WO2016022915A1 - Composés 6-sulfonylamino quinoléine utiles en tant que régulateurs de la croissance des plantes - Google Patents

Composés 6-sulfonylamino quinoléine utiles en tant que régulateurs de la croissance des plantes Download PDF

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WO2016022915A1
WO2016022915A1 PCT/US2015/044202 US2015044202W WO2016022915A1 WO 2016022915 A1 WO2016022915 A1 WO 2016022915A1 US 2015044202 W US2015044202 W US 2015044202W WO 2016022915 A1 WO2016022915 A1 WO 2016022915A1
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alkyl
propyl
alkoxy
cyano
cycloalkyl
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PCT/US2015/044202
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Sebastian Volker Wendeborn
Sean R. CUTLER
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The Regent Of The University Of California
Syngenta Participations Ag
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Publication of WO2016022915A1 publication Critical patent/WO2016022915A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/38—Nitrogen atoms

Definitions

  • the present invention relates to novel sulfonamide derivatives, to processes and intermediates for preparing them, to plant growth regulator compositions comprising them and to methods of using them for controlling the growth of plants, improving plant tolerance to abiotic stress (including environmental and chemical stresses) and/or inhibiting the germination of seeds.
  • Abscisic acid is a plant hormone that plays a major role in plant growth, development and response to abiotic stress.
  • ABA causes many of its cellular responses by binding to a soluble family of receptors called PYR/PYL proteins, which contain a ligand- binding pocket for ABA and other agonists.
  • PYR/PYL proteins a soluble family of receptors
  • Direct application of ABA to plants has been shown to improve their water use efficiency.
  • ABA is difficult and expensive to prepare and itself unstable to environmental conditions and therefor unsuitable for large scale agricultural applications. It is therefore desirable to search for ABA agonists that may be useful for improving plant tolerance to environment stress such as drought, inhibit seed germination, regulate plant growth and improve crop yield.
  • WO2013/148339 reported a new ABA agonist, quinabactin, which binds to the PYR/PRL receptor proteins and causes an abscisic acid response in vivo. Quinabactin has been shown to induce stomatal closure, suppress of water loss and promote drought tolerance. [0005] There is a need to identify improved agonists of abscisic acid for improving plant growth and development, and plant tolerance to environmental stresses.
  • the present invention relates to novel analogs of quinabactin that have improved properties. Benefits of the compounds of the present invention include enhanced tolerance to abiotic stress, improved inhibition of seed germination, better regulation of crop growth, improved crop yield, and/or improved physical properties resulting in better plant uptake, water solubility, chemical stability or physical stability.
  • the present invention provides novel sulfonamide derivatives, processes and intermediates for preparing them, compositions comprising them and methods of using them.
  • the invention provides a compound of Formula (I):
  • Rl is selected from hydrogen, alkyl, cyano-alkyl, haloalkyl, alkoxy-alkyl, haloalkoxy-alkyl, cycloalkyl-alkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl and heterocycloalkyl; or Rl is selected from alkyl-aryl, cycloalkyl, phenyl and heteroaryl, each optionally substituted with one to three Rx.
  • Each Rx is independently selected from halogen, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulfanyl, haloalkylsulfanyl, alkylsulfmyl, haloalkylsulfmyl, alkylsulfonyl, haloalkylsulfonyl and cycloalkyl.
  • R2, R3, R4, R5 and R6 are independently selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy and cycloalkyl.
  • L is selected from alkyl, alkenyl, alkoxy and alkoxy-alkyl, each optionally substituted with one to three moieties independently selected from halogen, cyano, alkyl and alkoxy.
  • R7 is aryl optionally substituted with one to three Ry; or R7 is heteroaryl optionally substituted with one to three Rz.
  • Each Ry is independently selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulfanyl, haloalkylsulfanyl, alkylsulfmyl, haloalkylsulfmyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkyl, COOH, COOR9, CONHR9, CONR9aR9 and NHCOR9.
  • R9 and R9a are independently alkyl.
  • Each Rz is independently selected from halogen, cyano, alkyl, alkoxy, carbonyl, haloalkyl, haloalkoxy and cycloalkyl.
  • the compounds of the present invention may exist in different geometric or optical isomers (diastereoisomers and enantiomers) or tautomeric forms.
  • This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds.
  • the invention also covers all salts, N-oxides, and metalloidic complexes of the compounds of the present invention.
  • the invention provides formulations of these compounds formulated appropriately for administration to plants and methods of using the compounds and formulations.
  • FIG. 1 is a table showing thermal images of Arabidopsis leaves. DETAILED DESCRIPTION OF THE INVENTION
  • the near or approximating unrecited number may be a number, which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number.
  • alkyl by itself or as part of another substituent, means, unless otherwise stated, a straight- or branched-chain, or cyclic hydrocarbon radical, or combination thereof, which is fully saturated and can include mono-, di-, tri- and tetra-valent radicals, having the number of carbon atoms designated (i.e. Ci-Cio means one to ten carbons).
  • saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n- propyl, isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n- octyl, and the like.
  • alkyl refers to alkyl moieties, which can be mono-, di- or polyvalent species as appropriate to satisfy valence requirements.
  • alkenyl by itself or as part of another substituent, means, unless otherwise stated, a straight- or branched-chain, or cyclic alkyl radical, or combination thereof, having one or more carbon-carbon double bonds.
  • alkenyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, isopenten-2-yl, butadien-2-yl, 2,4-pentadienyl, l,4-pentadien-3-yl, and the higher homologs and isomers.
  • alkynyl by itself or as part of another substituent, means, unless otherwise stated, a straight- or branched-chain, or cyclic alkyl radical, or combination thereof, having one or more carbon-carbon triple bonds.
  • alkynyl groups include, but are not limited to, ethynyl, 1- and 3-propynyl, 3-butynyl, and the higher homologs and isomers.
  • alkylene by itself or as part of another substituent, means a divalent radical derived from an alkyl moiety, as exemplified, but not limited, by -CH 2 CH 2 CH 2 CH 2 - Typically, an alkyl (or alkylene) group will have from 1 to 24 carbon atoms, with those groups having 10 or fewer carbon atoms being preferred in the present invention.
  • alkylene and heteroalkylene linker groups it is optional that no orientation of the linker group is implied by the direction in which the formula of the linker group is written.
  • the formula -C(0) 2 R'- represents -C(0) 2 R'- and, optionally, -R'C(0) 2 -.
  • a “lower alkyl” or “lower alkylene” is a shorter chain alkyl or alkylene group, generally having eight, seven, six, five or fewer carbon atoms.
  • alkoxy alkylamino
  • alkylthio or thioalkoxy are used in their conventional sense, and refer to those alkyl groups attached to the remainder of the molecule via an oxygen atom, an amino group, or a sulfur atom, respectively.
  • heteroalkyl by itself or in combination with another term, means, unless otherwise stated, a stable straight- or branched-chain, or cyclic alkyl radical consisting of the stated number of carbon atoms and at least one heteroatom selected from the group consisting of B, O, N, Si and S, wherein the heteroatom may optionally be oxidized and the nitrogen atom may optionally be quaternized.
  • the heteroatom(s) may be placed at any internal position of the heteroalkyl group or at a terminus, e.g., the position through which the alkyl group is attached to the remainder of the molecule.
  • heteroalkyl examples include, but are not limited to, -CH 2 -CH 2 -0-CH 3 , -CH 2 -CH 2 -NH-CH 3 ,
  • heteroatoms may be consecutive, such as, for example, -CH 2 -NH-OCH 3 and -CH 2 -0-Si(CH 3 ) 3 .
  • heteroalkylene by itself or as part of another substituent refers to a divalent heteroalkyl radical, as exemplified, but not limited by, -CH 2 -CH 2 -S-CH 2 -CH 2 - and -CH 2 -S-CH 2 -CH 2 -NH-CH 2 -.
  • heteroatoms can also occupy either or both of the termini (e.g., alkyleneoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like).
  • cycloalkyl and “heterocycloalkyl”, by themselves or in combination with other terms, represent, unless otherwise stated, cyclic versions of "alkyl” and
  • heteroalkyl respectively. Additionally, for heterocycloalkyl, a heteroatom can occupy the position at which the heterocycle is attached to the remainder of the molecule. Examples of cycloalkyl include, but are not limited to, cyclopentyl, cyclohexyl, cycloheptyl, and the like.
  • heterocycloalkyl examples include, but are not limited to, 1-piperidinyl, 2-piperidinyl, 3- piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl, 2-piperazinyl, and the like.
  • any of the alkyl, alkenyl, alkynyl, alkylene, heteroalkylene, alkoxy, alkylamino, alkylthio, heteroalkyl, cycloalkyl and heterocycloalkyl groups is optionally substituted, e.g., with one or more groups referred to herein as an "alkyl group substituent.”
  • alkyl group substituent e.g., a fluorine, chlorine, bromine, or iodine atom.
  • haloalkyl are meant to include monohaloalkyl and polyhaloalkyl.
  • halo(Ci-C4)alkyl is meant to include, but not be limited to,
  • aryl means, unless otherwise stated, a polyunsaturated, aromatic substituent that can be a single ring or multiple rings (preferably from 1 to 3 rings), which are fused together.
