Rio, R 11 , R 12 and R 13 are independently selected from hydrogen, (Ci-C 3 )-alkyl and (C 1 -C 3 )- haloalkyl;
- X and Y are independently CH or N;
- Ri 4 is hydrogen, halogen, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, hydroxy, (Ci-C 3 )-alkoxy, carboxylate, (Ci-C 3 )-alkylcarboxylate, carboxylic acid, (Ci-C 3 )-alkylcarboxylic acid, carboxamide, (Ci-C 3 )-alkylcarboxamide, cyano, nitro, phenyl, benzyl, pyridinyl or phenylamino, wherein said phenyl, benzyl, pyridinyl or phenylamino are optionally substituted with one to three same or different substituents independently selected from halogen, (Ci-C 3 )-alkyl, (C 3 -C 6 )-cycloalkyl, (Ci- C 3 )-haloalkyl, hydroxy, (Ci-C 3 )-alky
- L is N-Ris, O or S
- Ri5 is hydrogen, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, benzyl, pyridinyl or phenyl, wherein said benzyl, pyridinyl or phenyl are optionally substituted with one to three same or different substituents independently selected from halogen, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, hydroxy, (Ci-C 3 )-alkoxy, cyano, amino and nitro group;
- R 2 is a hydrogen atom
- R 3 is a phenyl group optionally substituted with one to three same or different substituents independently selected from a halogen atom, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (Ci-C 3 )-alkoxy, amino, cyano, hydroxy, nitro, carboxylic acid, (Ci-C 3 )-alkylcarboxylic acid, carboxylate, carboxamide, (Ci-C 3 )-alkylcarboxylate and (Ci-C 3 )-alkylcarboxamide group; and
- R 2 is a hydrogen atom
- R 3 is a phenyl or pyridinyl group substituted with the radical of the Formula (E) and optionally substituted at any available carbon atom of the phenyl or pyridinyl ring with (C 1 -C 3 )- alkyl, (Ci-C 3 )-haloalkyl, (Ci-C 3 )-alkoxy, carboxylic acid, carboxylate, (Ci-C 3 )-alkylcarboxylic acid, (Ci-C 3 )-alkylcarboxylate, (Ci-C 3 )-alkylcarboxamide, carboxamide, halogen, cyano, hydroxy or nitro group;
- the pyrrolidinyl ring of said indolinyl radical is substituted with one R 16 group attached to any available pyrrolidinyl ring carbon atom, and selected from hydrogen, halogen, nitro, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (Ci-C 3 )-alkoxy, hydroxy, cyano, carboxylic acid, carboxylate, (Ci- C 3 )-alkylcarboxylate, carboxamide, (Ci-C 3 )-alkylcarboxylic acid, (Ci-C 3 )-alkylcarboxamide, or amino group; and the phenyl aromatic ring of said radical is optionally substituted with one to three substituents Rn attached to any available phenyl ring carbon atom and independently selected from halogen, nitro, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (Ci-C
- R 2 is hydrogen or (Ci-C 3 )-alkyl
- R 3 is a radical of the formula:
- Ris is one to three same or different substituents attached to any available carbon atom of the phenyl ring and independently selected from hydrogen, amino, (Ci-C 3 )-alkyl, (C 1 -C 3 )- haloalkyl, (Ci-C 3 )-alkoxy, (Ci-C 3 )-alkylcarboxylic acid, carboxylic acid, (Ci-C 3 )-alkylcarboxylate, carboxylate, (Ci-C 3 )-alkylcarboxamide, carboxamide, halogen, cyano, hydroxy, nitro and acetylamino group; and either:
- G taken together with the two adjacent carbon atoms and with the nitrogen atom to which the second carbon atom is attached forms a five- or six-membered heterocyclic ring.
