WO2024172156A1 - ブラシノステロイド様活性を有する化合物 - Google Patents

ブラシノステロイド様活性を有する化合物 Download PDF

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WO2024172156A1
WO2024172156A1 PCT/JP2024/005548 JP2024005548W WO2024172156A1 WO 2024172156 A1 WO2024172156 A1 WO 2024172156A1 JP 2024005548 W JP2024005548 W JP 2024005548W WO 2024172156 A1 WO2024172156 A1 WO 2024172156A1
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健一郎 伊丹
一真 天池
彩果 上田
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Tokai National Higher Education and Research System NUC
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P21/00—Plant growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
    • C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms

Definitions

  • the present invention relates to compounds that have brassinosteroid-like activity.
  • Brassinosteroids are plant growth hormones with a steroid skeleton that were isolated and structurally determined by Grove et al. in 1979. To date, over 70 BRs have been discovered in nature, and some BRs have been chemically synthesized. BRs play an important role in plant growth and development, primarily promoting cell elongation, cell division, bending, xylem differentiation, and seed germination. BRs are also involved in conferring resistance to abiotic stresses induced by high salinity, high temperature, heavy metals, drought, etc., as well as resistance to biotic stresses induced by bacteria, viruses, fungi, parasites, insects, etc., and are therefore molecules that are expected to be used in agriculture.
  • oleic acid monoglyceride isolated from the fungus Talaromyces trachysoerms had BR-like activity. However, its activity was extremely weak, 1/100,000th of that of BR, and no interaction with the BR receptor, BRI1, was confirmed.
  • bikinin has the same activity as BR. Like lithium, bikinin causes BR signaling by inhibiting the enzyme activity of BIN2. Bikinin covers almost all of the genes expressed by BR, and has been widely used as a tool to research basic botany. Its activity has been improved by using a group of derivatives, and research has also been conducted with a view to the prospect of agricultural applications. However, bikinin has low metabolic stability, and is rapidly inactivated in the body by binding to glutamic acid or malic acid.
  • the first example was a compound synthesized in 2001 that showed high BR activity when used in combination with auxin indole-3-acetic acid, which synergizes BR activity, but showed almost no BR activity on its own.
  • BL9 non-steroidal BR mimetic molecule
  • the present invention aims to solve the problems described above and provide a non-steroidal molecule with high brassinosteroid (BR)-like activity.
  • the inventors have found that by changing the piperazine ring at the central position in BL9 to a piperidine ring, in other words, by changing the number of nitrogen atoms at the central position from two to one (changing from a piperazine ring to a piperidine ring), it is possible to exhibit strong activity equivalent to that of natural BR. Based on this finding, the inventors have further intensively researched and completed the present invention. In other words, the present invention encompasses the following configurations.
  • Ring A and ring B may be the same or different and each represents a monocyclic aromatic or non-aromatic ring.
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a nitro group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkanoyl group, a substituted or unsubstituted alkylsulfonyl group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted amino group.
  • L 1 and L 2 are the same or different and each represents a bond, an alkylene group, -NH-, -O-, -S-, -C(O)-, -CS-, -S(O)- or -S(O) 2 -.
  • n represents 0 or 1.
  • Item 2 The compound or salt thereof according to item 1, wherein L 1 and L 2 are the same or different and each represent a bond, —C(O)—, —CS—, —S(O)—, or —S(O) 2 —.
  • Item 3 The compound or salt thereof according to item 1 or 2, wherein L 1 is —C(O)— and L 2 is a bond.
  • Item 4 The compound or salt thereof according to any one of items 1 to 3, wherein ring A and ring B are the same or different and are 6-membered monocyclic aromatic or non-aromatic rings.
  • Item 6 The compound or salt thereof according to any one of items 1 to 5, wherein n is 1.
  • R 1 , R 2 and R 3 are the same or different and each represents a hydrogen atom, a hydroxyl group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted amino group; Items 7.
  • R 4 , R 5 and R 6 are the same or different and each is a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, or a substituted or unsubstituted alkanoyl group, or two groups among R 4 , R 5 and R 6 are bonded to adjacent atoms on ring B, and the two groups, together with the atoms on ring B to which they are bonded, form a monocyclic heteroaromatic ring.
  • R 1a and R 2a are the same or different and each represent a hydrogen atom, a hydroxyl group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, or a substituted or unsubstituted carbamoyl group.
  • R 4a represents a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, or a substituted or unsubstituted alkanoyl group.
  • R 5a represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, or a substituted or unsubstituted alkanoyl group.
  • Item 8 The compound or salt thereof according to any one of items 1 to 7, represented by the following formula:
  • Item 9 An agricultural composition containing the compound or salt thereof described in any one of items 1 to 8.
  • Item 10 The agricultural composition according to Item 9, which is applied to at least one species selected from the group consisting of agricultural crops, vegetables, fruit trees, weeds, and ornamental plants.
  • Item 11 The agricultural composition according to item 9 or 10, which is a plant growth regulator.
  • Item 12 The agricultural composition according to any one of items 9 to 11, which is a plant growth promoter.
  • Item 13 The agricultural composition according to Item 12, wherein the plant is at least one selected from the group consisting of vegetables and fruit trees.
  • Item 14 The agricultural composition according to any one of items 9 to 11, which is a plant growth inhibitor.
  • Item 15 The agricultural composition according to Item 14, wherein the plant is a weed.
  • Item 16 A method for regulating plant growth, comprising the step of applying the compound or salt thereof according to any one of Items 1 to 8, or the agricultural composition according to any one of Items 9 to 15, to a plant.
  • Ring B is a monocyclic aromatic or non-aromatic ring.
  • R 4 , R 5 and R 6 are the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a nitro group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkanoyl group, a substituted or unsubstituted alkylsulfonyl group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted amino group.
  • R7 represents a substituted or unsubstituted alkyl group.
  • L2 represents a bond, an alkylene group, -NH-, -O-, -S-, -C(O)-, -CS-, -S(O)-, or -S(O) 2 -.
  • n represents 0 or 1.
  • Ring B is a monocyclic aromatic or non-aromatic ring.