  • heteroaryl refers to aryl groups (or rings) that contain from one to four heteroatoms selected from N, O, and S, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom(s) are optionally quaternized.
  • a heteroaryl group can be attached to the remainder of the molecule through a heteroatom.
  • Non-limiting examples of aryl and heteroaryl groups include phenyl, 1-naphthyl, 2-naphthyl, 1-pyrrolyl, 2- pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4- oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5- thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4- pyrimidyl, 5-benzothiazolyl, purinyl, 2-benzimidazolyl, 5-indolyl, 1-isoquinolyl, 5- isoquinolyl, 2-quinoxaliny
  • any of the aryl and heteroaryl groups is optionally substituted, e.g. , with one or more groups referred to herein as an "aryl group substituent.”
  • arylalkyl includes those radicals in which an aryl group is attached to an alkyl group ⁇ e.g., benzyl, phenethyl, and the like).
  • R', R", R'" and R" each preferably independently refer to hydrogen, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, e.g., aryl substituted with 1-3 halogens, substituted or unsubstituted alkyl, alkoxy or thioalkoxy groups, or arylalkyl groups.
  • each of the R groups is independently selected as are each R', R", R'" and R"" groups when more than one of these groups is present.
  • R' and R" are attached to the same nitrogen atom, they can be combined with the nitrogen atom to form a 5-, 6-, or 7-membered ring.
  • -NR'R is meant to include, but not be limited to, 1-pyrrolidinyl and 4-morpholinyl.
  • substituted alkyl includes groups with carbon atoms bound to groups other than hydrogen, such as haloalkyl (e.g., ⁇ CF 3 and -CH 2 CF 3 ) and acyl (e.g., -C(0)CH 3 , -C(0)CF 3 , -C(0)CH 2 OCH 3 , and the like).
  • substituents for the aryl and heteroaryl groups are generically referred to as "aryl group substituents.”
  • each of the R groups is independently selected as are each R', R", R'" and R"" groups when more than one of these groups is present.
  • Two of the substituents on an aryl or heteroaryl ring, together with the atom to which they are attached, may optionally be joined to form a ring (e.g., a cycloalkyl or heterocycloalkyl ring) that is fused to the aryl or heteroaryl ring.
  • Two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -T-C(0)-(CRR') q -U-, wherein T and U are independently -NR-, -0-, -CRR'- or a single bond, and q is an integer from 0 to 3.
  • two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -A-(CH 2 ) r -B-, wherein A and B are independently -CRR'-, -0-, - R-, S ⁇ , S(0) ⁇ , -S(0) 2 - -S(0) 2 NR'- or a single bond, and r is an integer of from 1 to 4.
  • One of the single bonds of the new ring so formed may optionally be replaced with a double bond.
  • two of the substituents on adjacent atoms of the aryl or heteroaryl ring may optionally be replaced with a substituent of the formula -(CRR') s -X-(CR"R'")d _ , where s and d are independently integers of from 0 to 3, and X is -0-, - R'-, S ⁇ , -S(0)-, -S(0) 2 - or -S(0) 2 R'-.
  • the substituents R, R', R" and R'" are preferably independently selected from hydrogen or substituted or unsubstituted (Ci-Ci 6 )alkyl.
  • heteroatom includes oxygen (O), nitrogen (N), sulfur (S) and silicon (Si).
  • R is a general abbreviation that represents a substituent group that is selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocyclyl groups.
  • R can also refer to alkyl group substituents and aryl group substituents.
  • salt(s) includes salts of the compounds which are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein.
  • base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent.
  • base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt.
  • acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent.
  • acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic,
  • salts of amino acids such as arginate, and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see, for example, Berge et ah, Journal of Pharmaceutical Science, 66: 1-19 (1977)).
  • Certain specific compounds of the present invention contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. Hydrates of the salts are also included.
  • the symbol ⁇ » ⁇ displayed perpendicular to a bond, indicates the point at which the displayed moiety is attached to the remainder of the molecule.
  • the compounds herein described may have one or more asymmetric centers or planes.
  • Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms (racemates), by asymmetric synthesis, or by synthesis from optically active starting materials. Resolution of the racemates can be accomplished, for example, by conventional methods such as crystallization in the presence of a resolving agent, or chromatography, using, for example a chiral HPLC column.
  • enantiomerically pure compounds used herein are taken from Maehr, J. Chem. Ed., 62: 114- 120 (1985): solid and broken wedges are used to denote the absolute configuration of a chiral element; wavy lines indicate disavowal of any stereochemical implication which the bond it represents could generate; solid and broken bold lines are geometric descriptors indicating the relative configuration shown but not implying any absolute stereochemistry; and wedge outlines and dotted or broken lines denote enantiomerically pure compounds of indeterminate absolute configuration.
  • the term "charged group” refers to a group that bears a negative charge or a positive charge.
  • the negative charge or positive charge can have a charge number that is an integer selected from 1, 2, 3 or higher or that is a fractional number.
  • Exemplary charged groups include for example -OP0 3 2 ,-OP0 2 , -P + Ph 3 , -N + R'R"R" ', -S + R and -C(0)0 . It is understood that charged groups are accompanied by counterions of opposite charge, whether or not such counterions are expressly represented in the formulae provided herein.
  • the compounds herein described may have one or more charged groups.
  • the compounds may be zwitterionic, but may be neutral overall.
  • Other embodiments may have one or more charged groups, depending on the pH and other factors.
  • the compound may be associated with a suitable counter-ion.
  • salts or exchange counter-ions can be prepared by reacting free acid forms of these compounds with a stoichiometric amount of the appropriate base (such as Na, Ca, Mg, or K hydroxide, carbonate, bicarbonate, or the like), or by reacting free base forms of these compounds with a stoichiometric amount of the appropriate acid.
  • Counter-ions may be changed, for example, by ion-exchange techniques such as ion-exchange chromatography. All zwitterions, salts and counter-ions are intended, unless the counter-ion or salt is specifically indicated.
  • regulating or improving the growth of a crop means an improvement in plant vigour, an improvement in plant quality, improved tolerance to stress factors, and/or improved input use efficiency.
  • An 'improvement in plant vigour' means that certain traits are improved
  • Such traits include, but are not limited to, early and/or improved germination, improved
  • a plant with improved vigour may have an increase in any of the aforementioned traits or any combination or two or more of the aforementioned traits.
  • Such traits include, but are not limited to, improved visual appearance of the plant, reduced ethylene (reduced production and/or inhibition of reception), improved quality of harvested material, e.g. seeds, fruits, leaves, vegetables (such improved quality may manifest as improved visual appearance of the harvested material), improved carbohydrate content (e.g. increased quantities of sugar and/or starch, improved sugar acid ratio, reduction of reducing sugars, increased rate of development of sugar), improved protein content, improved oil content and composition, improved nutritional value, reduction in anti-nutritional
  • a plant with improved quality may have an increase in any of the aforementioned traits or any combination or two or more of the aforementioned traits.
  • An 'improved tolerance to stress factors' means that certain traits are improved qualitatively or quantitatively when compared with the same trait in a control plant which has been grown under the same conditions in the absence of the method of the invention.
  • Such traits include, but are not limited to, an increased tolerance and/or resistance to abiotic stress factors which cause sub-optimal growing conditions such as drought (e.g. any stress which leads to a lack of water content in plants, a lack of water uptake potential or a reduction in the water supply to plants), cold exposure, heat exposure, osmotic stress, UV stress, flooding, increased salinity (e.g. in the soil), increased mineral exposure, ozone exposure, high light exposure and/or limited availability of nutrients (e.g. nitrogen and/or phosphorus nutrients).
  • drought e.g. any stress which leads to a lack of water content in plants, a lack of water uptake potential or a reduction in the water supply to plants
  • cold exposure heat exposure
  • osmotic stress e.g. in the soil
  • a plant with improved tolerance to stress factors may have an increase in any of the aforementioned traits or any combination or two or more of the aforementioned traits.
  • such improved tolerances may be due to, for example, more efficient uptake, use or retention of water and nutrients.
  • the compounds or compositions of the present invention are useful to improve tolerance to drought stress.
  • An 'improved input use efficiency' means that the plants are able to grow more effectively using given levels of inputs compared to the grown of control plants which are grown under the same conditions in the absence of the method of the invention.
  • the inputs include, but are not limited to fertiliser (such as nitrogen, phosphorous, potassium, micronutrients), light and water.
  • a plant with improved input use efficiency may have an improved use of any of the aforementioned inputs or any combination of two or more of the aforementioned inputs.
  • plants refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
  • locus means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation.
  • plant propagation material denotes all generative parts of a plant, for example seeds or vegetative parts of plants such as cuttings and tubers. It includes seeds in the strict sense, as well as roots, fruits, tubers, bulbs, rhizomes, and parts of plants.
  • the invention provides a compound of Formula (I):
  • Rl, R2, R3, R4, R5, R6, L, and R7 are as defined herein. Any combination of Rl, R2, R3, R4, R5, R6, L, and R7 is encompassed by this disclosure and specifically provided by the invention.
  • Rl is selected from hydrogen, alkyl, cyano-alkyl, haloalkyl, alkoxy-alkyl, haloalkoxy-alkyl, cycloalkyl-alkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl and heterocycloalkyl.