- the present invention provides the compounds of Formula (IA):
- R 2 is a phenyl group optionally substituted with one to three same or different substituents independently selected from a halogen atom, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl, (C 1 -C 3 )- alkoxy, amino, cyano, hydroxy, nitro, carboxylic acid, (Ci-C 3 )-alkylcarboxylic acid, carboxylate, carboxamide, (Ci-C 3 )-alkylcarboxylate and (Ci-C 3 )-alkylcarboxamide;
- R 3 is a five-membered heteroaromatic ring radical selected from:
- said five-membered heteroaromatic ring is optionally substituted with a halogen atom, or hydroxy, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl or (Ci-C 3 )-alkoxy group; and
- R 4 is hydrogen, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl or (Ci-C 3 )-alkoxy group.
- the compounds of Formula (IA) have R 2 defined as a phenyl group optionally substituted with one to three same or different substituents independently selected from a halogen atom, (Ci-C 3 )-alkyl, carboxylic acid, carboxylate, carboxamide, (C 1 -C 3 )- alkylcarboxylic acid and (Ci-C 3 )-alkylcarboxylate;
- R 3 is a 1,3-thiazolyl radical optionally substituted with a halogen atom, or hydroxy, (C 1 -C 3 )- alkyl, (Ci-C 3 )-haloalkyl or (Ci-C 3 )-alkoxy group;
- R 4 is hydrogen, (Ci-C 3 )-alkyl, (Ci-C 3 )-haloalkyl or (Ci-C 3 )-alkoxy group.
- the compounds of Formula (IA) have R 2 defined as a phenyl group optionally substituted with one substituent selected from a halogen atom, (Ci-C 3 )-alkyl and carboxylic acid group.
- R 2 defined as a phenyl group optionally substituted with one substituent selected from a halogen atom, (Ci-C 3 )-alkyl and carboxylic acid group.
- the present invention provides the compounds having Formulae (IB-1) or (IB-2):
- R6, R 7 , Rs and R9 are independently selected from hydrogen, halogen, (Ci-C3)-alkyl, (Ci-C3)-alkoxy and (Ci-C3)-haloalkyl.
- X and Y are independently CH or N;
- Z is C-R19 or N
- R19 is hydrogen, ethyl, cyclopentyl, trifluoromethyl, hydroxy, benzyl or phenylamino, wherein said benzyl or phenylamino are optionally substituted with one to three same or different substituents independently selected from halogen, methyl, trifluoromethyl, hydroxy, methoxy or carboxylic acid group;
- L is N-R20, O or S;
- R 20 is hydrogen, methyl or benzyl group
- Q is C-R 21 or N
- R21 is carboxylic acid, carboxylate, (Ci-C3)-alkylcarboxylic acid or (Ci-C3)-alkylcarboxylate group.
- the present invention provides the compounds of Formulae
- pyrrolidinyl ring of said compounds is substituted with one Ri 6 group attached to any available pyrrolidinyl ring carbon atom, and selected from methyl, carboxamide, carboxylate, carboxylic acid or acetic acid group; and optionally with one to three substituents Rn attached to any available phenyl ring carbon atom, and independently selected from (Ci-C3)-alkyl, (C1-C3)- alkoxy group or halogen atom.
- the present invention provides the compounds of Formula (ID):
- R is one substituent attached to any available carbon atom of the phenyl ring and selected from hydrogen, (Ci-C3)-alkyl and acetylamino group;
- Rio, Rn, Ri 2 , and Ris are independently selected from hydrogen and (Ci-C3)-alkyl;
- - is either a double bond and G is O; or a single bond and G taken together with the two adjacent carbon atoms and with the nitrogen atom to which the second carbon atom is attached forms a five- or six-membered heterocyclic ring.
- the compounds of the present invention are indeed herbicidally active and would be effective in regulating growth of a wide variety of undesirable plants, i.e., weeds, when applied, in herbicially effective amount, to the growth medium prior to emergence of the weeds or to the weeds subsequent to emergence from the growth medium.
- herbicidally effective amount is that amount of a compound or mixture of compounds of the present invention required to so injure or damage weeds such that the weeds are incapable of recovering following application.
