CN117342990A - Sulfonamide compound, preparation method and application thereof, pesticide preparation and medicament - Google Patents

Sulfonamide compound, preparation method and application thereof, pesticide preparation and medicament Download PDF

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CN117342990A
CN117342990A CN202310812021.2A CN202310812021A CN117342990A CN 117342990 A CN117342990 A CN 117342990A CN 202310812021 A CN202310812021 A CN 202310812021A CN 117342990 A CN117342990 A CN 117342990A
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compound
hydroxy
formula
nmr
amino
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郝格非
张帅
金银
张晓�
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Guizhou University
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Guizhou University
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C07C311/17—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
    • A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
    • A01N41/04—Sulfonic acids; Derivatives thereof
    • A01N41/06—Sulfonic acid amides
    • 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
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • A01N43/38—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A01N47/44—Guanidine; Derivatives thereof
    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/38—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof
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    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C07C311/18—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups
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    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
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    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
    • C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
    • C07C311/39—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C07C311/42—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
    • C07C319/12—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols by reactions not involving the formation of mercapto groups
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    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
    • C07C323/59—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton with acylated amino groups bound to the carbon skeleton
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    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
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Abstract

The invention relates to the field of pesticides, and discloses a sulfonamide compound, a preparation method and application thereof, a pesticide preparation and a medicament; the compound has a structure shown in a formula (I); the sulfonamide compound shown in the formula (I) provided by the invention can obviously enhance the soil emergence capacity of plant seedlings, delay the flowering phase of plants and has higher application value.

Description

Sulfonamide compound, preparation method and application thereof, pesticide preparation and medicament
Technical Field
The invention relates to the field of pesticides, in particular to a sulfonamide compound, a preparation method and application thereof, a pesticide preparation containing the sulfonamide compound and a medicament for enhancing the soil emergence capacity of young plants and/or delaying the flowering phase of the plants.
Background
The seed emergence time influences the emergence rate and uniformity, especially under the condition of soil hardening or adverse stress, the seed can be early subjected to photosynthesis in advance, so that the adaptability to the environment is improved. Seed emergence is primarily dependent on the elongation of the hypocotyl/coleoptile, which is primarily related to the plant's induction of external light. Photomorphogenesis is an important mechanism by which plants rely on light to control plant growth. The plant senses the change of the external photoperiod through various light receptor proteins; the plant light receptor protein family mainly comprises photopigments, cryptomelane, chromotropic 1 and UVR8 proteins. Cryptochrome (CRY) is one of the main members of the plant photoreceptor protein family, is a highly conserved blue light receptor, and can sense external blue light signals so as to regulate and control processes of plant photomorphogenesis, photoperiod flowering, circadian rhythm, and air-hole switching. By regulating and controlling the activity of CRY protein, the photopoietic formation, the photoperiod flowering process, the vegetative growth and the reproductive growth of plants can be effectively regulated and controlled, and the method has important roles in regulating and controlling the growth, the development and the quality of crops. Inhibiting activity of CRY, relieving CRY inhibition of hypocotyl/coleoptile elongation under blue light, and promoting seedling emergence; can inhibit stomatal guard cells, promote stomatal closure, and inhibit transpiration; can also inhibit photoperiod flowering process, delay flowering process, and regulate flowering phase.
The cryptomelane has wide biological activity, and the plant growth regulator using the cryptomelane as target protein has important potential application value. In recent years, there have been groups who have obtained the cryptoanthocyanin inhibitor 3-bromo-7-nitroindazole (3B 7N) by high throughput screening techniques, which are capable of releasing the inhibition of hypocotyl elongation by blue light (see in particular WO2018074554 A1). However, the activity of this compound is not satisfactory and the stability is poor, limiting its application in agriculture.
Therefore, designing and synthesizing compounds to regulate the activity of cryptoanthocyanin, and thus regulating plant photomorphogenesis and growth and development is one of the hot fields of chemical research. The compound for regulating and controlling the photomorphogenesis is developed, so that the uniformity of the seedlings can be better improved by promoting the seedlings to come out of the soil in advance, and the adaptability of the seedlings to the external environment is improved. The research and development of the compound for regulating and controlling the activity of the cryptoanthocyanin can also realize the function of regulating and controlling the flowering phase of plants.
Disclosure of Invention
The invention aims to provide a sulfonamide compound which is used for enhancing the soil emergence capacity of plant seedlings and delaying the flowering phase of plants.
In order to achieve the above object, a first aspect of the present invention provides a sulfonamide compound, or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, a prodrug, a hydrate, a solvate, a metabolite thereof, the compound having a structure represented by formula (I):
wherein, in the formula (I),
R 1 selected from-CH 2 R 5 、-CHR 6 R 7 、-C(R 8 ) 3 Hydroxy-substituted C 3-8 Cycloalkyl of (c);
R 5 is C 2-4 or-L 1 -R a ；
L 1 Is C 1-6 Alkylene group, R a Selected from-CH (OH) CH 2 OH, halogen, amino, C 2-4 Ester and carboxyl groups; or L 1 Is phenylene, R a Selected from carboxyl, hydroxyl and hydroxymethyl; or L 1 is-CH (OH) -, R a Selected from hydroxymethyl, -CH (OH) CH 2 OH；
R 6 、R 7 Each independently selected from substituted or unsubstituted C 1-6 Alkyl, carboxyl, C 2-4 Ester group, -CONH 2 ；
R 6 、R 7 Optionally containing substituents selected from hydroxy, imidazolyl, amino, C 2-4 Ester group, mercapto group, phenyl group, hydroxyphenyl group, indolyl group, -NHC (NH) NH 2 、-CONH 2 、-S-C 1-3 At least one of the alkyl groups of (a);
R 8 selected from hydroxy-substituted C 1-6 Alkyl of (a);
R 2 selected from H, hydroxy, amino, halogen;
R 3 、R 4 each independently selected from H, amino, halogen, hydroxy, -SO 2 NHR 1 Any one of the following.
In a second aspect, the present invention provides a process for preparing a sulfonamide compound of the structure of formula (I), or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, the process comprising: contacting a compound represented by formula (a) with a compound represented by formula (B) in the presence of a solvent;
H 2 N-R 1 (B),
wherein in formula (A), R 3 、R 4 Each independently selected from H, amino, halogen, hydroxy,
In the formula (A) and the formula (B), R 1 、R 2 The definition of (a) corresponds to the definition of the first aspect.
A third aspect of the present invention provides a pesticidal formulation comprising a sulfonamide compound of the first aspect or at least one of a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, and an agrochemically acceptable carrier.
In a fourth aspect the present invention provides the use of the first aspect of the sulfonamide compound or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, for enhancing the soil-out capability of a plant seedling and/or delaying the flowering phase of a plant.
In a fifth aspect, the present invention provides an agent for enhancing the soil emergence ability of young plants and/or delaying the flowering phase of plants, wherein the active ingredient of the agent is at least one of the sulfonamide compound according to the first aspect or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, a prodrug, a hydrate, a solvate, a metabolite thereof, and the content of the active ingredient is 0.1 to 100% by weight based on the total weight of the agent.
The sulfonamide compound shown in the formula (I) provided by the invention can obviously enhance the soil emergence capacity of plant seedlings, delay the flowering phase of plants and has higher application value.
Drawings
FIG. 1 is a length phenotype of the hypocotyl of Arabidopsis thaliana treated with Compound 10 (concentration 5. Mu.M) in test example 1 and after 5 days of room temperature culture in the control (DMSO) with a blue light intensity of 1300lux continuous irradiation.
FIG. 2 is a statistical plot of the length of the hypocotyl of Arabidopsis after 5 days of incubation at room temperature with a blue light intensity of 1300lux for the compound 10 (5. Mu.M concentration) treated Arabidopsis in test example 1 and control (DMSO).
FIG. 3 is a length phenotype of the hypocotyls of Arabidopsis thaliana treated with compounds 21, 22, 30, 32 (5. Mu.M concentration) of test example 1 and control (DMSO) after room temperature incubation for 5 days at a blue light intensity of 400lux continuous irradiation.
FIG. 4 is a statistical plot of the length of the hypocotyl of Arabidopsis treated with compounds 21, 22, 30, 32 (5. Mu.M concentration) of test example 1 and control (DMSO) after incubation at room temperature for 5 days under continuous irradiation at a blue light intensity of 400 lux.
FIG. 5 is a phenotypic chart of the hypocotyl length of Arabidopsis treated with varying concentrations of Compound 10 in test example 2 under continuous irradiation with a blue light intensity of 1300 lux.
FIG. 6 is a statistical plot of the length of the hypocotyl of Arabidopsis treated with varying concentrations of Compound 10 in test example 2 under continuous irradiation at a blue light intensity of 1300 lux.
FIG. 7 is a phenotype plot of the hypocotyl length of 5 days after treatment of wild type Arabidopsis thaliana (Col-0), CRY1 mutant (CRY 1), CRY2 mutant (CRY 2), CRY1-CRY2 double mutant (CRY 1CRY 2), CRY1 overexpressing Arabidopsis thaliana (CRY 1-OX), CRY2 overexpressing Arabidopsis thaliana (CRY 2-OX) at a concentration of 5. Mu.M compound 10 in test example 3 with a continuous irradiation of 1300lux blue light intensity at room temperature.
FIG. 8 is a statistical plot of hypocotyl length of wild-type Arabidopsis thaliana (Col-0), CRY1 mutant (CRY 1), CRY2 mutant (CRY 2), CRY1-CRY2 double mutant (CRY 1CRY 2), CRY1 overexpressing Arabidopsis thaliana (CRY 1-OX), CRY2 overexpressing Arabidopsis thaliana (CRY 2-OX) treated with compound 10 at a concentration of 5. Mu.M in test example 3 after 5 days of room temperature culture at a blue light intensity of 1300lux continuous irradiation.