  • R 4 , R 5 and R 6 are the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a nitro group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkanoyl group, a substituted or unsubstituted alkylsulfonyl group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted amino group.
  • L2 represents a bond, an alkylene group, -NH-, -O-, -S-, -C(O)-, -CS-, -S(O)-, or -S(O) 2 -.
  • n represents 0 or 1.
  • the present invention provides a non-steroidal molecule with high BR-like activity.
  • FIG. 1 is a diagram showing the results of Test Example 1.
  • FIG. 1 is a diagram showing the results of Test Example 1.
  • FIG. 1 is a diagram showing the results of Test Example 1.
  • FIG. 13 is a diagram showing the results of Test Example 2.
  • FIG. 13 is a diagram showing the results of Test Example 3.
  • Ring A and ring B may be the same or different and each represents a monocyclic aromatic or non-aromatic ring.
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are the same or different and each represents a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, a nitro group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkanoyl group, a substituted or unsubstituted alkylsulfonyl group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted amino group.
  • L 1 and L 2 are the same or different and each represents a bond, an alkylene group, -NH-, -O-, -S-, -C(O)-, -CS-, -S(O)- or -S(O) 2 -.
  • n represents 0 or 1. or a salt thereof.
  • the halogen atom represented by R 1 , R 2 , R 3 , R 4 , R 5 and R 6 is not particularly limited, and examples thereof include a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, etc.
  • a fluorine atom, a chlorine atom and a bromine atom are preferred, and a fluorine atom is more preferred.
  • the alkyl groups represented by R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are not particularly limited, but are preferably linear or branched saturated hydrocarbon groups having 1 to 6 carbon atoms (C1-C6).
  • R 1 , R 2 and R 3 are preferably alkyl groups having 1 to 4 carbon atoms (C1-C4 alkyl groups), and more preferably alkyl groups having 1 to 3 carbon atoms (C1-C3 alkyl groups).
  • R 4 , R 5 and R 6 are preferably alkyl groups having 2 to 6 carbon atoms (C2-C6 alkyl groups), and more preferably alkyl groups having 3 to 6 carbon atoms (C3-C6 alkyl groups).
  • the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isoamyl group, a 1,2-dimethylpropyl group, a 2,2-dimethylpropyl group, an n-hexyl group, a 1,2,2-trimethylpropyl group, a 1,1,2-trimethylpropyl group, etc.
  • R 1 , R 2 and R 3 are preferred as R 1 , R 2 and R 3 .
  • R 4 , R 5 and R 6 include an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isoamyl group, a 1,2-dimethylpropyl group, a 2,2-dimethylpropyl group, an n-hexyl group, a 1,2,2-trimethylpropyl group and a 1,1,2-trimethylpropyl group.
  • the alkyl group described above may have a substituent.
  • the number of the substituents is not particularly limited and may be, for example, 1 or more (for example, 1 to 5, particularly 1 to 3, etc.), and the substituents may be the same or different. Examples of such substituents include the above-mentioned halogen atoms, hydroxyl groups, cyano groups, nitro groups, alkoxy groups described below, and imino groups which may be substituted with alkoxy groups described below.
  • the substituents which the alkyl groups represented by R 1 , R 2 , and R 3 may have may be 1 to 3 hydroxyl groups, imino groups which may be substituted with alkoxy groups described below, and the substituents which the alkyl groups represented by R 4 , R 5 , and R 6 may have may be 1 to 3 hydroxyl groups.
  • the alkoxy group represented by R 1 , R 2 , R 3 , R 4 , R 5 and R 6 means a monovalent group in which a hydrogen atom is bonded to at least one carbon atom in the alkyl group.
  • R 1 , R 2 and R 3 are preferably alkoxy groups having 1 to 4 carbon atoms (C1-C4 alkoxy groups), more preferably alkoxy groups having 1 to 3 carbon atoms (C1-C3 alkoxy groups).
  • R 4 , R 5 and R 6 are preferably alkoxy groups having 2 to 6 carbon atoms (C2-C6 alkoxy groups), more preferably alkoxy groups having 3 to 6 carbon atoms (C3-C6 alkoxy groups). More specific examples of the alkoxy group include a methoxy group, an ethoxy group, an n-propyloxy group, an isopropyloxy group, a 1-hydroxybutyl group, an n-butyloxy group, an isobutyloxy group, a sec-butyloxy group, a tert-butyloxy group, an n-pentyloxy group, an isoamyloxy group, a 1,2-dimethylpropyloxy group, a 2,2-dimethylpropyloxy group, an n-hexyloxy group, a 1,2,2-trimethylpropyloxy group, a 1,1,2-trimethylpropyloxy group, etc.
  • R 1 , R 2 and R 3 preferred examples of R 4 , R 5 and R 6 include a 1-hydroxybutyl group, an n-butyloxy group, an isobutyloxy group, a sec-butyloxy group, a tert-butyloxy group, an n-pentyloxy group, an isoamyloxy group, a 1,2-dimethylpropyloxy group, a 2,2-dimethylpropyloxy group, an n-hexyloxy group, a 1,2,2-trimethylpropyloxy group and a 1,1,2-trimethylpropyloxy group.
  • the above-mentioned alkoxy group may also have a substituent.
  • the number of the substituents is not particularly limited and may be, for example, one or more (e.g., 1 to 5, particularly 1 to 3, etc.), and the substituents may be the same or different.
  • substituents include the above-mentioned halogen atoms, hydroxyl groups, cyano groups, nitro groups, and the above-mentioned alkoxy groups.
  • the substituents that the alkoxy group may have may be 1 to 5 halogen atoms (particularly fluorine atoms).
  • the alkanoyl group represented by R 1 , R 2 , R 3 , R 4 , R 5 and R 6 means a monovalent group in which a carbonyl group is bonded to the alkyl group, and an alkanoyl group having 2 to 7 carbon atoms (C2-C7 alkyl group) is preferred.
  • an alkanoyl group having 3 to 7 carbon atoms (C3-C7 alkyl group) is preferred, and an alkanoyl group having 3 to 6 carbon atoms (C3-C6 alkyl group) is more preferred.
  • alkanoyl group examples include an acetyl group, a propionyl group, a pivaloyl group, a butanoyl group, a pentanoyl group, a hexanoyl group, and a heptanoyl group.