- the quantity of a compound or mixture of compounds of the present invention applied in order to exhibit a satisfactory herbicidal effect may vary over a wide range and depends on a variety of factors, such as, for example, hardiness of a particular weed species, extent of weed infestation, climatic conditions, soil conditions, method of application and the like.
- the efficacy of a particular compound against a particular weed species may readily be determined by routine laboratory or field testing in a manner well known to the art.
- a compound or compounds of the present invention can be used in various formulations with agronomically acceptable adjuvants, inert carriers, other herbicides, or other commonly used agricultural compounds, for example, insecticides, fungicides, pesticides, stabilisers, safeners, fertilisers or the like.
- the compounds of the present invention alone or in formulation with other agronomically used materials are typically applied in the form of dusts, granules, wettable powders, solutions, suspensions, aerosols, emulsions, dispersions or the like in a manner well known to the art.
- the amount of compound or compounds of this invention may vary over a wide range, for example, from about 0.05 to about 95 percent by weight on weight of the formulation. Typically, such formulations would contain from about 5 to 75 percent by weight of a compound or compounds of the present invention.
- Weeds that may be effectively controlled by the application of compounds of the present invention are for example, barnyard grass ( Echinochloa crusgalli ), crabgrass ( Digitaria sauguinalis ), rockcress ( Arabidopsis thaliana), coffee weed ( Daubentonia punices), jimsonweed ( Datura stamonium ), Johnson grass ( Sorghum halepense ), tall morning glory ( Ipomoea purpurea ), wild mustard ( Brassica caber), tea weed (Sida Spinosa ), velvetleaf ( Abutilin Theophrasti ), wild oat ( Avena fatua ), yellow foxtail ( Setaria glauca ), yellow nutsedge ( Cyperus esculentus) and the like.
- barnyard grass Echinochloa crusgalli
- crabgrass Digitaria sauguinalis
- rockcress Arabidopsis thaliana
- coffee weed Daubentonia punices
- jimsonweed D
- the compounds of the present invention are applied to the locus of the unwanted vegetation, to the undesired plants or to a habitat thereof, in a form of herbicidal compositions comprising a herbicially effective amount of the compound or compounds.
- the herbicides of the invention may be applied to the locus of the unwanted vegetation neat or as an emulsion or solution.
- Any solvent in which the herbicide is soluble or may be emulsified may be employed as a diluent. Suitable solvents include water or water-soluble alcohols, such as methanol, ethanol, and isopropyl alcohol, or a ketone such as acetone or methyl ethyl ketone. Such compounds further form emulsions with water.
- a method for the control of undesired vegetation or clearing areas from the undesired vegetation comprises applying to the locus of said undesired vegetation a herbicidally effective amount of a compound or compounds of the present invention.
- the method of the invention may be used to control established vegetation in the vicinity of a seeded crop or in a weed concentrate area by contacting the foliage of the unwanted vegetation with the herbicidal composition.
- the herbicidal activity of such herbicidal compositions rapidly dissipates in the unwanted vegetation upon contact.
- the locus of the undesired plants treated by the compounds of the present invention may be agricultural areas, crop fields, gardens, waste grounds, industrial or constructions sites, railways or railway embankments.
- the compounds of formula (I) have been discovered by in-silico screening method. A thorough structural analysis of the CGS protein structure (based on published X-ray structures) and identification of potential binding sites for small molecule inhibitors was performed. Virtual screening was carried out based on herbicide-like profiled library of small molecules. The profiled library was generated based on an in-house database of approximately 30 million small organic compounds taken from various commercial sources. Based on a list of all available herbicides, the chemical space of in-planta active compounds was defined. The database was filtered based on this set of unique properties, for example profiling to yield the initial set of compounds which may have the potential to be active in plants. These were used for the virtual and in-vitro screening.