  • Rl is selected from hydrogen, Ci-C 6 alkyl, cyano-Ci-C 6 alkyl, Ci-C 6 haloalkyl, C1-C3 alkoxy-Ci-C 6 alkyl, C1-C3 haloalkyl-Ci-C6 alkyl, C 1 -C 3 haloalkoxy-Ci-C 6 alkyl, C 3 -C5 cycloalkyl-Ci-C 4 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl and C 4 -C 5 heterocycloalkyl.
  • Rl is selected from hydrogen, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C 1 -C3 alkoxy-Ci- C 3 alkyl, Ci-haloalkoxy-Ci-C 3 alkyl, C 3 -C 4 cycloalkyl-Ci-C 3 alkyl, C 2 -C 6 alkenyl and C 2 -C 6 alkynyl.
  • Rl is selected from alkyl-aryl, cycloalkyl, phenyl and heteroaryl, each optionally substituted with one to three (i.e., one, two, or three) Rx.
  • Rx is as defined herein.
  • Rl is selected from C 1 -C 4 alkyl-aryl, C 3 -C5 cycloalkyl, phenyl and 5- or 6- membered heteroaryl, each optionally substituted with one to three Rx.
  • Rl is selected from C 3 -C 4 cycloalkyl, phenyl and 5- or 6-membered heteroaryl, each optionally substituted with one to three Rx.
  • Rl is selected from C 3 -C 4 cycloalkyl, phenyl, and 5- or 6-membered heteroaryl, each optionally substituted with one to three Rx; or Rl is selected from hydrogen, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C1-C3 alkoxy-Ci-C 3 alkyl, Ci-haloalkoxy-Ci-C 3 alkyl, C3-C4 cycloalkyl-Ci-C 3 alkyl , C 2 -C 6 alkenyl and C 2 -C 6 alkynyl.
  • Rl is selected from hydrogen, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C 3 -C 4 cycloalkyl, methylisoxazolyl and phenyl. More preferably Rl is Ci-C 6 alkyl. In some embodiments, the alkyl group is linear or branched. In some embodiments, Rl is methyl. In some embodiments, Rl is ethyl. In some embodiments, Rl is n-propyl, z ' so-propyl or cyclopropyl. In some embodiments, Rl is n-propyl. In some embodiments, Rl is n-butyl, zso-butyl, sec-butyl or tert-butyl.
  • each Rx is independently selected from halogen, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulfanyl, haloalkylsulfanyl, alkylsulfinyl, haloalkylsulfmyl, alkylsulfonyl, haloalkylsulfonyl and cycloalkyl.
  • each Rx is independently selected from halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylsulfanyl, C 1 -C 4 haloalkylsulfanyl, C 1 -C 4 alkylsulfinyl, C 1 -C 4 haloalkylsulfmyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl and C 3 -C 4 cycloalkyl.
  • each Rx is independently selected from halogen, cyano, C 1 -C 3 alkyl, Ci- C 3 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy and C 3 -C 4 cycloalkyl. More preferably each Rx is independently selected from halogen, C 1 -C 2 alkyl, C 1 -C 2 haloalkyl and C 1 -C 2 alkoxy.
  • R2, R3, R4, R5 and R6 are independently selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy and cycloalkyl.
  • R2, R3, R4, R5 and R6 are independently selected from hydrogen, halogen, cyano, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy and C3-C 4 cycloalkyl.
  • R2, R3, R4 and R5 are each hydrogen.
  • R6 is selected from hydrogen and C 1 -C 4 alkyl. In some embodiments, at least one of R2, R3, R4, R5 and R6 is not hydrogen.
  • R2 and R3 are independently selected from hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, halogen and cyano. More preferably R2 and R3 are both hydrogen. In some embodiments, R2 is methoxy. In some embodiments, R3 is hydrogen.
  • R4, R5 and R6 are independently selected from hydrogen, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, halogen and cyano. More preferably R4 and R5 are each hydrogen. More preferably R6 is selected from hydrogen, methyl, ethyl, n-propyl, fluoro, chloro, bromo and cyano. In some embodiments, R6 is hydrogen. In some embodiments, R6 is methyl. In some embodiments, R6 is ethyl. In some embodiments, R6 is n-propyl. In some embodiments, R6 is fluoro. In some
  • R6 is chloro. In some embodiments, R6 is bromo. In some embodiments, R6 is cyano.
  • R2, R3, R4, R5 and R6 are all hydrogen. In some embodiments at least one of R2, R3, R4, R5 and R6 is not hydrogen. Preferably at least one of R2, R3, R4, R5 and R6 is methyl.
  • R2 is selected from hydrogen, fluoro, chloro, methoxy, and methyl.
  • R3 is selected from hydrogen, methyl, methoxy, chloro, and hydroxy.
  • R4 is H.
  • R5 is H.
  • R6 is selected from hydrogen, methyl, chloro, and fluoro.
  • R2 is selected from hydrogen, fluoro, chloro, methoxy, and methyl
  • R3 is selected from hydrogen, methyl, methoxy, chloro, and hydroxy
  • R4 is H
  • R5 is H
  • R6 is selected from hydrogen, methyl, chloro, and fluoro.
  • L is selected from alkyl, alkenyl, alkoxy and alkoxy-alkyl, each optionally substituted with one to three (i.e., one, two, or three) moieties independently selected from halogen, cyano, alkyl and alkoxy.
  • L is selected from C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy and C 1 -C 2 alkoxy-Ci-C 2 alkyl, each optionally substituted with one to three moieties independently selected from halogen, cyano, C 1 -C 4 alkyl and C 1 -C 4 alkoxy.
  • L is C 1 -C 4 alkyl optionally substituted with one or two moieties independently selected from halogen, cyano and C 1 -C 2 alkyl.
  • L is Ci-C 2 alkyl.
  • L is Ci-C 6 alkyl optionally substituted with one or two moieties independently selected from halogen, cyano and C 1 -C 4 alkyl. More preferably L is Ci-C 2 alkyl optionally substituted with one or two moieties independently selected from halogen, cyano and Ci-C 2 alkyl. In some embodiments, L is CH 2 . In some embodiments L is
  • R7 is aryl optionally substituted with one to three (i.e., one, two, or three) Ry. Ry is as defined herein.
  • R7 is heteroaryl optionally substituted with one to three (i.e., one, two, or three) Rz. Rz is as defined herein.
  • R7 is a 5- or 6-membered heteroaryl containing from 1 to 3 (i.e., 1, 2, or 3) heteroatoms, each independently selected from oxygen, nitrogen and sulphur, wherein the heteroaromatic ring is optionally substituted with one to three Rz.
  • R7 is phenyl optionally substituted with one to three Ry.
  • R7 is phenyl optionally substituted with one to three (i.e., one, two, or three) moieties independently selected from halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylsulfanyl and C3-C 4 cycloalkyl.
  • R7 is phenyl optionally substituted with one to three moieties independently selected from halogen, cyclopropyl and C 1 -C 4 alkyl.
  • R7 is phenyl substituted with halogen, cyclopropyl or C 1 -C 4 alkyl at the para position
  • R7 is phenyl substituted with halogen, cyclopropyl or C 1 -C 4 alkyl at the meta position (relative to the attachment point to L). In some embodiments, R7 is phenyl substituted with halogen, cyclopropyl or C 1 -C 4 alkyl at the ortho position (relative to the attachment point to L). In some embodiments, R7 is phenyl independently substituted with halogen, cyclopropyl or C 1 -C 4 alkyl at both the para and ortho position (relative to the attachment point to L). In some embodiments, R7 is phenyl substituted with halogen.
  • R7 is phenyl substituted with cyclopropyl. In some embodiments, R7 is phenyl substituted with C 1 -C 4 alkyl. In some embodiments, R7 is phenyl substituted with methyl, fluorine, chlorine or carboxylic acid at the para position (relative to the attachment point to L).
  • each Ry is independently selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulfanyl, haloalkylsulfanyl, alkylsulfinyl, haloalkylsulfmyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkyl, COOH, COOR9, CONHR9, CONR9aR9 and NHCOR9.
  • R9 and R9a are as defined herein.
  • each Ry is independently selected from halogen, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylsulfanyl, C 1 -C 4 haloalkylsulfanyl, C 1 -C 4 alkylsulfinyl, C 1 -C 4 haloalkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl, C 3 -C 4 cycloalkyl, COOH, COOR9, CONHR9, CONR9aR9 and NHCOR9.
  • each Ry is independently selected from halogen, cyano, C 1 -C 4 alkyl, Ci- C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylsulfanyl and C 3 -C 4 cycloalkyl. More preferably each Ry is independently selected from halogen, cyano, methyl, ethyl,
  • R9 and R9a are independently alkyl. In some embodiments, R9 and R9a are independently C 1 -C 4 alkyl.
  • each Rz is independently selected from halogen, cyano, alkyl, alkoxy, carbonyl, haloalkyl, haloalkoxy and cycloalkyl. In some embodiments, each Rz is independently selected from halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, carbonyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy and C 3 -C 4 cycloalkyl.
  • each Rz is independently selected from halogen, cyano, methyl, ethyl, cyclopropyl, trifluoromethyl, difluoromethyl, trifluoromethyloxy, difluoromethyloxy and trifluoromethylsulfanyl.
