CN104098549A - Piperazinedione derivative and preparation and application thereof - Google Patents

Piperazinedione derivative and preparation and application thereof Download PDF

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Publication number
CN104098549A
CN104098549A CN201410378163.3A CN201410378163A CN104098549A CN 104098549 A CN104098549 A CN 104098549A CN 201410378163 A CN201410378163 A CN 201410378163A CN 104098549 A CN104098549 A CN 104098549A
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unsubstituted
replacement
compound
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alkyl
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CN104098549B (en
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宋恭华
孙海洋
王佳毅
黄瑾
李晖
张小灵
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East China University of Science and Technology
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East China University of Science and Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/30—Derivatives containing the group >N—CO—N aryl or >N—CS—N—aryl
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/36—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the group >N—CO—N< directly attached to at least one heterocyclic ring; Thio analogues thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
    • C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Abstract

The invention discloses a piperazinedione derivative and preparation and application thereof. Specifically, the invention discloses a compound with structure as shown in formula I, or pharmaceutically acceptable salt or agrochemically acceptable salt thereof. The compound has excellent insecticidal activity and can be used as the human 5-HT2a receptor stimulant, and detailed definition of the compound of the formula I refers to specification.

Description

Diketopiperazines and preparation thereof and purposes
Technical field
The invention belongs to agricultural chemicals and pharmaceutical field.Particularly, the present invention relates to a kind of diketopiperazines and preparation thereof and purposes.
Background technology
Sterilant is the Main Means of controlling insect pest, plays very important effect in modern agriculture.Mostly the sterilant using is at present nerve poison, for example: the effect in insect body of organic phosphorous insecticide and carbamate insecticides is mainly the activity that suppresses enzyme acetylcholine, causes that insect is poisoned to death; Pyrethroid insecticides is as nerve poison, and the sodium-ion channel that its toxicity mechanism is considered to directly and on neu interacts and produces toxic effect; It is a kind of acetylcholine receptor toxic agent that anabasine insecticide is recognized, and it is the sterilant that acts on acetylcholine receptor.
But nearly twenty or thirty is since year, and wide variation have occurred the sterilant market structure, and large quantities of sterilants are extruded market.Its reason has two aspects:
The one, the safety issue of sterilant, some traditional sterilants eliminated due to its toxicity with on the impact of environmental ecology, enter the nineties, the organic phosphorous insecticide of high malicious high residue grows to even greater heights as disabled cries such as aldicarb, carbofuran, methomyls as the carbamate insecticides of acephatemet, thiophos, omethoate etc. and high poison, and these important insecticide varieties are worldwide disabled or soon disabled at present.
The 2nd, insect resistance to insecticide problem, due to long-term abuse chemical insecticide, the resistance of insect improves, and on the one hand the consumption of sterilant is on the increase, and forms vicious cycle, and environment and ecology are caused to very big infringement; Make on the other hand the cost accounting of insect constantly increase.
Being the market requirement constantly expanding on the one hand, is the insecticide variety being constantly eliminated on the other hand, and therefore, the environmentally friendly agricultural chemicals of development of new seems extremely important.
Summary of the invention
The object of this invention is to provide diketopiperazines a kind of novel structure, that there is good insecticidal activity.
Another object of the present invention is to provide preparation method and the purposes of above-mentioned diketopiperazines, for example, for the preparation of the composition of kill pests, or for the preparation of people 5-HT2a receptors ligand or agonist.
A first aspect of the present invention provides acceptable salt in a kind of compound with structure shown in formula (I) or its pharmacy acceptable salt or Pesticide Science,
Wherein, R 1for that replace or unsubstituted C 1～C 10c alkyl, replacement or unsubstituted 1～C 10c alkoxyl group, replacement or unsubstituted 2～C 10c thiazolinyl, replacement or unsubstituted 2～C 10alkene oxygen base, replacement or unsubstituted C 2～C 10c alkynyl, replacement or unsubstituted 2～C 10c alkynyloxy group, replacement or unsubstituted 1～C 10c ester group, replacement or unsubstituted 1～C 10c alkyl-carbonyl, replacement or unsubstituted 1～C 10c alkoxy carbonyl, replacement or unsubstituted 5～C 10c aryl, replacement or unsubstituted 2～C 8c heteroaryl, replacement or unsubstituted 3～C 8heterocyclylalkyl, replacement or unsubstituted-C 1～C 6alkylidene group-C 5～C 10aryl or that replace or unsubstituted-C 1～C 6alkylidene group-C 2～C 8heteroaryl; Wherein, described replacement refers to that being selected from one or more (being preferably 1,2,3 or 4) substituting group of lower group replaces: nitro, halogen, cyano group, amino, diazanyl, C 1～C 6acyl amino, hydroxyl, C 1～C 6alkyl, hydroxyl C 1～C 6alkyl, C 1～C 6alkoxyl group, halo C 1～C 6alkyl, halo C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkene oxygen base, C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkynyl, C 1～C 6ester group, C 1～C 6alkyl-carbonyl, C 1～C 6alkoxy carbonyl, C 5～C 10aryl, halo C 5～C 10aryl and C 3～C 8heterocyclylalkyl;
N is 1 to 3 integer (1,2 or 3); X is carbonyl (C=O), thiocarbonyl (C=S) or CH 2; Y does not exist, or is NH;
R 2for that replace or unsubstituted C 1～C 10c alkyl, replacement or unsubstituted 1～C 10c ester group, replacement or unsubstituted 1～C 10c alkyl-carbonyl, replacement or unsubstituted 1～C 10c alkoxy carbonyl, replacement or unsubstituted 5～C 10c aryl, replacement or unsubstituted 3～C 8c Heterocyclylalkyl, replacement or unsubstituted 5～C 10aryl or that replace or unsubstituted C 2～C 8heteroaryl; Wherein, described replacement refers to that being selected from one or more (being preferably 1,2,3 or 4) substituting group of lower group replaces: nitro, halogen, cyano group, amino, diazanyl, C 1～C 6acyl amino, hydroxyl, C 1～C 6alkyl, hydroxyl C 1～C 6alkyl ,-O-C 1～C 6alkylidene group-O-, C 1～C 6alkoxyl group, halo C 1～C 6alkyl, halo C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkene oxygen base, C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkynyl, C 1～C 6ester group, C 1～C 6alkyl-carbonyl, C 1～C 6alkoxy carbonyl, C 5～C 10aryl, halo C 5～C 10aryl and C 3～C 8heterocyclylalkyl.
In another preference, described C 3～C 8heterocyclylalkyl or described C 2～C 8heteroaryl contains, and one or more (preferably 1-4 or 1-3) are selected from the heteroatoms of N, S and O.
In another preference, described compound has the structure shown in formula 10, formula 11, formula 14 or formula 15,
In various, n, R 1, R 2definition is the same.
In another preference, R 1for that replace or unsubstituted C 1～C 10c alkyl, replacement or unsubstituted 1～C 10alkoxyl group, replacement or unsubstituted-CH 2-indyl, replacement or unsubstituted-CH 2-phenyl, replacement or unsubstituted-CH 2-pyridyl, replacement or unsubstituted-CH 2-benzo pyridyl, replacement or unsubstituted-CH 2-pyrryl, replacement or unsubstituted-CH 2-thienyl, replacement or unsubstituted-CH 2-benzothienyl, replacement or unsubstituted-CH 2-furyl, replacement or unsubstituted-CH 2-benzofuryl; Wherein, described replacement refers to that being selected from one or more (being preferably 1,2,3 or 4) substituting group of lower group replaces: nitro, halogen, cyano group, amino, diazanyl, C 1～C 6acyl amino, hydroxyl, C 1～C 6alkyl, hydroxyl C 1～C 6alkyl, C 1～C 6alkoxyl group, halo C 1～C 6alkyl, halo C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkene oxygen base, C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkynyl, C 1～C 6ester group, C 1～C 6alkyl-carbonyl, C 1～C 6alkoxy carbonyl, C 5～C 10aryl, halo C 5～C 10aryl and C 3～C 8heterocyclylalkyl.
In another preference, R 2for that replace or unsubstituted phenyl, replacement or unsubstituted pyridyl, replacement or unsubstituted thiazolyl, replacement or unsubstituted 1, benzothiazolyl 3,4-thiadiazoles, replacement or unsubstituted, replacement or unsubstituted thienyl, replacement or unsubstituted benzothienyl, replacement or unsubstituted furyl, replacement or unsubstituted benzofuryl; Wherein, described replacement refers to that being selected from one or more (being preferably 1,2,3 or 4) substituting group of lower group replaces: nitro, halogen, cyano group, amino, diazanyl, C 1～C 6acyl amino, hydroxyl, C 1～C 6alkyl, hydroxyl C 1～C 6alkyl ,-O-C 1～C 6alkylidene group-O-, C 1～C 6alkoxyl group, halo C 1～C 6alkyl, halo C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkene oxygen base, C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkynyl, C 1～C 6ester group, C 1～C 6alkyl-carbonyl, C 1～C 6alkoxy carbonyl, C 5～C 10aryl, halo C 5～C 10aryl and C 3～C 8heterocyclylalkyl.
In another preference, the referring to of described replacement is selected from one or more (being preferably 1,2,3 or 4) substituting group of lower group and replaced: nitro, fluorine, chlorine, bromine, iodine, cyano group, methyl ,-O-C 1～C 3alkylidene group-O-, methoxyl group, trifluoromethyl, methoxycarbonyl, ethoxycarbonyl, methoxycarbonyl, ethoxycarbonyl, methyl carbonyl, ethyl carbonyl, phenyl, chlorophenyl.
Second aspect present invention provides a kind of composition, it comprises acceptable salt, (b) acceptable carrier in pharmaceutically acceptable carrier or Pesticide Science in compound described in (a) first aspect present invention or its pharmacy acceptable salt or Pesticide Science.
In another preference, described composition is pharmaceutical composition or agricultural composition.
In another preference, described composition also contains other active substance, and described other active substance is selected from: sterilant, bait formulation, sterilant, miticide, nematocides, mycocide or growth control agent.
Third aspect present invention provides the purposes of composition described in acceptable salt in compound described in first aspect present invention or its pharmacy acceptable salt or Pesticide Science or second aspect present invention, for killing or prevent Agricultural pests; Or for the preparation of the sterilant of killing or prevent Agricultural pests.
In another preference, in described compound or its pharmacy acceptable salt or Pesticide Science, the application concentration of acceptable salt or described composition is 0.05-5000ppm; Preferably, be 0.1-1000ppm; More preferably, be 0.5-500ppm; More preferably, be 0.5-100ppm or 0.5-50ppm.
In another preference, for the preparation of killing or prevent the sterilant of lepidopterous insects, the sterilant that takes food, grows for the preparation of inhibition lepidopterous insects, or for the preparation of the sterilant of killing or prevent nematode.
Fourth aspect present invention provides the purposes of composition described in acceptable salt in compound described in first aspect present invention or its pharmacy acceptable salt or Pesticide Science or second aspect present invention, for the preparation of people 5-HT2a receptors ligand or people 5-HT2a receptor stimulant.
The preparation method of acceptable salt in compound described in fifth aspect present invention provides or its pharmacy acceptable salt or Pesticide Science,
(a) described method comprises step: under the existence of alkali, in inert solvent, compound 7 and compound 5 are reacted, thereby obtain compound 10;
(b) described method comprises step: under the existence of alkali, in inert solvent, compound 9 and compound 5 are reacted, thereby obtain compound 10;
(c) described method comprises step: under the existence of condensing agent, in inert solvent, compound 12 and compound 5 are reacted, thereby obtain compound 10;
(d) described method comprises step: under the existence of reductive agent, in inert solvent, compound 13 and compound 5 are reacted, thereby obtain compound 10;
In various, n, R 1, R 2definition is the same.
Sixth aspect present invention provides a kind of desinsection and/or insect-prevention method, and described method comprises composition described in acceptable salt or second aspect present invention in the compound described in first aspect present invention or its pharmacy acceptable salt or Pesticide Science is put in the plant materials or its soil or environment around that suffers or may insect infestation.
In another preference, in described compound or its pharmacy acceptable salt or Pesticide Science, the application concentration of acceptable salt or described composition is 0.05-5000ppm; Preferably, be 0.1-1000ppm; More preferably, be 0.5-500ppm; More preferably, be 0.5-100ppm or 0.5-50ppm.
In should be understood that within the scope of the present invention, above-mentioned each technical characterictic of the present invention and can combining mutually between specifically described each technical characterictic in below (eg embodiment), thus form new or preferred technical scheme.As space is limited, at this, tire out and state no longer one by one.
Embodiment
The inventor, through extensive and deep research, has synthesized the piperazinedione analog derivative of a series of novel structures first, its have excellent kill Agricultural pests (as lepidopterous insects, mythimna separata for example; Or as nematode, such as Meloidogyne incognita etc.) or suppress the effects that takes food, grows of Agricultural pests, and also this compounds can also be as people 5-HT2a receptor stimulant.On this basis, contriver has completed the present invention.
Term
Term " C 1～C 10alkyl " refer to have the alkyl of the straight or branched of 1-10 carbon atom, for example methyl, ethyl, propyl group, sec.-propyl, 1-butyl, 2-butyl, amyl group, hexyl, heptyl, octyl group, nonyl, decyl or similar group.Can be preferably C1～C6 alkyl or C1～C3 alkyl.
Term " C 1～C 10alkoxyl group " refer to have the alkoxyl group of the straight or branched of 1-10 carbon atom, for example methoxyl group, oxyethyl group, propoxy-, isopropoxy, 1-butoxy, 2-butoxy, pentyloxy, hexyloxy, heptan oxygen base, octyloxy, the ninth of the ten Heavenly Stems oxygen base, the last of the ten Heavenly stems oxygen base or similar group.Can be preferably C1～C6 alkoxyl group or C1～C3 alkoxyl group.
Term " C 2～C 10thiazolinyl " refer to have the thiazolinyl of the straight or branched of 2-10 carbon atom, for example vinyl, propenyl, pseudoallyl, 1-butylene base, crotyl, pentenyl, hexenyl, heptenyl, octenyl, nonene base, decene base or similar group.Can be preferably C2～C6 thiazolinyl or C2～C3 thiazolinyl.
Term " C 2～C 10alkene oxygen base " refer to have the thiazolinyl oxygen base of the straight or branched of 2-6 carbon atom, for example vinyloxy group, propenyloxy group, different propenyloxy group, 1-butylene oxygen base, 2-butylene oxygen base, amylene oxygen base, hexene oxygen base, heptene oxygen base, octene oxygen base, nonene oxygen base, decene oxygen base or similar group.Can be preferably C2～C6 alkene oxygen base or C2～C3 alkene oxygen base.
Term " C 2～C 10alkynyl " refer to have the alkynyl of the straight or branched of 2-10 carbon atom, for example ethynyl, proyl, isopropyl alkynyl, ethyl acetylene base, 2-butyne base, pentynyl, hexin base, heptyne base, octyne base, n-heptylacetylene base, decynyl or similar group.Can be preferably C2～C6 alkynyl or C2～C3 alkynyl.
Term " C 5～C 10aryl " refer to have the group with aromaticity of 5-10 carbon atom, for example phenyl, naphthyl or similar group.
Term " C 2～C 8heteroaryl " refer to have the one or more heteroatomic aromatic bases that are selected from nitrogen, oxygen and sulphur of having of 2-8 carbon atom; for example pyridyl, benzo pyridyl, pyrryl, benzopyrrole base, benzothienyl, thienyl, benzofuryl, furyl, thiazolyl, benzothiazolyl, imidazolyl, oxazolyl, indyl, pyrazinyl; pyrimidyl, pyridazinyl, quinolyl, acridyl or similar group.
Term " C 1～C 6acyl group " refer to have the acyl group of 1-6 carbon atom, for example formyl radical, ethanoyl, propionyl, isopropyl acyl group, 1-butyryl radicals, 2-butyryl radicals or similar group.Can be preferably C1～C3 acyl group.
Term " C 3～C 8heterocyclylalkyl " refer to have the one or more heteroatomic cyclic groups that are selected from nitrogen, oxygen and sulphur of having of 3-8 carbon atom, for example piperidyl, piperazinyl, Oxyranyle, propylene oxide base, tetrahydrofuran base or similar group.