- the phosphate that is released as a by-product in this reaction can then be monitored by its conjugation in the additional selective chemical reaction, the conversion of 2-amino-6-mercapto-7- methylpurine riboside (MESG) to ribose 1-phosphate and 2-amino-6-mercapto-7-methylpurine by the enzyme purine nucleoside phosphorylase (PNP).
- the latter product has a unique absorbance in the UV spectrum at 360 nm.
- Figs. 2a-2b showing the assay development for monitoring CGS activity.
- the bar plots in Fig. 2a show the light absorbance at 360 nm following the incubation of CGS, cysteine and phospho-serine ester in the assay together with 7-methyl-6-thioguanosine (MESG) and purine nucleoside phosphorylase (PNP).
- EGS 7-methyl-6-thioguanosine
- PNP purine nucleoside phosphorylase
- the assay incorporates the coupled enzyme system with purine nucleoside phosphorylase and the chromophoric substrate 7-methyl-6-thioguanosine (MESG) used for the quantitation of inorganic phosphate.
- Fig. 2a shows the obtained preliminary results of the assay, which measures the light absorbance at 360 nm of the reaction mixture (Row 1). The increased light absorbance clearly indicates the phosphate release. The results where each of the initial components was removed from the mixture are shown in Rows 2-4. The results with the addition of external free phosphate are shown in Row 5.
- Fig. 2b presents a table showing the corresponding initial components used in the reaction.
- MST Micro Scale Thermophoresis
- the pET-11 vector containing the DNA sequence of Tobacco CGS with an N-terminus 6xHIS tag followed by a TEV-cleavable GB 1 solubility tag was cloned and transformed into the bacteria cells.
- the soluble fraction was passed through the nickel column and the bound HIS-tagged protein was eluted by 300 mM imidazole. Then, the tags 6xHIS and GB 1 were cleaved in dialysis o/n and the mixtures passed again through the nickel column to separate the CGS from the TEV and HIS-GB1 constructs. As a final step the CGS was run on S75 size exclusion chromatography .
- the MST assay was performed to measure the biding of the compounds to the CGS protein.
- the CGS was labelled with commercially available amine reactive fluorophore (Cat# MO-LOO 1, NanoTemper) according to the manufacture instructions.
- the MST binding curves were then measured using the Monolith NT. l 15 apparatus by incubating the labelled protein with the indicated compounds in a dose-response manner.
- the following Table 1 summarises the dose-response of the exemplary compounds of the present invention with the MST full curve validation. Table 1 shows evaluation of binding to Tobacco CGS using the MST experiment, where the activity scale is from 0 to 5 (these values describe qualitatively the significance of the apparent effect with 0 indicating no effect and 5 standing for the most pronounced effect):
- the plates with Arabidopsis thaliana seeds were placed at 4°C for two days and then transferred for seven days to growth chamber (22 ⁇ 2°C) at day /light cycles of 16/8h.
- the plates were placed vertically.
- a control including 0.1% DMSO in the medium was added.
- the compounds of the present invention were tested for their herbicidal efficiency by diluting 1000 times a 50 mM stock in DMSO leading to a final concentration of 50 m M with 0.1% DMSO.
- Table 3 shows the results of the BY-2 viability assay.
- viability of the BY2 Tobacco cells was tested following treatment with the compounds of the present invention.
- cells were cultured in Murashige and Skoog basal medium (Sigma-Aldrich, Cat# M0404), supplemented with 2,4-dichloro-phenoxyacetic acid (0.2 mg/L), and sucrose (3%), and incubated in the dark, at 25°C and then sub-cultured at a 1 : 15 dilution in fresh media every 7 days.
- the exemplified compounds were then added to the wells, at a final concentration of 25 mM (0.05% DMSO), and incubated for 48 hours.
- Cellular viability was measured using the commercially available PrestoBlueTM assay (ThermoFisher Scientific, PrestoBlueTM Cell Viability Reagent Cat# A 13261).
- the PrestoBlueTM reagent is a cell- permeant non-fluorescent compound, which is reduced by metabolically active cells and providing a quantitative fluorescent signal.