  • each Rz is independently selected from halogen, cyano, C 1 -C 4 alkyl and C 3 -C 4 cycloalkyl. More preferably each Rz is independently selected from halogen, cyano, methyl, ethyl, propyl, cyclopropyl and butyl.
  • the invention provides a compound of Formula (II):
  • Rl , R6, L, and R7 are as defined herein.
  • the invention provides a compound of Formula (III):
  • the invention provides a compound of Formula (IV):
  • Rl , R6, R7, R8a, and R8b are as defined herein.
  • R8a and R8b are independently selected from hydrogen, halogen, cyano, alkyl and alkoxy. In some embodiments, R8a and R8b are independently selected from hydrogen, halogen, cyano, C 1 -C4 alkyl and Ci-C 4 alkoxy.
  • the invention provides a compound of structure 1.xxx, 2.xxx, 3. xxx, 4. xxx, 5. xxx, 6.xxx, 7. xxx, 8.xxx, 9. xxx, lO.xxx, 1 1. xxx, 12.xxx, 13. xxx, 14.xxx, 15. xxx, 16.XXX, 17. xxx, 18.xxx, 19. xxx, 20.xxx, 21. xxx, 22.xxx, 23. xxx, 24.xxx, 25. xxx, 26. xxx, 27.XXX, 28. xxx, 29.xxx, 30. xxx, 31. xxx, 32. xxx, 33.xxx, 34. xxx, 35.xxx, or 36. xxx (see Table 1), wherein Rl , R2, R3, R4, R5, and R6 are as defined herein.
  • the invention provides a compound of Formula (I):
  • Rl is selected from hydrogen, Ci-C 6 alkyl, cyano-Ci-C 6 alkyl, Ci-C 6 haloalkyl, Ci- C 3 alkoxy-Ci-C 6 alkyl, C1-C3 haloalkyl-Ci-C6 alkyl, C1-C3 haloalkoxy-Ci-C6 alkyl, C3-C5 cycloalkyl-Ci-C 4 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl and C 4 -C 5 heterocycloalkyl; or Rl is selected from C 1 -C 4 alkyl-aryl, C 3 -C 5 cycloalkyl, phenyl and 5- or 6-membered heteroaryl, each optionally substituted with one to three Rx; each Rx is independently selected from halogen
  • alkylsulfanyl C 1 -C 4 haloalkylsulfanyl, C 1 -C 4 alkylsulfinyl, C 1 -C 4 haloalkylsulfinyl, C 1 -C 4 alkylsulfonyl, C C 4 haloalkylsulfonyl, C 3 -C 4 cycloalkyl, COOH, COOR9, CONHR9, CONR9aR9 and NHCOR9; R9 and R9a are independently C 1 -C4 alkyl; each Rz is independently selected from halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, carbonyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy and C 3 -C 4 cycloalkyl; or salts or N-oxides thereof.
  • the invention provides a compound of Formula (I) wherein Rl is selected from C 3 -C 4 cycloalkyl, phenyl, and 5- or 6-membered heteroaryl, each optionally substituted with one to three Rx; or Rl is selected from hydrogen, Ci-C 6 alkyl, Ci- C 6 haloalkyl, C 1 -C 3 alkoxy-Ci-C 3 alkyl, Ci-haloalkoxy-Ci-C 3 alkyl, C 3 -C 4 cycloalkyl-Ci-C 3 alkyl, C 2 -C 6 alkenyl and C 2 -C 6 alkynyl; R2, R3, R4, R5 and R6 are independently selected from hydrogen and C 1 -C 4 alkyl; L is Ci-C 6 alkyl optionally substituted with one to three moieties independently selected from halogen and C 1 -C 4 alkyl; R7 is phenyl optionally substituted with one to three
  • Rl is selected from C 1 -C4 alkyl-aryl, C 3 -C 5 cycloalkyl, phenyl and 5- or 6-membered heteroaryl, each optionally substituted with one to three Rx; or Rl is selected from hydrogen, Ci-C 6 alkyl, cyano-Ci-C 6 alkyl, Ci-C 6 haloalkyl, C1-C3 alkoxy-Ci-C 6 alkyl, C1-C3 haloalkyl- Ci-C 6 alkyl, C r C 3 haloalkoxy-Ci-C 6 alkyl, C 3 -C 5 cycloalkyl-Ci-C 4 alkyl, C 2 -C 6 alkenyl, C 2 - C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl and C 4 -C 5 heterocycloalkyl; R2, R3, R4, R5 and
  • Rl is selected from C 1 -C 4 alkyl-aryl, C 3 -C5 cycloalkyl, phenyl and 5- or 6-membered heteroaryl, each optionally substituted with one to three Rx; or Rl is selected from hydrogen, Ci-C 6 alkyl, cyano-Ci-C 6 alkyl, Ci-C 6 haloalkyl, C1-C3 alkoxy-Ci-C 6 alkyl, C1-C3 haloalkyl- Ci-C 6 alkyl, C1-C3 haloalkoxy-Ci-C6 alkyl, C3-C5 cycloalkyl-Ci-C4 alkyl, C2-C6 alkenyl, C 2 - C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl and C 4 -C5 heterocycloalkyl; R2, R3, R4, R5 and R6 are
  • the invention provides a compound of Formula (I):
  • Rl is selected from hydrogen and Ci-C 6 alkyl optionally substituted with one to three Rx;
  • R2, R3, R4, R5 and R6 are independently selected from hydrogen, C 1 -C 4 alkyl, Ci- C 4 alkoxy, halogen and cyano;
  • L is Ci-C 6 alkyl optionally substituted with one or two moieties independently selected from halogen, cyano and C 1 -C 4 alkyl;
  • R7 is phenyl optionally substituted with one to three Ry; or R7 is a 5- or 6-membered heteroaryl containing from 1 to 3 heteroatoms, each independently selected from oxygen, nitrogen and sulphur, wherein the heteroaromatic ring is optionally substituted with one or more Rz;
  • each Rx is independently selected from halogen, Ci-C 2 alkyl, Ci-C 2 haloalkyl and Ci-C 2 alkoxy;
  • each Ry is independently selected from halogen, cyano, nitro, C 1 -
  • the invention provides a compound of Formula (II):
  • Rl is selected from hydrogen, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C 3 -C 4 cycloalkyl and phenyl;
  • R6 is selected from hydrogen and C 1 -C 4 alkyl;
  • L is Ci-C 6 alkyl optionally substituted with one to three moieties independently selected from halogen, cyano and C 1 -C 4 alkyl;
  • R7 is phenyl optionally substituted with one to three Ry; or R7 is a 5- or 6- membered heteroaryl containing from 1 to 3 heteroatoms each independently selected from oxygen, nitrogen and sulphur, wherein the heteroaromatic ring is optionally substituted with one to three Rz;
  • each Ry is independently selected from halogen, cyano, methyl, ethyl, cyclopropyl,
  • each Rz is independently selected from halogen, cyano, methyl, ethyl, propyl, cyclopropyl and butyl; or salts or N-oxides thereof.
  • the invention provides a compound of Formula (II) as defined above wherein Rl is propyl. In some embodiments, the invention provides a compound of Formula (II) as defined above wherein R6 is selected from hydrogen, methyl, chloro and fluoro. In some embodiments, the invention provides a compound of Formula (II) as defined above wherein Rl is propyl, and R6 is selected from hydrogen, methyl, chloro and fluoro.
  • the invention provides a compound of Formula (III):
  • Rl is selected from hydrogen, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C 3 -C 4 cycloalkyl and phenyl;
  • L is Ci-C 6 alkyl optionally substituted with one to three moieties independently selected from halogen, cyano and C 1 -C 4 alkyl;
  • R7 is phenyl optionally substituted with one to three Ry; or R7 is a 5- or 6- membered heteroaryl containing from 1 to 3 heteroatoms each independently selected from oxygen, nitrogen and sulphur, wherein the heteroaromatic ring is optionally substituted with one to three Rz;
  • each Ry is independently selected from halogen, cyano, methyl, ethyl, cyclopropyl, trifluoromethyl, difluoromethyl, trifiuoromethyloxy, difluoromethyloxy and trifluoromethylsulfanyl; and each Rz is independently selected from halogen, cyano, methyl,
  • the invention provides a compound of Formula (IV):
  • Rl is selected from hydrogen, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C 3 -C 4 cycloalkyl and phenyl;
  • R6 is selected from hydrogen and C 1 -C 4 alkyl;
  • R7 is phenyl optionally substituted with one to three Ry; or
  • R7 is a 5- or 6- membered heteroaryl containing from 1 to 3 heteroatoms each independently selected from oxygen, nitrogen and sulphur, wherein the heteroaromatic ring is optionally substituted with one to three Rz;
  • R8a and R8b are independently selected from hydrogen, halogen, cyano, C 1 -C 4 alkyl and C 1 -C 4 alkoxy;
  • each Ry is independently selected from halogen, cyano, methyl, ethyl, cyclopropyl,
  • each Rz is independently selected from halogen, cyano, methyl, ethyl, propyl, cyclopropyl and butyl; or salts or N-oxides thereof.
  • Table 1 below includes examples of compounds of the present invention.