Term " halogen " is fluorine, chlorine, bromine, iodine.Described " halo " is fluoro, chloro, bromo, iodo.
Preparation method
More specifically describe the preparation method of formula of the present invention (I) structural compounds below, but these concrete grammars do not form any restriction to the present invention.The compounds of this invention can also be optionally by describe in this manual or various synthetic method known in the art combine and make easily, such combination can be easy to carry out by those skilled in the art in the invention.
Conventionally, in preparation flow, each reaction is conventionally in inert solvent.Each reaction is carried out to reflux temperature (as 0 ℃～80 ℃, preferably 0 ℃～50 ℃) in room temperature.Reaction times is generally 0.1 hour-60 hours, is preferably 0.5-48 hour.
A kind of particularly preferred preparation flow is as follows:
(5) triphosgene (BTC) is dissolved in to inert solvent (as methylene dichloride, 1,2-ethylene dichloride, chloroform, tetracol phenixin, DMF etc.) in, compound 6 and organic bases are dissolved in inert solvent (as methylene dichloride, 1,2-ethylene dichloride, chloroform, tetracol phenixin etc.) in, low temperature adds in inert solvent (as the methylene dichloride) solution of triphosgene, obtains compound 7.
(6) compound 7 is splashed in inert solvent (as methylene dichloride, 1,2-ethylene dichloride, chloroform, tetracol phenixin, the DMF etc.) solution of compound 5 and organic bases, obtain compound 10.
(7) by compound 6, dithiocarbonic anhydride, organic bases is dissolved in in inert solvent (as THF, toluene, methylene dichloride, 1,2-ethylene dichloride, chloroform, tetracol phenixin etc.) solution, obtains compound 8, adds triphosgene, obtains compound 9.
(8) compound 9 is dissolved in inert solvent (as methyl alcohol, DMF, DMSO, toluene, methylene dichloride, 1,2-ethylene dichloride, chloroform, tetracol phenixin etc.), adds compound 5 and appropriate organic bases, obtain compound 11.
(9) by compound 5, compound 12 is dissolved in inert solvent (as DMF, DMSO, acetonitrile, methylene dichloride, 1,2-ethylene dichloride, chloroform, tetracol phenixin etc.) in, add condensing agent (as EDCI) and catalyzer (as HoBt, DMAP etc.), react to obtain compound 14.
(10) by compound 5, compound 13 is dissolved in inert solvent (as DMF, DMSO, acetonitrile, methylene dichloride, 1,2-ethylene dichloride, chloroform, tetracol phenixin etc.) in, add reductive agent (as sodium triacetoxy borohydride, sodium cyanoborohydride, sodium borohydride etc.), react to obtain compound 15.
In another preference, described compound 5 can make by the following method:
(1) compound 1, tert-Butyl dicarbonate ((Boc) 2o) for raw material is dissolved in inert solvent (as acetone and water, acetonitrile, water, ethyl acetate etc.), under alkaline condition, obtain compound 2.
(2) compound 2 and amino acid acid methyl ester hydrochloride salt are dissolved in inert solvent (as methylene dichloride, acetonitrile, acetone, chloroform etc.), add condensing agent (as EDCI etc.) and catalyzer (as HoBt, DMAP etc.), react to obtain compound 3.
(3) compound 3 is dissolved in inert solvent (as methylene dichloride, acetonitrile, acetone, chloroform etc.), adds acid (as trifluoroacetic acid, hydrochloric acid etc.), obtain compound 4.
(4) compound 4 is dissolved in inert solvent (as propyl carbinol, n-propyl alcohol, toluene etc.), back flow reaction, obtains compound 5.
In above-mentioned reaction, described organic bases is triethylamine, triethylene diamine, pyridine etc.Under alkaline condition, refer to that, under the existence of the alkali that is being selected from lower group, described alkali comprises various organic basess known in the art and mineral alkali.
Pesticide composition
Term " active substance of the present invention " or " active compound of the present invention " refer to acceptable salt in the compounds of this invention or its Pesticide Science.
In described Pesticide Science, acceptable salt can comprise the salt of inorganic salt, organic acid salt, basic aminoacids or acidic amino acid.In the present invention, inorganic acid salt for example comprises: hydrochloric acid, hydrogen borate, nitric acid, sulfuric acid or phosphoric acid.In the present invention, organic acid for example comprises: lactic acid, formic acid, acetic acid (being acetic acid), trifluoroacetic acid, fumaric acid, oxalic acid, toxilic acid, citric acid, succsinic acid, oxysuccinic acid, methylsulfonic acid, Phenylsulfonic acid or tosic acid.Acidic amino acid for example comprises: glycine, aspartic acid or L-glutamic acid.
Actives mass-energy of the present invention is as controlling and eliminate the insect of agriculture and forestry plant insect, storage cereal, the insect of harm animal health and public health insect etc. widely.In this manual, " sterilant " is the general designation with the material of the effect that prevents and treats above-mentioned all insects of mentioning.
The example of insect includes but not limited to: lepidopterous insects is (as waved malicious pretty young woman (Lymantria dispar), tent caterpillar (Malacosoma neustria testacea), Diaphania perspectalis (Diaphania perspectalis), Clania variegata Snellen (Clania variegata), cnidocampa flavescens walker (Cnidocampa flauescens), dendrolimus punctatus (Dendrolimus punctatus), orgyia antiqua (Orgyia gonostigma), paranthrene tabaniformis (Paranthrene tabaniformis), prodenia litura (Spodoptera litura), striped rice borer (Chilo suppressalis), Pyrausta nubilalis (Hubern). (Ostrinia nubilalis), meal moth (Ephestia cautella), lap moth (Adoxophyes orana), chestnut steinernema (laspyresia splendana), black cutworm (Agrotis fucosa), greater wax moth (Galleria mellonella), diamond-back moth (Plutella xylostella), tangerine lyonetid (Phyllocnistis citrella), or oriental armyworm (Mythimna separata)), or nematode (as Meloidogyne incognita).
Active substance of the present invention can be prepared into insecticides with conventional method.These active compounds can be made conventional preparation, solution for example, emulsion, suspensoid, pulvis, foaming agent, paste, granule, the preparations such as aerosol.
These preparations can be produced by known method, for example, by active compound with expand agent and mix, these expansion agent are exactly the diluent or carrier of liquid or liquefied gas or solid, and can to select arbitrarily tensio-active agent be emulsifying agent and/or dispersion agent and/or formation of foam agent.For example, when using water as expansion agent, organic solvent also can be used as auxiliary agent.
While making diluent or carrier with liquid solvent, be suitable substantially, as arene, dimethylbenzene for example, toluene or alkylnaphthalene; The fragrance of chlorination or the fat hydrocarbon of chlorination, chlorobenzene for example, vinylchlorid or methylene dichloride; Fat hydrocarbon, for example hexanaphthene or paraffin, for example mineral oil fractions; Alcohols, for example ethanol or ethylene glycol and their ether and lipid; Ketone, acetone for example, methylethylketone, methyl iso-butyl ketone (MIBK) or cyclohexanone; Or the polar solvent being of little use, for example dimethyl formamide and dimethyl sulfoxide (DMSO), and water.
Diluent or carrier with regard to liquefied gas is said, refers at normal temperatures and pressures and will become the liquid of gas, and aerosol propellants for example, as the hydro carbons of halogenation and butane, propane, nitrogen and carbonic acid gas.
Solid carrier can be with (ground) the natural mineral substance grinding, kaolin for example, clay, talcum, quartz, atlapulgite, polynite, or diatomite, and the synthetic mineral substance grinding, for example silicic acid of high dispersing, aluminum oxide and silicate.For the solid carrier of particle, be that pulverize and natural announcement stone classification, calcite for example, marble, float stone, sepiolite and rhombspar, and the synthetic particle of inorganic and organic meal, with organic materials wood sawdust for example, Exocarpium cocois (Cocos nucifera L), the particle of corn cob and tobacco stems etc.
Emulsification row non-ionic and negatively charged ion can be used as emulsifying agent and/or formation of foam agent.Polyoxyethylene-fatty acid ester for example, polyoxyethylene-fatty alcohol ethers, for example alkaryl polyoxyethylene glycol ethers, alkyl sulfonates, alkyl sulfuric ester class, aromatic yl sulphonate class and albumin hydrolysate.Dispersion agent comprises, for example xylogen sulfite waste lye and methylcellulose gum.
In preparation, can use tackiness agent, carboxymethyl cellulose and with powder for example, the natural and synthetic polymer of particle or emulsion form, for example gum arabic, polyvinyl alcohol and polyvinyl acetate.
Can be with tinting material inorganic dyestuff for example, as ferric oxide, oxidation is bored and is Prussian blue; Organic dye, as organic dye, as azo dyes or metal titanium cyanine dyes; With use trace nutrition agent, as iron, violent, boron, copper, cobalt, the salt of aluminum and zinc etc.
These preparations conventionally contain and account for described insecticides 0.001-99.99 % by weight, preferably 0.01-99.9 % by weight, the more preferably active compound of the present invention of 0.05-90 % by weight.From commodity preparation, make and use the concentration of the active compound formulation in wide scope, to change.Use the concentration of the active compound in formulation from 0.0000001-100% (g/v), to be preferably between 0.0001 and 1% (g/v).
Pharmaceutical composition
Term " active substance of the present invention " or " active compound of the present invention " refer to pharmaceutically that acceptable salt of the compounds of this invention or its.
Described pharmacy acceptable salt can comprise the salt of inorganic salt, organic acid salt, basic aminoacids or acidic amino acid.In the present invention, inorganic acid salt for example comprises: hydrochloric acid, hydrogen borate, nitric acid, sulfuric acid or phosphoric acid.In the present invention, organic acid for example comprises: lactic acid, formic acid, acetic acid (being acetic acid), trifluoroacetic acid, fumaric acid, oxalic acid, toxilic acid, citric acid, succsinic acid, oxysuccinic acid, methylsulfonic acid, Phenylsulfonic acid or tosic acid.Acidic amino acid for example comprises: glycine, aspartic acid or L-glutamic acid.
Because the compounds of this invention has the excellent agonist activity to 5-HT2a acceptor, so the compounds of this invention and pharmacy acceptable salt thereof, and to contain the compounds of this invention be that the pharmaceutical composition of main active ingredient can be used for treatment or the relevant disease of prevention 5-HT2a acceptor, for example can anti-inflammatory, analgesia, prevention or treatment psychosis, dysthymia disorders etc.
Pharmaceutical composition of the present invention comprises in the compounds of this invention in safe and effective weight range or its pharmacology acceptable vehicle or carrier on acceptable salt and pharmacology.Wherein " safe and effective amount " refers to: the amount of compound is enough to obviously improve the state of an illness, and is unlikely to produce severe side effect.Conventionally, pharmaceutical composition contains 1-2000mg the compounds of this invention/agent, more preferably, contains 10-200mg the compounds of this invention/agent.Preferably, described " potion " is a capsule or tablet.
" pharmaceutically acceptable carrier " refers to: one or more consistency solids or liquid filler or gelatinous mass, they are suitable for people uses, and must have enough purity and enough low toxicity." consistency " referred to herein as each component energy and compound of the present invention and blending mutually between them in composition, and the drug effect of not obvious reduction compound.Pharmaceutically acceptable carrier part example has Mierocrystalline cellulose and derivative (as Xylo-Mucine, ethyl cellulose sodium, cellulose ethanoate etc.) thereof, gelatin, talcum, solid lubricant (as stearic acid, Magnesium Stearate), calcium sulfate, vegetables oil (as soya-bean oil, sesame oil, peanut oil, olive wet goods), polyvalent alcohol (as propylene glycol, glycerine, N.F,USP MANNITOL, sorbyl alcohol etc.), emulsifying agent (as tween ), wetting agent (as sodium lauryl sulphate), tinting material, seasonings, stablizer, antioxidant, sanitas, apirogen water etc.
5-HT2a acceptor is Gq coupled receptor, connects phospholipid inositol signal path.The method for screening active ingredients of the compounds of this invention can be luciferase reporter gene detection method.Its principle is extracellular signaling molecule and cell surface G protein coupling receptor (as 5-HT2a acceptor) combination in phosphatidylinositols signal path; activate the Phospholipase C (PLC-β) on plasma membrane; make on plasma membrane 4; 5-bisphosphate phosphatidylinositols (PIP2) is hydrolyzed into 1; 4; 5-InsP3 (IP3) and two second messengers of DG (DG); extracellular signal is converted to intracellular signal, and this signalling system is called again " double messenger system " (double messenger system).The IP3 part door calcium channel of IP3 in endoplasmic reticulum is combined, and opens calcium channel, makes Ca in born of the same parents 2+ionic concn raises.Thereby calcium current makes the phosphorylation of CREB by CaMKII and CaMKIV, thereby cause the expression of downstream gene (as luciferase reporter gene pCRE-luc).Therefore can detect by luciferase reporter gene pCRE-luc the activation situation of acceptor.
Major advantage of the present invention comprises:
1. compound of the present invention has excellent insecticidal activity, and especially can effectively kill lepidopterous insects or suppress taking food of lepidopterous insects, growth, and can be used for preventing and treating nematode, for example Meloidogyne incognita.
2. compound of the present invention not only contributes to the further research of insect 5-HT acceptor, and can be used as people 5-HT2a receptors ligand.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment are only not used in and limit the scope of the invention for the present invention is described.The experimental technique of unreceipted actual conditions in the following example, conventionally according to normal condition, such as people such as Sambrook, molecular cloning: laboratory manual (New York:Cold Spring Harbor Laboratory Press, 1989) condition described in, or the condition of advising according to manufacturer.Unless otherwise indicated, otherwise per-cent and umber calculate by weight.
Embodiment 1: piperazinedione intermediate 5a's is synthetic
(1) get ornithine hydrochloride 1a (337mg, 2mmol), tert-Butyl dicarbonate ((Boc) 2o) (1310mg, 6mmol), triethylamine (Et 3n) (404mg, 4mmol) adds in 6ml acetone and 6ml water and dissolves, stirring at room, and TCL follows the tracks of reaction.After having reacted, acetone is removed in first underpressure distillation, then uses dichloromethane extraction 3 times.The water washing of organic phase saturated common salt, anhydrous magnesium sulfate drying, vacuum rotary steam, except desolventizing, obtains the crude product of compound 2a.
(2) in 100ml round-bottomed flask, add the first step to react the crude product of the compound 2a obtaining, tryptophan methyl ester hydrochloride (1019mg, 4mmol), then add triethylamine (6mmol), HOBt (297mg, 2.2mmol), EDCl (460mg, 2.4mmol), add 30ml methylene dichloride, ice bath stirs 1 hour, then stirring at room 15 hours.After having reacted, reaction solution washes with water, separatory, and methylene dichloride is removed in organic phase underpressure distillation, the crude product obtaining is crossed to post and purify, and obtains compound 3a.