  • a propionyl group, a pivaloyl group, a butanoyl group, a pentanoyl group, a hexanoyl group, and a heptanoyl group are preferred.
  • the above-mentioned alkanoyl group may also have a substituent.
  • the number of the substituents is not particularly limited and may be, for example, one or more (e.g., 1 to 5, particularly 1 to 3, etc.), and the substituents may be the same or different.
  • substituents include the above-mentioned halogen atoms, hydroxyl groups, cyano groups, nitro groups, and the above-mentioned alkoxy groups.
  • the substituents that the alkanoyl group may have may be 1 to 5 halogen atoms (particularly fluorine atoms).
  • the alkylsulfonyl group represented by R 1 , R 2 , R 3 , R 4 , R 5 and R 6 means a monovalent group in which a sulfonyl group is bonded to the alkyl group, and an alkylsulfonyl group having 1 to 6 carbon atoms (C1-C6 alkylsulfonyl group) is preferred.
  • an alkylsulfonyl group having 1 to 4 carbon atoms (C1-C4 alkylsulfonyl group) is preferred, and an alkylsulfonyl group having 1 to 3 carbon atoms (C1-C3 alkylsulfonyl group) is more preferred.
  • Specific examples of the alkylsulfonyl group include a methylsulfonyl group, an ethylsulfonyl group, a propylsulfonyl group, etc.
  • an ethylsulfonyl group, a propylsulfonyl group, etc. are preferred.
  • the above-mentioned alkylsulfonyl group may also have a substituent.
  • the number of the substituents is not particularly limited and may be, for example, one or more (e.g., 1 to 5, particularly 1 to 3, etc.), and the substituents may be the same or different.
  • substituents include the above-mentioned halogen atoms, hydroxyl groups, cyano groups, nitro groups, and alkoxy groups.
  • the substituents that the alkylsulfonyl group may have may be 1 to 5 halogen atoms (particularly fluorine atoms).
  • the carbamoyl groups represented by R 1 , R 2 , R 3 , R 4 , R 5 and R 6 may also have a substituent.
  • the number of the substituents is not particularly limited and may be, for example, 1 to 2, and the substituents may be the same or different.
  • substituents include the above-mentioned halogen atoms, hydroxyl groups, alkyl groups, and alkanoyl groups. Among them, from the viewpoints of BR-like activity, ease of synthesis, and the like, the substituents that the carbamoyl group may have may be 1 to 2 of the above-mentioned alkyl groups (particularly 1 to 2 methyl groups).
  • the amino group represented by R 1 , R 2 , R 3 , R 4 , R 5 and R 6 may have a substituent.
  • the number of the substituents is not particularly limited and may be, for example, 1 to 2, and the substituents may be the same or different. Examples of such substituents include the above-mentioned halogen atom, hydroxyl group, alkyl group, alkanoyl group, and optionally substituted carbamoyl group.
  • the substituent that the amino group may have may be 1 to 2 of the above-mentioned alkanoyl groups, a carbamoyl group optionally substituted with 1 to 2 of the above-mentioned alkyl groups, and the like (particularly a carbamoyl group optionally substituted with 1 to 2 acetyl groups or 1 to 2 methyl groups).
  • R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are, from the viewpoint of BR-like activity, ease of synthesis and the like, a hydrogen atom; the above-mentioned halogen atom; a hydroxyl group; a nitro group; the above-mentioned alkyl group (particularly, an imino group which may be substituted with the above-mentioned alkoxy group and an alkyl group which may be substituted with 1 to 3 hydroxyl groups); the above-mentioned alkoxy group; the above-mentioned alkanoyl group (particularly, an alkanoyl group which may be substituted with 1 to 5 halogen atoms); an alkylsulfonyl group (particularly, an alkylsulfonyl group which may be substituted with 1 to 5 halogen atoms); a substituted or unsubstituted carbamoyl group (particularly, a carbamoyl group which may be substituted
  • R 1 , R 2 and R 3 are a hydrogen atom, a hydroxyl group, the above-mentioned substituted or unsubstituted alkyl group (particularly, the above-mentioned imino group which may be substituted with an alkoxy group, and an alkyl group which may be substituted with 1 to 3 hydroxyl groups), the above-mentioned substituted or unsubstituted alkoxy group, the above-mentioned substituted or unsubstituted carbamoyl group (particularly, the carbamoyl group which may be substituted with 1 to 2 alkyl groups), the above-mentioned substituted or unsubstituted amino group (particularly, the above-mentioned alkanoyl group, the above-mentioned amino group which may be substituted with 1 to 2 carbamoyl groups, etc.), etc.; R 4 , R 5 and R 6 are a hydrogen atom, a hydroxyl group, the above-mentioned substituted
  • R 1 , R 2 and R 3 are a hydrogen atom, a hydroxyl group, a fluorine atom, a bromine atom, a C1-C4 alkyl group, a C1-C4 alkoxy group, an amino group optionally substituted with one carbamoyl group which may be substituted with one methyl group, etc.
  • R 4 , R 5 and R 6 are a hydrogen atom, a hydroxyl group, a fluorine atom, a nitro group, a C2-C6 alkyl group optionally substituted with 1 to 3 hydroxyl groups, a C2-C6 alkoxy group optionally substituted with 1 to 5 fluorine atoms, a C3-C7 alkanoyl group optionally substituted with 1 to 5 fluorine atoms, a C1-C4 alkylsulfonyl group optionally substituted with 1 to 5 fluorine
  • R 1 , R 2 and R 3 are a hydrogen atom, a hydroxyl group, a methoxy group, an acetylamino group, or the like, with at least one being a hydrogen atom
  • R 4 , R 5 and R 6 are a hydrogen atom, a hydroxyl group, a fluorine atom, a C2-C6 alkyl group which may be substituted with 1 to 3 hydroxyl groups (particularly an n-butyl group which may be substituted with one hydroxyl group), a C2-C6 alkoxy group which may be substituted with 1 to 5 fluorine atoms (particularly a 1-hydroxybutyl group), a C3-C7 alkanoyl group (particularly a butanoyl group, a 3-methylbutanoyl group, or the like), or the like.