  • the compounds of the present invention are applied in combination with an agriculturally acceptable adjuvant.
  • an agriculturally acceptable adjuvant comprising a compound of the present invention and an agriculturally acceptable adjuvant.
  • an agrochemical composition comprising a compound of the present invention.
  • the present invention provides a method of improving the tolerance of a plant to abiotic stress, wherein the method comprises applying to the plant, plant part, plant propagation material, or plant growing locus a compound, composition or mixture according to the present invention.
  • the present invention provides a method for regulating or improving the growth of a plant, wherein the method comprises applying to the plant, plant part, plant propagation material, or plant growing locus a compound, composition or mixture according to the present invention.
  • plant growth is regulated or improved when the plant is subject to abiotic stress conditions.
  • the present invention also provides a method for inhibiting seed germination of a plant, comprising applying to the seed, or a locus containing seeds, a compound, composition or mixture according to the present invention.
  • the present invention also provides a method for safening a plant against phytotoxic effects of chemicals, comprising applying to the plant, plant part, plant propagation material, or plant growing locus a compound, composition or mixture according to the present invention. [0091] Suitably the compound or composition is applied in an amount sufficient to elicit the desired response.
  • Improved sugar acid ratios means that, where it is possible to take a quantitative measurement, the yield of a product of the respective plant is increased by a measurable amount over the yield of the same product of the plant produced under the same conditions, but without application of the present invention. According to the present invention, it is preferred that the yield be increased by at least 0.5%, more preferred at least 1%, even more preferred at least 2%, still more preferred at least 4% , preferably 5% or even more.
  • any or all of the above crop enhancements may also lead to an improved utilisation of land, i.e. land which was previously unavailable or sub-optimal for cultivation may become available.
  • land i.e. land which was previously unavailable or sub-optimal for cultivation
  • plants which show an increased ability to survive in drought conditions may be able to be cultivated in areas of sub-optimal rainfall, e.g. perhaps on the fringe of a desert or even the desert itself.
  • crop enhancements are made in the substantial absence of pressure from pests and/or diseases and/or abiotic stress.
  • improvements in plant vigour, stress tolerance, quality and/or yield are made in the substantial absence of pressure from pests and/or diseases.
  • pests and/or diseases may be controlled by a pesticidal treatment that is applied prior to, or at the same time as, the method of the present invention.
  • improvements in plant vigour, stress tolerance, quality and/or yield are made in the absence of pest and/or disease pressure.
  • improvements in plant vigour, quality and/or yield are made in the absence, or substantial absence, of abiotic stress.
  • the compounds of the present invention can be used alone, but are generally formulated into compositions using formulation adjuvants, such as carriers, solvents and surface-active agents (SFAs).
  • formulation adjuvants such as carriers, solvents and surface-active agents (SFAs).
  • the present invention further provides a composition comprising a compound of the present invention and an agriculturally acceptable formulation adjuvant.
  • a composition consisting essentially of a compound of the present invention and an agriculturally acceptable formulation adjuvant There is also provided a composition consisting of a compound of the present invention and an
  • the present invention further provides a plant growth regulator composition comprising a compound of the present invention and an agriculturally acceptable formulation adjuvant.
  • a plant growth regulator composition consisting essentially of a compound of the present invention and an agriculturally acceptable formulation adjuvant.
  • a plant growth regulator composition consisting of a compound of the present invention and an agriculturally acceptable formulation adjuvant.
  • the present invention further provides a plant abiotic stress management composition comprising a compound of the present invention and an agriculturally acceptable formulation adjuvant.
  • a plant abiotic stress management composition consisting essentially of a compound of the present invention and an agriculturally acceptable formulation adjuvant.
  • a plant abiotic stress management composition consisting of a compound of the present invention and an agriculturally acceptable formulation adjuvant.
  • the present invention further provides a seed germination inhibitor composition comprising a compound of the present invention and an agriculturally acceptable formulation adjuvant.
  • a seed germination inhibitor composition consisting essentially of a compound of the present invention and an agriculturally acceptable formulation adjuvant.
  • a seed germination inhibitor composition consisting of a compound of the present invention and an agriculturally acceptable formulation adjuvant.
  • the composition can be in the form of concentrates which are diluted prior to use, although ready-to-use compositions can also be made. The final dilution is usually made with water, but can be made instead of, or in addition to, water, with, for example, liquid fertilisers, micronutrients, biological organisms, oil or solvents.
  • the compositions generally comprise from 0. 1 to 99 % by weight, especially from 0. 1 to 95 % by weight, compounds of the present invention and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface- active substance.
  • compositions can be chosen from a number of formulation types, many of which are known from the Manual on Development and Use of FAO Specifications for Plant Protection Products, 5th Edition, 1999. These include dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultralow volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro- emulsions (ME), suspension concentrates (SC), aerosols, capsule suspensions (CS) and seed treatment formulations.
  • the formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of the present invention.
  • Dustable powders may be prepared by mixing a compound of the present invention with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.
  • solid diluents for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers
  • Soluble powders may be prepared by mixing a compound of the present invention with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).
  • water-soluble inorganic salts such as sodium bicarbonate, sodium carbonate or magnesium sulphate
  • water-soluble organic solids such as a polysaccharide
  • WP Wettable powders
  • WG water dispersible granules
  • Granules may be formed either by granulating a mixture of a compound of the present invention and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of the present invention (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of the present invention (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary.
  • a hard core material such as sands, silicates, mineral carbonates, sulphates or phosphates
  • Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils).
  • solvents such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters
  • sticking agents such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils.
  • One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).
  • Dispersible Concentrates may be prepared by dissolving a compound of the present invention in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank).
  • Emulsifiable concentrates (EC) or oil-in- water emulsions (EW) may be prepared by dissolving a compound of the present invention in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents).
  • Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as
  • alkylbenzenes or alkylnaphthalenes exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as Cs-Cio fatty acid dimethylamide) and chlorinated hydrocarbons.
  • An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment.
  • Preparation of an EW involves obtaining a compound of the present invention either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion.
  • Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.
  • Microemulsions may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation.
  • a compound of the present invention is present initially in either the water or the solvent/SFA blend.
  • Suitable solvents for use in MEs include those hereinbefore described for use in ECs or in EWs.
  • An ME may be either an oil-in- water or a water-in-oil system (which system is present may be determined by conductivity
  • An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.
  • SC Suspension concentrates
  • SCs may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of the present invention.
  • SCs may be prepared by ball or bead milling the solid compound of the present invention in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound.
  • One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle.
  • a compound of the present invention may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.
  • Aerosol formulations comprise a compound of the present invention and a suitable propellant (for example n-butane).
  • a compound of the present invention may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.
  • Capsule suspensions may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of the present invention and, optionally, a carrier or diluent therefor.
  • the polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure.
  • the compositions may provide for controlled release of the compound of the present invention and they may be used for seed treatment.
  • a compound of the present invention may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.
  • the composition may include one or more additives to improve the biological performance of the composition, for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of the present invention.
  • additives include surface active agents (SFAs), spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of the present invention).
  • Wetting agents, dispersing agents and emulsifying agents may be SFAs of the cationic, anionic, amphoteric or non-ionic type.
  • SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
  • Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium
  • tetraphosphoric acid additionally these products may be ethoxylated
  • sulphosuccinamates paraffin or olefine sulphonates, taurates and lignosulphonates.
  • Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.
  • Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins.
  • alkylene oxides such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof
  • fatty alcohols such as oleyl alcohol or cetyl alcohol
  • alkylphenols such as octylphenol, nonyl
  • Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).
  • hydrophilic colloids such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose
  • swelling clays such as bentonite or attapulgite.
  • the application is generally made by spraying the composition, typically by tractor mounted sprayer for large areas, but other methods such as dusting (for powders), drip or drench can also be used.
  • the composition may be applied in furrow or directly to a seed before or at the time of planting.
  • the compound or composition of the present invention may be applied pre- emergence or post-emergence.
  • the composition may be applied post- emergence of the crop.
  • the composition may be applied pre-emergence.
  • the present invention envisages application of the compounds or compositions of the invention to plant propagation material prior to, during, or after planting, or any combination of these.
  • active ingredients can be applied to plant propagation material in any physiological state
  • a common approach is to use seeds in a sufficiently durable state to incur no damage during the treatment process.
  • seed would have been harvested from the field; removed from the plant; and separated from any cob, stalk, outer husk, and surrounding pulp or other non-seed plant material. Seed would preferably also be biologically stable to the extent that treatment would not cause biological damage to the seed. It is believed that treatment can be applied to seed at any time between seed harvest and sowing of seed including during the sowing process.
  • ingredients may be applied on a suitable substrate sown together with the plant
  • the rates of application of compounds of the present invention may vary within wide limits and depend on the nature of the soil, the method of application (pre- or post- emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop.
  • the compounds of the present invention according to the invention are generally applied at a rate of from 1 to 2000 g/ha, especially from 5 to 1000 g/ha.
  • the rate of application is generally between 0.0005 and 150g per 100kg of seed.
  • compositions of the present invention may be applied to dicotyledonous or monocotyledonous crops.