- the first reaction in methionine biosynthesis in plants is catalyzed by the CGS enzyme.
- the formation of cystathionine is conducted by the g-replacement of the phosphoryl substituent of ( -phospho-homoserine by cysteine and consecutive release of an orthophosphate group.
- the following experiment demonstrates evaluation of the direct inhibition of a number of the compounds of the present invention on the CGS activity.
- Table 5 shows the results of E. Coli assay LE395 and E. Coli specificity (MOA) for several compounds of the present invention
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Agronomy & Crop Science (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR112022000109A BR112022000109A2 (en) | 2019-07-04 | 2020-07-01 | Methionine metabolic pathway inhibitors |
CN202080046303.0A CN114514224A (en) | 2019-07-04 | 2020-07-01 | Methionine metabolic pathway inhibitors |
EP20747153.3A EP3994127A1 (en) | 2019-07-04 | 2020-07-01 | Methionine metabolic pathway inhibitors |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201962870711P | 2019-07-04 | 2019-07-04 | |
US62/870,711 | 2019-07-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2021001825A1 true WO2021001825A1 (en) | 2021-01-07 |
Family
ID=71842738
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IL2020/050732 WO2021001825A1 (en) | 2019-07-04 | 2020-07-01 | Methionine metabolic pathway inhibitors |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP3994127A1 (en) |
CN (1) | CN114514224A (en) |
BR (1) | BR112022000109A2 (en) |
WO (1) | WO2021001825A1 (en) |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004103953A1 (en) * | 2003-05-21 | 2004-12-02 | Bayer Cropscience Aktiengesellschaft | Difluoromethylbenzanilides and use thereof for combating micro-organisms, intermediate products and use thereof |
WO2010051926A2 (en) * | 2008-11-05 | 2010-05-14 | Bayer Cropscience Aktiengesellschaft | New halogen-substituted bonds |
WO2019142192A1 (en) * | 2018-01-17 | 2019-07-25 | Gavish-Galilee Bio Applications Ltd. | New methionine metabolic pathway inhibitors |
WO2019142191A1 (en) * | 2018-01-17 | 2019-07-25 | Gavish-Galilee Bio Applications Ltd. | New methionine metabolic pathway inhibitors |
-
2020
- 2020-07-01 WO PCT/IL2020/050732 patent/WO2021001825A1/en unknown
- 2020-07-01 EP EP20747153.3A patent/EP3994127A1/en active Pending
- 2020-07-01 CN CN202080046303.0A patent/CN114514224A/en active Pending
- 2020-07-01 BR BR112022000109A patent/BR112022000109A2/en unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004103953A1 (en) * | 2003-05-21 | 2004-12-02 | Bayer Cropscience Aktiengesellschaft | Difluoromethylbenzanilides and use thereof for combating micro-organisms, intermediate products and use thereof |
WO2010051926A2 (en) * | 2008-11-05 | 2010-05-14 | Bayer Cropscience Aktiengesellschaft | New halogen-substituted bonds |
WO2019142192A1 (en) * | 2018-01-17 | 2019-07-25 | Gavish-Galilee Bio Applications Ltd. | New methionine metabolic pathway inhibitors |
WO2019142191A1 (en) * | 2018-01-17 | 2019-07-25 | Gavish-Galilee Bio Applications Ltd. | New methionine metabolic pathway inhibitors |
Non-Patent Citations (4)
Title |
---|
DATKO ET AL.: "Homocysteine biosynthesis in green plants", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 249A, 1974, pages 1139 - 1155 |
M. R. WEBB, PROC. NATL. ACAD. SCI. USA, vol. 89, 1992, pages 4884 - 4887 |
STEEGBORN ET AL.: "Crystal structures of cystathionine gamma-synthase inhibitor complexes rationalize the increased affinity of a novel inhibitor", JOURNAL OF MOLECULAR BIOLOGY, vol. 311, 2001, pages 789 - 801, XP004480502, DOI: 10.1006/jmbi.2001.4880 |