(3) compound 3a is dissolved in methylene dichloride, adds the trifluoroacetic acid of 5 times of equivalents, stirring at room is after 12 hours, and vacuum rotary steam is removed trifluoroacetic acid and methylene dichloride, and obtaining brown liquid is the crude product of 4a.The crude product of 4a is dissolved in 20ml propyl carbinol, is slowly added drop-wise in the propyl carbinol of 20ml backflow, TLC follows the tracks of reaction process.After having reacted, propyl carbinol is removed in underpressure distillation, obtains the crude product of compound 5a.Crude product methylene dichloride: methyl alcohol=95:5 washing, filter, obtain pure compound 5a, overall yield of reaction is 47%. 1HNMR(400MHz,DMSO)δ11.15(s,1H),8.15(d,J＝1.7Hz,1H),8.06(s,1H),7.91(s,2H),7.57(d,J＝7.9Hz,1H),7.33(d,J＝8.0Hz,1H),7.06-6.93(m,3H),6.94(t,J＝7.2Hz,1H),4.12(t,J＝7.9Hz,1H),3.53(s,1H),3.40(s,1H),3.23(dd,J＝14.4,4.2Hz,1H),3.05(dd,J＝14.4,4.4Hz,1H),2.31(t,J＝7.4Hz,2H),1.14-0.82(m,3H),0.72-0.54(m,1H)。
Embodiment 2: piperazinedione carbamide compounds 10a-1's is synthetic
In 50ml round-bottomed flask, add triphosgene (BTC) (223mg, 0.75mmol), be dissolved in 5ml methylene dichloride.Again aniline 6a (140mg, 1.5mmol) and triethylamine (152mg, 1.5mmol) are dissolved in to 5ml methylene dichloride, in the flask before being added drop-wise to, ice bath stirs, and drip off about half an hour, and stirring at room (TLC follows the tracks of reaction) obtains compound 7a.Get again a 50ml round-bottomed flask, compound 5a (300mg, 1mmol) is dissolved in 1ml DMF, and add triethylamine (101mg, 1mmol), magnetic agitation.Back sluggish is added drop-wise in flask to room temperature reaction.(TLC follows the tracks of reaction) after dropwising, reacts completely.Underpressure distillation is removed after the solvent in reaction system, and after washing with water, the crude product obtaining uses column chromatography purification (methylene chloride/methanol (V/V=10:1) wash-out) and obtains compound 10a, yield 70%. 1H?NMR(400MHz,DMSO)δ10.86(d,J＝14.6Hz,1H),8.36(s,1H),8.00(dd,J＝24.5,13.8Hz,2H),7.58(d,J＝7.8Hz,1H),7.44-6.82(m,9H),5.83(t,J＝5.3Hz,1H),4.12(t,J＝7.8Hz,1H),3.55(t,J＝7.8Hz,1H),3.14(ddd,J＝84.7,14.5,4.2Hz,2H),2.78-2.55(m,2H),1.12-0.57(m,4H). 13C?NMR(101MHz,DMSO)δ167.60,167.43,155.52,141.03,136.42,129.08,128.28,125.03,121.34,121.24,119.42(2C),118.81,117.98(2C),111.56,109.15,55.90,54.18,38.96,31.39,29.49,25.01.
Embodiment 3: piperazinedione thiourea 11a-1's is synthetic
In 50ml round-bottomed flask, aniline 6a (140mg, 1.5mmol), Isosorbide-5-Nitrae-diazabicylo [2.2.2] octane DABCO (336mg, 3mmol) joins in THF solution, slowly drips CS 2(228mg, 3mmol), after stirring at room 24h, leach solid and wash 3 times with THF, solid suspension, in THF solvent, is cooled to below 0 ℃, BTC (150mg, 0.75mmol) is dissolved in to solvent and splashes into, under room temperature, react 2h, stirring at room 5h, by reaction solution suction filtration, after filtrate is spin-dried for, petroleum ether dissolution, elimination insolubles, obtains the crude product of lsothiocyanates.The crude product of lsothiocyanates is dissolved in to methyl alcohol, adds 5a (300mg, 1mmol), triethylamine (152mg, 1.5mmol), stirring at room, TLC follows the tracks of reaction process, after completion of the reaction, steaming desolventizes, and column chromatography for separation is purified, and obtains target compound 11a, yield 64%. 1H?NMR(400MHz,DMSO)δ10.88(d,J＝1.6Hz,1H),9.46(s,1H),8.08-7.95(m,2H),7.58(d,J＝7.9Hz,1H),7.49-7.26(m,6H),7.14-6.88(m,4H),4.12(d,J＝1.3Hz,1H),3.58(d,J＝7.9Hz,1H),3.25(dd,J＝14.4,4.5Hz,1H),3.16-2.98(m,3H),1.13-0.85(m,3H),0.72-0.53(m,1H). 13C?NMR(101MHz,DMSO)δ180.64,167.67,167.48,139.75,136.41,129.04(2C),128.25,125.02,124.51,123.40(2C),121.28,119.40,118.83,111.61,109.16,55.91,54.09,43.64,31.43,29.57,23.93.
Embodiment 4: piperazinedione amides 14a-1's is synthetic
In 50ml round-bottomed flask, 4-cyanobenzoic acid 12a (177mg, 1.2mmol), compound 5a (300mg, 1mmol), 1-hydroxy benzo triazole (HOBt) (162mg, 1.2mmol), 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDCI) (230mg, 1.2mmol), triethylamine (152mg, 1.5mmol) be dissolved in 2ml DMF, magnetic agitation, room temperature reaction, makes its 12h that reacts completely (TLC follows the tracks of reaction).The DMF in reaction system is removed in underpressure distillation, the crude product deionized water wash obtaining, then use washed with dichloromethane, column chromatography for separation is purified and is obtained compound 14a, yield 72%. 1H?NMR(400MHz,DMSO)δ10.87(s,1H),8.49(s,1H),8.03(d,J＝16.3Hz,2H),7.95(s,4H),7.57(d,J＝7.8Hz,1H),7.29(d,J＝8.0Hz,1H),7.07(s,1H),7.02(t,J＝7.4Hz,1H),6.93(t,J＝7.4Hz,1H),4.13(t,J＝5.4Hz,1H),3.59(t,J＝5.4Hz,1H),3.23(dd,J＝14.3,4.0Hz,1H),3.06(dd,J＝14.3,3.9Hz,1H),2.93(ddd,J＝30.1,12.9,6.3Hz,2H),1.18-0.90(m,3H),0.75-0.51(m,1H). 13C?NMR(101MHz,DMSO)δ167.71,167.54,165.11,139.10,136.41,132.82(2C),128.47(2C),128.23,124.99,121.26,119.36,118.85,118.81,113.88,111.58,109.17,55.85,54.12,39.28,31.39,29.49,24.39.
Embodiment 5: piperazinedione secondary-amine compound 15a-6's is synthetic
In 50ml round-bottomed flask, compound 5a (300mg, 1mmol), phenyl aldehyde 13a (145mg, 1.2mmol) be dissolved in 1mlDMF, after stirring at room 2h, add sodium triacetoxy borohydride (318mg, 1.5mmol), stirred overnight at room temperature, crosses post separating-purifying, productive rate 65%. 1H?NMR(400MHz，DMSO)δ10.96(d,J＝1.7Hz,1H),8.12(d,J＝2.1Hz,1H),8.03(d,J＝2.2Hz,1H),7.57(d,J＝7.8Hz,1H),7.35-7.21(m,5H),7.07(d,J＝2.2Hz,1H),7.02-6.90(m,2H),4.13(d,J＝1.3Hz,1H),3.95-3.83(m,2H),3.56(t,J＝4.9Hz,1H),3.24(dd,J＝14.4,4.3Hz,1H),3.05(dd,J＝14.4,4.6Hz,1H),2.44-2.35(m,2H),2.33(s,3H),1.21-1.00(m,2H),0.99-0.82(m,1H),0.63-0.43(m,1H). 13C?NMR(101MHz,DMSO)δ167.75,167.32,138.74,136.34,130.23(2C),129.70,129.64(2C),128.24,125.17,121.29,119.44,118.88,111.56,109.14,55.89,53.75,50.14,46.22,31.01,29.40,21.56,21.31.
Embodiment 6: piperazinedione amides 14b-1's is synthetic
In 50ml round-bottomed flask, 4-bromo-benzoic acid 12b (240mg, 1.2mmol), compound 5b (300mg, 1mmol), 1-hydroxy benzo triazole (HOBt) (162mg, 1.2mmol), 1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride (EDCI) (230mg, 1.2mmol), triethylamine (152mg, 1.5mmol) be dissolved in 2ml DMF, magnetic agitation, room temperature reaction, makes its 12h that reacts completely (TLC follows the tracks of reaction).The DMF in reaction system is removed in underpressure distillation, the crude product deionized water wash obtaining, then use washed with dichloromethane, column chromatography for separation is purified and is obtained compound 14b, yield 79%. 1H?NMR(400MHz,DMSO)δ8.38(t,J＝5.4Hz,1H),8.13(s,1H),8.05(s,1H),7.79(d,J＝8.5Hz,2H),7.68(d,J＝8.4Hz,2H),7.14(qd,J＝14.7,7.4Hz,5H),4.19(s,1H),3.63(s,1H),3.14(dd,J＝13.4,3.6Hz,1H),2.97(d,J＝6.1Hz,2H),2.85(dd,J＝13.5,4.8Hz,1H),1.15-0.87(m,3H),0.77(d,J＝7.1Hz,1H). 13C?NMR(100MHz,DMSO)δ166.9,166.1,164.9,136.0,133.7,131.2(2C),130.2(2C),129.2(2C),127.9(2C),126.4,124.6,55.2,53.6,38.8,38.0,30.7,23.9.
Embodiment 7: piperazinedione carbamide compounds 15b-1's is synthetic
In 50ml round-bottomed flask, add triphosgene (BTC) (223mg, 0.75mmol), be dissolved in 5ml methylene dichloride.Again 4-5-trifluoromethylaniline 6a (240mg, 1.5mmol) and triethylamine (152mg, 1.5mmol) are dissolved in to 5ml methylene dichloride, in flask before being added drop-wise to, ice bath stirs, and drip off about half an hour, and stirring at room (TLC follows the tracks of reaction) obtains compound 7b.Get again a 50ml round-bottomed flask, compound 5b (300mg, 1mmol) is dissolved in 1ml DMF, and add triethylamine (101mg, 1mmol), magnetic agitation.Back sluggish is added drop-wise in flask to room temperature reaction.(TLC follows the tracks of reaction) after dropwising, reacts completely.Underpressure distillation is removed after the solvent in reaction system, and after washing with water, the crude product obtaining uses column chromatography purification (methylene chloride/methanol (V/V=10:1) wash-out) and obtains compound 10a, yield 70%. 1H?NMR(400MHz,DMSO)δ8.85(s,1H),8.13(s,1H),8.06(s,1H),7.58(q,J＝8.9Hz,4H),7.30-7.10(m,5H),6.08(t,J＝5.6Hz,1H),4.20(s,1H),3.62(s,1H),3.14(d,J＝3.8Hz,1H),2.90-2.80(m,3H),1.11(dd,J＝10.1,4.8Hz,1H),1.02-0.84(m,2H),0.79-0.63(m,1H). 13C?NMR(100MHz,DMSO)δ166.9,166.2,154.6,144.2,136.0,130.2(2C),127.9(2C),125.9(q,J＝4Hz),126.5,124.6(q,J＝270Hz),120.8(q,J＝31Hz),117.1(2C),55.3,53.6,48.5,38.6,38.1,30.6,24.4.
Preparation in accordance with the present invention (as embodiment 1～7), adopts the following compound of different raw materials.
1H?NMR(400MHz,DMSO)δ10.89(s,1H),8.26(s,1H),8.01(d,J＝26.4Hz,2H),7.58(d,J＝7.9Hz,1H),7.26(dt,J＝24.7,12.3Hz,3H),7.11-6.87(m,5H),5.79(t,J＝5.2Hz,1H),4.12(t,J＝7.8Hz,1H),3.55(t,J＝7.8Hz,1H),3.14(ddd,J＝84.8,14.4,4.2Hz,2H),2.75-2.55(m,2H),2.21(s,3H),1.09-0.57(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.6,138.4,136.4,130.0,129.4(2C),128.2,125.0,121.2,119.4,118.8,118.1(2C),111.5,109.1,55.9,54.1,38.9,31.4,29.4,25.0,20.7.
1H?NMR(400MHz,DMSO)δ10.88(s,1H),8.16(s,1H),8.04(s,1H),7.98(s,1H),7.57(s,1H),7.26(d,J＝8.9Hz,2H),7.00(d,J＝48.7Hz,4H),6.80(d,J＝8.8Hz,2H),5.72(t,J＝5.3Hz,1H),4.12(s,1H),3.69(s,3H),3.53(t,J＝5.3Hz,1H),3.25-2.98(m,2H),2.73-2.56(m,2H),1.06-0.58(m,4H). 13C?NMR(100MHz,DMSO)δ167.7,167.5,155.6,138.5,136.4,130.0,128.28,126.23(2C),125.0,121.2,119.4,118.8,114.1(2C),111.6,109.1,55.9,55.6，54.2,38.9,31.4,29.5,25.1
1H?NMR(400MHz,DMSO)δ10.80(d,J＝69.9Hz,1H),8.20(s,1H),8.02(d,J＝26.8Hz,2H),7.58(d,J＝7.9Hz,1H),7.32(d,J＝8.1Hz,1H),7.10-6.85(m,5H),6.52(s,1H),5.80(t,J＝7.8Hz,1H),4.12(t,J＝7.8Hz,1H),3.55(t,J＝7.8Hz,1H),3.34-3.04(m,2H),2.78-2.54(m,2H),2.19(s,6H),1.09-0.57(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.5,140.8,137.9(2C),136.4,128.2,125.0,123.0,121.2,119.4,118.8,115.8(2C),111.5,109.1,55.9,54.2,38.9,31.4,29.4,25.0,21.6(2C).
1H?NMR(400MHz,DMSO)δ10.88(s,1H),8.95(s,1H),8.02(d,J＝29.2Hz,2H),7.71-7.50(m,5H),7.32(d,J＝8.1Hz,1H),6.98(ddd,J＝33.1,19.8,12.4Hz,3H),6.08(t,J＝5.2Hz,1H),4.12(t,J＝7.8Hz,1H),3.54(t,J＝7.8Hz,1H),3.29-2.97(m,2H),2.82-2.56(m,2H),0.98-0.51(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,154.9,145.4,136.4,133.6(2C),128.2,125.0,121.2,119.9,119.4,118.8,117.8(2C),111.5,109.1,102.6,55.8,54.1,38.9,31.2,29.4,24.7.
1H?NMR(400MHz,DMSO)δ10.88(s,1H),9.40(s,1H),8.15(s,1H),8.06(s,1H),8.01-7.91(m,2H),7.63(dd,J＝38.6,8.1Hz,2H),7.31(d,J＝8.1Hz,1H),7.09-6.87(m,3H),6.27(t,J＝5.2Hz,1H),4.12(t,J＝7.8Hz,1H),,3.56(t,J＝7.8Hz,1H),3.30-2.97(m,2H),2.81-2.58(m,2H),0.98-0.51(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,154.6,145.9,136.6,136.4,132.1(t,J＝31Hz),128.2,125.0,123.5(t,J＝273Hz),121.2,120.5,119.4,118.7,116.6,115.1(t,J＝6Hz),111.5,109.1,99.1,55.8,54.1,39.0,31.2,29.4,24.6.
1H?NMR(400MHz,DMSO)δ10.88(s,1H),8.64(s,1H),8.13-7.94(m,3H),7.58(d,J＝7.9Hz,1H),7.31(d,J＝8.1Hz,1H),7.08-6.89(m,3H),6.43(t,J＝5.2Hz,1H),4.12(s,1H),3.55(s,1H),3.30-2.95(m,2H),2.71-2.56(m,2H),1.10-0.47(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,166.5(d,J＝214Hz),167.3,154.7,136.4,128.3,126.9(d,J＝206Hz),125.5(d,J＝106Hz),125.0,121.2,120.3(d,J＝206Hz),119.4,118.8,111.5,110.3(d,J＝288Hz),109.1,102.1(d,J＝25Hz),55.9,54.1,38.9,31.3,29.4,24.5.
1H?NMR(400MHz,DMSO)δ10.92(s,1H),8.06(s,1H),7.99(s,1H),7.87(s,1H),7.59(d,J＝7.8Hz,1H),7.44(s,1H),7.34(d,J＝8.1Hz,1H),7.13-7.00(m,4H),6.95(t,J＝7.4Hz,1H),6.12(t,J＝5.0Hz,1H),4.12(t,J＝7.8Hz,1H),3.55(t,J＝7.8Hz,1H),3.25(dd,J＝14.4,3.9Hz,1H),3.04(dd,J＝14.2,4.2Hz,1H),2.73-2.51(m,2H),1.11-0.51(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.44,159.5(d,J＝5Hz),157.1(d,J＝5Hz),155.3,136.4,128.2,126.6(t,J＝10Hz),125.0,121.2,119.1,118.8,116.5(t,J＝8Hz),112.1,111.9,111.5,109.1,55.9,54.1,39.4,31.4,29.4,25.0.