  • Crops of useful plants in which the composition according to the invention can be used include perennial and annual crops, such as berry plants for example
  • cereals for example barley, maize (corn), millet, oats, rice, rye, sorghum triticale and wheat; fibre plants for example cotton, flax, hemp, jute and sisal; field crops for example sugar and fodder beet, coffee, hops, mustard, oilseed rape (canola), poppy, sugar cane, sunflower, tea and tobacco; fruit trees for example apple, apricot, avocado, banana, cherry, citrus, nectarine, peach, pear and plum; grasses for example Bermuda grass, bluegrass, bentgrass,
  • Crops are to be understood as being those which are naturally occurring, obtained by conventional methods of breeding, or obtained by genetic engineering. They include crops which contain so-called output traits (e.
  • Crops are to be understood as also including those crops which have been rendered tolerant to herbicides like bromoxynil or classes of herbicides such as ALS-, EPSPS-, GS-, HPPD- and PPO-inhibitors.
  • herbicides like bromoxynil or classes of herbicides such as ALS-, EPSPS-, GS-, HPPD- and PPO-inhibitors.
  • An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer canola.
  • crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate- resistant maize varieties commercially available under the trade names RoundupReady®, Herculex I® and LibertyLink®.
  • Crops are also to be understood as being those which naturally are or have been rendered resistant to harmful insects. This includes plants transformed by the use of recombinant DNA techniques, for example, to be capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria. Examples of toxins which can be expressed include ⁇ -endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonising nematodes, and toxins
  • thuringiensis toxin is the Bt maize KnockOut® (Syngenta Seeds).
  • An example of a crop comprising more than one gene that codes for insecticidal resistance and thus expresses more than one toxin is VipCot® (Syngenta Seeds).
  • Crops or seed material thereof can also be resistant to multiple types of pests (so-called stacked transgenic events when created by genetic modification).
  • a plant can have the ability to express an insecticidal protein while at the same time being herbicide tolerant, for example Herculex I® (Dow AgroSciences, Pioneer Hi-Bred International).
  • Compounds of the present invention may also be used to inhibit or delay the germination of seeds of non-crop plants, for example as part of an integrated weed control program.
  • a delay in germination of weed seeds may provide a crop seedling with a stronger start by reducing competition with weeds.
  • compounds of the present invention may be used to delay the germination of seeds of crop plants, for example to increase the flexibility of timing of planting for the grower.
  • agronomic chemicals or biologicals include pesticides, such as acaricides, bactericides, fungicides, herbicides, insecticides, nematicides, plant growth regulators, crop enhancing agents, safeners as well as plant nutrients and plant fertilizers.
  • pesticides such as acaricides, bactericides, fungicides, herbicides, insecticides, nematicides, plant growth regulators, crop enhancing agents, safeners as well as plant nutrients and plant fertilizers.
  • suitable mixing partners may be found in the Pesticide Manual, 15th edition (published by the British Crop Protection Council).
  • Such mixtures may be applied to a plant, plant propagation material or plant growing locus either simultaneously (for example as a pre-formulated mixture or a tank mix), or sequentially in a suitable timescale.
  • Co-application of pesticides with the present invention has the added benefit of minimising farmer time spent applying products to crops.
  • the combination may also encompass specific plant traits incorporated into the plant using any means, for example conventional breeding or genetic modification.
  • the present invention also provides the use of a compound of Formula (I), (II), (III), or (IV) wherein Rl, R2, R3, R4, R5, R6, L, and R7 are as defined herein; or salts or N-oxides thereof; or a composition comprising a compound according to Formula (I), (II), (III), or (IV) and an agriculturally acceptable formulation adjuvant, for improving the tolerance of a plant to abiotic stress, regulating or improving the growth of a plant, and/or inhibiting seed germination.
  • the present invention provides the use of a compound of Formula (I):
  • Rl is selected from hydrogen, Ci-C 6 alkyl, cyano-Ci-C 6 alkyl, Ci-C 6 haloalkyl, Ci-
  • Rl is selected from C 1 -C 4 alkyl-aryl, C 3 -C 5 cycloalkyl, phenyl and 5- or 6-membered heteroaryl, each optionally substituted with one to three Rx; each Rx is independently selected from halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, Ci- C 4
  • R9 and R9a are independently C 1 -C4 alkyl; each Rz is independently selected from halogen, cyano, C 1 -C4 alkyl, C 1 -C4 alkoxy, carbonyl, C 1 -C4 haloalkyl, C 1 -C4 haloalkoxy and C3-C4 cycloalkyl; or salts or N-oxides thereof; or a composition comprising a compound according to Formula (I) and an
  • Schemes 1-3 provide exemplary methods of preparing the compounds of Formula (I).
  • SCHEME 1
  • a compound of Formula (D) can be prepared from a compound of Formula (C) by reaction with a compound of formula RIX wherein X is a leaving group such as halogen or tosylate, and a base such as potassium carbonate, potassium tert-butoxide or sodium hydride in a polar solvent such as DMF or THF.
  • a compound of Formula (C) can be obtained from a compound of Formula (A) by reaction with nitric acid in the presence of an acid such as sulphuric acid, acetic acid or trifluoroacetic acid.
  • a compound of Formula (D) can be prepared through nitration of a compound of Formula (B) by reaction with nitric acid in the presence of an acid such as sulphuric acid, acetic acid or trifluoroacetic acid.
  • a compound of Formula (B) can be prepared from a compound of Formula (A) by reaction with a compound of formula RIX wherein X is a leaving group such as halogen or tosylate, and a base such as potassium carbonate, potassium tert-butoxide or sodium hydride in a polar solvent such as DMF or THF.
  • a compound of Formula (E) can be prepared by reduction of a compound of Formula (D) using a metal such as tin chloride, iron or zinc chloride.
  • Compounds of Formula (I) can be prepared from a compound of Formula (E) and sulfonyl chloride of formula R7LS0 2 C1 in the presence of an organic base such as triethyl amine.
  • Sulfonyl chlorides of formula R7LS0 2 C1 are either commercially available or can be prepared by a person skilled in the art following known procedures from the literature.
  • Rl is selected from hydrogen, alkyl, cyano-alkyl, haloalkyl, alkoxy-alkyl, haloalkoxy-alkyl, cycloalkyl-alkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl and heterocycloalkyl; or Rl is selected from alkyl-aryl, cycloalkyl, phenyl and heteroaryl, each optionally substituted with one to three Rx.
  • Each Rx is independently selected from halogen, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulfanyl, haloalkylsulfanyl, alkylsulfmyl, haloalkylsulfmyl, alkylsulfonyl, haloalkylsulfonyl and cycloalkyl.
  • R2, R3, R4, R5 and R6 are independently selected from hydrogen, halogen, cyano, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, haloalkoxy and cycloalkyl.
  • L is selected from alkyl, alkenyl, alkoxy and alkoxy-alkyl, each optionally substituted with one to three moieties independently selected from halogen, cyano, alkyl and alkoxy.
  • R7 is aryl optionally substituted with one to three Ry; or R7 is heteroaryl optionally substituted with one to three Rz.
  • Each Ry is independently selected from halogen, cyano, nitro, alkyl, haloalkyl, alkoxy, haloalkoxy, alkylsulfanyl, haloalkylsulfanyl, alkylsulfmyl, haloalkylsulfmyl, alkylsulfonyl, haloalkylsulfonyl, cycloalkyl, COOH, COOR9, CONHR9, CONR9aR9 and NHCOR9.
  • R9 and R9a are independently alkyl.
  • Each Rz is independently selected from halogen, cyano, alkyl, alkoxy, carbonyl, haloalkyl, haloalkoxy and cycloalkyl.
  • halogen independently selected from halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, Ci- C 4 haloalkoxy, C 1 -C 4 alkylsulfanyl, C 1 -C 4 haloalkylsulfanyl, C 1 -C 4 alkylsulfmyl, C 1 -C 4 haloalkylsulfmyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl and C 3 -C 4 cycloalkyl.
  • Rx is selected from halogen, cyano, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkoxy and C 3 -C 4 cycloalkyl.
  • Rl is selected from hydrogen, Ci-C 6 alkyl, cyano-Ci-C 6 alkyl, Ci-C 6 haloalkyl, C1-C3 alkoxy-Ci-C 6 alkyl, C1-C3 haloalkyl-Ci-C 6 alkyl, C 1 -C 3 haloalkoxy-Ci-C 6 alkyl, C 3 -C5 cycloalkyl-Ci-C 4 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl and C 4 -C 5 heterocycloalkyl; or Rl is selected from C 1 -C 4 alkyl-aryl, C 3 -C 5 cycloalkyl, phenyl and 5- or 6-membered heteroaryl, each optionally substituted with
  • Rl is selected from C 3 - C 4 cycloalkyl, phenyl and 5- or 6-membered heteroaryl, each optionally substituted with one to three Rx; or Rl is selected from hydrogen, Ci-C 6 alkyl, Ci-C 6 haloalkyl, C 1 -C 3 alkoxy-Ci- C 3 alkyl, Ci-haloalkoxy-Ci-C 3 alkyl, C 3 -C 4 cycloalkyl-Ci-C 3 alkyl, C 2 -C 6 alkenyl and C 2 -C 6 alkynyl.
  • R2, R3, R4, R5 and R6 are independently selected from hydrogen, halogen, cyano, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy and C 3 -C 4 cycloalkyl.