STEEGBORN ET AL.: "The crystal structure of cystathionine y-synthase from Nicotiana tabacum reveals its substrate and reaction specificity", JOURNAL OF MOLECULAR BIOLOGY, vol. 290, no. 5, 1999, pages 983 - 996, XP004461979, DOI: 10.1006/jmbi.1999.2935 |
Also Published As
Publication number | Publication date |
---|---|
EP3994127A1 (en) | 2022-05-11 |
CN114514224A (en) | 2022-05-17 |
BR112022000109A2 (en) | 2022-03-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Li et al. | Novel bisthioether derivatives containing a 1, 3, 4‐oxadiazole moiety: design, synthesis, antibacterial and nematocidal activities | |
US20230250086A1 (en) | Methionine metabolic pathway inhibitors | |
Ma et al. | Synthesis and herbicidal activity of novel N-(2, 2, 2)-trifluoroethylpyrazole derivatives | |
CN109790153A (en) | Plant with increased herbicide tolerant | |
UA127971C2 (en) | Plants having increased tolerance to herbicides | |
US11737462B2 (en) | Methods for modulating plant response to environmentally-induced stress | |
US20230232828A1 (en) | Sulphonamides as methionine metabolic pathway inhibitors | |
CN107535504A (en) | Application of 1,3,4 thiadiazole compounds in bacterial blight of rice is prevented and treated | |
Xu et al. | Synthesis and herbicidal activity of novel α, α, α‐trifluoro‐m‐tolyl pyridazinone derivatives | |
Zhang et al. | Discovery of pyrido [1, 2-a] pyrimidinone mesoionic compounds incorporating a dithioacetal moiety as novel potential insecticidal agents | |
CN110903279B (en) | Pyrazole compound, salt and application thereof | |
Li et al. | γ‐Aminobutyric acid plays a key role in alleviating Glomerella leaf spot in apples | |
US11076597B2 (en) | High stress resistant plant growth regulator and preparation method and use thereof | |
WO2021001825A1 (en) | Methionine metabolic pathway inhibitors | |
TW200301078A (en) | N-heteroaryl nicotinamid derivatives | |
Wang et al. | Design, Synthesis, and Herbicidal Activity of Naphthalimide–Aroyl Hybrids as Potent Transketolase Inhibitors | |
JP5618235B2 (en) | Plant disease control agent comprising pyridylpyrimidine derivative as an active ingredient | |
CN109970704A (en) | A kind of chalcone derivative, preparation method and the application of the ester containing thiophene-sulfonic acid | |
CN111423388B (en) | 7-methoxy-3-phenylquinoxaline-2 (1H) -one derivative and preparation method and application thereof | |
McFadden et al. | Synthesis, structure and herbicidal activity of pyrazol‐4‐yl alkyl ketone derivatives | |
EP1333098A2 (en) | Method for identification of inhibitors of ferredoxin: NADP reductase | |
CN110396083B (en) | Pyridazinonyl-contained butenolide compound and application thereof | |
JP6908226B2 (en) | Plant disease control agent containing a thienopyrimidine derivative as an active ingredient | |
Zhang et al. | The Amino Acid Transporter PtCAT7 and Ammonium Nutrition Enhance the Uptake of Thiamethoxam in Citrus Rootstock Seedlings | |
CN114773328A (en) | Oxadiazole-containing thioether and sulfone compound, stereoisomer thereof, salt thereof or solvate thereof, preparation method, composition and application |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 20747153 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
REG | Reference to national code |
Ref country code: BR Ref legal event code: B01A Ref document number: 112022000109 Country of ref document: BR |
|
ENP | Entry into the national phase |
Ref document number: 2020747153 Country of ref document: EP Effective date: 20220204 |
|
ENP | Entry into the national phase |
Ref document number: 112022000109 Country of ref document: BR Kind code of ref document: A2 Effective date: 20220104 |