1H?NMR(400MHz,DMSO)δ10.92(s,1H),9.35(s,1H),8.13(d,J＝9.0Hz,2H),8.07(s,1H),7.99(s,1H),7.60(t,J＝9.5Hz,3H),7.32(d,J＝8.0Hz,1H),7.10-6.88(m,3H),6.23(t,J＝5.2Hz,1H),4.13(t,J＝7.8Hz,1H),3.57(t,J＝7.8Hz,1H),3.28-3.18(m,1H),3.11-2.99(m,1H),2.82-2.58(m,2H),1.12-0.54(m,4H). 13C?NMR(100MHz,DMSO)δ167.5,167.3,154.7,147.7,140.7,136.4,128.2,125.6(2C),125.0,121.2,119.4,118.8,117.1(2C),111.5,109.2,55.8,54.1,39.0,31.2,29.4,24.6.
1H?NMR(400MHz,DMSO)δ10.80(d,J＝68.3Hz,1H),8.91(s,1H),8.54(s,1H),8.02(d,J＝28.6Hz,2H),7.58(d,J＝7.9Hz,1H),7.51-7.41(m,3H),7.32(d,J＝8.5Hz,1H),7.11-6.89(m,3H),5.90(t,J＝5.2Hz,1H),4.12(t,J＝7.82Hz,1H),3.55(t,J＝7.8Hz,1H),3.25(dd,J＝14.3,4.1Hz,1H),3.04(dd,J＝14.4,4.3Hz,1H),2.79-2.55(m,2H),1.11-0.43(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.3,140.4,136.4,131.9,131.7,128.2,125.0,121.2,120.6,119.8,119.4,118.8,112.5,111.5,109.1,55.9,54.1,38.9,31.3,29.4,24.9.
1H?NMR(400MHz,DMSO)δ10.95(s,1H),8.28(s,1H),8.12-7.93(m,3H),7.58(d,J＝7.9Hz,1H),7.32(d,J＝8.0Hz,1H),7.28-7.17(m,1H),7.06-6.87(m,4H),6.42(t,J＝5.0Hz,1H),4.12(t,J＝7.82Hz,1H),3.55(t,J＝7.82Hz,1H),3.26(dd,J＝14.4,3.8Hz,1H),3.03(dd,J＝14.4,3.8Hz,1H),2.74-2.57(m,2H),1.07-0.59(m,4H). 13C?NMR(100MHz,DMSO)δ167.5,167.3,156.4(dd,J＝239,11Hz),155.2,151.2(dd,J＝243,12Hz)136.4,128.2,125.4(dd,J＝10,4Hz),125.02,121.6(t,J＝7,4Hz),121.2,119.4,118.7,111.5,111.2(dd,J＝224Hz),109.0,103.9(t,J＝27,23Hz),55.9,54.1,39.0,31.4,29.4,24.8.
1H?NMR(400MHz,DMSO)δ10.88(s,1H),8.84(s,1H),8.01(dd,J＝27.6,2.1Hz,2H),7.62-7.49(m,5H),7.32(d,J＝8.1Hz,1H),7.09-6.89(m,3H),6.02(t,J＝5.5Hz,1H),4.12(t,J＝5.5Hz,1H),3.55(t,J＝5.5Hz,1H),3.25(dd,J＝14.4,4.3Hz,1H),3.04(dd,J＝14.4,4.6Hz,1H),2.76-2.58(m,2H),1.10-0.49(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.1,144.7,136.4,128.2,126.4,126.3,125.0(q,J＝267Hz),125.0,121.2(q,J＝32Hz),121.2,119.4,118.8,117.5(2C),111.5,109.1,55.8,54.1,38.9,31.3,29.4,24.8.
1H?NMR(400MHz,DMSO)δ10.93(s,1H),9.02(s,1H),8.05(s,1H),7.97(s,1H),7.84(d,J＝8.6Hz,2H),7.58(d,J＝7.9Hz,1H),7.50(d,J＝8.6Hz,2H),7.31(d,J＝8.0Hz,1H),6.99(ddd,J＝33.0,12.6,4.4Hz,3H),6.12(t,J＝5.4Hz,1H),4.12(t,J＝5.4Hz,1H),3.56(t,J＝5.4Hz,1H),3.25(dd,J＝14.4,4.2Hz,1H),3.03(dd,J＝14.5,4.5Hz,1H),2.77-2.55(m,2H),1.08-0.50(m,4H). 13C?NMR(100MHz,DMSO)δ196.6,167.5,167.3,155.0,145.7,136.4,130.1(2C),128.2,125.0,121.2,119.4,118.7,116.8(2C),111.5,109.1,99.9,55.9,54.1,39.0,31.3,29.4,26.7,24.8.
1H?NMR(400MHz,DMSO)δ10.86(s,1H),8.50(s,1H),8.00(dd,J＝25.9,1.9Hz,2H),7.58(d,J＝7.8Hz,1H),7.44-7.20(m,5H),7.10-6.85(m,3H),5.87(t,J＝5.5Hz,1H),4.10(t,J＝5.2Hz,1H),3.55(t,J＝5.2Hz,1H),3.24(dd,J＝14.4,4.4Hz,1H),3.04(dd,J＝14.4,4.5Hz,1H),2.79-2.56(m,2H),1.11-0.59(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.3,140.0,136.4,128.8(2C),128.2,125.0,124.7,121.2,119.4(2C),119.4,118.8,111.5,109.1,55.8,54.1,38.9,31.3,29.4,24.9.
1H?NMR(400MHz,DMSO)δ10.88(s,1H),8.77(s,1H),8.07-7.91(m,3H),7.57(t,J＝7.0Hz,1H),7.49-7.40(m,2H),7.32(d,J＝8.0Hz,1H),7.21(d,J＝7.0Hz,1H),7.10-6.99(m,2H),6.98-6.89(m,1H),5.97(t,J＝5.6Hz,1H),4.12(t,J＝5.6Hz,1H),3.56(t,J＝5.6Hz,1H),3.25(dd,J＝14.4,4.3Hz,1H),3.04(dd,J＝14.4,4.6Hz,1H),2.78-2.55(m,2H),1.10-0.53(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.3,141.8,136.4,130.1,129.8(q,J＝31Hz),128.2,125.0,124.7(q,J＝270Hz),121.4,121.2,119.4,118.8,117.5(q,J＝3Hz),113.8(q,J＝4Hz),111.6,109.1,55.9,54.1,38.9,31.3,29.4,24.8.
1H?NMR(400MHz,DMSO)δ10.88(s,1H),8.77(s,1H),8.07-7.91(m,3H),7.57(t,J＝7.0Hz,1H),7.49-7.40(m,2H),7.32(d,J＝8.0Hz,1H),7.21(d,J＝7.0Hz,1H),7.10-6.99(m,2H),6.98-6.89(m,1H),5.97(t,J＝5.6Hz,1H),4.12(t,J＝5.6Hz,1H),3.56(t,J＝5.6Hz,1H),3.25(dd,J＝14.4,4.3Hz,1H),3.04(dd,J＝14.4,4.6Hz,1H),2.78-2.55(m,2H),1.10-0.53(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.3,141.8,136.4,130.1,129.8(q,J＝31Hz),128.2,125.0,124.7(q,J＝270Hz),121.4,121.2,119.4,118.8,117.5(q,J＝3Hz),113.8(q,J＝4Hz),111.6,109.1,55.9,54.1,38.9,31.3,29.4,24.8.
1H?NMR(400MHz,DMSO)δ10.88(d,J＝1.6Hz,1H),8.44(d,J＝8.8Hz,1H),8.30(s,1H),8.06(d,J＝2.0Hz,1H),7.98(d,J＝2.1Hz,1H),7.78(d,J＝1.7Hz,1H),7.60(dd,J＝11.4,4.7Hz,2H),7.32(d,J＝8.1Hz,1H),7.08-6.89(m,4H),4.12(s,1H),3.55(s,1H),3.30-2.99(m,2H),2.80-2.58(m,2H),1.10-0.51(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.3,154.5,141.0,136.4,128.2,126.5(q,J＝4Hz),125.1(q,J＝4Hz),125.0(q,J＝270Hz),122.5(q,J＝32Hz),121.2,120.9,120.0,119.4,118.8,111.5,109.1,100.0,55.9,54.1,39.0,31.4,29.4,24.5.
1H?NMR(400MHz,DMSO)δ10.98(s,1H),8.33(s,1H),8.15-8.04(m,2H),7.98(s,1H),7.58(d,J＝7.9Hz,1H),7.32(d,J＝8.0Hz,1H),7.20-6.87(m,6H),6.55(t,J＝5.1Hz,1H),4.12(t,J＝5.4Hz,1H),3.57(t,J＝5.4Hz,1H),3.25(dd,J＝14.4,4.3Hz,1H),3.04(dd,J＝14.4,4.5Hz,1H),2.78-2.63(m,2H),1.10-0.53(m,4H). 13C?NMR(100MHz,DMSO)δ167.5,167.4,155.2,152.0(d,J＝239Hz),136.4,128.9(d,J＝10Hz),128.3,125.0,124.7(d,J＝4Hz),121.8(d,J＝8Hz),121.2,120.6,119.4,118.7,115.1(d,J＝9Hz),111.5,109.0,55.9,54.1,39.0,31.4,29.4,24.8.
1H?NMR(400MHz,DMSO)δ10.87(s,1H),9.11(s,1H),8.17(dd,J＝5.0,1.1Hz,1H),8.00(dd,J＝20.2,2.0Hz,3H),7.71-7.54(m,2H),7.31(d,J＝8.0Hz,2H),7.08-6.86(m,4H),4.11(t,J＝5.4Hz,1H),3.54(t,J＝5.4Hz,1H),3.25(dd,J＝14.4,4.2Hz,1H),3.03(dd,J＝14.4,4.6Hz,1H),2.74(dd,J＝12.7,6.7Hz,2H),1.15-0.43(m,4H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.1,153.9,147.1,138.5,136.4,128.2,125.0,121.2,119.4,118.8,117.1,111.9,111.5,109.1,55.9,54.1,38.9,31.5,29.5,24.9.
1H?NMR(400MHz,DMSO)δ10.86(d,J＝10.3Hz,1H),10.27(d,J＝10.0Hz,1H),8.02(dd,J＝32.1,10.4Hz,2H),7.64-7.48(m,1H),7.30(dd,J＝13.8,10.2Hz,2H),7.10-6.80(m,4H),6.24(s,1H),4.11(s,1H),3.55(s,1H),3.24(d,J＝8.9Hz,1H),3.04(d,J＝11.5Hz,1H),2.68(s,2H),1.06-0.96(m,1H),0.77(s,2H),0.56(s,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.3,160.5,154.1,137.7,136.4,128.2,125.0,121.2,119.5,118.8,112.1,111.5,109.1,55.9,541,39.1,31.2,29.5,24.7.
1H?NMR(400MHz,DMSO)δ10.89(s,1H),8.85(s,1H),8.01(dd,J＝19.1,15.3Hz,2H),7.89(d,J＝5.7Hz,1H),7.58(d,J＝7.8Hz,1H),7.32(d,J＝8.1Hz,1H),7.10-6.82(m,5H),6.07(s,1H),4.12(s,1H),3.79(s,3H),3.55(s,1H),3.25(dd,J＝14.3,4.1Hz,1H),3.03(dd,J＝14.4,4.4Hz,1H),2.72-2.60(m,2H),1.04-1.02(m,1H),0.79-0.76(m?2H),0.58-0.57(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,164.9,154.8,147.1,136.4,134.6,128.2,125.0,121.2,119.4,118.8,111.5,109.1,107.5,96.6,55.8,54.1,53.4,38.9,31.2,29.4,24.7.
1H?NMR(400MHz,DMSO)δ10.86(s,1H),10.05(s,1H),8.05(s,1H),7.97(s,1H),7.58(d,J＝7.8Hz,1H),7.31(d,J＝8.0Hz,1H),7.11-6.86(m,4H),6.22(s,1H),4.11(s,1H),3.54(s,1H),3.25(dd,J＝14.3,4.1Hz,1H),3.03(dd,J＝14.4,4.4Hz,1H),2.78-2.61(m,2H),2.27(s,3H),1.10-0.95(m,1H),0.78-0.75(m,2H),0.59-0.54(m,1H). 13C?NMR(100MHz,DMSO)δ167.5,167.3,158.8,154.0,136.4,134.6,128.2,125.0,124.7,121.2,119.4,118.8,111.5,109.1,55.8,54.0,39.1,31.2,29.4,24.7,11.5.
1H?NMR(400MHz,DMSO)δ10.86(s,1H),10.77(s,1H),8.97(s,1H),8.02(dd,J＝34.8,1.5Hz,2H),7.58(d,J＝7.8Hz,1H),7.31(d,J＝8.0Hz,1H),6.99(ddd,J＝31.8,13.7,4.6Hz,3H),6.33(s,1H),4.12(s,1H),3.56(s,1H),3.26(dd,J＝14.4,4.1Hz,1H),3.03(dd,J＝14.4,4.5Hz,1H),2.76-2.70(m,2H),1.06-0.99(m,1H),0.88-0.69(m,2H),0.63-0.54(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.3,160.9,153.7,147.9,136.4,128.3,125.1,121.2,119.4,118.8,111.5,109.1,99.9,55.8,54.0,31.1,29.4,24.5.
1H?NMR(400MHz,DMSO)δ10.87(s,1H),10.60(s,1H),8.07(s,1H),7.99(s,1H),7.86(d,J＝7.4Hz,1H),7.60(t,J＝7.5Hz,2H),7.33(d,J＝7.5Hz,2H),7.21(d,J＝6.9Hz,1H),7.13-6.87(m,3H),6.49(s,1H),4.13(s,1H),3.58(s,1H),3.27(d,J＝13.7Hz,1H),3.04(d,J＝11.6Hz,1H),2.73(s,2H),1.08-0.95(m,1H),0.89-0.70(m,2H),0.68-0.56(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.3,160.2,154.0,149.5,136.4,131.8,128.3,126.1,125.1,123.0,121.7,121.2,120.0,119.4,118.8,111.5,109.1,55.9,54.1,39.2,31.2,29.4,24.5.
1H?NMR(400MHz,DMSO)δ10.86(d,J＝9.0Hz,1H),9.17(d,J＝10.3Hz,1H),8.19-7.84(m,3H),7.82-7.69(m,1H),7.58(d,J＝8.4Hz,1H),7.39(s,1H),7.29(t,J＝19.6Hz,1H),7.15-6.84(m,3H),4.11(s,1H),3.80(s,3H),3.54(s,1H),3.24(s,1H),3.05(d,J＝9.9Hz,1H),2.68(dd,J＝17.2,9.8Hz,2H),1.10-0.95(m,1H),0.78-0.75(m,2H),0.59-0.54(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,164.0,154.1,147.0,136.4,132.8,128.2,125.0,122.3,121.2,119.4,118.8,111.5,109.1,106.0,55.8,54.2,52.1,39.3,31.5,29.5,24.7.
1H?NMR(400MHz,DMSO)δ10.93(s,1H),10.85(s,1H),7.95(dd,J＝44.3,19.3Hz,4H),7.59(s,3H),7.32(d,J＝7.2Hz,1H),7.17-6.87(m,3H),6.37(s,1H),4.12(s,1H),3.57(s,1H),3.24(d,J＝12.4Hz,1H),3.04(d,J＝12.4Hz,1H),2.74(s,2H),1.10-0.95(m,1H),0.78-0.75(m,2H),0.59-0.54(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.3,136.4,135.2,129.8,129.7,128.7,128.2,125.0,123.7,121.2,119.4,118.8,111.5,111.4,109.1,99.9,55.8,54.0,39.2,31.1,29.4,24.5.
1H?NMR(400MHz,DMSO)δ10.87(s,1H),8.43(s,1H),8.02(d,J＝16.3Hz,3H),7.77(dd,J＝22.1,8.4Hz,2H),7.57(d,J＝7.8Hz,1H),7.29(d,J＝8.0Hz,1H),7.13-6.88(m,3H),4.12(t,J＝5.4Hz,1H),3.59(t,J＝5.4Hz,1H),3.23(dd,J＝14.4,4.2Hz,1H),3.06(dd,J＝14.4,4.1Hz,1H),3.00-2.78(m,2H),1.18-0.90(m,3H),0.75-0.66(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.5,164.2,136.4,135.4,134.2,131.6,131.0,129.5,128.2,127.9,124.9,121.2,119.5,118.8,111.5,109.1,55.8,54.1,39.2,31.4,29.4,24.3.