FIGS. 9a and 9b are graphs showing the specific binding capacity of compounds 10 and 21 to the receptor protein Arabidopsis cryptoanthocyanin AtCRY2 using the micro-thermophoresis (MST) assay in test example 4; wherein,
FIG. 9a is a schematic diagram of MST test results for compound 10 and receptor protein AtCRY 2;
FIG. 9b is a schematic diagram of MST test results of compound 21 and receptor protein AtCRY 2.
FIG. 10 is a graph showing the result of compound 10 in test example 5 for promoting elongation of hypocotyl of mung bean in nutrient soil of 4cm depth; wherein (left) in fig. 10 is a picture of growth of mung bean seedlings in soil, (middle) in fig. 10 is a picture of length of hypocotyl of mung bean seedlings, and (right) in fig. 10 is a statistical picture of length of hypocotyl of mung bean seedlings.
FIG. 11 is a graph showing the result of compound 10 in test example 5 for promoting elongation of hypocotyl of mung bean in nutrient soil at a depth of 6 cm; wherein, (left) in fig. 11 is a growth picture of mung bean seedlings in soil, (middle) in fig. 11 is a mung bean seedling hypocotyl length picture, and (right) in fig. 11 is a mung bean seedling hypocotyl length statistical picture.
FIG. 12 is a graph showing the result of compound 10 in test example 5 for promoting elongation of hypocotyl of mung bean in nutrient soil at a depth of 8 cm; wherein, (left) in fig. 12 is a picture of growth of mung bean seedlings in soil, (middle) in fig. 12 is a picture of length of hypocotyl of mung bean seedlings, and (right) in fig. 12 is a statistical picture of length of hypocotyl of mung bean seedlings.
FIG. 13a is a graph showing the results of test example 6 in which compounds 17, 21 and 22 promote the emergence of wheat seedlings.
FIG. 13b is a statistical plot of the results of compounds 17, 21, 22 in test example 6 to promote the emergence of wheat seedlings.
FIG. 14a is a graph showing the results of compounds 17, 21 and 22 in test example 7 for delaying the flowering phase of Arabidopsis thaliana.
FIG. 14b is a statistical plot of the number of rosette leaves of Arabidopsis treated with compounds 17, 21, 22 in test example 7.
FIG. 14c is a statistical plot of the results of compounds 17, 21, 22 in test example 7 to delay the flowering phase of Arabidopsis.
Detailed Description
The endpoints and any values of the ranges disclosed herein are not limited to the precise range or value, and are understood to encompass values approaching those ranges or values. For numerical ranges, one or more new numerical ranges may be found between the endpoints of each range, between the endpoint of each range and the individual point value, and between the individual point value, in combination with each other, and are to be considered as specifically disclosed herein.
The following terms for the present invention are explained as follows:
in this context, wavy lines in the individual radicalsIndicating the bonding location.
"halogen" includes fluorine, chlorine, bromine, iodine.
“C 2-4 The term "ester group" as used herein means an ester group having a total of 2 to 4 carbon atoms, for example, the group may be Etc.
“C 1-6 The "alkylene group" of (a) represents an alkylene group having 1 to 6 carbon atoms, and the number of carbon atoms may be 1, 2, 3, 4, 5, or 6. For example C 1-6 The alkylene group of (a) may be methylene, ethylene, n-propylene, isopropylene, butylene, pentylene, n-hexylene, etc. For "C 1-4 The alkylene group "of (2) has a similar explanation to this except that the number of carbon atoms is different.
In the present invention, the alkylene group means a residue after an alkane loses two hydrogen atoms, which may be two hydrogen atoms on the same carbon atom, or two hydrogen atoms on different carbon atoms, which may be linear or branched, for example, theThe ethylene group may be-CH 2 CH 2 -or-CH (CH) 3 )-。
In the present invention, "phenylene" may beEtc.
"substituted or unsubstituted C 1-6 The "alkyl group" of (C) represents an alkyl group having 1 to 6 carbon atoms, including C 1-6 Straight chain alkyl, C 1-6 Branched alkyl of (a); the number of carbon atoms may be 1, 2, 3, 4, 5 or 6, and optionally C 1-6 At least one H in the alkyl group of (a) is substituted by a corresponding group as defined herein. For "substituted or unsubstituted C 1-4 The "alkyl group" of (a) has a similar explanation to this except that the number of carbon atoms is different.
"hydroxy-substituted C 3-8 "cycloalkyl" of (C) 3, 4, 5, 6, 7 or 8 cycloalkyl groups having at least one H substituted by a hydroxy group, e.g. the group may beEtc. For "hydroxy-substituted C 3-6 The cycloalkyl group "of (2) has a similar explanation to this except that the number of carbon atoms is different.
"hydroxy-substituted C 1-6 The term "alkyl" as used herein means that at least one H in a straight or branched chain alkyl group having a total of 1 to 6 carbon atoms is replaced by a hydroxyl group, for example, the group may be-CH 2 OH、-CH 2 CH 2 OH、-CH(CH 3 )OH、-CH 2 CH 2 CH 2 OH, and the like. For "hydroxy-substituted C 1-4 The "alkyl group" of (a) has a similar explanation to this except that the number of carbon atoms is different.
In the present invention, "-S-C 1-3 The alkyl group "of (C) may be-SCH 2 CH 2 CH 3 、-SCH 2 CH 3 、-SCH 3 、-SCH(CH 3 ) 2 Etc.
In the present invention, at "-SO ] 2 NHR 1 "wherein R is 1 And R in formula (I) 1 The definitions are the sameSelected from-CH 2 R 5 、-CHR 6 R 7 、-C(R 8 ) 3 Hydroxy-substituted C 3-8 Any one of cycloalkyl groups of (a).
"hydrate" refers to a compound of formula (I) provided by the present invention, which forms a solid or liquid molecular compound by hydration with water, and can be said to be an association formed by water as a solvent molecule. Solid state hydrates contain stoichiometric proportions of water as so-called crystal water, wherein water molecules do not have to be equivalent to their bound state. For example, the hydrate may be a monohydrate, a dihydrate, or the like.
"solvate" refers to an association of one or more solvent molecules with a compound of the invention. Solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, and the like.
"prodrug" refers to a compound of the above general formula (I) provided herein, which may be biologically active or inactive in itself, but may be converted to the corresponding biologically active form (e.g., metabolizing, dissolving or otherwise).
"metabolite" refers to the product of a particular compound or salt thereof by metabolism in a plant. The metabolites of a compound may be identified by techniques well known in the art and their activity may be characterized by employing the assay methods as described herein. Such products may be obtained by oxidation, reduction, hydrolysis, amidization, deamination, esterification, degreasing, enzymatic cleavage, etc. of the administered compound.
As previously described, a first aspect of the present invention provides a sulfonamide compound, or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, the compound having a structure according to formula (I):
wherein, in the formula (I),
R 1 selected from-CH 2 R 5 、-CHR 6 R 7 、-C(R 8 ) 3 Hydroxy-substituted C 3-8 Cycloalkyl of (c);
R 5 is C 2-4 or-L 1 -R a ；
L 1 Is C 1-6 Alkylene group, R a Selected from-CH (OH) CH 2 OH, halogen, amino, C 2-4 Ester and carboxyl groups; or L 1 Is phenylene, R a Selected from carboxyl, hydroxyl and hydroxymethyl; or L 1 is-CH (OH) -, R a Is hydroxymethyl, -CH (OH) CH 2 OH；
R 6 、R 7 Each independently selected from substituted or unsubstituted C 1-6 Alkyl, carboxyl, C 2-4 Ester group, -CONH 2 ；
R 6 、R 7 Optionally containing substituents selected from hydroxy, imidazolyl, amino, C 2-4 Ester group, mercapto group, phenyl group, hydroxyphenyl group, indolyl group, -NHC (NH) NH 2 、-CONH 2 、-S-C 1-3 At least one of the alkyl groups of (a);
R 8 selected from hydroxy-substituted C 1-6 Alkyl of (a);
R 2 selected from H, hydroxy, amino, halogen;
R 3 、R 4 each independently selected from H, amino, halogen, hydroxy, -SO 2 NHR 1 Any one of the following.
Preferably, R 1 Selected from-CH 2 R 5 、-CHR 6 R 7 、-C(R 8 ) 3 Hydroxy-substituted C 3-6 Cycloalkyl of (c); more preferably, R 1 Selected from-CH 2 R 5 、-CHR 6 R 7 、-C(R 8 ) 3 Hydroxyl-substituted cyclohexyl, hydroxyl-substituted cyclopentyl.
Preferably L 1 Is C 1-4 Alkylene group, R a Selected from bromine,Amino, C 2-4 Ester group, -carboxyl group, -CH (OH) CH 2 OH; or L 1 Is phenylene, R a Selected from carboxyl, hydroxyl and hydroxymethyl; or L 1 is-CH (OH) -, R a Selected from hydroxymethyl, -CH (OH) CH 2 OH。
Preferably, R 6 、R 7 Each independently selected from substituted or unsubstituted C 1-4 Alkyl, carboxyl, C 2-4 Ester group, -CONH 2 。
Preferably, R 6 、R 7 Optionally containing substituents selected from hydroxy,Amino, C 2-4 Ester group, mercapto group, phenyl group,/->-NHC(NH)NH 2 、-CONH 2 、-S-C 1-3 At least one of the alkyl groups of (a).