  • the alkylene group represented by L1 and L2 means a divalent group obtained by removing one hydrogen atom from the above alkyl group. Among them, from the viewpoints of BR-like activity, ease of synthesis, etc., an alkylene group having 1 to 3 carbon atoms (C1-C3 alkylene group) is preferred, and an alkylene group having 1 to 2 carbon atoms (C1-C2 alkylene group) is more preferred. Specific examples of the alkylene group include a methylene group, an ethylene group, a trimethylene group, a propylene group, etc. Among them, from the viewpoints of BR-like activity, ease of synthesis, etc., a methylene group is preferred.
  • L1 and L2 are preferably a bond, -C(O)-, -CS-, -S(O)-, -S(O) 2- , etc., more preferably a bond, -C(O)-, -CS-, -S(O)-, etc., further preferably L1 is -C(O)-, -CS-, -S(O)-, etc. and L2 is a bond, and particularly preferably L1 is -C(O)-, and L2 is a bond.
  • the monocyclic aromatic rings represented by ring A and ring B include, but are not limited to, monocyclic aromatic carbon rings (benzene rings), monocyclic aromatic heterocycles, etc.
  • the monocyclic aromatic carbocyclic ring may have a substituent.
  • the number of the substituents is not particularly limited and may be, for example, 1 to 4, and the substituents may be the same or different. Examples of such substituents include the above-mentioned halogen atoms, hydroxyl groups, the above-mentioned alkyl groups, the above-mentioned alkanoyl groups, and carbamoyl groups which may be substituted with 1 to 2 of the above-mentioned alkyl groups.
  • the substituents that the monocyclic aromatic carbocyclic ring (benzene ring) may have may be 1 to 2 of the above-mentioned halogen atoms, hydroxyl groups, alkyl groups, etc. (particularly alkyl groups).
  • the monocyclic aromatic heterocycle is preferably a 5- to 6-membered monocyclic aromatic heterocycle containing 1 to 4 heteroatoms such as oxygen atoms, sulfur atoms, nitrogen atoms, etc., in addition to carbon and hydrogen atoms.
  • monocyclic aromatic heterocycles include 5-membered monocyclic aromatic heterocycles such as pyrrole ring, furan ring, thiophene ring, pyrazole ring, imidazole ring, triazole ring, tetrazole ring, oxazole ring, isoxazole ring, thiazole ring, isothiazole ring, and thiadiazole ring; and 6-membered monocyclic aromatic heterocycles such as pyridine ring, pyrimidine ring, pyrazine ring, pyridazine ring, thiazine ring, and triazine ring.
  • a pyrazole ring is preferred.
  • the monocyclic aromatic heterocycle may have a substituent.
  • the number of the substituents is not particularly limited and may be, for example, 1 to 4, and the substituents may be the same or different.
  • substituents include the above-mentioned halogen atoms, hydroxyl groups, the above-mentioned alkyl groups, the above-mentioned alkanoyl groups, and carbamoyl groups which may be substituted with 1 to 2 of the above-mentioned alkyl groups.
  • Examples of the monocyclic non-aromatic rings represented by ring A and ring B include monocyclic non-aromatic carbocycles and monocyclic non-aromatic heterocycles.
  • the monocyclic non-aromatic carbocycle from the viewpoints of BR-like activity, ease of synthesis, etc., a 5- to 6-membered monocyclic non-aromatic carbocycle is preferred.
  • the monocyclic non-aromatic carbocycle include 5-membered monocyclic non-aromatic carbocycles such as a cyclopentane ring and a cyclopentene ring; and 6-membered monocyclic non-aromatic carbocycles such as a cyclohexane ring and a cyclohexene ring.
  • a 6-membered monocyclic non-aromatic carbocycle is preferred.
  • the substituents that the monocyclic non-aromatic carbocycle may have may be 1 to 2 of the above-mentioned halogen atoms, hydroxyl groups, alkyl groups, etc. (particularly alkyl groups).
  • the monocyclic non-aromatic heterocycle is preferably a 5- or 6-membered monocyclic non-aromatic heterocycle containing, for example, 1 to 4 heteroatoms such as oxygen atoms, sulfur atoms, nitrogen atoms, etc., in addition to carbon and hydrogen atoms.
  • preferred rings A and B are 6-membered monocyclic aromatic rings (monocyclic aromatic carbocyclic rings (benzene rings), 6-membered monocyclic aromatic heterocyclic rings, etc.), 6-membered monocyclic non-aromatic rings (6-membered monocyclic non-aromatic carbocyclic rings, 6-membered monocyclic non-aromatic heterocyclic rings), etc.
  • preferred rings A and B are cyclohexane rings, cyclohexene rings, piperidine rings, piperazine rings, tetrahydropyran rings, tetrahydrothiopyran rings, morpholine rings, thiomorpholine rings, benzene rings, pyridine rings, pyrimidine rings, pyrazine rings, pyridazine rings, thiazine rings, triazine rings, etc., with a benzene ring being more preferred.
  • the compound of the present invention that satisfies the above conditions is, for example, the compound represented by the general formula (1A):
  • R 1a and R 2a are the same or different and each represent a hydrogen atom, a hydroxyl group, the above-mentioned substituted or unsubstituted alkyl group, the above-mentioned substituted or unsubstituted alkoxy group, or the above-mentioned substituted or unsubstituted carbamoyl group.
  • R 4a represents the above halogen atom, the above substituted or unsubstituted alkyl group, the above substituted or unsubstituted alkoxy group, or the above substituted or unsubstituted alkanoyl group. or a salt thereof is preferred.
  • the compounds of the present invention can exist in the free form or in the form of salts.
  • salts include acid addition salts such as hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, phosphate, formate, acetate, propionate, fumarate, oxalate, malonate, succinate, methanesulfonate, ethanesulfonate, benzenesulfonate, maleate, lactate, malate, tartrate, citrate, and trifluoroacetate; metal salts such as lithium salt, potassium salt, calcium salt, magnesium salt, sodium salt, zinc salt, and aluminum salt; and base addition salts such as ammonium salt, diethanolamine salt, ethylenediamine salt, triethanolamine salt, and triethylamine salt.