  • R6 is selected from hydrogen and C 1 -C 4 alkyl.
  • R2, R3, R4, R5 and R6 is not hydrogen.
  • L is selected from Ci- C 4 alkyl, C 2 -C 4 alkenyl, C 1 -C 4 alkoxy and C 1 -C 2 alkoxy-Ci-C 2 alkyl, each optionally substituted with one to three moieties independently selected from halogen, cyano, C 1 -C 4 alkyl and C 1 -C 4 alkoxy.
  • L is C 1 -C 4 alkyl optionally substituted with one or two moieties independently selected from halogen, cyano and Ci-C 2 alkyl.
  • each Ry is independently selected from halogen, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 4 alkylsulfanyl, C 1 -C 4 haloalkylsulfanyl, C 1 -C 4 alkylsulfinyl, C 1 -C 4 haloalkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkylsulfonyl, C 3 -C 4 cycloalkyl, COOH, COOR9, CONHR9, CONR9aR9 and NHCOR9; wherein R9 and R9a are
  • R7 is phenyl optionally substituted with one to three Ry; or R7 is a 5- or 6-membered heteroaryl containing from 1 to 3 heteroatoms, each independently selected from oxygen, nitrogen and sulphur, wherein the heteroaromatic ring is optionally substituted with one to three Rz.
  • R7 is phenyl optionally substituted with one to three moieties independently selected from halogen, cyano, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 haloalkylsulfanyl and C 3 -C 4 cycloalkyl.
  • composition comprising a compound according to any preceding paragraph, and an agriculturally acceptable formulation adjuvant.
  • a mixture comprising a compound as defined in any preceding paragraph, and a further active ingredient.
  • a method for improving the tolerance of a plant to abiotic stress comprises applying to the plant, plant part, plant propagation material, or plant growing locus a compound according to any preceding paragraph, a composition according to any preceding paragraph, or a mixture according to any preceding paragraph.
  • a method for inhibiting seed germination of a plant comprising applying to the plant, plant part, plant propagation material or plant growing locus a compound according to any preceding paragraph, a composition according to any preceding paragraph, or a mixture according to any preceding paragraph.
  • a method for regulating or improving the growth of a plant wherein the method comprises applying to the plant, plant part, plant propagation material, or plant growing locus a compound according to any preceding paragraph, a composition according to any preceding paragraph, or a mixture according to any preceding paragraph.
  • the materials and methods of the present invention are further illustrated by the examples which follow. These examples are offered to illustrate, but not to limit the claimed invention.
  • 6-nitro- 1 -propyl-quinolin-2-one 6-nitro-2(lH)-Quinolinone (951 mg) was suspended in DMF (7.5 mL) and caesium carbonate (2.46 g) was added. After stirring for 5 min at room temperature, 1-bromopropane (0.682 mL) was added dropwise to the reaction mixture and stirring was continued for 3 h at room temperature. The reaction was poured on ice/water, the precipitated material was filtered, washed with water and dissolved in CH 2 C1 2 (50 mL) and the resulting solution was dried over Na 2 S0 4 , filtered and concentrated.
  • 6-amino- 1 -propyl-quinolin-2-one 6-Nitro-l-propyl-quinolin-2-one (4.83 g) was suspended in ethanol (48 mL) and water (24 mL) and NH 4 C1 (1 l . lg) and Fe-powder (3.48g) was added. The reaction mixture was heated to reflux for 45 min, cooled to room temperature and filtered over Celite®. The filtrate was washed with ethyl acetate and water. The aqueous phases were extracted with ethyl acetate and the combined organic phases were washed with brine and concentrated.
  • 6-amino- l-propyl-quinolin-2-one (245 mg) was dissolved in ethyl acetate (5 mL), and diisopropylethylamine (0.518 mL) and p-tolylmethansulfonylchloride (0.248 g) were added. The reaction was stirred for 22 h at room temperature, diluted with CH 2 C1 2 and washed with water, 5% HC1 (aq) and brine. The combined aqueous phases were extracted again with ethyl acetate and the combined organic phases were concentrated and crystallized from MeOH/diethyl ether. Further purification by chromatography provided 228 mg of Compound 1.001.
  • 6-amino-4-hydroxy- 1 -propyl-quinolin-2-one was prepared from 4-hydroxy-6-nitro- l-propyl-quinolin-2-one (900 mg, 3.63 mmol) in a similar manner to 6-amino-l-propyl- quinolin-2-one.
  • 1H NMR 400 MHz, DMSO-d6) ⁇ ppm 10.94 (s, 1 H), 7.20 (d, 1 H), 7.05 (d, 1 H), 6.91 (dd, 1 H), 5.75 (s, 1 H), 5.05 (br. s., 2 H), 4.02 (m, 2 H), 3.31 (s, 1 H), 1.54 (m, 2 H) , 0.90 (t, 4 H).
  • 6-amino-4-methoxy- 1 -propyl-quinolin-2-one was prepared from 4-methoxy-6-nitro- l-propyl-quinolin-2-one in a similar manner to 6-amino-l-propyl-quinolin-2-one; 1H NMR (400 MHz, CHLOROFORM-d) ⁇ ppm 1.02 (t, 3 H), 1.74 (dq, 2 H), 3.92 (s, 3 H), 4.13 - 4.26 (m, 2 H), 6.01 (s, 1 H), 6.97 (dd, 1 H), 7.16 (d, 1 H), 7.26 (d, 1 H).
  • 6-amino-4-chloro-l-propyl-quinolin-2-one for compound 1.049
  • 6-amino-4-chloro-l-propyl-quinolin-2-one was prepared from 4-chloro-6-nitro-l- propyl-quinolin-2-one in a similar manner to 6-amino-l-propyl-quinolin-2-one.
  • 6-Amino-3-methyl-4-methoxy-l-propyl-quinolin-2-one was prepared by reduction of 3-methyl-4-methoxy-6-nitro-l-propyl-quinolin-2-one (see compound 1.033) in a similar manner to 6-amino-l-propyl-quinolin-2-one; 1H NMR (400 MHz, CHLOROFORM-d) ⁇ ppm 1.03 (t, 3 H), 1.66 - 1.81 (m, 2 H), 2.20 (s, 3 H), 3.32 (br. s, 2 H), 3.88 (s, 3 H), 4.13 - 4.27 (m, 2 H), 6.94 (dd, 1 H), 7.12 - 7.14 (m, 1 H), 7.18 (d, 1 H).
  • N-(2-Formyl-4-nitro-phenyl)-2-methoxy-acetamide (810 mg) was suspended in DMF (17 mL) and NaH (163 mg, 55% dispersion in oil) was added portionwise at room temperature. The reaction mixture was stirred 15 min then 1-bromopropane (0.618 mL) was added. The reaction mixture was heated 2.5 h at 100 °C, cooled to room temperature and a solution of NH 4 C1 was added. The aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, washed twice with water, once with brine, dried over Na 2 S0 4 and concentrated under reduced pressure.
  • 6-Amino-3-methoxy-l-propyl-quinolin-2-one was prepared from 3-methoxy-6- nitro-l-propyl-quinolin-2-one in a similar manner to 6-amino-l-propyl-quinolin-2-one.
  • 6-amino-3 -fluoro- l-propyl-quinolin-2-one for compound 1.005 1 ) 3 -fluoro- 1 -propyl-quinolin-2-one
  • 6-Amino-3-fluoro-l-propyl-quinolin-2-one was prepared from 3-fluoro-6-nitro-l- propyl-quinolin-2-one in a similar manner to 6-amino-l-propyl-quinolin-2-one.
  • 1H NMR (CDC13, 400MHz) ⁇ 7.25 (d, 1H), 7.18 (d, 1H), 6.93 (dd, 1H), 6.80 (d, 1H), 4.31 (m, 2H), 3.72 (br. s., 2H), 1.79 (sxt, 2H), 1.05 (t, 3H).
  • 6-Amino-l -ethyl-4-methyl-quinolin-2-one was prepared from l-ethyl-4-methyl-6- nitro-quinolin-2-one in a similar manner to 6-amino- l-propyl-quinolin-2-one.
  • 1H NMR (DMSO-d6, 400MHz) ⁇ 7.29 (d, 1H), 6.95 (dd, 1H), 6.90 (d, 1H), 6.40 (d, 1H), 5.10 (s, 2H), 4.18 (q, 2H), 2.32 (m, 3H), 1.15 (t, 3H).
  • 6-Amino-8-methyl-l-propyl-quinolin-2-one was prepared from 8-methyl-6-nitro-l- propyl-quinolin-2-one in a similar manner to 6-amino-l-propyl-quinolin-2-one.
  • IH NMR (CDC13, 400MHz) ⁇ 7.43 (d, IH), 6.76 (d, IH), 6.66 (d, IH), 6.61 (d, IH), 4.38 (m, 2H), 3.59 (br. s., 2H), 2.65 (s, 3H), 1.69 (dd, 2H), 0.89 (t, 3H).
  • 6-Amino-8-fluoro-l-propyl-quinolin-2-one and 6-amino-8-chloro-l-propyl- quinolin-2-one were prepared following similar procedures to 6-amino-8-methyl-l-propyl- quinolin-2-one.