Preferably, R 8 Selected from hydroxy-substituted C 1-4 Alkyl of (a); more preferably-CH 2 OH or-CH 2 CH 2 OH。
Preferably, R 2 Selected from H, hydroxy, amino, bromo.
Preferably, R 3 、R 4 Each independently selected from H, amino, bromo, hydroxy, -SO 2 NHR 1 Any one of the following.
The invention is hereinafter provided in several preferred embodiments to illustrate preferred aspects of the compounds of formula (I) of the invention.
Preferred embodiment 1:
in the case of the formula (I),
R 1 selected from-CH 2 R 5 、-CHR 6 R 7 、-C(R 8 ) 3 Hydroxy-substituted C 3-6 Cycloalkyl of (c);
R 5 is C 2-4 or-L 1 -R a ；
L 1 Is C 1-4 Alkylene group, R a Selected from-CH (OH) CH 2 OH, bromine, amino, C 2-4 Ester and carboxyl groups; or L 1 Is phenylene, R a Selected from carboxyl, hydroxyl and hydroxymethyl; or L 1 is-CH (OH) -, R a Selected from hydroxymethyl, -CH (OH) CH 2 OH；
R 6 、R 7 Each independently selected from substituted or unsubstituted C 1-4 Alkyl, carboxyl, C 2-4 Ester group, -CONH 2 ；
R 6 、R 7 Optionally containing substituents selected from hydroxy,Amino, C 2-4 Ester group, mercapto group, phenyl group, -NHC(NH)NH 2 、-CONH 2 、-S-C 1-3 At least one of the alkyl groups of (a);
R 8 selected from hydroxy-substituted C 1-4 Alkyl of (a);
R 2 selected from H, hydroxy, amino, fluoro, chloro, bromo;
R 3 、R 4 each independently selected from H, amino, fluoro, chloro, bromo, hydroxy, -SO 2 NHR 1 Any one of the following.
Preferred embodiment 2:
in the case of the formula (I),
R 1 selected from-CH 2 R 5 、-CHR 6 R 7 、-C(R 8 ) 3 Hydroxyl-substituted cyclohexyl, hydroxyl-substituted cyclopentyl;
R 5 selected from-COOCH 3 、-CH 2 NH 2 、-CH 2 CH 2 NH 2 、-CH 2 Br、-CH 2 CH 2 Br、-CH 2 (CH 2 ) 2 Br、-CH 2 COOCH 3 、-CH(OH)CH(OH)CH 2 OH、-CH 2 CH(OH)CH 2 OH、-CH(OH)CH 2 OH；
R 6 、R 7 Each independently selected from-CH 3 、-CH(CH 3 )CH 3 、-CH(CH 3 )CH 2 CH 3 、-CH 2 CH(CH 3 )CH 3 、-COOH、-CONH 2 、-CH 2 SH、-CH 2 CH 2 SCH 3 、-CH 2 OH、-CH(OH)CH 3 、-CH 2 (CH 2 ) 3 NH 2 、-COOCH 3 、-COOCH 2 CH 3 、-CH 2 COOCH 3 、-CH 2 CH 2 COOCH 3 、-CH 2 COOCH 2 CH 3 、-CH 2 CH 2 CONH 2 、-CH 2 CONH 2 、
R 8 Selected from-CH 2 OH、-CH 2 CH 2 OH；
R 2 Selected from H, hydroxy, amino, bromo;
R 3 、R 4 each independently selected from H, amino, bromo, hydroxy, -SO 2 NHR 1 Any one of the following.
Preferred embodiment 3:
the sulfonamide compound disclosed by the invention is selected from any one of the following compounds:
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as previously described, the second aspect of the present invention provides a process for preparing a sulfonamide compound of the structure of formula (I), or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, the process comprising: contacting a compound represented by formula (a) with a compound represented by formula (B) in the presence of a solvent;
H 2 N-R 1 (B),
wherein in formula (A), R 3 、R 4 Each independently selected from H, amino, halogen, hydroxy,
In the formula (A) and the formula (B), R 1 、R 2 The definition of (a) corresponds to the definition of the first aspect. The invention is not described in detail herein, and those skilled in the art should not understand the limitation of the invention.
Preferably, the contacting conditions include: the reaction temperature is 0-200 ℃ and the reaction time is 0.5-24h. The contacting in the present invention is preferably performed under stirring conditions, and the stirring speed is not particularly limited in the present invention, and a person skilled in the art may perform the contacting by using known technical means.
Preferably, the solvent is at least one selected from tetrahydrofuran, 1, 4-dioxane, N-dimethylformamide, dimethyl sulfoxide, ethyl acetate, acetone, ethanol, water, dichloromethane, chloroform, and acetonitrile.
Preferably, the solvent is used in an amount of 1 to 100mL relative to 1mmol of the compound represented by the formula (A).
Preferably, the molar ratio of the compound of formula (a) to the compound of formula (B) is 1:0.8-2.4.
The aforementioned preparation method of the present invention may also involve various post-treatment operations known in the art, such as extraction, washing, filtration, column chromatography, recrystallization, etc., to which the present invention is not particularly limited, and those skilled in the art should not understand the limitation of the present invention.
The raw materials involved in the preparation method of the invention can be obtained by synthesis according to the structural formula of the raw materials and combining with the organic synthesis method in the field, and can also be obtained by commercial availability. The following of the invention exemplifies a few processes for the preparation of the starting materials, and the person skilled in the art shall not be construed as limiting the invention.
As previously mentioned, a third aspect of the present invention provides a pesticide formulation comprising a sulfonamide compound of the first aspect or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, and at least one of an agrochemically acceptable carrier.
As previously mentioned, a fourth aspect of the present invention provides the use of a sulfonamide compound according to the first aspect or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, for enhancing the soil emergence capacity of young plants and/or for delaying the flowering phase of plants.
Preferably, the plant is selected from at least one of wheat, peanut, corn, cotton, mung bean, rice, soybean, arabidopsis, sorghum, rape.
As described above, the fifth aspect of the present invention provides an agent for enhancing the soil emergence ability of young plants and/or delaying the flowering phase of plants, the active ingredient of the agent being at least one of the sulfonamide compound of the first aspect or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, a prodrug, a hydrate, a solvate, a metabolite thereof, the active ingredient being contained in an amount of 0.1 to 100% by weight, based on the total weight of the agent.
Preferably, the active ingredient is present in an amount of 5 to 90% by weight. Illustratively, the active ingredient is present in an amount of 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, 55 wt%, 60 wt%, 65 wt%, 70 wt%, 75 wt%, 80 wt%, 85 wt%, etc.
The agent for enhancing the soil emergence ability of young plants and/or delaying the flowering phase of plants of the present invention may further contain various additives and adjuvants commonly used in the art, solvents, etc., and the present invention is not particularly limited thereto.
Preferably, the dosage form of the medicament is selected from at least one of hydration agent, powder, granule, suspending agent and emulsion.
The sulfonamide compound shown in the formula (I) is prepared according to the preparation method provided by the invention. In order to avoid repetition, only some specific methods for preparing the compounds are listed in the examples of the present invention, and the person skilled in the art can obtain the compounds 1 to 53 of the present invention by replacing the raw materials according to the synthesis methods of the listed compounds, and the person skilled in the art should not understand the limitation of the present invention.
The present invention will be described in detail by way of preparation examples and test examples. In the following preparation examples and test examples, all the raw materials used were commercially available products unless otherwise specified.
Unless otherwise specified, room temperature is hereinafter represented as 25.+ -. 3 ℃.
Preparation example 1: preparation of Compound 9
Step 1: into a 100mL single-necked round bottom flask at room temperature was successively added 40mL of thionyl chloride, 0.2mL of N, N-dimethylformamide, 4.96g of sodium anthraquinone-1-sulfonate. Then the reaction system is heated to 80 ℃ to reflux and react for 5 hours. After the reaction, most of the remaining thionyl chloride was removed by using a rotary evaporator, and the remaining mixture was slowly added into ice water to precipitate a large amount of solid matters, which was filtered under reduced pressure and dried to obtain 9, 10-anthracenedione-1-sulfonyl chloride as a yellow solid compound in a yield of 90%.
Step 2: in a 100mL single neck round bottom flask, 20mL of distilled water, 9, 10-anthracenedione-1-sulfonyl chloride (2.0 mmol), L-serine (2.0 mmol), cs were added sequentially 2 CO 3 (2.5 mmol). The reaction was stirred at room temperature for 12 hours. After the reaction was completed, the pH of the solution was adjusted to 3 using a 1.0mol/L hydrochloric acid solution. The target product was extracted with ethyl acetate (20 ml×3 times) and dried over anhydrous sodium sulfate, and purified by column chromatography to give a pale yellow solid in 70% yield.
1 H NMR(400MHz,DMSO-d 6 )δ12.86(s,1H),8.53(dd,1H),8.46(dd,1H),8.33–8.15(m,2H),8.09(t,1H),7.99(ddd,2H),5.22(s,1H),4.02(dt,1H),3.69(ddd,2H),3.35(s,1H). 13 C NMR(101MHz,DMSO-d 6 )δ183.14,182.07,171.56,141.21,135.82,135.56,135.36,135.33,134.89,134.13,132.28,131.67,131.62,127.83,127.02,62.92,59.05.