  • the compounds of the present invention or their salts include their intramolecular salts, adducts, solvates, and hydrates.
  • the agricultural compositions containing the compound of the present invention or a salt thereof can be formulated into oil concentrates, emulsifiable concentrates, flowable concentrates, wettable concentrates, water dispersible granules, dust concentrates, granules, and the like by appropriately adding inert carriers, surfactants, other formulation adjuvants, and the like.
  • the inert carrier may be either a solid carrier or a liquid carrier.
  • the solid carrier include minerals such as kaolin clay, attapulgite clay, bentonite, montmorillonite, acid clay, pyrophyllite, talc, diatomaceous earth, and calcite; natural organic substances such as corncob flour and walnut shell flour; synthetic organic substances such as urea; salts such as calcium carbonate and ammonium sulfate; and synthetic inorganic substances such as synthetic hydrous silicon oxide, in the form of fine powders or granules.
  • liquid carrier examples include aromatic hydrocarbon compounds such as toluene, xylene, ethylbenzene, and methylnaphthalene; alcohol compounds such as methanol, ethanol, isopropanol, ethylene glycol, propylene glycol, and ethylene glycol monoethyl ether; ketone compounds such as acetone, methyl ethyl ketone, and cyclohexanone; vegetable oils such as soybean oil and cottonseed oil; petroleum-based aliphatic hydrocarbon compounds; ester compounds; dimethyl sulfoxide; acetonitrile; and water.
  • aromatic hydrocarbon compounds such as toluene, xylene, ethylbenzene, and methylnaphthalene
  • alcohol compounds such as methanol, ethanol, isopropanol, ethylene glycol, propylene glycol, and ethylene glycol monoethyl ether
  • ketone compounds such as acetone, methyl ethyl
  • Surfactants include, for example, nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene alkylaryl ethers, and polyethylene glycol fatty acid esters; and anionic surfactants such as alkyl sulfonates, alkylbenzene sulfonates, and alkyl sulfates.
  • nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene alkylaryl ethers, and polyethylene glycol fatty acid esters
  • anionic surfactants such as alkyl sulfonates, alkylbenzene sulfonates, and alkyl sulfates.
  • formulation adjuvants include, for example, water-soluble polymers such as polyvinyl alcohol and polyvinylpyrrolidone; polysaccharides such as gum arabic, alginic acid and its salts, CMC (carboxymethylcellulose), and xanthan gum; inorganic substances such as aluminum magnesium silicate and alumina sol; preservatives; colorants; PAP (isopropyl acid phosphate); and stabilizers such as BHT.
  • water-soluble polymers such as polyvinyl alcohol and polyvinylpyrrolidone
  • polysaccharides such as gum arabic, alginic acid and its salts, CMC (carboxymethylcellulose), and xanthan gum
  • inorganic substances such as aluminum magnesium silicate and alumina sol
  • preservatives colorants
  • PAP isopropyl acid phosphate
  • stabilizers such as BHT.
  • the agricultural composition of the present invention can contain the compound of the present invention or its salt in an amount of usually 0.01 to 99% by mass, particularly 0.1 to 95% by mass, and furthermore 0.5 to 90% by mass, etc.
  • the compound or salt thereof, or the agricultural composition of the present invention when applied to a plant, it may be applied to the whole or a part of the plant (stems, leaves, buds, flowers, fruits, ears, seeds, roots, etc.), and may be applied to various growth stages of the plant (germination period, such as before or after emergence after sowing; vegetative growth period, such as when raising seedlings, when transplanting seedlings, when taking cuttings or cuttings, and when growing after planting; reproductive growth period, such as just before or during heading, etc.).
  • the method of the present invention for regulating plant growth for example, the method for promoting or inhibiting plant growth, can be carried out by applying an effective amount of the compound of the present invention or a salt thereof, or the agricultural composition of the present invention to the plant or its cultivation area.
  • the compound of the present invention or a salt thereof, or the agricultural composition of the present invention can be applied once or multiple times.
  • the number of times of spraying treatment is usually 1 to 3 times.
  • Application methods in the present invention include, for example, treatment of the stems and leaves, inflorescences, or spikes of plants, such as spraying the stems and leaves (i.e., spraying treatment), treatment of plant seeds before they are sown in soil or cultivation medium (i.e., seed treatment), treatment of the soil (cultivation area) before or after planting the plants (i.e., soil treatment), treatment of seedlings (for example, seedling box treatment, seedling tray treatment, etc.), etc.
  • spraying the stems and leaves i.e., spraying treatment
  • treatment of plant seeds before they are sown in soil or cultivation medium i.e., seed treatment
  • treatment of the soil cultivation area
  • seedlings for example, seedling box treatment, seedling tray treatment, etc.
  • examples of spray treatments on the stems, leaves, floral organs, or panicles of plants include methods of applying an effective amount of the compound of the present invention or a salt thereof, or the agricultural composition of the present invention to the surface of the plant, such as by spraying on the stems, or to the panicles at the heading stage or to the entire plant.
  • One embodiment of treatment on plants is treatment on plants growing in paddy fields.
  • examples of the time of spray treatment include the flowering period, including before, during, and after flowering.
  • examples of the plant seed treatment include a method of applying an effective amount of the compound of the present invention or a salt thereof, or the agricultural composition of the present invention to the seeds of a plant before they are sown in soil or a cultivation medium.
  • Specific treatment methods include, for example, spraying, smearing, immersion, impregnation, coating, film coating, pellet coating, etc., and these methods can be used to prepare seeds that retain an effective amount of the compound of the present invention or a salt thereof, or the agricultural composition of the present invention on the surface and/or inside.
  • the soil treatment may be, for example, a method of applying an effective amount of the compound or salt thereof of the present invention, or the agricultural composition of the present invention to the soil before or after planting a plant.
  • Specific treatment methods include, for example, spraying the soil, mixing the soil, and irrigating the soil with a chemical solution (chemical solution irrigation, soil injection, chemical solution drip, etc.).
  • Treatment locations include, for example, planting holes, rows, near planting holes, near rows, the entire cultivated area, the plant edge, between plants, under the tree trunk, the main trunk ridge, soil, seedling boxes, seedling trays, seedling beds, etc.