1H?NMR(400MHz,DMSO)δ10.90(s,1H),8.50(t,J＝4.9Hz,1H),8.03(d,J＝20.0Hz,2H),7.84(s,2H),7.79(s,1H),7.57(d,J＝7.8Hz,1H),7.28(d,J＝8.0Hz,1H),7.13-6.86(m,3H),4.12(t,J＝5.4Hz,1H),3.59(t,J＝5.4Hz,1H),3.23(dd,J＝14.3,4.2Hz,1H),3.06(dd,J＝14.4,4.1Hz,1H),3.00-2.78(m,2H),1.18-0.90(m,3H),0.75-0.66(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.5,163.7,138.2,136.4,134.6(2C),130.8,128.2,126.5(2C),124.9,121.2,119.3,118.7,111.5,109.1,55.8,54.0,39.2,31.3,29.4,24.2.
1H?NMR(400MHz,DMSO)δ10.87(s,1H),8.47(s,1H),8.02(t,J＝10.3Hz,4H),7.84(d,J＝8.1Hz,2H),7.58(d,J＝7.8Hz,1H),7.29(d,J＝8.0Hz,1H),7.08(s,1H),6.98(dt,J＝33.4,7.2Hz,2H),4.13(t,J＝5.4Hz,1H),3.59(t,J＝5.4Hz,1H),3.24(dd,J＝14.4,4.2Hz,1H),3.06(dd,J＝14.4,4.1Hz,1H),3.02-2.84(m,2H),1.18-0.90(m,3H),0.75-0.66(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.5,165.3,138.8,136.4,131.4(q,J＝32Hz),128.5(2C),128.2,125.7(q,J＝4Hz,2C),124.9,124.4(q,J＝270Hz),121.2,119.3,118.8,111.5,109.1,55.8,54.1,39.2,31.4,29.5,24.4.
1H?NMR(400MHz,DMSO)δ10.88(s,1H),8.80(s,1H),8.51(s,1H),8.20(d,J＝7.9Hz,1H),8.03(d,J＝19.1Hz,2H),7.60(dd,J＝24.2,7.9Hz,2H),7.28(d,J＝7.9Hz,1H),7.16-6.82(m,3H),4.13(t,J＝4.2Hz,1H),3.59(t,J＝4.2Hz,1H),3.24(d,J＝10.7Hz,1H),3.06(d,J＝10.7Hz,1H),2.92(dd,J＝15.3,6.4Hz,2H),1.09-0.90(m,3H),0.75-0.64(m,1H).
13C?NMR(100MHz,DMSO)δ167.7,167.5,163.9,152.8,149.3,138.9,136.4,129.9,128.2,125.0,124.5,121.2,119.3,118.8,111.5,109.1,55.8,54.1,39.2,31.3,29.4,24.3.
1H?NMR(400MHz,DMSO)δ10.88(s,1H),8.13(t,J＝4.9Hz,1H),8.01(t,J＝10.5Hz,2H),7.72(d,J＝8.0Hz,2H),7.58(d,J＝7.9Hz,1H),7.30(d,J＝8.0Hz,1H),7.25(d,J＝7.9Hz,2H),7.08(s,1H),7.03(t,J＝7.5Hz,1H),6.94(t,J＝7.4Hz,1H),4.12(t,J＝4.9Hz,1H),3.59(t,J＝4.9Hz,1H),3.23(dd,J＝14.3,4.3Hz,1H),3.07(dd,J＝14.4,4.1Hz,1H),3.00-2.81(m,2H),1.21-0.95(m,3H),0.79-0.68(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.5,166.3,141.2,136.4,132.3,129.1(2C),128.2,127.6(2C),124.9,121.2,119.3,118.8,111.6,109.1,55.8,54.2,39.0,31.4,29.5,24.7,21.3.
1H?NMR(400MHz,DMSO)δ10.88(s,1H),8.31(s,1H),8.02(d,J＝13.2Hz,2H),7.71(dd,J＝37.0,8.2Hz,4H),7.57(d,J＝7.7Hz,1H),7.29(d,J＝7.9Hz,1H),7.08(s,1H),6.98(dt,J＝14.6,7.0Hz,2H),4.12(t,J＝7.4Hz,1H),3.59(t,J＝7.4Hz,1H),3.23(dd,J＝14.1,3.9Hz,1H),3.12-3.02(dd,J＝14.1,3.9Hz,1H),3.00-2.79(m,2H),1.22-0.90(m,3H),0.81-0.67(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.5,165.5,136.4,134.2,131.6(2C),129.7(2C),128.2,125.1,124.9,121.2,119.3,118.8,111.5,109.1,55.8,54.1,39.1,31.4,29.5,24.5.
1H?NMR(400MHz,DMSO)δ10.86(s,1H),9.07-8.88(m,4H),8.04(d,J＝14.6Hz,2H),7.56(d,J＝7.8Hz,1H),7.27(d,J＝8.0Hz,1H),7.11-6.86(m,3H),4.12(t,J＝7.4Hz,1H),305.60(t,J＝7.4Hz,1H),3.23(dd,J＝14.3,4.0Hz,1H),3.11-2.84(m,3H),1.21-0.92(m,3H),0.79-0.68(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.5,162.3,148.5(2C),137.5,136.3,128.2,127.8(2C),125.0,121.2,121.2,119.3,118.8,111.5,109.1,55.8,54.0,39.6,31.4,29.4,24.2.
1H?NMR(400MHz,DMSO)δ10.87(d,J＝1.6Hz,1H),8.22(t,J＝5.5Hz,1H),8.03(dd,J＝10.3,2.1Hz,2H),7.84-7.78(m,2H),7.58(d,J＝7.9Hz,1H),7.54-7.40(m,3H),7.30(d,J＝8.0Hz,1H),7.08(d,J＝2.3Hz,1H),7.06-6.98(m,1H),6.97-6.91(m,1H),4.13(t,J＝7.4Hz,1H),3.60(t,J＝7.4Hz,1H),3.23(dd,J＝14.4,4.6Hz,1H),3.06(dd,J＝14.4,4.5Hz,1H),3.01-2.82(m,2H),1.19-0.94(m,3H),0.80-0.65(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.59,166.5,136.4,135.1,131.4,128.6(2C),128.2,127.5(2C),124.9,121.2,119.3,118.8,111.6,109.1,55.8,54.1,39.0,31.4,29.5,24.6.
1H?NMR(400MHz,DMSO)δ10.87(s,1H),8.01(d,J＝18.9Hz,3H),7.80(d,J＝0.8Hz,1H),7.57(d,J＝7.7Hz,1H),7.29(d,J＝8.1Hz,1H),7.05(d,J＝8.2Hz,2H),7.01(t,J＝7.4Hz,1H),6.93(t,J＝7.4Hz,1H),6.60(dd,J＝3.3,1.7Hz,1H),4.12(t,J＝7.4Hz,1H),3.58(t,J＝7.4Hz,1H),3.21(dd,J＝14.4,4.6Hz,1H),3.09-2.97(dd,J＝14.4,4.6Hz,1H),2.94-2.75(m,2H),1.14-0.87(m,3H),0.76-0.57(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.5,158.0,148.5,145.1,136.4,128.2,124.9,121.2,119.3,118.8,113.4,112.2,111.5,109.1,55.8,54.1,38.2,31.2,29.4,24.5.
1H?NMR(400MHz,DMSO)δ10.87(d,J＝1.7Hz,1H),8.20(t,J＝5.5Hz,1H),8.02(dd,J＝8.7,2.1Hz,2H),7.57(d,J＝7.9Hz,1H),7.30(d,J＝8.0Hz,1H),7.10-6.88(m,5H),6.63(t,J＝2.3Hz,1H),4.12(t,J＝5.1Hz,1H),3.77(s,6H),3.59(t,J＝5.1Hz,1H),3.25(dd,J＝14.4,4.5Hz,1H),3.06(dd,J＝14.4,4.5Hz,1H),3.00-2.80(m,2H),1.21-0.95(m,3H),0.79-0.60(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.5,166.0,160.7(2C),137.2,136.4,128.2,124.9,121.2,119.3,118.8,111.5,109.1,105.5(2C),103.3,55.8(2C),54.1,49.0,39.1,31.4，29.5，24.6.
1H?NMR(400MHz,DMSO)δ11.01(d,J＝1.6Hz,1H),8.07(dd,J＝18.7,2.1Hz,2H),7.60-7.53(m,2H),7.49(t,J＝7.0Hz,1H),7.46-7.36(m,1H),7.24(d,J＝7.9Hz,1H),7.05(d,J＝2.3Hz,1H),6.99-6.85(m,2H),4.11(t,J＝5.1Hz,1H),3.62(s,2H),3.52(t,J＝5.1Hz,1H),3.25(dd,J＝14.4,4.1Hz,1H),3.03(dd,J＝14.4,4.6Hz,1H),2.16-2.00(m,1H),1.12-0.99(m,1H),0.91-0.71(m,2H),0.61-0.47(m,1H). 13C?NMR(100MHz,DMSO)δ167.5,167.4,137.2,136.3,133.8,132.2,131.5,128.8,128.3,127.5,125.1,121.0,119.4,118.7,111.4,109.0,55.8,54.3,49.5,48.5,31.9,29.4,24.3.
1H?NMR(400MHz,DMSO)δ10.93(s,1H),8.21(d,J＝8.3Hz,2H),8.06(d,J＝9.2Hz,2H),7.66-7.51(m,3H),7.24(d,J＝8.0Hz,1H),7.04(d,J＝15.4Hz,1H),6.95(dt,J＝14.7,7.2Hz,2H),4.12(t,J＝7.4Hz,1H),3.76(s,2H),3.53(t,J＝7.4Hz,1H),3.29-3.16(dd,J＝14.4,4.3Hz,1H),3.02(dd,J＝14.4,4.3Hz,1H),2.16-2.00(m,2H),1.14-0.96(m,1H),0.91-0.71(m,2H),0.67-0.42(m,1H). 13C?NMR(100MHz,DMSO)δ167.5,167.4,147.0,136.3,129.7(2C),128.3,125.1,123.7(2C),121.1,119.4,118.7,111.4,109.0,55.8,54.2,51.7,49.0,48.1,31.7,29.3,23.8.
1H?NMR(400MHz,DMSO)δ10.97(d,J＝1.6Hz,1H),8.08(dd,J＝37.7,2.1Hz,2H),7.58(d,J＝7.8Hz,1H),7.55-7.45(m,2H),7.25-7.31(m,3H),7.07(d,J＝2.2Hz,1H),7.03-6.88(m,2H),4.13(t,J＝4.9Hz,1H),4.00-3.87(s,2H),3.56(t,J＝4.9Hz,1H),3.24(dd,J＝14.4,4.2Hz,1H),3.05(dd,J＝14.4,4.6Hz,1H),2.40(t,J＝7.5Hz,2H),1.23-0.83(m,3H),0.65-0.47(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.3,162.7(d,J＝244Hz),136.3,132.6,132.5,129.2,128.2,125.1,121.2,119.4,118.8,116.0,115.8,111.5,109.1,55.8,53.7,49.6,46.3,31.0,29.4,21.5.
1H?NMR(400MHz,DMSO)δ10.97(d,J＝1.7Hz,1H),8.07(dd,J＝36.0,2.1Hz,2H),7.62-7.40(m,5H),7.25(d,J＝8.0Hz,1H),7.11-6.87(m,3H),4.11(t,J＝11.6Hz,1H),3.99-3.83(m,2H),3.56(t,J＝11.6Hz,1H),3.24(dd,J＝14.4,4.2Hz,1H),3.04(dd,J＝14.4,4.5Hz,1H),2.38(t,J＝7.3Hz,2H),1.18-0.85(m,3H),0.63-0.46(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.3,136.3,133.8,132.4,132.0(2C),129.0(2C),128.2,125.1,121.2,119.4,118.8,111.5,109.1,55.8,53.7,49.7,46.5,31.0,29.3,21.5.
1H?NMR(400MHz,DMSO)δ10.95(d,J＝1.7Hz,1H),8.12(d,J＝2.1Hz,1H),8.03(d,J＝2.2Hz,1H),7.68-7.62(m,2H),7.57(d,J＝7.8Hz,1H),7.39(d,J＝8.4Hz,2H),7.25(d,J＝8.0Hz,1H),7.06(d,J＝2.2Hz,1H),7.03-6.89(m,2H),4.13(d,J＝1.3Hz,1H),3.96-3.83(m,2H),3.56(s,1H),3.24(dd,J＝14.4,4.2Hz,1H),3.04(dd,J＝14.4,4.6Hz,1H),2.38(t,J＝7.3Hz,2H),1.19-0.86(m,3H),0.64-0.45(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.3,136.3,132.8,132.3(2C),131.9(2C),128.2,125.1,122.5,121.2,119.4,118.8,111.5,109.1,55.8,53.7,49.8,46.5,31.0,29.3,21.5.
1H?NMR(400MHz,DMSO)δ10.96(d,J＝1.6Hz,1H),8.12(d,J＝2.1Hz,1H),8.04(d,J＝2.1Hz,1H),7.81(d,J＝8.2Hz,2H),7.66(d,J＝8.1Hz,2H),7.58(d,J＝7.7Hz,1H),7.24(d,J＝7.9Hz,1H),7.07(d,J＝2.2Hz,1H),7.05-6.85(m,2H),4.13(t,J＝7.2Hz,1H),4.06-3.95(m,2H),3.56(t,J＝7.2Hz,1H),3.25(dd,J＝14.4,4.2Hz,1H),3.05(dd,J＝14.4,4.6Hz,1H),2.39(t,J＝7.2Hz,2H),1.22-0.89(m,3H),0.55(dt,J＝12.8,7.3Hz,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.3,138.7,136.3(2C),130.7,129.4(q,J＝31Hz),128.2,125.8(q,J＝4Hz,2C),125.1,124.6(q,J＝271Hz),121.2,119.4,118.8,111.5,109.1,55.8,53.8,50.1,46.8,31.1,29.3,21.8.
1H?NMR(400MHz,DMSO)δ10.95(d,J＝1.7Hz,1H),8.12(d,J＝2.1Hz,1H),8.03(d,J＝2.2Hz,1H),7.57(d,J＝7.8Hz,1H),7.36(d,J＝8.7Hz,2H),7.26(d,J＝8.0Hz,1H),7.10-6.89(m,5H),4.13(d,J＝1.4Hz,1H),3.92-3.81(m,2H),3.78(s,3H),3.56(t,J＝5.0Hz,1H),3.24(dd,J＝14.4,4.3Hz,1H),3.05(dd,J＝14.4,4.6Hz,1H),2.38(t,J＝7.5Hz,2H),1.20-0.84(m,3H),0.63-0.42(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.3,160.1,136.3,131.7(2C),128.2,125.1,124.6,121.2,119.4,118.8,114.4(2C),111.5,109.1,55.8,55.6,53.7,49.9,46.1,31.0,29.4,21.5.
1H?NMR(400MHz,DMSO)δ10.96(d,J＝1.6Hz,1H),8.12(d,J＝2.1Hz,1H),8.03(d,J＝2.1Hz,1H),7.57(d,J＝7.9Hz,1H),7.27(d,J＝8.0Hz,1H),7.11-6.87(m,6H),6.09(s,2H),4.13(d,J＝1.3Hz,1H),3.92-3.77(m,2H),3.55(d,J＝4.9Hz,1H),3.24(dd,J＝14.4,4.2Hz,1H),3.05(dd,J＝14.4,4.2Hz,1H),2.36(t,J＝7.5Hz,2H),1.20-0.86(m,3H),0.65-0.39(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.3,148.0,147.8,136.3,128.2,126.5,125.1,124.2,121.2,119.4,118.8,111.5,110.4,109.1,108.7,101.7,55.8,53.7,49.0,46.1,31.0,29.4,21.4.