Preparation example 2: preparation of Compound 10
To a 100mL single-necked round bottom flask, 20mL of 1, 4-dioxane, 2.0mmol of 9, 10-anthracenedione-1-sulfonyl chloride, 2.0mmol of L-serine methyl ester hydrochloride and 1.0mL of triethylamine were successively added, and the mixture was stirred at room temperature for 6 hours. After the reaction was completed, all solvents were removed using a rotary evaporator. To the mixture was added 20mL of saturated brine, and the target product was extracted with ethyl acetate (20 mL. Times.3). The organic layer was collected and dried over anhydrous sodium sulfate, and purified by column chromatography to give a pale yellow solid in 75% yield.
1 H NMR(400MHz,CDCl 3 )δ8.64(dd,1H),8.53(dd,1H),8.35(s,1H),8.32–8.26(m,1H),7.99–7.82(m,4H),4.32(dd,1H),4.05(d,2H),3.53(s,3H),2.29(s,1H). 13 C NMR(101MHz,CDCl 3 )δ181.84,170.10,140.68,135.85,135.26,134.89,134.73,134.12,133.75,132.10,131.98,128.25,127.06,64.05,58.59,52.75.
Preparation example 3: preparation of Compound 47
Step 1: 40mL of thionyl chloride, 0.2mL of N, N-dimethylformamide, 3.55g of dipotassium anthraquinone-1, 8-disulfonate and then heating to 80 ℃ for reflux reaction for 5 hours are sequentially added into a 100mL single-neck round-bottom flask at room temperature. After the reaction, the vast majority of the residual thionyl chloride is removed by using a rotary evaporator, and the residual mixture is slowly added into ice water to separate out a large amount of solid matters, and the yellow solid compound is obtained by decompression, filtration and drying, wherein the yield is 85 percent.
Step 2: into a 100mL single-necked round bottom flask, 20mL of 1, 4-dioxane, 2.0mmol of anthraquinone-1, 8-disulfonyl chloride, 4.4mmol of L-serine methyl ester hydrochloride and 2mL of triethylamine were successively added, and the reaction was stirred at room temperature for 6 hours. After the reaction was completed, all solvents were removed using a rotary evaporator. To the mixture was added 20mL of saturated brine, and the target product was extracted with ethyl acetate (20 mL. Times.3). The organic layer was collected and dried over anhydrous sodium sulfate, and the filtrate was dried under reduced pressure and purified by column chromatography to give a reddish brown solid.
1 H NMR(400MHz,DMSO-d 6 )δ8.46(ddd,4H),8.08(t,2H),7.24(t,2H),4.32(m,2H),4.05(m,4H),3.53(s,6H). 13 C NMR(101MHz,DMSO-d 6 )δ184.55,181.20,140.90,136.09,135.07,134.58,133.24,131.07,64.08,58.62,52.78.
Other compounds of the invention can be prepared by adopting a method similar to the preparation example, and adjusting the raw materials and the process conditions according to the characteristic adaptability of the structural formula. The nuclear magnetic data are respectively:
compound 1:
1 H NMR(400MHz,DMSO-d 6 )δ8.54-8.52(dd,1H),8.50-8.47(dd,1H),8.20-8.17(m,2H),8.14-8.10(t,1H),7.99-7.95(m,2H),3.19(t,2H),2.92(t,2H). 13 C NMR(101MHz,DMSO-d 6 )δ182.23,181.59,139.92,135.79,135.36,134.98,134.71,134.29,133.87,131.95,131.66,131.30,127.01,126.56,40.60,38.93.
compound 2:
1 H NMR(400MHz,DMSO-d 6 )δ8.50-8.47(ddd,2H),8.16(td,2H),8.10(t,1H),7.94(m,2H),7.20(q,1H),4.92(d,1H),4.62(t,1H),3.46(m,1H),3.27(m,1H),3.19(m,2H),2.83(m,1H). 13 C NMR(101MHz,DMSO-d 6 )δ182.88,181.61,140.19,135.76,135.48,134.96,134.75,134.33,133.87,131.91,131.48,131.22,127.21,126.50,69.60,63.54,46.66.
compound 3:
1 H NMR(400MHz,DMSO-d 6 )δ8.50-8.47(ddd,2H),8.16(td,2H),8.10(t,1H),7.94(m,2H),7.20(q,1H),4.92(d,1H),4.62(t,1H),3.46(m,1H),3.27(m,1H),3.19(m,2H),2.83(m,1H). 13 C NMR(101MHz,DMSO-d 6 )δ182.88,181.61,140.19,135.76,135.48,134.96,134.75,134.33,133.87,131.91,131.48,131.22,127.21,126.50,69.60,63.54,46.66.
compound 4:
1 H NMR(400MHz,CDCl 3 )δ9.88(s,1H),8.27–8.16(m,2H),7.72(m,2H),7.62(dd,1H),7.58–7.52(m,1H),7.02(d,1H),4.37(q,2H),3.88(t,2H). 13 C NMR(101MHz,CDCl 3 )δ185.37,183.43,150.36,135.64,134.05,133.29,126.83,126.76,116.86,116.56,66.61,37.37.
compound 5:
1 H NMR(600MHz,DMSO-d 6 )δ8.55–8.50(m,2H),8.21(ddd,2H),8.10(t,1H),8.01–7.95(m,2H),7.15(d,1H),4.66(s,2H),3.40(m,3H),3.32–3.28(m,2H). 13 C NMR(151MHz,DMSO-d 6 )δ183.21,182.24,141.98,136.10,135.46,135.39,135.25,134.82,134.38,132.40,131.53,127.76,126.96,60.66,57.89.
compound 6:
1 H NMR(400MHz,DMSO-d 6 )δ8.68–8.56(m,2H),8.29(s,2H),8.18(s,1H),8.07(s,2H),4.70(s,3H),3.59(d,6H). 13 C NMR(101MHz,DMSO-d 6 )δ183.33,182.24,144.40,135.69,135.43,135.21,134.81,134.75,134.42,132.39,131.21,131.14,127.75,126.93,65.16,61.63.
compound 7:
1 H NMR(400MHz,CDCl 3 )δ8.58(dd,1H),8.49(dd,1H),8.35–8.24(m,1H),8.24–8.16(m,1H),7.90(t,1H),7.86–7.74(m,3H),4.27(dd,1H),4.00(q,2H),3.93(m,2H),2.66(s,1H),1.01(t,3H). 13 CNMR(101MHz,CDCl 3 )δ183.36,181.87,169.67,140.72,135.78,135.30,134.90,134.70,134.07,133.80,132.02,131.94,131.82,128.18,127.01,64.05,62.01,58.73,13.90.
compound 8:
1 H NMR(400MHz,CDCl 3 )δ8.64(dd,1H),8.53(dd,1H),8.35(s,1H),8.32–8.26(m,1H),7.99–7.82(m,4H),4.32(dd,1H),4.05(d,2H),3.53(s,3H),2.29(s,1H). 13 C NMR(101MHz,CDCl 3 )δ181.84,170.10,140.68,135.85,135.26,134.89,134.73,134.12,133.75,132.10,131.98,128.25,127.06,77.04,64.05,58.59,52.75.
compound 11:
1 H NMR(600MHz,DMSO-d 6 )δ8.51(t,2H),8.23–8.16(m,2H),8.10(t,1H),7.97(dt,2H),7.13(d,1H),4.53–4.31(m,1H),3.59–3.51(m,1H),3.25(m,1H),1.67(m,2H),1.35–1.26(m,1H),1.12–1.03(m,1H). 13 C NMR(101MHz,DMSO)δ183.71,183.33,182.05,142.16,136.38,135.55,135.37,135.22,134.85,134.48,132.53,131.79,131.54,127.60,126.96,67.95,64.58,52.95,51.96,34.07,31.31,28.31.
compound 12:
1 H NMR(400MHz,DMSO-d 6 )δ8.41(d,1H),8.35(d,1H),8.17(t,2H),8.05–7.87(m,3H),7.78(t,1H),7.04(d,2H),6.91(d,2H),5.31–4.75(m,1H),4.26(s,2H),4.17(d,2H). 13 C NMR(101MHz,DMSO-d 6 )δ182.76,182.02,141.76,136.00,135.72,135.39,135.09,134.52,134.33,132.25,131.51,131.15,128.03,127.55,126.89,126.53,62.89,47.07.
compound 13:
1 H NMR(400MHz,DMSO-d 6 )δ8.53(dd,1H),8.46(dd,1H),8.30–8.23(m,1H),8.21(dd,1H),8.10(t,1H),7.99(ddd,2H),7.52(d,1H),7.36(s,1H),7.06(s,1H),5.03(t,1H),3.95–3.81(m,1H),3.61(m,1H),3.51(m,1H). 13 C NMR(101MHz,DMSO-d 6 )δ182.89,182.11,170.88,141.01,135.83,135.54,135.47,135.29,134.78,134.20,132.26,131.71,131.64,127.85,126.99,63.25,59.24.
compound 14:
1 H NMR(400MHz,CDCl 3 )δ8.60(d,1H),8.51(d,1H),8.38–8.28(m,1H),8.28–8.13(m,1H),7.92(s,1H),7.88–7.75(m,2H),7.48(t,1H),4.06(s,2H),3.52(s,3H). 13 C NMR(101MHz,CDCl 3 )δ183.62,181.85,169.62,140.83,135.77,135.30,134.85,134.85,134.70,134.12,133.76,132.10,131.85,128.10,127.04,52.38,44.96.
compound 15:
1 H NMR(400MHz,CDCl 3 )δ8.59(dd,1H),8.50(dd,1H),8.36–8.28(m,1H),8.28–8.22(m,1H),7.91(t,1H),7.87–7.79(m,2H),7.50(s,1H),4.29(q,1H),3.41(s,3H),1.50(d,3H). 13 C NMR(101MHz,CDCl 3 )δ183.46,181.84,172.43,141.04,135.75,135.26,134.86,134.69,134.15,133.71,132.09,131.78,128.14,127.03,52.47,52.33,19.79.