  • Treatment times include before sowing, at the time of sowing, immediately after sowing, the seedling period, before planting, at the time of planting, and the growth period after planting.
  • a solid fertilizer such as a paste fertilizer containing the compound or salt thereof or the agricultural composition of the present invention may be applied to the soil.
  • the compound or salt thereof, or the agricultural composition of the present invention can also be mixed with an irrigation solution, for example, by injection into irrigation equipment (irrigation tubes, irrigation pipes, sprinklers, etc.), mixing into inter-row flooding solution, mixing into hydroponic solution, etc.
  • the compound or salt thereof, or the agricultural composition of the present invention can be mixed with an irrigation solution in advance, and then treated using the above-mentioned irrigation method or other appropriate irrigation method such as sprinkling or flooding.
  • Examples of treatments for seedlings in the present invention include a spraying treatment in which a diluted solution prepared by diluting the compound or a salt thereof, or the agricultural composition of the present invention with water to an appropriate active ingredient concentration is sprayed over the entire seedling, an immersion treatment in which the seedlings are immersed in the diluted solution, and a coating treatment in which the compound or a salt thereof, or the agricultural composition of the present invention, prepared as a powder, is applied over the entire seedling.
  • Examples of treatments for soil before or after planting the seedlings include a method in which a diluted solution prepared by diluting the compound or a salt thereof, or the agricultural composition of the present invention with water to an appropriate active ingredient concentration is sprayed over the seedlings and surrounding soil after planting the seedlings, and a method in which the compound or a salt thereof, or the agricultural composition of the present invention, prepared as a granule or a solid agent such as a granule, or the agricultural composition of the present invention, is sprayed over the surrounding soil after planting the seedlings.
  • plants to which the compound or a salt thereof, or the agricultural composition of the present invention can be applied include: Agricultural crops, such as corn, rice, wheat, barley, rye, oats, sorghum, cotton, soybeans, adzuki beans, kidney beans, peanuts, buckwheat, sugar beets, rapeseed, sunflowers, sugarcane, tobacco, etc.; Vegetables, for example, Solanaceae vegetables (eggplant, tomato, bell pepper, chili pepper, potato, etc.), Cucurbitaceae vegetables (cucumber, pumpkin, zucchini, watermelon, melon, squash, etc.), Cruciferae vegetables (radish, turnip, horseradish, kohlrabi, Chinese cabbage, cabbage, mustard, broccoli, cauliflower, etc.), Asteraceae vegetables (burdock, chrysanthemum, artichoke, lettuce, etc.), Liliaceae vegetables (green onion, onion, garlic, asparagus, etc.), Apiaceae vegetables (carcino
  • the compound or its salt, or the agricultural composition of the present invention may be applied to rice, but is not limited thereto.
  • rice include japonica varieties such as Nipponbare, Hinohikari, Koshihikari, Akitakomachi, Haenuki, Sasanishiki, Hitomebore, Kinuhikari, Hoshino Yume, Kirara 397, Tsugaru Roman, Yumeakari, Hanaechizen, Yumetsukushi, Hatsushimo, Yukihikari, Nanatsuboshi, Masshigura, Asahi no Yume, Koshibuki, Aichi no Kaori, Iro no Kagayaki, Oborozuki, and Yumehikari; indica varieties; Javanica varieties; Sally Queen, Basmati, Kitakaori, Princess Sally, Khao Home Mali, Arborio, Carnaroli, and Vialone Nano.
  • the compound of the present invention or a salt thereof has brassinosteroid (BR)-like agonist or antagonist activity, and is therefore useful as a plant growth regulator, for example, a growth promoter or growth inhibitor.
  • BR brassinosteroid
  • the compound of the present invention or a salt thereof can be used as a plant growth promoter.
  • "promotion of plant growth” can include, for example, promotion of seed germination; promotion of rooting; promotion of rooting; promotion of development and elongation of branches, leaves and stems; promotion of flowering; promotion of fruit set; promotion of fruit maturation; promotion of fruit enlargement; imparting disease resistance; imparting resistance to stress (for example, high salt concentration, dryness, high temperature, low temperature, nutritional deficiency, etc.), etc.
  • Plants to which the compound or a salt thereof of the present invention is applied as a growth promoter include, but are not limited to, agricultural crops such as corn, rice, wheat, barley, rye, oats, sorghum, cotton, soybean, adzuki bean, kidney bean, peanut, buckwheat, sugar beet, rapeseed, sunflower, sugarcane, and tobacco; pome fruits (apple, European pear, Japanese pear, quince, quince, etc.), stone fruits (peach, plum, nectarine, plum, cherry, apricot, prune, etc.), citrus fruits (Satsuma mandarin, orange, lemon, lime, grapefruit, etc.), nuts (chestnut, walnut, hazel, almond, pistachio, cashew nut, macadamia nut, etc.), berries (blueberry, cranberry, blackberry, raspberry, etc.), grape, persimmon, olive, loquat, banana, coffee, date palm, coconut
  • the compound of the present invention or a salt thereof can be used as a growth inhibitor.
  • “inhibition of plant growth” refers to, for example, inhibition of seed germination, inhibition of root growth, inhibition of root establishment, inhibition of branch, leaf and stem development and elongation, inhibition of flowering, inhibition of fruit set, inhibition of fruit ripening, inhibition of fruit enlargement, and the like, and particularly includes an action as a herbicide.
  • Plants to which the compound of the present invention or a salt thereof can be applied as a growth inhibitor include russet greens, russet rose, sowberry, thistle, Bidens frondosa, American geranium, ragweed, evening primrose, Japanese knotweed, Japanese mustard, Polygonum quinquefolia, Arabidopsis thaliana, ragweed, nightshade, chickweed, alfalfa, white-breasted hackberry, Chinese hackberry, Japanese laurel, and Japanese laurel.
  • the method for producing the compound of the present invention is not particularly limited, and the compound can be produced by various methods.
  • the compound can be produced by the following reaction scheme:
  • ring A, ring B, R1 , R2 , R3 , R4 , R5 , R6 , L1 , L2 and n are the same as those described above.
  • R7 represents the above alkyl group.