1H?NMR(400MHz,DMSO)δ10.86(s,1H),9.35(s,1H),8.10–7.95(m,2H),7.90(s,2H),7.59(d,J＝7.9Hz,1H),7.34(d,J＝8.1Hz,1H),7.06(dd,J＝15.3,4.7Hz,2H),6.95(t,J＝7.4Hz,1H),4.13(s,1H),3.58(s,1H),3.25(dd,J＝14.4,4.5Hz,1H),3.14–2.97(m,3H),1.15–0.88(m,3H),0.65–0.55(m,1H). 13C?NMR(100MHz,DMSO)δ180.9,167.2,166.9,145.1(dm,J＝241Hz),141.5(dm,J＝252Hz),140.2(dm,J＝241Hz),136.7(dm,J＝244Hz),135.9,127.7,124.5,124.4–124.1(m),120.7,118.8,118.3,111.1,109.3(dm,J＝20Hz),108.6,55.4,53.6,43.6,31.0,29.0,23.2.
1H?NMR(400MHz,DMSO)δ10.88(d,J＝1.7Hz,1H),8.91(s,1H),8.06-7.97(m,2H),7.75(s,1H),7.58(d,J＝7.9Hz,1H),7.40-7.27(m,2H),7.18-6.89(m,5H),4.12(t,J＝5.0Hz,1H),3.56(t,J＝5.0Hz,1H),3.24(dd,J＝14.4,4.6Hz,1H),3.16-3.04(m,3H),1.13-0.92(m,3H),0.70-0.51(m,1H). 13C?NMR(100MHz,DMSO)δ182.8,167.6,167.5,160.5(d,J＝4Hz),158.0(d,J＝5Hz),136.4,128.8(t,J＝10Hz),128.2,125.0,121.3,119.3,118.8,116.7(t,J＝8Hz),112.3,112.1,111.6,109.1,55.9,54.1,49.0,31.5,29.6,24.0.
1H?NMR(400MHz,DMSO)δ10.79(d,J＝54.7Hz,1H),9.23(s,1H),8.01(d,J＝23.6Hz,2H),7.58(d,J＝7.9Hz,1H),7.32(d,J＝8.0Hz,1H),7.27-6.82(m,8H),4.11(d,J＝7.9Hz,1H),3.74(s,3H),3.57(t,J＝7.9Hz,1H),3.23(dd,J＝14.3,4.3Hz,1H),3.15-2.95(m,3H),1.16-0.84(m,3H),0.72-0.61(m,1H). 13C?NMR(100MHz,DMSO)δ180.9,167.6,167.5,156.9,136.4,132.1,128.2,126.2(2C),125.0,121.2,119.3,118.8,114.3(2C),111.6,109.1,55.9,55.6(2C),54.0,31.3,29.6,24.0.
1H?NMR(400MHz,DMSO)δ11.05(s,1H),9.64(s,1H),8.50(t,J＝13.4Hz,1H),8.34-7.91(m,4H),7.58(d,J＝7.8Hz,1H),7.44-6.87(m,5H),4.21-4.14(m,1H),3.57(t,J＝5.7Hz,1H),3.26(dd,J＝13.7,3.0Hz,1H),3.12-2.90(m,3H),1.14-0.54(m,4H).
13C?NMR(100MHz,DMSO)δ181.7,167.5,167.3,155.0,141.7,137.3,136.3,134.5,128.2,124.9,123.7,123.0,121.2,119.3,118.8,111.5,109.0,55.9,54.1,45.8,31.3,29.4,24.5.
1H?NMR(400MHz,DMSO)δ10.87(d,J＝1.5Hz,1H),9.41(s,1H),8.09-7.95(m,2H),7.58(d,J＝7.9Hz,1H),7.46-7.28(m,4H),7.19-6.86(m,5H),4.12(d,J＝1.3Hz,1H),3.58(t,J＝5.7Hz,1H),3.24(dd,J＝14.4,4.5Hz,1H),3.12-3.01(m,3H),1.15-0.84(m,3H),0.7-0.54(m,1H). 13C?NMR(100MHz,DMSO)δ181.0,167.6,167.4,159.3(d,J＝240Hz),136.4,128.2,125.9(d,J＝5Hz,2C),125.0,121.2,119.4,118.8,115.7,115.5(d,J＝23Hz,2C),111.6,109.1,55.9,54.0,43.6,31.4,29.5,23.9.
1H?NMR(400MHz,DMSO)δ10.91(d,J＝1.9Hz,1H),9.76(s,1H),8.03(dd,J＝28.4,1.8Hz,2H),7.80(t,J＝5.3Hz,1H),7.58(d,J＝7.9Hz,1H),7.49-7.41(m,4H),7.33(d,J＝8.1Hz,1H),7.07(d,J＝2.3Hz,1H),7.05-6.98(m,1H),6.98-6.89(m,1H),4.13(d,J＝1.5Hz,1H),3.57(t,J＝4.8Hz,2H),3.25(dd,J＝14.4,4.4Hz,1H),3.15-3.04(m,3H),1.12-0.87(m,3H),0.61(m,1H). 13C?NMR(100MHz,DMSO)δ180.7,167.7,167.4,139.5,136.4,131.6,128.6,128.2,125.0,124.5,121.3,119.3,119.0,118.8,116.0,111.6,109.1,55.9,54.1,43.6,31.4,29.5,23.8.
1H?NMR(400MHz,DMSO)δ10.86(d,J＝1.7Hz,1H),9.34(s,1H),8.01(dd,J＝24.6,2.0Hz,2H),7.58(d,J＝7.9Hz,1H),7.39-7.19(m,4H),7.16-6.85(m,5H),4.11(d,J＝1.4Hz,1H),3.57(t,J＝4.8Hz,1H),3.24(dd,J＝14.4,4.5Hz,1H),3.10-3.01(m,3H),2.16(s,3H),1.18-0.80(m,3H),0.68-0.54(m,1H). 13C?NMR(100MHz,DMSO)δ180.6,167.6,167.4,136.9,136.4,133.9,129.5(2C),128.2,125.0,123.9(2C),121.2,119.3,118.8,111.6,109.1,55.9,54.0,43.6,31.4,29.5,24.0,20.9.
1H?NMR(400MHz,DMSO)δ10.83(t,J＝22.4Hz,1H),9.01(s,1H),8.05-7.95(m,2H),7.57(d,J＝7.9Hz,1H),7.43-6.87(m,10H),4.10(d,J＝1.7Hz,1H),3.56(t,J＝4.8Hz,1H),3.23(dd,J＝14.4,4.6Hz,1H),3.10-3.01(m,3H),2.16(s,3H),1.11-0.88(m,3H),0.65-0.49(m,1H). 13C?NMR(100MHz,DMSO)δ181.3,167.6,167.5,137.5,136.4,130.9,128.5,128.2,126.8,126.7,125.0,124.5,121.2,119.3,118.8,111.6,109.1,55.9,54.0,31.4,29.6,24.2,21.2,18.1.
1H?NMR(400MHz,DMSO)δ10.87(d,J＝1.5Hz,1H),9.41(s,1H),8.09-7.95(m,2H),7.58(d,J＝7.9Hz,1H),7.46-7.28(m,4H),7.19-6.86(m,5H),4.12(d,J＝1.3Hz,1H),3.58(t,J＝5.7Hz,1H),3.24(dd,J＝14.4,4.5Hz,1H),3.12-3.01(m,3H),1.15-0.84(m,3H),0.7-0.54(m,1H). 13C?NMR(100MHz,DMSO)δ181.0,167.6,167.4,152.0(d,J＝239Hz),136.4,128.8(d,J＝10Hz),128.2,125.0,124.7(d,J＝4Hz),121.7(d,J＝8Hz),121.2,120.6,119.4,118.8,115.1(d,J＝9Hz),111.6,109.1,55.9,54.0,43.6,31.4,29.5,23.9.
1H?NMR(400MHz,DMSO)δ10.92(d,J＝1.8Hz,1H),9.81(s,1H),8.10-7.97(m,2H),7.84(t,J＝5.0Hz,1H),7.63-7.45(m,3H),7.36-7.29(m,3H),7.11-6.86(m,3H),4.12(d,J＝1.4Hz,1H),3.58(t,J＝5.7Hz,1H),3.25(dd,J＝14.4,4.4Hz,1H),3.16-2.96(m,3H),1.11-0.82(m,3H),0.65-0.53(m,1H). 13C?NMR(101MHz,DMSO)δ180.8,167.7,167.4,139.1,136.4,128.6,128.3,127.9,125.0,124.7,121.2,119.3,119.0,118.8,116.0,111.62,109.0,55.9,54.1,43.5,31.4,29.5,23.8.
1H?NMR(400MHz,DMSO)δ10.87(d,J＝1.6Hz,1H),9.08(s,1H),8.10-7.97(m,2H),7.59(d,J＝7.9Hz,3H),7.41-7.21(m,2H),7.12-6.88(m,4H),4.13(d,J＝1.5Hz,1H),3.57(t,J＝4.8Hz,1H),3.25(dd,J＝14.4,4.5Hz,1H),3.16-2.96(m,3H),1.11-0.82(m,3H),0.71-0.53(m,1H). 13C?NMR(100MHz,DMSO)δ182.0,167.6,167.5,159.3(dd,J＝233,11Hz),156.7(dd,J＝222,10Hz),136.4,130.0(dd,J＝10,3Hz),128.2,125.0,123.9(t,J＝20Hz),121.3,119.4,118.8,111.6,111.4(dd,J＝19,3Hz),109.1,104.6(t,J＝239,11Hz),55.92,54.1,44.0,31.4,29.5,23.9.
1H?NMR(400MHz,DMSO)δ10.88(d,J＝1.6Hz,1H),9.46(s,1H),8.08–7.95(m,2H),7.58(d,J＝7.9Hz,1H),7.49–7.26(m,5H),7.14–6.88(m,4H),4.12(d,J＝1.3Hz,1H),3.58(d,J＝7.9Hz,1H),3.25(dd,J＝14.4,4.5Hz,1H),3.16–2.98(m,3H),1.13–0.85(m,3H),0.72–0.53(m,1H). 13C?NMR(100MHz,DMSO)δ180.73,167.70,167.49,158.8,139.54,136.41,131.60,128.60,128.24,125.04,124.50,121.30,119.38,119.01,118.86,116.05,111.63,109.11,55.93,54.10,43.61,31.46,29.55,23.86.
1H?NMR(400MHz,DMSO)δ10.91(d,J＝1.8Hz,1H),8.40-8.32(m,2H),8.13(d,J＝2.3Hz,1H),7.99(d,J＝2.4Hz,1H),7.76(d,J＝1.7Hz,1H),7.59(d,J＝7.6Hz,2H),7.33(d,J＝8.1Hz,1H),7.11-6.91(m,4H),4.14(d,J＝2.3Hz,1H),3.54(t,J＝3.9Hz,1H),3.27(dd,J＝14.4,4.2Hz,1H),3.04(dd,J＝14.4,4.2Hz,1H),2.78-2.53(m,2H),1.08-1.00(m,1H),0.51-0.42(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.4,154.9,140.9,136.4,128.2,126.6(q,J＝4Hz),125.1(q,J＝4Hz),125.0,125.2(q,J＝270Hz),122.6(q,J＝32Hz),121.3,121.2,120.4,119.4,118.9,111.6,109.0,56.0,52.0,35.1,34.9,29.7.
1H?NMR(400MHz,DMSO)δ10.91(d,J＝1.9Hz,1H),8.35(s,1H),8.11(d,J＝2.4Hz,1H),7.97(d,J＝2.5Hz,1H),7.59(d,J＝7.9Hz,1H),7.34(d,J＝8.0Hz,1H),7.10-6.92(m,5H),6.52(s,1H),5.89(t,J＝6.0Hz,1H),4.15-4.10(m,1H),3.50-3.43(m,1H),3.28(dd,J＝14.4,4.1Hz,1H),3.04(dd,J＝14.4,4.6Hz,1H),2.68-2.45(m,2H),2.18(s,6H),1.14-1.04(m,1H),0.26-0.18(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.5,156.0,140.6,137.9(2C),136.4,128.2,125.1,123.2,121.4,119.4,118.9,116.1(2C),111.6,109.0,56.0,51.9,35.4,34.8,29.8,21.6(2C).
1H?NMR(400MHz,DMSO)δ10.89(t,J＝7.8Hz,1H),8.87(s,1H),8.12(d,J＝2.3Hz,1H),7.94(d,J＝2.5Hz,1H),7.78(d,J＝2.5Hz,1H),7.58(d,J＝7.9Hz,1H),7.48-7.40(m,1H),7.33(d,J＝7.2Hz,1H),7.20(dd,J＝8.8,2.5Hz,1H),7.09-6.91(m,3H),6.04(t,J＝6.0Hz,1H),4.12(d,J＝2.5Hz,1H),3.53-3.43(m,1H),3.26(dd,J＝14.4,4.2Hz,1H),3.03(dd,J＝14.4,4.6Hz,1H),2.67-2.52(m,2H),1.14-0.97(m,1H),0.38-0.22(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.5,155.4,141.1,136.4,131.3,130.8,128.2,125.0,122.6,121.3,119.4,119.2,118.8,118.2,111.6,109.0,55.9,51.9,35.0(2C),29.7.
1H?NMR(400MHz,DMSO)δ10.91(d,J＝1.9Hz,1H),9.08(s,1H),8.14(d,J＝2.3Hz,1H),7.97(d,J＝2.5Hz,1H),7.69-7.49(m,5H),7.33(d,J＝8.0Hz,1H),7.14-6.93(m,3H),6.12(t,J＝5.9Hz,1H),4.13(dd,J＝6.4,4.0Hz,1H),3.53-3.47(m,1H),3.28(dd,J＝14.4,4.1Hz,1H),3.04(dd,J＝14.4,4.6Hz,1H),2.66-2.53(m,2H),1.13-0.98(m,1H),0.37-0.21(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.1,145.3,136.3,133.5(2C),128.1,125.0,121.3,119.9,119.4,118.9,117.9(2C),111.6,109.0,102.8,56.0,51.9,35.0,34.9,29.7.
1H?NMR(400MHz,DMSO)δ10.90(d,J＝1.8Hz,1H),8.44(dd,J＝8.2,1.6Hz,1H),8.20-8.06(m,2H),7.97-7.95(m,2H),7.58(d,J＝7.9Hz,1H),7.35-7.28(m,2H),7.10-6.84(m,4H),4.19-4.08(m,1H),3.60-3.47(m,1H),3.27(dd,J＝14.4,4.2Hz,1H),3.04(dd,J＝14.4,4.7Hz,1H),2.75-2.52(m,2H),1.13-0.98(m,1H),0.50-0.35(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.2,142.0,138.9,136.6,134.2,128.7,128.1,125.0,123.8,121.3,119.4,118.8,111.6,109.0,55.9,51.9,35.0,35.0,29.6.
1H?NMR(400MHz,DMSO)δ10.92(d,J＝1.8Hz,1H),8.14(t,J＝4.6Hz,1H),8.00(d,J＝2.4Hz,1H),7.91-7.82(m,1H),7.60(d,J＝7.2Hz,3H),7.39-7.29(m,2H),7.23-7.17(m,1H),7.09-6.90(m,3H),6.54(t,J＝5.7Hz,1H),4.20-4.07(m,1H),3.51(d,J＝5.7Hz,1H),3.28(dd,J＝14.4,4.1Hz,1H),3.05(dd,J＝14.4,4.6Hz,1H),2.73-2.55(m,2H),1.17-1.00(m,1H),0.50-0.35(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.3,160.3,154.3,136.4,136.3,131.8,128.1,126.2,125.1,123.1,123.0,121.7,121.3,119.4,118.9,111.6,109.0,56.0,51.9,35.4,34.7,29.7.
1H?NMR(400MHz,DMSO)δ10.96(d,J＝1.8Hz,1H),8.97(d,J＝6.5Hz,1H),8.15(d,J＝2.3Hz,1H),7.98(d,J＝2.5Hz,1H),7.58(d,J＝7.9Hz,1H),7.33(d,J＝8.0Hz,1H),7.11-6.87(m,4H),6.67(t,J＝5.9Hz,1H),4.12(d,J＝2.4Hz,1H),3.49(t,J＝3.1Hz,1H),3.26(dd,J＝14.4,4.0Hz,1H),3.05(dd,J＝14.4,4.6Hz,1H),2.70-2.54(m,2H),1.13-0.98(m,1H),0.50-0.35(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.3,160.8,154.0,147.9,136.3,128.1,125.0,121.3,119.4,118.8,111.6,109.0,56.0,51.9,35.5,34.7,29.6.