compound 16:
1 H NMR(400MHz,CDCl 3 )δ8.61(ddd,2H),8.36–8.23(m,2H),7.96(t,1H),7.90–7.78(m,2H),3.62(s,3H),3.39(q,2H),2.62(t,2H). 13 C NMR(101MHz,CDCl 3 )δ183.91,181.89,172.04,140.95,136.05,135.98,134.95,134.78,134.30,133.96,132.12,131.99,128.18,127.12,52.02,39.32,34.41.
compound 17:
1 H NMR(400MHz,CDCl 3 )δ8.70–8.55(m,1H),8.55–8.41(m,1H),8.38–8.31(m,1H),8.31–8.24(m,1H),7.91(t,1H),7.88–7.80(m,2H),7.73(d,1H),4.40–4.25(m,1H),4.15(dd,1H),3.42(s,3H),2.07(s,1H),1.41(d,3H). 13 C NMR(101MHz,CDCl 3 )δ183.38,181.90,170.61,140.94,135.74,135.05,134.88,134.69,134.16,133.69,132.11,131.83,131.80,128.24,127.04,68.50,62.02,52.47,20.08.
compound 18:
1 H NMR(400MHz,DMSO-d 6 )δ8.48(dd,1H),8.26(dd,1H),8.13(m,2H),8.00–7.79(m,3H),3.66(s,3H),3.09(m,3H),1.19(m,,4H). 13 C NMR(101MHz,DMSO-d 6 )δ182.67,182.04,172.99,171.64,141.08,135.82,135.60,135.56,135.31,134.81,134.17,132.35,131.72,131.65,127.65,127.07,55.85,52.46,51.84,29.69,27.26.
compound 19:
1 H NMR(600MHz,DMSO-d 6 )8.49(t,2H),8.38(d,1H),8.27(s,1H),8.15(m,2H),8.07(t,1H),7.90-7.98(m,4H),7.43(t,1H),4.48(dd,1H),3.36(s,3H),3.04(m,2H). 13 C NMR(101MHz,DMSO-d 6 )δ182.26,181.39,170.87,138.84,138.32,134.95,134.77,134.31,133.57,132.73,131.92,131.16,127.14,126.96,126.61,117.04,55.90,52.07,30.27.
compound 20:
1 H NMR(400MHz,CDCl 3 )δ8.61(ddd,3H),8.42(dd,1H),8.34–8.28(m,2H),7.95(t,1H),7.88(t,1H),4.11(m,5.0Hz,1H),3.33(s,3H),3.11(d,2H),1.87–1.75(m,1H),1.75–1.65(m,1H),1.59(dt,4H),1.51(dd,2H). 13 C NMR(101MHz,CDCl 3 )δ184.29,183.43,181.80,171.72,140.88,140.73,136.12,135.17,134.86,134.80,134.31,133.90,133.67,128.14,127.02,77.06,56.39,52.25,43.40,32.78,29.21,22.30.
compound 21:
1 H NMR(400MHz,DMSO-d 6 )δ8.55(dd,1H),8.47(dd,1H),8.27–8.20(m,2H),8.11(t,1H),8.06–7.94(m,3H),4.49(d,1H),3.53(s,3H),3.33(s,2H),2.90(d,2H). 13 C NMR(101MHz,DMSO-d 6 )δ182.92,182.01,171.01,170.84,141.32,135.87,135.53,135.45,135.36,134.88,134.15,132.41,131.69,131.52,127.68,127.07,53.29,52.76,52.19,37.34.
compound 22:
1 H NMR(400MHz,DMSO-d 6 )δ8.54(d,1H),8.43(d,1H),8.23(ddd,2H),8.10(t,1H),8.00(td,2H),7.89(d,1H),4.12(m,1H),3.55(s,3H),3.30(s,3H),2.42(t,2H),2.13–1.86(m,2H). 13 C NMR(101MHz,DMSO-d 6 )δ182.67,182.04,172.99,171.64,141.08,135.82,135.60,135.56,135.31,134.81,134.17,132.35,131.72,131.65,127.65,127.07,55.85,52.46,51.84,29.69,27.26.
compound 23:
1 H NMR(400MHz,DMSO-d 6 )δ8.55(dd,1H),8.47(dd,1H),8.24(m,2H),8.11(t,1H),8.03(m,3H),4.45(d,1H),3.53(s,3H),3.13(m,2H),2.67(d,2H). 13 C NMR(101MHz,DMSO-d 6 )δ182.82,182.05,171.11,169.84,141.22,135.86,135.52,135.44,135.39,134.88,134.15,132.41,131.59,131.42,127.61,127.02,53.29,52.09,37.24.
compound 24:
1 H NMR(400MHz,DMSO-d 6 )δ8.54(d,1H),8.45(d,1H),8.23(m,2H),8.08(t,1H),7.98(m,2H),7.89(d,1H),4.15(m,1H),3.45(s,3H),2.18(t,2H),2.05(m,2H). 13 C NMR(101MHz,DMSO-d 6 )δ182.66,182.08,173.84,171.54,141.02,135.80,135.61,135.53,135.31,134.79,134.27,132.31,131.62,131.65,127.65,127.07,55.85,51.89,33.12,26.26.
compound 25:
1 H NMR(400MHz,DMSO-d 6 )δ8.54(m,1H),8.40(m,1H),8.24(m,2H),8.10(t,1H),8.01(m,2H),7.62(d,1H),4.28(m,1H),3.62(s,3H),3.29(m,2H). 13 C NMR(101MHz,DMSO-d 6 )δ183.25,181.81,171.42,140.65,135.91,135.67,135.49,135.44,134.95,134.15,132.37,131.89,131.70,127.75,127.09,64.12,58.62,25.86.
compound 26:
1 H NMR(400MHz,DMSO-d 6 )δ8.54(dd,1H),8.45(dd,1H),8.23(ddd,2H),8.10(t,1H),8.05–7.94(m,2H),7.91(d,1H),4.22(m,1H),3.32(s,3H),2.54(d,1H),2.49–2.39(m,1H),1.98(m,5H). 13 CNMR(101MHz,DMSO-d 6 )δ182.68,182.03,171.83,141.18,135.85,135.63,135.53,135.29,134.79,134.20,132.39,131.70,127.63,127.07,55.54,52.47,31.57,29.78,14.88.
compound 27:
1 H NMR(400MHz,DMSO-d 6 )δ8.55(dd,1H),8.44(dd,1H),8.27–8.20(m,2H),8.11(t,1H),8.04–7.96(m,2H),7.62(d,1H),3.66–3.55(m,1H),3.26(s,3H),2.15–2.02(m,1H),0.90(dd,6H). 13 C NMR(101MHz,DMSO-d 6 )δ183.30,181.88,171.46,140.61,135.93,135.57,135.49,135.44,134.95,134.15,132.37,131.89,131.70,127.75,127.09,62.29,52.28,31.11,19.19,18.36.
compound 28:
1 H NMR(400MHz,DMSO-d 6 )δ8.55(dd,1H),8.43(dd,1H),8.27–8.20(m,2H),8.10(t,1H),8.04–7.96(m,2H),7.62(d,1H),3.62(m,1H),3.25(s,3H),2.14(m,1H),1.55(m,2H),1.11(d,3H),0.99(t,3H). 13 C NMR(101MHz,DMSO-d 6 )δ183.30,181.88,171.46,140.61,135.93,135.57,135.49,135.44,134.95,134.15,132.37,131.89,131.70,127.75,127.09,62.28,52.20,35.40,25.12,15.14,11.34.
compound 29:
1 H NMR(400MHz,DMSO-d 6 )δ8.54(dd,1H),8.45(dd,1H),8.28–8.17(m,2H),8.10(t,1H),8.05–7.95(m,2H),7.77(d,1H),4.06(d,1H),3.24(s,3H),1.71(s,2H),1.46(s,1H),0.85(dd,6H). 13 C NMR(101MHz,DMSO-d 6 )δ182.76,181.98,172.34,141.09,135.80,135.54,135.31,134.81,134.17,132.34,131.72,127.66,127.06,55.29,52.28,24.39,23.03,21.42.
compound 30:
1 H NMR(400MHz,DMSO-d 6 )δ8.46(dd,1H),8.27(dd,1H),8.23–8.16(m,2H),8.02–7.97(m,3H),7.77(d,1H),7.05(dd,2H),6.97–6.87(m,3H),4.27(m,1H),3.46(s,3H),3.08–2.92(m,2H). 13 CNMR(101MHz,DMSO-d 6 )δ182.22,181.99,171.69,140.74,136.64,135.82,135.52,135.30,135.26,134.71,134.07,132.21,131.48,130.96,129.57,128.39,127.65,126.98,126.90,58.27,52.52,37.60.
compound 31:
1 H NMR(400MHz,DMSO-d 6 )δ8.44(dd,1H),8.22(dd,1H),8.21(m,2H),8.01(m,3H),7.77(d,1H),7.05(dd,2H),6.97–6.87(m,3H),4.23(t,1H),3.66(s,3H),3.18(m,2H). 13 C NMR(101MHz,DMSO-d 6 )δ182.32,181.84,171.59,155.72,140.64,136.64,135.71,135.52,135.30,135.26,134.71,134.07,132.21,131.48,130.26,128.39,127.65,126.80,58.27,52.52,37.60.