  • X1 and X2 may be the same or different and represent the above halogen atoms. It can be synthesized according to the following:
  • the compound represented by the general formula (2) and the compound represented by the general formula (3) may be a known or commercially available product, or may be synthesized from a commercially available product by a known method.
  • the compound represented by general formula (4) can be obtained by coupling the compound represented by general formula (2) with the compound represented by general formula (3).
  • the coupling reaction between the compound represented by general formula (2) and the compound represented by general formula (3) can be carried out in a suitable solvent in the presence of a base according to a conventional method.
  • solvents there are no limitations on the solvent as long as it does not interfere with the reaction, and examples include amide compounds such as N,N-dimethylformamide; ether compounds such as tetrahydrofuran; halogenated aliphatic hydrocarbon compounds such as chloroform and dichloromethane; aromatic hydrocarbon compounds such as toluene and xylene; and nitrile compounds such as acetonitrile.
  • amide compounds such as N,N-dimethylformamide
  • ether compounds such as tetrahydrofuran
  • halogenated aliphatic hydrocarbon compounds such as chloroform and dichloromethane
  • aromatic hydrocarbon compounds such as toluene and xylene
  • nitrile compounds such as acetonitrile.
  • bases examples include triethylamine, diisopropylethylamine, N-methylpyrrolidine, N-methylpiperidine, N-methylmorpholine (NMM), pyridine, lutidine, collidine, imidazole, 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc. These bases can be used alone or in combination of two or more.
  • DMAP 4-dimethylaminopyridine
  • DABCO 1,4-diazabicyclo[2.2.2]octane
  • DBN 1,5-diazabicyclo[4.3.0]non-5-ene
  • DBU 1,8-diazabicyclo[5.4.0]undec-7-ene
  • the amount of the compound represented by general formula (3) used can be 1.5 to 10.0 equivalents, preferably 2.0 to 5.0 equivalents, in molar ratio relative to the compound represented by general formula (2).
  • the amount of base used can be 0.3 to 3.0 equivalents, preferably 0.5 to 2.0 equivalents, in molar ratio relative to the compound represented by general formula (2).
  • This reaction can be carried out at 0 to 100°C, preferably 10 to 50°C. There is no particular limit to the reaction time, and the reaction can be carried out until completion.
  • the compound represented by formula (4) can be obtained by purifying it in a conventional manner as necessary. Alternatively, the next step can be carried out without purification.
  • the compound represented by general formula (6) can be obtained by coupling the compound represented by general formula (4) with the compound represented by general formula (5).
  • the coupling reaction between the compound represented by general formula (4) and the compound represented by general formula (5) can be carried out in a suitable solvent in the presence of a Lewis acid catalyst according to a conventional method.
  • solvents there are no limitations on the solvent as long as it does not interfere with the reaction, and examples include amide compounds such as N,N-dimethylformamide; ether compounds such as tetrahydrofuran; halogenated aliphatic hydrocarbon compounds such as chloroform and dichloromethane; aromatic hydrocarbon compounds such as toluene and xylene; and nitrile compounds such as acetonitrile.
  • amide compounds such as N,N-dimethylformamide
  • ether compounds such as tetrahydrofuran
  • halogenated aliphatic hydrocarbon compounds such as chloroform and dichloromethane
  • aromatic hydrocarbon compounds such as toluene and xylene
  • nitrile compounds such as acetonitrile.
  • Lewis acid catalysts include aluminum chloride, aluminum bromide, aluminum iodide, iron chloride, gallium chloride, gallium bromide, indium chloride, indium bromide, tin chloride, titanium chloride, zirconium chloride, ruthenium chloride, antimony fluoride, antimony chloride, tungsten chloride, zinc chloride, boron trifluoride, boron trichloride, boron tribromide, niobium chloride, etc. These Lewis acid catalysts can be used alone or in combination of two or more.
  • the amount of the compound represented by general formula (5) used can be 1.0 to 5.0 equivalents, preferably 1.5 to 3.0 equivalents, in molar ratio relative to the compound represented by general formula (4).
  • the amount of the oxidizing agent used can be 1.0 to 5.0 equivalents, preferably 1.5 to 3.0 equivalents, in molar ratio relative to the compound represented by general formula (4).
  • This reaction can be carried out at 30 to 200°C, preferably 40 to 150°C, and particularly preferably under reflux. There is no particular limit to the reaction time, and the reaction can be carried out sufficiently until completion.
  • the amount of acid used can be an excess amount, and can be 5 to 200 equivalents, preferably 10 to 100 equivalents, in molar ratio relative to the compound represented by formula (6).
  • the compound represented by general formula (1) can be obtained by coupling the compound represented by general formula (7) with the compound represented by general formula (8).
  • solvents there are no limitations on the solvent as long as it does not interfere with the reaction, and examples include amide compounds such as N,N-dimethylformamide; ether compounds such as tetrahydrofuran; halogenated aliphatic hydrocarbon compounds such as chloroform and dichloromethane; aromatic hydrocarbon compounds such as toluene and xylene; and nitrile compounds such as acetonitrile.
  • amide compounds such as N,N-dimethylformamide
  • ether compounds such as tetrahydrofuran
  • halogenated aliphatic hydrocarbon compounds such as chloroform and dichloromethane
  • aromatic hydrocarbon compounds such as toluene and xylene
  • nitrile compounds such as acetonitrile.
  • bases examples include triethylamine, diisopropylethylamine, N-methylpyrrolidine, N-methylpiperidine, N-methylmorpholine (NMM), pyridine, lutidine, collidine, imidazole, 4-dimethylaminopyridine (DMAP), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), etc. These bases can be used alone or in combination of two or more.
  • DMAP 4-dimethylaminopyridine
  • DABCO 1,4-diazabicyclo[2.2.2]octane
  • DBN 1,5-diazabicyclo[4.3.0]non-5-ene
  • DBU 1,8-diazabicyclo[5.4.0]undec-7-ene
  • the amount of base used can be 0.5 to 5.0 equivalents, preferably 1.0 to 2.0 equivalents, in molar ratio relative to the compound represented by general formula (7).
  • This reaction can be carried out at 0 to 100°C, preferably 10 to 50°C. There is no particular limit to the reaction time, and the reaction can be carried out until completion.