1H?NMR(400MHz,DMSO)δ10.91(d,J＝1.5Hz,1H),8.92(s,1H),8.13(d,J＝2.1Hz,1H),7.97(d,J＝2.3Hz,1H),7.91(s,1H),7.60(d,J＝7.9Hz,1H),7.51-7.32(m,3H),7.20(d,J＝7.5Hz,1H),7.10-6.93(m,3H),6.04(t,J＝5.9Hz,1H),4.13(d,J＝2.4Hz,1H),3.55-3.46(m,1H),3.28(dd,J＝14.4,4.1Hz,1H),3.05(dd,J＝14.4,4.5Hz,1H),2.70-2.52(m,2H),1.18-1.01(m,1H),0.39-0.24(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.5,155.6,141.7,136.3,130.1,129.8(q,J＝29Hz),128.2,125.1,124.7(q,J＝271Hz),121.6,121.3,119.4,118.9,117.7(q,J＝4Hz),114.1(q,J＝4Hz),111.6,109.0,56.0,51.9,35.1,35.2,29.7.
1H?NMR(400MHz,DMSO)δ10.92(s,1H),8.33(s,1H),8.10(d,J＝2.1Hz,1H),7.97(d,J＝2.3Hz,1H),7.59(d,J＝7.8Hz,1H),7.34(dd,J＝8.4,5.2Hz,1H),7.23(d,J＝8.9Hz,2H),7.10-6.74(m,5H),5.83(t,J＝6.0Hz,1H),4.11(d,J＝2.4Hz,1H),3.68(s,4H),3.49-3.41(m,1H),3.27(dd,J＝14.3,4.1Hz,1H),3.03(dd,J＝14.4,4.5Hz,1H),2.69-2.43(m,3H),1.09(td,J＝13.7,6.5Hz,1H),0.19(qd,J＝9.8,4.9Hz,1H). 13C?NMR(100MHz,DMSO)δ167.6,156.2,154.4,136.3,133.9,128.2,125.0,121.3,120.3,120.1,119.4,118.9,114.4,114.3,111.6,109.0,56.0,55.6,55.6,51.9,35.4,34.9,29.8.
1H?NMR(400MHz,DMSO)δ10.91(s,1H),9.50(s,1H),8.15(s,1H),8.09(s,1H),7.94(dd,J＝14.7,5.2Hz,2H),7.67(d,J＝8.7Hz,1H),7.59(d,J＝7.9Hz,1H),7.32(t,J＝7.0Hz,1H),7.13-6.99(m,2H),6.95(t,J＝7.4Hz,1H),6.28(t,J＝5.8Hz,1H),4.14(d,J＝1.9Hz,1H),3.51(s,1H),3.28(dd,J＝14.4,4.0Hz,1H),3.04(dd,J＝14.4,4.5Hz,1H),2.70-2.52(m,2H),1.10-1.02(m,1H),0.39-0.33(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.5,154.9,145.7,136.6,136.3,132.1(q,J＝30Hz),129.6,128.2,125.1,123.0(q,J＝272Hz),121.3,120.6,119.4,118.9,116.6,115.2(q,J＝6Hz),111.6,109.0,99.3,56.0,51.9,35.2,34.8,29.7.
1H?NMR(400MHz,DMSO)δ10.90(s,1H),8.73(s,1H),8.14(s,1H),8.00(d,J＝15.0Hz,2H),7.59(d,J＝7.8Hz,1H),7.33(d,J＝8.0Hz,1H),7.14-6.90(m,3H),6.47(t,J＝5.5Hz,1H),4.13(s,1H),3.50(s,1H),3.27(dd,J＝14.3,3.8Hz,1H),3.04(dd,J＝14.2,4.2Hz,1H),2.69-2.54(m,2H),1.02-0.98(m,1H),0.43-0.38(m,1H). 13C?NMR(101MHz,DMSO)δ167.67,167.36,166.5(d,J＝214Hz),155.02,136.37,128.18,127.0(d,J＝206Hz),125.5(d,J＝106Hz),125.06,121.34,120.3(d,J＝206Hz),119.43,118.87,111.60,110.3(d,J＝288Hz),109.04,102.1(d,J＝25Hz),56.01,51.95,35.07,34.96,29.69.
1H?NMR(400MHz,DMSO)δ10.91(s,1H),8.98(s,1H),8.13(d,J＝1.8Hz,1H),7.97(d,J＝2.0Hz,1H),7.62-7.53(m,5H),7.34(d,J＝8.1Hz,1H),7.10-6.91(m,3H),6.07(t,J＝5.9Hz,1H),4.13(d,J＝2.3Hz,1H),3.49(s,1H),3.28(dd,J＝14.3,4.0Hz,1H),3.04(dd,J＝14.4,4.5Hz,1H),2.69-2.53(m,2H),1.10-1.02(m,1H),0.35-0.33(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,167.4,155.4,144.5,136.3,128.2,126.3(q,J＝3Hz，2C),125.1,125.0(q,J＝267Hz)，121.5(q,J＝31Hz)，121.3,119.4,118.8,117.7(2C),111.6,109.0,56.0,51.9,35.1,35.0,29.7.
1H?NMR(400MHz,DMSO)δ10.91(s,1H),8.53(s,1H),8.42(d,J＝8.8Hz,1H),8.08(d,J＝20.8Hz,2H),7.77(s,1H),7.57(dd,J＝20.1,8.4Hz,2H),7.34(d,J＝8.1Hz,1H),7.24(t,J＝5.9Hz,1H),7.13(d,J＝1.8Hz,1H),7.05(t,J＝7.4Hz,1H),6.95(t,J＝7.4Hz,1H),4.15(s,1H),3.77(s,1H),3.29-3.08(m,2H),2.92-2.78(m,1H),2.67-2.55(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,166.4,154.7,140.9,136.4,128.0,126.5(q,J＝4Hz),125.1(q,J＝3Hz),124.7,124.1(q,J＝270Hz),122.5(q,J＝33Hz),121.3,121.1,120.3,119.1,118.9,111.7,109.2,55.7,54.8,42.9,29.9.
1H?NMR(400MHz,DMSO)δ10.91(s,1H),8.48(s,1H),8.07(d,J＝25.8Hz,2H),7.56(d,J＝7.8Hz,1H),7.34(d,J＝8.1Hz,1H),7.14-6.93(m,6H),6.52(s,1H),6.00(s,1H),4.14(s,1H),3.69(s,1H),3.29-3.08(m,2H),2.75-2.54(m,2H),2.18(s,6H). 13C?NMR(100MHz,DMSO)δ167.7,166.9,155.3,140.6,137.9(2C),136.3,128.0,124.8,123.2,121.3,119.2,118.9,115.9(2C),111.7,109.2,55.6,54.9,42.7,29.6,21.6(2C).
1H?NMR(400MHz,DMSO)δ10.91(s,1H),8.12(s,2H),8.01(d,J＝1.5Hz,1H),7.58(d,J＝7.9Hz,1H),7.34(d,J＝8.1Hz,1H),7.23(dd,J＝11.4,5.2Hz,1H),7.12-7.04(m,4H),6.97(t,J＝7.4Hz,1H),6.25(t,J＝5.9Hz,1H),4.15(s,1H),3.69(t,J＝5.7Hz,1H),3.29-3.08(m,2H),2.92-2.78(m,1H),2.66-2.52(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,167.0,159.5(d,J＝5Hz),156.9(d,J＝5Hz),155.1,136.3,128.0,126.7(t,J＝10Hz),124.8,121.3,119.2,118.8,116.4(t,J＝8Hz),112.1,111.9,111.7,109.1,55.5,54.9,43.0,29.4.
1H?NMR(400MHz,DMSO)δ10.92(s,1H),9.23(s,1H),8.18(d,J＝1.4Hz,1H),8.06(d,J＝1.7Hz,1H),7.71-7.49(m,5H),7.33(d,J＝8.0Hz,1H),7.10(d,J＝2.1Hz,1H),7.05(t,J＝7.2Hz,1H),6.95(d,J＝7.5Hz,1H),6.24-6.15(m,1H),4.16(s,1H),3.70(t,J＝5.6Hz,1H),3.21(dd,J＝14.5,4.4Hz,1H),3.11(dd,J＝14.5,4.4Hz,1H),2.72-2.64(m,1H),2.54-2.41(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,166.8,154.6,145.2,136.3,133.6(2C),128.0,124.8,121.4,119.9,119.2,118.9,117.8(2C),111.7,109.1,102.9,55.6,54.4,42.7,29.6.
1H?NMR(400MHz,DMSO)δ10.91(s,1H),8.49(d,J＝7.7Hz,1H),8.35(s,1H),8.06(d,J＝22.1Hz,2H),7.96(dd,J＝4.5,1.5Hz,1H),7.55(d,J＝7.9Hz,1H),7.39-7.27(m,2H),7.12(s,2H),7.05(t,J＝7.5Hz,1H),6.95(t,J＝7.4Hz,1H),4.15(s,1H),3.76(s,1H),3.24-3.09(m,2H),2.88-2.74(m,1H),2.70-2.54(m,1H). 13C?NMR(100MHz,DMSO)δ167.7,166.4,155.0,141.9,138.8,136.3,134.3,128.5,128.0,124.7,123.8,121.4,119.1,118.9,111.7,109.2,55.7,54.8,42.9,29.9.
1H?NMR(400MHz,DMSO)δ10.92(s,1H),8.22-8.05(m,2H),7.86(d,J＝7.8Hz,1H),7.70-7.49(m,2H),7.42-6.88(m,7H),6.70(s,1H),4.21-4.09(m,1H),3.85-3.73(m,1H),3.25-3.10(m,2H),3.07-2.55(m,2H). 13C?NMR(100MHz,DMSO)δ167.6,167.3,160.3,154.3,136.4,136.3,131.8,128.1,126.2,125.1,123.1,123.0,121.7,121.3,119.4,118.9,111.6,109.0,55.6,54.4,42.7,29.6.
1H?NMR(400MHz,DMSO)δ10.92(s,1H),9.64(s,1H),8.21(s,1H),8.12(d,J＝1.6Hz,1H),8.07(s,1H),7.95(d,J＝8.6Hz,1H),7.63(dt,J＝10.3,5.1Hz,1H),7.56(d,J＝7.9Hz,1H),7.32(d,J＝8.1Hz,1H),7.14-6.86(m,3H),6.34-6.16(m,1H),4.14(t,J＝5.4Hz,1H),3.72(t,J＝5.4Hz,1H),3.28-3.05(m,2H),2.77-2.61(m,1H),2.51-2.39(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,166.8,154.4,145.7,136.7,136.3,132.2(q,J＝32Hz),128.0,124.8,123.0(q,J＝271Hz),121.3,120.5,119.2,118.9,116.6,115.9(q,J＝5Hz),111.6,109.0,99.3,55.7,54.2,42.8,29.6.
1H?NMR(400MHz,DMSO)δ10.92(s,1H),9.03(d,J＝23.5Hz,1H),8.17(d,J＝1.4Hz,1H),8.07(d,J＝1.7Hz,1H),7.94(s,1H),7.57(d,J＝7.9Hz,1H),7.50-7.39(m,2H),7.34(d,J＝8.0Hz,1H),7.21(d,J＝6.7Hz,1H),7.11(d,J＝2.1Hz,1H),7.05(t,J＝7.5Hz,1H),6.96(t,J＝7.4Hz,1H),6.09(t,J＝5.9Hz,1H),4.16(t,J＝5.4Hz,1H),3.72(t,J＝5.4Hz,1H),3.28-3.05(m,2H),2.77-2.61(m,1H),2.51-2.39(m,1H). 13C?NMR(100MHz,DMSO)δ167.6,166.9,155.1,129.9(q,J＝31Hz),141.7,136.3,130.1,128.0,124.8,124.7(q,J＝271Hz),121.5,121.3,119.2,118.9,117.7(q,J＝4Hz),113.93(q,J＝4Hz),111.7,109.1,55.6,54.6,42.8,29.6.
1H?NMR(400MHz,DMSO)δ10.92(s,1H),8.48(s,1H),8.07(d,J＝30.1Hz,2H),7.57(d,J＝7.9Hz,1H),7.34(d,J＝8.1Hz,1H),7.25(d,J＝8.9Hz,2H),7.11(s,1H),7.05(t,J＝7.5Hz,1H),6.96(t,J＝7.4Hz,1H),6.80(d,J＝9.0Hz,2H),5.92(s,1H),4.14(s,1H),3.68(s,4H),3.28-3.05(m,2H),2.73-2.54(m,2H). 13C?NMR(100MHz,DMSO)δ167.7,166.9,155.5,154.4,136.3,133.9,128.0,124.8,121.3,119.8(2C),119.2,118.9,114.3(2C),111.7,109.1,55.6,55.8,54.9,42.8,29.6.
1H?NMR(400MHz,DMSO)δ10.91(s,1H),8.90(s,1H),8.19-8.04(m,3H),7.55(d,J＝7.7Hz,1H),7.34(d,J＝8.0Hz,1H),7.11(d,J＝7.4Hz,1H),7.05(t,J＝7.5Hz,1H),6.95(t,J＝7.4Hz,1H),6.65(d,J＝5.8Hz,1H),4.15(s,1H),3.72(s,1H),3.29-3.08(m,2H),2.75-2.54(m,2H). 13C?NMR(100MHz,DMSO)δ167.7,166.6,166.4(d,J＝214Hz),154.6,136.3,128.0,126.9(d,J＝206Hz),125.4(d,J＝106Hz),124.7,121.3,120.2(d,J＝206Hz),119.1,118.8,111.7,110.3(d,J＝288Hz),109.1,102.1(d,J＝25Hz),55.7,54.5,42.7,29.7.
1H?NMR(400MHz,DMSO)δ10.92(s,1H),9.11(s,1H),8.17(s,1H),8.07(s,1H),7.57(d,J＝7.9Hz,5H),7.34(d,J＝8.1Hz,1H),7.13-6.87(m,3H),6.13(t,J＝5.8Hz,1H),4.16(t,J＝5.8Hz,1H),3.70(t,J＝5.8Hz,1H),3.27-2.96(m,2H),2.72-2.47(m,2H). 13C?NMR(100MHz,DMSO)δ167.6,166.9,154.9,144.5,136.3,128.0,126.4,126.3,125.0(q,J＝267Hz),124.8,121.5(q,J＝31Hz),121.3,119.2,118.9,117.6(2C),111.7,109.1,55.6,54.5,42.7,29.6.
Embodiment 8: the eelworm-killing activity test of the compounds of this invention.
The selected Meloidogyne incognita (Meloidogyne incongnita) of the present invention is by modern agriculture center, Chinese Academy of Sciences Huzhou long-term cultivation.Adopt test tube method, test the eelworm-killing activity of determining the compounds of this invention.
Concrete test operating procedure: take Meloidogyne incognita (Meloidogyne incongnita) as test target, take cucumber seedling as for examination host, adopt test tube planting method.To treat that test agent prepares by desired concn, and be ready to enough root knot nematode second instar larvaes.After the cucumber seedling in one week age is planted in test tube, in test tube, add the liquid preparing in right amount, and access approximately 2000 larvas in every test tube.Test tube is placed in 20-25 ℃, cultivates 20d " Invest, Then Investigate " result under 10h illumination.Count the root knot number on every strain plant root, by root knot quantity, carry out classification, statistics inhibiting rate.Take distilled water as blank, and distilled water adds the negative contrast of Meloidogyne incognita, usings the positive contrast of fenamiphos and abamectin solution (respectively as positive control).
Inhibiting rate (%)=(contrast goals for-processing goals for)/contrast goals for * 100%
Result shows: the compounds of this invention has good inhibition to root knot nematode.