compound 32:
1 H NMR(400MHz,DMSO-d 6 )δ10.57(d,1H),8.30(dd,1H),8.16(ddd,2H),8.09–8.05(m,1H),8.00–7.93(m,2H),7.83(t,1H),7.38(d,1H),7.12–7.02(m,2H),6.79–6.69(m,2H),6.58(ddd,1H),4.39–4.13(m,1H),3.60(s,3H),3.21–3.01(m,2H). 13 C NMR(101MHz,DMSO-d 6 )δ181.73,181.52,172.15,139.35,136.18,135.34,135.12,134.94,134.20,133.73,132.13,131.49,130.30,127.56,126.84,126.75,125.50,121.37,118.90,117.97,111.69,108.10,57.18,52.63,28.14.
compound 33:
1 H NMR(400MHz,DMSO-d 6 )δ8.50-8.45(m,2H),8.14(m,2H),8.10(t,1H),7.94(m,2H),7.20(q,1H),4.92(d,1H),4.62(t,1H),3.62-3.45(m,6H),3.40(m,1H),3.27(m,1H). 13 C NMR(101MHz,DMSO-d 6 )δ182.82,181.51,140.18,135.72,135.41,134.92,134.78,134.31,133.77,131.99,131.58,131.21,127.21,126.50,75.61,73.32,63.81,42.15.
compound 34:
1 H NMR(400MHz,DMSO-d 6 )δ8.50-8.42(m,2H),8.13(m,2H),8.08(t,1H),7.95(m,2H),7.16(q,1H),3.60(m,2H),3.55(m,1H),3.16(t,2H),1,68(m,2H). 13 C NMR(101MHz,DMSO-d 6 )δ182.81,181.55,140.12,135.75,135.47,134.92,134.78,134.31,133.87,131.90,131.51,131.26,127.21,126.54,71.21,66.25,36.64,31.54.
compound 35:
1 H NMR(400MHz,DMSO-d 6 )δ8.51(dd,1H),8.46(dd,1H),8.20(m,2H),8.14(d,2H),8.09(t,1H),6.95(d,2H),6.71(d,2H),3.96(s,2H). 13 C NMR(101MHz,DMSO-d6)δ182.28,182.15,156.55,141.08,136.25,135.68,135.57,135.23,134.74,134.42,131.05,130.57,130.04,128.12,127.09,115.81,46.13.
compound 36:
1 H NMR(400MHz,DMSO-d 6 )δ8.52(dd,1H),8.47(dd,1H),8.23–8.16(m,2H),8.15(d,2H),8.10(t,1H),7.97(m,2H),7.50(t,1H),7.37(d,2H),4.02(s,2H). 13 C NMR(101MHz,DMSO-d6)δ182.28,182.05,168.28,146.82,141.08,136.25,135.68,135.47,135.13,134.74,132.42,132.05,131.57,130.14,128.22,127.49,126.94,126.81,46.22.
compound 37:
1 H NMR(400MHz,DMSO-d 6 )δ8.52(dd,1H),8.47(dd,1H),8.23–8.16(m,2H),8.10(t,1H),7.97(m,2H),7.50(t,1H),3.48(t,2H),3.07(q,2H),1.96(m,2H). 13 C NMR(101MHz,DMSO-d6)δ182.25,182.11,141.06,136.21,135.78,135.42,135.13,134.74,132.42,132.05,131.57,127.49,126.99,42.05,39.94,32.93,32.32.
compound 38:
1 H NMR(400MHz,CDCl 3 )δ8.66–8.56(m,2H),8.32–8.24(m,2H),7.95(t,1H),7.90–7.81(m,2H),6.78(t,1H),3.39(t,2H),3.15(q,2H),1.92(m,2H),1.70(m,2H). 13 C NMR(101MHz,CDCl 3 )δ184.26,181.72,140.86,136.11,135.90,134.88,134.77,134.20,133.95,132.05,132.01,131.86,127.96,127.07,77.10,42.77,33.00,29.53,28.39.
compound 39:
1 H NMR(400MHz,CDCl 3 )δ8.29(dd,2H),7.94(d,1H),7.85 -7.78(m,2H),7.34(d,1H),6.27(br,2H),4.34(dd,1H),4.08(d,2H),3.54(s,3H),2.32(s,1H). 13 C NMR(101MHz,CDCl 3 )δ185.7,182.1,171.2,154.1,137.6,137.2,133.6,133.4,132.1,132.4,131.5,126.8,126.5,120.1,112.9,64.1,58.5,52.6.
compound 40:
1 H NMR(400MHz,CDCl 3 )δ8.12-8.20(m,2H),7.89(d,1H),7.31-7.40(m,2H),6.84(d,1H),4.36(dd,1H),4.10(d,2H),3.50(s,3H),2.30(s,1H). 13 C NMR(101MHz,CDCl 3 )δ182.1,182.0,171.5,150.9,136.4,134.2,134.4,133.9,132.4,130.0,127.0,123.4,112.6,116.8,64.1,58.5,52.7.
compound 41:
1 H NMR(400MHz,CDCl 3 )δ8.29-8.25(m,2H),8.08(d,1H),7.98(d,1H),7.85 -7.78(m,2H),4.34(dd,1H),4.08(d,2H),3.54(s,3H),2.32(s,1H). 13 C NMR(101MHz,CDCl 3 )δ182.4,182.1,171.5,139.8,138.6,135.3,133.6,133.4,132.8,132.1,126.8,126.7,125.6,64.1,58.5,52.6.
compound 42:
1 H NMR(400MHz,CDCl 3 )δ8.20(d,2H),8.08(d,1H),7.89(d,1H),7.83(m,1H),7.61(dd,1H),4.34(dd,1H),4.08(d,2H),3.54(s,3H). 13 C NMR(101MHz,CDCl 3 )δ182.4,182.1,171.4,141.2,136.4,134.4,133.9,133.1,132.8,132.4,127.0,125.8,122.4,64.2,58.5,52.6.
compound 43:
1 H NMR(400MHz,CDCl 3 )δ8.29-8.26(m,2H),7.92(d,1H),7.85 -7.78(m,2H),7.35(d,1H)4.35(dd,1H),4.05(d,2H),3.51(s,3H),2.30(s,1H). 13 C NMR(101MHz,CDCl 3 )δ182.3,182.1,171.5,165.1,137.8,133.6,133.4,132.1,131.8,131.6,126.8,126.3,122.3,119.6,64.1,58.5,52.6.
compound 44:
1 H NMR(400MHz,CDCl 3 )δ8.20(d,1H),8.09(d,1H),8 7.85 -7.74(m,2H),7.65(dd,1H),7.06(d,1H),4.38(dd,1H),4.10(d,2H),3.52(s,3H),2.35(s,1H). 13 C NMR(101MHz,CDCl 3 )δ182.4,182.1,161.9,140.8,136.4,136.2,133.9,133.1,132.4,130.0,127.0,124.1,116.3,64.2,58.4,52.6.
compound 45:
1 H NMR(400MHz,DMSO-d 6 )δ8.50(d,2H),8.44(d,2H),8.06(t,2H),6.84(s,2H),4.70(s,4H),3.38(d,8H),3.25(m,2H). 13 C NMR(101MHz,DMSO-d 6 )δ184.79,181.75,141.88,135.56,134.39,134.32,133.21,130.83,60.79,58.47.
compound 46:
1 H NMR(400MHz,DMSO-d 6 )δ8.50(d,2H),8.44(d,2H),8.06(t,2H),6.84(s,2H),4.61(s,6H),3.52(s,12H). 13 C NMR(101MHz,DMSO-d 6 )δ184.79,181.75,141.88,135.56,134.39,134.32,133.21,130.83,61.62,58.40.
compound 48:
1 H NMR(400MHz,DMSO-d 6 )δ8.52(d,2H),8.47(d,2H),8.02(t,2H),6.85(s,2H),4.35(m,2H),4.15(m,2H),3.64(s,6H),1.16(d,6H). 13 C NMR(101MHz,DMSO-d 6 )δ184.55,181.20,140.90,136.09,135.07,134.58,133.24,131.07,63.82,58.62,52.72,19.41.
compound 49:
1 H NMR(400MHz,DMSO-d 6 )δ8.46(m,4H),8.09(t,2H),7.25(t,2H),4.28(m,2H),3.62(s,6H),3.29(m,4H). 13 C NMR(101MHz,DMSO-d 6 )δ184.55,181.20,140.90,136.09,135.07,134.58,133.24,131.07,64.12,58.62,25.86.
compound 50:
1 H NMR(400MHz,DMSO-d 6 )δ8.46(m,4H),8.19(t,2H),7.28(t,2H),4.12(m,2H),3.69(s,6H),2.65(t,4H),2.17(m,4H). 13 C NMR(101MHz,DMSO-d 6 )δ184.55,181.20,140.90,136.09,135.07,134.58,133.24,131.07,55.21,51.92,30.15,29.72,15.44.
compound 51:
1 H NMR(400MHz,DMSO-d 6 )δ8.46(m,4H),8.09(t,2H),7.25(t,2H),4.70(s,4H),3.38(d,8H),3.25(m,2H). 13 C NMR(101MHz,DMSO-d 6 )δ182.55,141.45,136.92,135.28,135.13,131.76,130.31,60.88,58.51.
compound 52:
1 H NMR(400MHz,DMSO-d 6 )δ8.46(m,4H),8.09(t,2H),7.25(t,2H),4.28(m,2H),3.62(s,6H),3.29(m,4H). 13 C NMR(101MHz,DMSO-d 6 )δ182.55,140.90,136.09,135.07,134.58,133.24,131.07,64.12,58.62,25.86.
compound 53:
1 H NMR(400MHz,DMSO-d 6 )δ8.46(m,4H),8.08(t,2H),7.24(t,2H),4.35(m,2H),4.15(m,2H),3.64(s,6H),1.16(d,6H). 13 C NMR(101MHz,DMSO-d 6 )δ182.58,140.95,136.19,135.20,134.68,133.34,131.17,63.82,58.62,52.72,19.41.
test example 1
This test example is for explaining the inhibitory activity of the sulfonamide compound having the structure represented by formula (I) against the elongation of the hypocotyl by blue light.