  • NBR1 1-(4-(4-(3,4-difluorobenzoyl)piperazin-1-yl)-3-fluorophenyl)butan-1-one (NSBR1; BL9) (31 mg, 0.080 mmol) was dissolved in methanol (1 mL) in a 5 mL screw-cap tube equipped with a magnetic stir bar. The mixture was cooled to -10 °C. To the mixture was added a solution of NaBH4 (9.2 mg, 0.24 mmol) in anhydrous methanol ( 0.5 mL). The resulting mixture was stirred at 0 °C for 30 min.
  • Example 2 4-(4-(4-(1-hydroxybutyl)phenyl)piperidine-1-carbonyl)benzene-1,2-diol (compound 17)
  • 1-(4-(piperidin-4-yl)phenyl)butan-1-one hydrochloride (compound 16 ⁇ HCl; a solid obtained by adding 4 M hydrochloric acid ⁇ dioxane solution and methanol to compound 16 obtained in Example 1 was used) (100.3 mg, 0.37 mmol), 3-hydroxybenzoic acid (63.6 mg, 0.46 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCl ⁇ HCl) (109.3 mg, 0.57 mmol), 1-hydroxybenzotriazole (HOBt) (79.3 mg, 0.59 mmol), and diisopropylethylamine (0.26 mL, 1.45 mmol) were dissolved in dimethylformamide (DMF) (2.0 mL).
  • DMF dimethylformamide
  • Test Example 1 Rice Lamina Joint Assay The lamina joint assay was adapted to the bioprotocol. Seeds of Taiwanese rice variety Taichung 65 were grown in a greenhouse by Professor Motoyuki Ashikari and Associate Professor Shiro Miya of the National University Corporation Tokai National Higher Education and Research System. Seeds were vacuum-packed and stored at 4°C before use, and heat-treated at 50°C for 2 days.
  • the husks were removed manually, washed with 70% ethanol, rinsed with sterile distilled water, and sterilized with 20 mL of 5% sodium hypochlorite solution (Fujifilm Wako Pure Chemical Industries, Ltd.) and one drop of Tween 20 (Sigma-Aldrich) for 1 hour by stirring. Seeds were washed again 10 times with sterile distilled water and dried on sterile filter paper in a clean bench. The sterilized seeds were sown in a 1 L glass beaker containing 1/2 MS with 2% water added and the pH adjusted to 5.7, and germinated in a growth chamber (PCBI Japan) at 28°C under long-day conditions (lights on for 16 hours).
  • a growth chamber PCBI Japan
  • Seedlings were harvested on the 8th day and the same length (approximately 8 cm) at the third leaf stage was used for the assay. 2 cm from the second leaf joint was cut with a fresh razor and placed in sterile distilled water for 10 min. Three lamina joint sections were then placed in 55 mM diameter petri dishes containing 10 mL of sterile distilled water containing appropriate concentrations of epiBL (natural brassinosteroids) and brassinosteroid-like compounds diluted from 10 mM stocks in DMSO (Fujifilm Wako Pure Chemicals). An equal volume of DMSO was used as a control. Lamina joint sections were incubated in the dark at 28°C for 2 days with regular agitation before being measured. Photographs of lamina joint sections were taken with a Canon digital camera and analysed using the “measure angle” function in ImageJ 1.53k (NIH USA). The assay was independently repeated three times (total of 9 lamina joint sections per concentration).
  • Test Example 2 Titration of EpiBL and UA1 by Lamina Joint Assay
  • Lamina joint sections were prepared as described above. Appropriate concentrations of EpiBL (natural brassinosteroids) and brassinosteroid-like compounds diluted from 10 mM stocks in DMSO (Fujifilm Wako Pure Chemical Industries, Ltd.) were added to 10 mL of sterile distilled water at the highest concentration. Serial dilutions of 1:10 were made by vortexing the first dilution, removing 1 mL, and adding it to 9 mL of water in the next concentration dish. This was repeated until all dilutions were completed, and the last 1 mL was discarded.
  • DMSO Flujifilm Wako Pure Chemical Industries, Ltd.
  • Test Example 3 Quantitative real-time PCR Hypocotyl elongation assays were performed according to the procedure proposed by Asami et al. Wild-type Arabidopsis (WT) plants were grown in the dark for 7 days on 1/2 MS medium containing 0.8% Phytoagar and 1.5% sucrose. They were immersed in a solution of 0.1% (v/v) DMSO (control), 0.1 ⁇ M EpiBL, 0.1 ⁇ M UA1, 1 ⁇ M UA1, or 10 ⁇ M UA1 for 3 h and prepared in 1/2 MS medium without Phytoagar and sucrose. Plant samples were removed and stored in liquid nitrogen for later RNA extraction.
  • WT Wild-type Arabidopsis
  • Complementary DNA cDNA was synthesized using ReverTra Ace (Toyobo Co., Ltd.) and used for quantitative real-time PCR (qRT-PCR).
  • qRT-PCR was performed using the THUNDERBIRD SYBR qPCR system (Takara) according to the instructions provided with the LightCycler 96 System (Roche Diagnostics).
  • DWARF4 uses 5'-GTGATCTCAGCCGTACATTTGGA-3' and 5'-CACGTCGAAAAACTACCACTTCCT-3'.
  • BR6ox2 uses 5'-CAATAGTCTCAATGACGCAGT-3' and 5'-AACCGCAGCTATGTTG CATG-3';
  • UBQ2 uses 5'-CCAAGATCCAGGACAAAGAAGGA-3' and 5'-TGGAGACGAGC ATAACTTGC-3';
  • ACT2 5'-CGCCATCCAAGCTGTTCTC-3' and 5'-TCACGTCCAGC AAGGTCAAG-3' were used.
  • UBQ2 and ACT2 were used as constitutive expression control genes.
  • UA1 obtained in Example 1 has brassinosteroid-like activity that is comparable to that of EpiBL, a natural brassinosteroid, and it can be understood that it is a compound with significantly higher brassinosteroid-like activity than conventional non-steroidal BRI1 agonist molecules. Furthermore, the compounds obtained in Examples 2 to 4 also had brassinosteroid-like activity equivalent to that of UA1 obtained in Example 1.

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