  • 6-amino-l-phenyl-quinolin-2-one for compound 1.260
  • Methyl (Z)-3-(2-hydroxy-5-nitro-phenyl)prop-2-enoate [0199] 6-nitrochromen-2-one (9.56 g) was suspended in MeOH (100 mL) and sodium methanolate 5.4M in MeOH was added (13 mL). The reaction mixture was stirred at room temperature for 15min then poured on a mixture ice/water/HCl 4N. The precipitated material was filtered, washed with water. Then it was dissolved in ethyl acetate, dried over Na 2 S0 4 and concentrated under reduced pressure.
  • 6-nitro- l-phenyl-quinolin-2-one 25 mg was dissolved in EtOH (3 mL). The reaction mixture was passed through H-Cube (Pd/C 10%, lObar, room temperature) and the solvents were evaporated under reduced pressure to give 20 mg of 6-amino- 1-phenyl- quinolin-2-one.
  • ⁇ 7.63 (d, 1H), 7.57 (m, 2H), 7.49 (m, 1H), 7.28 (m, 2H), 6.85 (d, 1H), 6.73 (m, 2H), 6.46 (d, 1H).
  • 6-l-(5-methylisoxazol-3-yl)quinolin-2-one was prepared from l-(5-methylisoxazol-3- yl)-6-nitro-quinolin-2-one in a similar manner to 6-amino-l-propyl-quinolin-2-one.
  • NMR (CDC13, 400MHz) ⁇ 7.63 (d, 1H), 6.83 (m, 3H), 6.67 (d, 1H), 6.19 (d, 1H), 3.70 (br. s., 2H), 2.57 (s, 3H).
  • the protein HAB 1 a type 2 protein phosphatase (PP2C) is inhibited by PYR/PYL proteins in dependence of abscisic acid or other agonists.
  • the potency of an agonist correlates with the level of inhibition of the PP2C, and therefore the IC50 (PYR1-HAB1) can be used to compare the relative activity of different chemical analogues. Since inhibition of PP2C correlates to inhibition of seed-germination and increase in plant water-use efficiency, it serves as a powerful tool to quantify biological potential of a chemical acting as an analogue of abscisic acid.
  • HABl and PYL proteins were expressed and purified as described in Park et al.
  • HABl cDNA was cloned into pGex-2T. Expression was conducted in BL21 [DE3]pLysS host cells. Transformed cells were pre-cultured overnight, transferred to LB medium and cultured at 30°C to culture A600 of -0.5. [0214] The culture was then cooled on ice and MnC12 added to 4 mM and IPTG added to 0.3mM. After 16 hours incubation at 15°C, cells were harvested and recombinant proteins were purified on glutathione agarose as described in Park et al.. To obtain 6XHis-PYL receptor fusion proteins, we used expression constructs previously described by Okamoto et al. 2013, (PNAS 110(29): 12132-12137). ABA receptors were expressed and purified as described above.
  • PP2C activity assays using recombinant receptors and PP2Cs were carried out as follows: Purified proteins were pre-incubated in 160 ⁇ assay buffer containing (100 mM Tris-HCl -pH7.9, lOOmM NaCl, 3 ⁇ g bovine serum albumin and 0.1% 2-mercaptoethanol), 1 mM MnCl 2 with carrier solvent (DMSO), quinabactin or quinabactin analogs (compounds of the present invention) for 30 minutes at room temperature.
  • DMSO carrier solvent
  • Reactions were started by adding 40 of a reaction solution containing 25 mM 4-nitrophenyl phosphate in assay buffer, after which absorbance measurements were immediately collected (405 nm) using a Wallac plate reader. Reactions contained 100 nM HABl PP2C and 200 nM receptor.
  • Reactions contained 100 nM HABl PP2C and 200 nM receptor.
  • compounds at concentrations ranging from 1 ⁇ to 4 nM were used in assays conducted in triplicate and the acquired dose response data was fitted to a log (inhibitor) vs response-(variable slope) model using non-linear regression to infer the IC50S, using Graph Pad Prism 6.0. The results are expressed in Tables B4, B5 and B6. TABLE B4: Inhibition of PP2C

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Abstract

La présente invention concerne de nouveaux dérivés sulfamides, des procédés et des produits intermédiaires permettant de les préparer, des compositions de régulation de la croissance des plantes les comprenant et des procédés d'utilisation de ces compositions pour réguler la croissance des plantes, pour améliorer la tolérance des plantes au stress abiotique (y compris le stress environnemental et le stress chimique) et/ou pour favoriser la germination des graines.
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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017036153A1 (fr) * 2015-08-28 2017-03-09 中国科学院上海生命科学研究院 Composé à petite molécule pour améliorer la résistance des plantes au stress
CN106749044A (zh) * 2015-12-28 2017-05-31 中国科学院上海生命科学研究院 增强植物抗逆性的aba类似物
WO2017114052A1 (fr) * 2015-12-28 2017-07-06 中国科学院上海生命科学研究院 Régulateur de croissance des plantes fortement résistantes au stress, son procédé de préparation et son utilisation
JP2017530942A (ja) * 2014-08-08 2017-10-19 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア 植物成長調節剤化合物
CN112794818A (zh) * 2019-11-13 2021-05-14 邵阳学院 一种n-丙基氨基喹啉酮的制备方法及其用于合成脱落酸激动剂am1及其衍生物
WO2023016562A1 (fr) * 2021-08-12 2023-02-16 浙江同源康医药股份有限公司 Composé polycyclique et son utilisation

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013027168A1 (fr) * 2011-08-22 2013-02-28 Pfizer Inc. Nouveaux composés hétérocycliques utilisés en tant qu'inhibiteurs de bromodomaine
WO2013033270A2 (fr) * 2011-08-29 2013-03-07 Coferon, Inc. Ligands de brodomaines capables de se dimériser dans une solution aqueuse, et procédés d'utilisation de ceux-ci
WO2013148339A1 (fr) 2012-03-30 2013-10-03 The Regents Of The University Of California Composés synthétiques pour réponses aba végétatives

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013027168A1 (fr) * 2011-08-22 2013-02-28 Pfizer Inc. Nouveaux composés hétérocycliques utilisés en tant qu'inhibiteurs de bromodomaine
WO2013033270A2 (fr) * 2011-08-29 2013-03-07 Coferon, Inc. Ligands de brodomaines capables de se dimériser dans une solution aqueuse, et procédés d'utilisation de ceux-ci
WO2013148339A1 (fr) 2012-03-30 2013-10-03 The Regents Of The University Of California Composés synthétiques pour réponses aba végétatives

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
"Pesticide Manual", BRITISH CROP PROTECTION COUNCIL
"Plant Protection Products", 1999
BERGE ET AL., JOURNAL OF PHARMACEUTICAL SCIENCE, vol. 66, 1977, pages 1 - 19
MAEHR, J. CHEM. ED., vol. 62, 1985, pages 114 - 120
MAJUMDAR, K., C. ET L.: "Regioselective synthesis of pyridoquinolones and pyridocoumarins via molecular iodine-mediated 6-endo-dig electrophilic cyclization", SYNLETT., vol. 2010, no. 9, 2010, THIEME INTERNATIONAL, STUTTGART; DE, XP002744581, ISSN: 0936-5214, DOI: 10.1016/j.tetlet.2010.11.066 *
OKAMOTO ET AL., PNAS, vol. 110, no. 29, 2013, pages 12132 - 12137
PARK ET AL., SCIENCE, vol. 324, no. 5930, 2009, pages 1068 - 1071

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017530942A (ja) * 2014-08-08 2017-10-19 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア 植物成長調節剤化合物
WO2017036153A1 (fr) * 2015-08-28 2017-03-09 中国科学院上海生命科学研究院 Composé à petite molécule pour améliorer la résistance des plantes au stress
AU2016314390B2 (en) * 2015-08-28 2019-07-11 CAS Center of Excellence in Molecular Plant Sciences Small molecule compound for enhancing plant stress resistance
US10842151B2 (en) 2015-08-28 2020-11-24 Cas Center For Excellence In Molecular Plant Sciences Small molecule compound for enhancing plant stress resistance
CN106749044A (zh) * 2015-12-28 2017-05-31 中国科学院上海生命科学研究院 增强植物抗逆性的aba类似物
WO2017114052A1 (fr) * 2015-12-28 2017-07-06 中国科学院上海生命科学研究院 Régulateur de croissance des plantes fortement résistantes au stress, son procédé de préparation et son utilisation
AU2016380736B2 (en) * 2015-12-28 2019-11-14 CAS Center of Excellence in Molecular Plant Sciences High stress resistant plant growth regulator and preparation and use thereof
CN106749044B (zh) * 2015-12-28 2020-04-21 中国科学院上海生命科学研究院 增强植物抗逆性的aba类似物
US11076597B2 (en) 2015-12-28 2021-08-03 Cas Center For Excellence In Molecular Plant Sciences High stress resistant plant growth regulator and preparation method and use thereof
CN112794818A (zh) * 2019-11-13 2021-05-14 邵阳学院 一种n-丙基氨基喹啉酮的制备方法及其用于合成脱落酸激动剂am1及其衍生物
WO2023016562A1 (fr) * 2021-08-12 2023-02-16 浙江同源康医药股份有限公司 Composé polycyclique et son utilisation

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