Preliminary screening test (MS medium method):
the plants were examined as wild type (Columbia type, col-0) Arabidopsis thaliana.
Culturing sterilized and vernalized Arabidopsis thaliana seeds in an illumination incubator under the culture conditions of 23 ℃ and 16 hours of illumination and 8 hours of darkness, and transferring for standby after the Arabidopsis thaliana seeds germinate and are exposed to white.
Compounds 1 to 53 were added to the MS medium at a final concentration of 5 μm, respectively, and the above compounds were all dissolved using DMSO and tested with 0.5% (volume fraction) DMSO added to the medium, while the blank was the MS medium containing 0.5% (volume fraction) DMSO. And selecting Arabidopsis seedlings with consistent growth vigor, transplanting, vertically placing the Arabidopsis seedlings into an incubator for culture after transplanting, and collecting phases after growing for 5 days under the conditions that the temperature is 23 ℃ and the illumination intensity is 1300lux or 400lux of continuous blue light respectively.
Illustratively, a hypocotyl length phenotype map of seedlings of compound 10 treated arabidopsis and a blank under blue light (1300 lux) irradiation is given in fig. 1; in FIG. 2, a statistical plot of hypocotyl length of seedlings of Arabidopsis thaliana treated with Compound 10 and a blank under blue light irradiation is given. In FIG. 3, there are shown graphs of hypocotyl length of seedlings of Arabidopsis thaliana treated with Compound 21, compound 22, compound 30, compound 32, and a blank under blue light (400 lux) irradiation; in FIG. 4, there is shown a statistical plot of hypocotyl length of seedlings of Arabidopsis treated with Compound 21, compound 22, compound 30, compound 32 and a blank under blue light irradiation. As can be seen from fig. 1 to 4, the compound 10, the compound 21, the compound 22, the compound 30, the compound 32 are capable of promoting the elongation of hypocotyls and enhancing the soil emergence ability of young plants, compared with the control group.
The hypocotyl length of each Arabidopsis seedling was measured using ImageJ-2x software, the average value of the hypocotyl length of the total number of seedlings on the culture dish was calculated, and the ratio of the hypocotyl length of the experimental group (treated with the compound of the structure shown in formula (I)) to that of the control group was calculated, and the results are shown in Table 1.
The calculating method of the hypocotyl length ratio comprises the following steps:
table 1. Experimental results (Arabidopsis hypocotyl length ratio) of compounds 1 to 53 to release the inhibition of hypocotyl elongation by blue light (400 lux).
From the results shown in Table 1, the sulfonamide compound having the structure shown in formula (I) provided by the invention can effectively relieve the inhibitory activity of cryptosporidium under blue light on hypocotyl elongation.
Test example 2:
experimental methods for treatment of arabidopsis thaliana with different concentrations of compound 10:
examining the plants as wild type (Columbia type, col-0) Arabidopsis thaliana;
culturing sterilized and vernalized Arabidopsis thaliana seeds in an illumination incubator under the culture conditions of 23 ℃ and 16 hours of illumination and 8 hours of darkness, and transferring for standby after the Arabidopsis thaliana seeds germinate and are exposed to white.
Compound 10 was tested by adding to MS medium at final concentrations of 5 μm, 2.5 μm, 1 μm, 0.1 μm, respectively, and 0 μm was the control (0.5% DMSO in volume). After the seedling transplanting is completed, the seedling is sealed, vertically placed into an incubator with continuous blue light (the blue light intensity is 1300 lux) and at 23 ℃ for cultivation, and subjected to phase picking after 5 days of growth.
The length pictures of hypocotyls of control (DMSO) and compound 10 treated arabidopsis at various concentrations at a blue light intensity of 1300lux are given in fig. 5, and the length statistics of hypocotyls of arabidopsis after compound 10 treatment are given in fig. 6. As can be seen from fig. 5 and 6, the ability of compound 10 to release cryptoanthocyanin to inhibit hypocotyl elongation is concentration dependent.
Test example 3
Compound 10 experimental methods for treating wild type arabidopsis thaliana, CRY1 mutant, CRY2 mutant, CRY1-CRY2 double mutant, CRY1 overexpressed arabidopsis thaliana, CRY2 overexpressed arabidopsis thaliana:
examining the plants as wild type (Columbia type, col-0), mutant (CRY 1 mutant, CRY2 mutant, CRY1-CRY2 double mutant), CRY1 over-expression (CRY 1-OX), CRY2 over-expression (CRY 2-OX) Arabidopsis thaliana;
culturing sterilized and vernalized Arabidopsis thaliana seeds in an illumination incubator under the culture conditions of 23 ℃ and 16 hours of illumination for 8 hours in the dark, and grafting for standby after the Arabidopsis thaliana seeds germinate and are exposed to white.
Compound 10 was tested by adding it to MS medium at a final concentration of 5 μm and the blank was 0.5% volume fraction in DMSO in water. After the seedling transplanting is completed, the seedling is sealed, vertically placed into an incubator with continuous blue light (the blue light intensity is 1300 lux) and at 23 ℃ for cultivation, and subjected to phase picking after 5 days of growth.
In fig. 7 and 8, length pictures (fig. 7) and length statistics (fig. 8) of hypocotyls of wild type arabidopsis thaliana and cryptoanthocyanin mutant plants treated with the compound 10 under continuous irradiation with blue light intensity of 1300lux are shown, and it can be seen from fig. 7 and 8 that the compound 10 targets plant cryptoanthocyanin proteins, thereby regulating and controlling the elongation of hypocotyls.
Test example 4
Microphoresis (MST): in a micro thermophoresis experiment, the arabidopsis cryptoanthocyanin AtCRY2 protein is marked by a Kit RED fluorescent probe; dissolving compound 10 and compound 21 in buffer solution (20mM HEPES,100mM NaCl) with DMSO content of 5 vol%, diluting at equal ratio, mixing with 10 μm AtCRY2 protein solution, transferring into capillary, and detecting thermophoresis when AtCRY2 protein interacts with inhibitors with different concentrations on MST instrument to obtain dissociation constant K d The result of the same parameters is shown in fig. 9a and 9 b. The test result shows that the invention provides the K of the compound 10, the compound 21 and the AtCRY2 protein d The values were 4.18. Mu.M (FIG. 9 a) and 1.02. Mu.M (FIG. 9 b), respectively, demonstrating the strong binding capacity of compound 10, compound 21 and AtCRY2 protein.
Test example 5
Green bean seedling emergence test: in the same culture basin, adding nutrient soil with the same mass, respectively transferring into 12 mung bean seeds, and then respectively covering the seeds with nutrient soil of 4cm, 6cm and 8 cm. 100mL of a 10-concentration solution of the compound (0.4% by volume in DMSO) was added to the culture well; the positive control group was added with 100mL of a solution of the compound 3-bromo-7-nitroindazole (3B 7N) at a concentration of 10. Mu.M (0.4% by volume in DMSO); 100mL of 0.4% volume fraction DMSO aqueous solution was added to the blank, and all the culture dishes were incubated at 23℃in the dark. When the mung bean seedlings are out of the soil, the seedlings are taken out of the soil, the hypocotyl length of the mung bean seedlings is photographed and counted, and the results are shown in fig. 10 to 12. In particular, the method comprises the steps of,
FIG. 10 shows the effect of compound 10, positive control (3B 7N) and blank control (DMSO) on the elongation of the hypocotyl of mung bean seedlings in 4cm deep nutrient soil; wherein (left) in fig. 10 is a picture of growth of mung bean seedlings in soil, (middle) in fig. 10 is a picture of length of hypocotyl of mung bean seedlings, and (right) in fig. 10 is a statistical picture of length of hypocotyl of mung bean seedlings.
FIG. 11 shows the effect of compound 10, positive control (3B 7N) and blank control (DMSO) on the elongation of the hypocotyl of mung bean seedlings in 6cm deep nutrient soil; wherein (left) in fig. 11 is a picture of growth of mung bean seedlings in soil, (middle) in fig. 11 is a picture of length of hypocotyl of mung bean seedlings, and (right) in fig. 11 is a statistical picture of length of hypocotyl of mung bean seedlings.
FIG. 12 shows the effect of compound 10, positive control (3B 7N) and blank control (DMSO) on the elongation of the hypocotyl of mung bean seedlings in 8cm deep nutrient soil; wherein (left) in fig. 12 is a picture of growth of mung bean seedlings in soil, (middle) in fig. 12 is a picture of length of hypocotyl of mung bean seedlings, and (right) in fig. 11 is a statistical picture of length of hypocotyl of mung bean seedlings.
As can be seen from the results of fig. 10 to 12, the experimental group of mung bean seedlings had a longer hypocotyl than the blank group (DMSO) and the positive control group (3B 7N) after the treatment with the compound 10.
Test example 6
Wheat seedling emergence test: taking the same culture sleeve basin (big basin and small basin), filling nutrient soil with the same quality into the small basin, transferring the same quantity (150 grains) of wheat seeds (variety: shannong No. 46), and covering river sand with the same thickness (5 cm) and 20 meshes of grain size. 2L of compounds 17, 21, 22 (0.4% by volume in DMSO in water) were added to the large basin at a concentration of 10. Mu.M; to the blank, 2L of 0.4% by volume DMSO in water was added. And then placing the small basin into the large basin, after the water solution in the large basin is absorbed and saturated by sand in the small basin, placing all the culture sleeve basins at 23 ℃ for culture, and photographing every day to record the emergence quantity of wheat. The results are shown in fig. 13a, 13b, wherein in fig. 13a, compound 17, compound 21, compound 22 accelerated wheat seedling emergence rate compared to the control group (CK). As can be seen from fig. 13b, after the compound 17, the compound 21 and the compound 22 provided by the invention are treated, the emergence time of wheat seedlings is obviously advanced, and the emergence rate is obviously improved. After the treatment of the compound 17, the compound 21 and the compound 22, the emergence rates of wheat seedlings are 1.88 times, 1.59 times and 1.47 times that of a control group (CK) respectively. (wheat seedling emergence rate = number of seedlings to be ground/total number of seeds)
Test example 7
Arabidopsis late flowering phase experiment: taking wild Arabidopsis seedling (cultured for 20 days, seedling grows strong and flower bud has differentiated) with uniform growth vigor, using 5 μm concentration of compound 17, compound 21, compound 22 (V) DMSO ：V Water and its preparation method =1: 10000 Soaking soil for planting, and supplementing 500mL of water once every 20 days; equivalent DMSO aqueous solution (V) was added to the blank group DMSO ：V Water and its preparation method =1: 10000). The flowering period interval is from seed germination to the occurrence of first flowers of arabidopsis plants; the flowering period of each Arabidopsis was recorded, as well as the number of rosette leaves. As shown in fig. 14a, 14b and 14c, it can be seen from fig. 14a that the flowering phase of arabidopsis after application of compound 17, compound 21 and compound 22 is significantly later than that of the control group; as can be seen from fig. 14b, the number of arabidopsis rosette leaves to which compound 17, compound 21, and compound 22 were applied was significantly higher than that of the control group; as can be seen from fig. 14c, the flowering phases (30.8 days, 30.7 days and 28.3 days, respectively) of arabidopsis thaliana, to which compound 17, compound 21 and compound 22 were applied, were delayed by 6.1 days, 6 days and 3.6 days, respectively, relative to the control group (24.7 days).
In conclusion, the sulfonamide compound provided by the invention can effectively relieve the inhibitory activity of cryptoanthocyanin under blue light on hypocotyl elongation, and obviously enhance the soil emergence capacity of plant seedlings; meanwhile, the compound provided by the invention can delay the flowering period of plants.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, a number of simple variants of the technical solution of the invention are possible, including combinations of the individual technical features in any other suitable way, which simple variants and combinations should likewise be regarded as being disclosed by the invention, all falling within the scope of protection of the invention.

Claims (10)

1. A sulfonamide compound, or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, characterized in that the compound has a structure represented by formula (I):
wherein, in the formula (I),
R 1 selected from-CH 2 R 5 、-CHR 6 R 7 、-C(R 8 ) 3 Hydroxy-substituted C 3-8 Cycloalkyl of (c);
R 5 is C 2-4 or-L 1 -R a ；
L 1 Is C 1-6 Alkylene group, R a is-CH (OH) CH 2 OH, halogen, amino, C 2-4 Ester and carboxyl groups; or L 1 Is phenylene, R a Selected from carboxyl, hydroxyl and hydroxymethyl; or L 1 is-CH (OH) -, R a Selected from hydroxymethyl, -CH (OH) CH 2 OH；
R 6 、R 7 Each independently selected from substituted or unsubstituted C 1-6 Alkyl, carboxyl, C 2-4 Ester group, -CONH 2 ；
R 6 、R 7 Optionally containing substituents selected from hydroxy, imidazolyl, amino, C 2-4 Ester group, mercapto group, phenyl group, hydroxyphenyl group, indolyl group, -NHC (NH) NH 2 、-CONH 2 、-S-C 1-3 At least one of the alkyl groups of (a);
R 8 selected from hydroxy-substituted C 1-6 Alkyl of (a);
R 2 selected from H, hydroxy, amino, halogen;
R 3 、R 4 each independently selected from H, amino, halogen, hydroxy, -SO 2 NHR 1 Any one of the following.
2. The sulfonamide compound according to claim 1, wherein, in the formula (I),
R 1 selected from-CH 2 R 5 、-CHR 6 R 7 、-C(R 8 ) 3 Hydroxy-substituted C 3-6 Cycloalkyl of (c);
R 5 is C 2-4 or-L 1 -R a ；
L 1 Is C 1-4 Alkylene group, R a Selected from-CH (OH) CH 2 OH, bromine, amino, C 2-4 Ester and carboxyl groups; or L 1 Is phenylene, R a Selected from carboxyl, hydroxyl and hydroxymethyl; or L 1 is-CH (OH) -, R a Is hydroxymethyl, -CH (OH) CH 2 OH；
R 6 、R 7 Each independently selected from substituted or unsubstituted C 1-4 Alkyl, carboxyl, C 2-4 Ester group, -CONH 2 ；
R 6 、R 7 Optionally containing substituents selected from hydroxy,Amino, C 2-4 Ester group, mercapto group, phenyl group,-NHC(NH)NH 2 、-CONH 2 、-S-C 1-3 At least one of the alkyl groups of (a);
R 8 selected from hydroxy-substituted C 1-4 Alkyl of (a);
R 2 selected from H, hydroxy, amino, fluoro, chloro, bromo;
R 3 、R 4 each independently selected from H, amino, fluoro, chloro, bromo, hydroxy, -SO 2 NHR 1 Any one of the following.
3. Sulfonamide compound according to claim 1 or 2, wherein, in formula (I),
R 1 selected from-CH 2 R 5 、-CHR 6 R 7 、-C(R 8 ) 3 Hydroxyl-substituted cyclohexyl, hydroxyl-substituted cyclopentyl;
R 5 selected from-COOCH 3 、-CH 2 NH 2 、-CH 2 CH 2 NH 2 、-CH 2 Br、-CH 2 CH 2 Br、-CH 2 (CH 2 ) 2 Br、-CH 2 COOCH 3 、-CH(OH)CH(OH)CH 2 OH、-CH 2 CH(OH)CH 2 OH、-CH(OH)CH 2 OH；
R 6 、R 7 Each independently selected from-CH 3 、-CH(CH 3 )CH 3 、-CH(CH 3 )CH 2 CH 3 、-CH 2 CH(CH 3 )CH 3 、-COOH、-CONH 2 、-CH 2 SH、-CH 2 CH 2 SCH 3 、-CH 2 OH、-CH(OH)CH 3 、-CH 2 (CH 2 ) 3 NH 2 、-COOCH 3 、-COOCH 2 CH 3 、-CH 2 COOCH 3 、-CH 2 CH 2 COOCH 3 、-CH 2 COOCH 2 CH 3 、-CH 2 CH 2 CONH 2 、-CH 2 CONH 2 、
R 8 Selected from-CH 2 OH、-CH 2 CH 2 OH；
R 2 Selected from H, hydroxy, amino, bromo;
R 3 、R 4 each independently selected from H, amino, bromo, hydroxy, -SO 2 NHR 1 Any one of the following.
4. A sulfonamide compound according to any one of claims 1 to 3, wherein the compound is selected from any one of the following compounds:
5. a process for the preparation of a sulfonamide compound of the structure of formula (I) or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, characterized in that it comprises: contacting a compound represented by formula (a) with a compound represented by formula (B) in the presence of a solvent;
H 2 N-R 1 (B),
wherein in formula (A), R 3 、R 4 Each independently selected from H, amino, halogen, hydroxy,
In the formula (A) and the formula (B), R 1 、R 2 Is correspondingly the same as the definition as defined in any one of claims 1 to 4.
6. The method of claim 5, wherein the contacting conditions comprise: the reaction temperature is 0-200 ℃ and the reaction time is 0.5-24h; and/or the number of the groups of groups,
the solvent is at least one selected from tetrahydrofuran, 1, 4-dioxane, N-dimethylformamide, dimethyl sulfoxide, ethyl acetate, acetone, ethanol, water, dichloromethane, chloroform and acetonitrile.
7. A pesticide formulation comprising at least one of the sulfonamide compounds of any one of claims 1-4, or stereoisomers, geometric isomers, tautomers thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, and an agrochemically acceptable carrier.
8. Use of a sulfonamide compound according to any one of claims 1 to 4, or a stereoisomer, a geometric isomer, a tautomer thereof, or an agrochemically acceptable salt, prodrug, hydrate, solvate, metabolite thereof, for enhancing the soil emergence capacity of young plants and/or delaying the flowering phase of plants.
9. An agent for enhancing the soil emergence ability of young plants and/or delaying the flowering phase of plants, characterized in that the active ingredient of the agent is at least one of the sulfonamide compounds according to any one of claims 1 to 4 or stereoisomers, geometric isomers, tautomers thereof, or agrochemically acceptable salts, prodrugs, hydrates, solvates, metabolites thereof, the content of the active ingredient being 0.1 to 100% by weight, based on the total weight of the agent;
preferably, the active ingredient is present in an amount of 5 to 90% by weight.
10. The medicament of claim 9, wherein the dosage form of the medicament is selected from at least one of a hydrating agent, a powder, a granule, a suspension, and an emulsion.
CN202310812021.2A 2022-07-05 2023-07-04 Sulfonamide compound, preparation method and application thereof, pesticide preparation and medicament Pending CN117342990A (en)

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