Under different concns part test compounds to the inhibition activity of nematode in Table 1:
The eelworm-killing activity test of table 1 compound
Compound Nematode inhibiting rate (%) Compound Nematode inhibiting rate (%) Compound Nematode inhibiting rate (%)
10a-1 18.0 a 14a-3 80.1 c 11a-11 68.9 c
10a-2 51.1 a 14a-4 83.6 c 11a-12 76.4 c
10a-3 48.4 a 14a-5 65.4 c 11a-13 86.7
10a-4 51.1 a 14a-6 78.2 c 10b-1 43.2 c
10a-5 29.9 a 14a-7 100.0 c 10b-2 57.7 c
10a-6 73.1 b 14a-8 84.1 c 10b-3 68.2 c
10a-7 89.3 b 14a-9 89.0 c 10b-4 65.7 c
10a-8 84.9 b 14a-10 68.6 c 10b-5 46.5 c
10a-9 72.2 b 14a-11 81.8 c 10b-6 43.7 c
10a-10 28.2 b 15a-1 97.7 c 10b-7 79.5 c
10a-11 58.3 b 15a-2 84.7 c 10b-8 69.7 c
10a-12 60.8 b 15a-3 100.0 c 10b-9 81.8 c
10a-13 65.1 b 15a-4 82.6 c 10b-10 72.3 c
10a-14 55.8 b 15a-5 89.4 c 10b-11 70.3 c
10a-15 39.2 b 15a-6 74.6 c 10b -12 68.8 c
10a-16 44.4 b 15a-7 90.9 c 10c-1 57.9 c
10a-17 72.5 b 15a-8 84.8 c 10c-2 58.0 c
10a-18 49.2 b 15a-9 86.4 c 10c-3 61.6 c
10a-19 77.9 b 11a-1 90.9 c 10c-4 60.7 c
10a-20 24.9 b 11a-2 64.5 c 10c-5 65.1 c
10a-21 75.8 b 11a-3 81.8 c 10c-6 65.1 c
10a-22 67.2 b 11a-4 75.0 c 10c-7 61.7 c
10a-23 50.6 b 11a-5 73.9 c 10c-8 67.3 c
10a-24 49.2 b 11a-6 62.9 c 10c-9 53.7 c
10a-25 82.2 b 11a-7 65.1 c 10c-10 47.3 c
10a-26 76.1 b 11a-8 44.9 c 10c-11 56.9 c
14a-1 61.7 c 11a-9 70.5 c 14b-1 80.1 c
14a-2 67.0 c 11a-10 45.8 c 15b-1 77.6 c
Inhibiting rate under a:40ppm; Inhibiting rate under b:10ppm; Inhibiting rate under c:25ppm
Embodiment 9: the eelworm-killing activity of the compounds of this invention sieves test again.
Select the active high compound of part primary dcreening operation to carry out multiple sieve test, implementation method is as embodiment 8, and under different concns, part test compounds is as shown in table 2 to the active repetition measurement result of the inhibition of nematode.
The nematode inhibiting rate of table 2 compound sieves test again
Note: "-" represents that inhibiting rate is low
Result shows: the compounds of this invention has good inhibition to root knot nematode, part of compounds can reach 100% inhibiting rate under low concentration, especially compound 15a-3 still has 100% inhibition under the concentration of 20ppm, concentration at 1ppm, inhibiting rate still can reach 75%, shows outstanding nematode inhibition.
Embodiment 10: the mythimna separate test of the compounds of this invention.
The mythimna separata that the present invention chooses (Pseudaletia Separate Walker)-belong to lepidopteran, the small softness of build, be a kind of common chewing type crop pest-for tested object, adopt pickling process, test the insecticidal activity of determining test compound.
Concrete test operating procedure: accurately weigh various samples, add respectively dimethyl sulfoxide (DMSO) (DMSO) 2ml and 18ml clear water, add again 3 emulsifying agent Triton to be made into liquid, blank with DMSO 2ml and 18ml clear water, then add 3 emulsifying agent Triton to be made into.The tender seedling of the corn of 2-3 leaf phase is immersed respectively in the above-mentioned liquid having prepared, and after blade complete wetting, taking-up is dried, and cuts off blade (length is 5cm) standby.Support in scolite and access 2 10 of mythimna separatas in age (taking after body weight), the above-mentioned blade soaking is put into foster scolite, with gauze, mouth mask is lived to (each compound repeats three groups).After 96 hours, check the body weight change of examination worm, in experimentation, keeping temperature is 22-27 ℃, and humidity is 70%-80%, within 96 hours, takes each foster scolite body weight.
Growth inhibition ratio (%)=[(96 hours contrast body weight-contrast body weights)-(body weight before administration body weight-administration in 96 hours)]/(96 hours contrast body weight-contrast body weights) * 100%.
Result shows: the compounds of this invention has obvious restraining effect to the growth of mythimna separata, by observing, can find, the mythimna separata health of administration group is obviously compared with control group slight of stature, and food-intake is also significantly less than control group.And the situation of growing of administration group mythimna separata also obviously lags behind control group.
Under 500ppm, partial test compound the results are shown in Table 3 to the growth inhibitory activity of mythimna separata.
The mythimna separata growth inhibition ratio test of table 3 compound
Compound Mythimna separata growth inhibition ratio (%) Compound Mythimna separata growth inhibition ratio (%) Compound Mythimna separata growth inhibition ratio (%)
10a-2 91.5 14a-7 95 11a-12 93.9
10a-4 88.5 14a-8 70.2 10b-1 96.6
10a-7 67.8 14a-9 65.4 10b-2 96.9
10a-8 69.4 14a-10 84.3 10b-3 97.9
10a-9 60.9 14a-11 85.7 10b-4 90.5
10a-10 56 15a-1 69.6 10b-5 91.9
10a-11 59.9 15a-2 86.9 10b-6 93.2
10a-12 80.5 15a-3 74.7 10b-7 75.8
10a-14 9.1 15a-4 74.4 10b-8 93.8
10a-15 24 15a-5 86.6 10b-9 97.7
10a-16 67.5 15a-6 64.4 10b-10 96.9
10a-17 89.5 15a-7 88.4 10b-11 95
10a-18 89.7 15a-8 86.2 10b-12 96.5
10a-20 95.5 15a-9 71.4 10c-1 86.6
10a-22 89.9 11a-1 92.5 10c-2 94.1
10a-23 92.9 11a-2 95 10c-3 94.8
10a-24 89.8 11a-3 84.8 10c-4 85.5
10a-25 90 11a-4 93.4 10c-5 99.3
10a-26 92.1 11a-6 88.9 10c-6 91.9
14a-1 89.1 11a-7 88 10c-7 92.4
14a-2 90.7 11a-8 88.7 10c-8 92.1
14a-3 85.1 11a-9 85.6 10c-9 92
14a-4 95.9 11a-10 83.8 10c-10 95.2
14a-5 72.7 11a-11 99.6 10c-11 87.8
14a-6 86.8 ? ? ? ?
Embodiment 11: the people 5-HT2a receptor active test of the compounds of this invention.
Screening method: luciferase reporter gene detection method
1. test raw material and reagent
Transfection plasmid: 5-HT2a (from Missouri, USA university roller branch school cDNA resource center (University of Missouri-Rolla Resource Center)), pCRE-luc (purchased from Ye Li bio tech ltd, Shanghai), pRL-SV40 (purchased from Beijing Bi Chenglan biotechnology company);
Cell culture medium: DMEM, 10%FBS; Host cell: CHO-K1 cell, (being Chinese hamster ovary cell, purchased from cell institute of the Shanghai Chinese Academy of Sciences); Target: 5-HT2a acceptor;
Testing compound: compound prepared by the embodiment of the present invention;
Positive control: native ligand-thrombotonin (Serotonin, 5-HT, purchased from lark prestige Science and Technology Ltd.)
2. test method
5-HT2a, pCRE-luc, pRL-SV40 plasmid co-transfection are entered to CHO-K1 cell, after the 5-HT2a of Gq coupling is activated, can open calcium channel, by calcium current activating transcription factor CREB, in conjunction with CRE, cause the expression of luciferase reporter gene.
If testing compound can exciting acceptor, with after co-culture of cells understand the expression that activates luciferase, otherwise, the expression of Fluorophotometry element enzyme, after adding luciferase substrate, fluorescence can be sent, by fluorescence intensity, the activation level of compound to acceptor can be judged.
The fluorescence intensity of the fluorescence intensity of the agonist activity=testing compound of testing compound/DMSO group, wherein, the agonist activity of DMSO group is designated as 1.
In pRL-SV40 plasmid, contain SV40 replication orgin, can make the renilla luciferase in downstream be expressed, in test experience, as internal reference, reduce the factor that experiment changes, test is not disturbed by experiment condition variation.
Result shows: the compounds of this invention has agonist activity to 5-HT2a.The experimental result of partial test compound is as shown in table 4.5-HT is agonist contrast; DMSO is blank.Wherein especially 10a-10 shows significant agonist activity, EC to people 5-HT2a 50value is 51.6nM.
Table 4 people 5-HT2a acceptor (5-HT2aR) active testing
Note: the agonist activity of the compounds of this invention is all measured under 50 μ M; The agonist activity of 5-HT is measured under 1 μ M.
Embodiment 12: oily suspension
Prepare in proportion following component: any compound in the prepared compound of 25% (weight percent, lower with) embodiment of the present invention; 5% polyoxyethylene sorbitol six oleic acid esters; 70% senior aliphatics hydrocarbon ils.Each component is ground together in sand mill, until solid particulate is down to approximately 5 microns below.The thickness suspension of gained can directly be used, but also can in water, after emulsification, use.
All documents of mentioning in the present invention are all quoted as a reference in this application, just as each piece of document, are quoted as a reference separately.In addition should be understood that those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims limited range equally.

Claims (10)

1. there is an acceptable salt in the compound of structure shown in formula (I) or its pharmacy acceptable salt or Pesticide Science,
Wherein,
R 1for that replace or unsubstituted C 1～C 10c alkyl, replacement or unsubstituted 1～C 10c alkoxyl group, replacement or unsubstituted 2～C 10c thiazolinyl, replacement or unsubstituted 2～C 10alkene oxygen base, replacement or unsubstituted C 2～C 10c alkynyl, replacement or unsubstituted 2～C 10c alkynyloxy group, replacement or unsubstituted 1～C 10c ester group, replacement or unsubstituted 1～C 10c alkyl-carbonyl, replacement or unsubstituted 1～C 10c alkoxy carbonyl, replacement or unsubstituted 5～C 10c aryl, replacement or unsubstituted 2～C 8c heteroaryl, replacement or unsubstituted 3～C 8heterocyclylalkyl, replacement or unsubstituted-C 1～C 6alkylidene group-C 5～C 10aryl or that replace or unsubstituted-C 1～C 6alkylidene group-C 2～C 8heteroaryl; Wherein, described replacement refers to that being selected from one or more substituting group of lower group replaces: nitro, halogen, cyano group, amino, diazanyl, C 1～C 6acyl amino, hydroxyl, C 1～C 6alkyl, hydroxyl C 1～C 6alkyl, C 1～C 6alkoxyl group, halo C 1～C 6alkyl, halo C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkene oxygen base, C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkynyl, C 1～C 6ester group, C 1～C 6alkyl-carbonyl, C 1～C 6alkoxy carbonyl, C 5～C 10aryl, halo C 5～C 10aryl and C 3～C 8heterocyclylalkyl;
N is 1 to 3 integer; X is carbonyl (C=O), thiocarbonyl (C=S) or CH 2; Y does not exist, or is NH;
R 2for that replace or unsubstituted C 1～C 10c alkyl, replacement or unsubstituted 1～C 10c ester group, replacement or unsubstituted 1～C 10c alkyl-carbonyl, replacement or unsubstituted 1～C 10c alkoxy carbonyl, replacement or unsubstituted 5～C 10c aryl, replacement or unsubstituted 3～C 8c Heterocyclylalkyl, replacement or unsubstituted 5～C 10aryl or that replace or unsubstituted C 2～C 8heteroaryl; Wherein, described replacement refers to that being selected from one or more substituting group of lower group replaces: nitro, halogen, cyano group, amino, diazanyl, C 1～C 6acyl amino, hydroxyl, C 1～C 6alkyl, hydroxyl C 1～C 6alkyl ,-O-C 1～C 6alkylidene group-O-, C 1～C 6alkoxyl group, halo C 1～C 6alkyl, halo C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkene oxygen base, C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkynyl, C 1～C 6ester group, C 1～C 6alkyl-carbonyl, C 1～C 6alkoxy carbonyl, C 5～C 10aryl, halo C 5～C 10aryl and C 3～C 8heterocyclylalkyl.
2. acceptable salt in compound or its pharmacy acceptable salt or Pesticide Science as claimed in claim 1, is characterized in that, it has the structure shown in formula 10, formula 11, formula 14 or formula 15,
In various, n, R 1, R 2definition is with claim 1.
3. acceptable salt in compound or its pharmacy acceptable salt or Pesticide Science as claimed in claim 1 or 2, is characterized in that R 1for that replace or unsubstituted C 1～C 10c alkyl, replacement or unsubstituted 1～C 10alkoxyl group, replacement or unsubstituted-CH 2-indyl, replacement or unsubstituted-CH 2-phenyl, replacement or unsubstituted-CH 2-pyridyl, replacement or unsubstituted-CH 2-benzo pyridyl, replacement or unsubstituted-CH 2-pyrryl, replacement or unsubstituted-CH 2-thienyl, replacement or unsubstituted-CH 2-benzothienyl, replacement or unsubstituted-CH 2-furyl, replacement or unsubstituted-CH 2-benzofuryl; Wherein, described replacement refers to that being selected from one or more substituting group of lower group replaces: nitro, halogen, cyano group, amino, diazanyl, C 1～C 6acyl amino, hydroxyl, C 1～C 6alkyl, hydroxyl C 1～C 6alkyl, C 1～C 6alkoxyl group, halo C 1～C 6alkyl, halo C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkene oxygen base, C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkynyl, C 1～C 6ester group, C 1～C 6alkyl-carbonyl, C 1～C 6alkoxy carbonyl, C 5～C 10aryl, halo C 5～C 10aryl and C 3～C 8heterocyclylalkyl.
4. acceptable salt in compound or its pharmacy acceptable salt or Pesticide Science as claimed in claim 1 or 2, is characterized in that R 2for that replace or unsubstituted phenyl, replacement or unsubstituted pyridyl, replacement or unsubstituted thiazolyl, replacement or unsubstituted 1, benzothiazolyl 3,4-thiadiazoles, replacement or unsubstituted, replacement or unsubstituted thienyl, replacement or unsubstituted benzothienyl, replacement or unsubstituted furyl, replacement or unsubstituted benzofuryl; Wherein, described replacement refers to that being selected from one or more substituting group of lower group replaces: nitro, halogen, cyano group, amino, diazanyl, C 1～C 6acyl amino, hydroxyl, C 1～C 6alkyl, hydroxyl C 1～C 6alkyl ,-O-C 1～C 6alkylidene group-O-, C 1～C 6alkoxyl group, halo C 1～C 6alkyl, halo C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkene oxygen base, C 1～C 6alkoxyl group, C 2～C 6thiazolinyl, C 2～C 6alkynyl, C 1～C 6ester group, C 1～C 6alkyl-carbonyl, C 1～C 6alkoxy carbonyl, C 5～C 10aryl, halo C 5～C 10aryl and C 3～C 8heterocyclylalkyl.
5. a composition, it is characterized in that, it comprises acceptable salt, (b) acceptable carrier in pharmaceutically acceptable carrier or Pesticide Science in (a) compound as described in claim 1～4 any one or its pharmacy acceptable salt or Pesticide Science.
6. acceptable salt or the purposes of composition as claimed in claim 5 in the compound as described in claim 1～4 any one or its pharmacy acceptable salt or Pesticide Science, is characterized in that, for killing or prevent Agricultural pests; Or for the preparation of the sterilant of killing or prevent Agricultural pests.
7. purposes as claimed in claim 6, is characterized in that, for the preparation of killing or prevent the sterilant of lepidopterous insects, the sterilant that takes food, grows for the preparation of inhibition lepidopterous insects, or for the preparation of the sterilant of killing or prevent nematode.
8. acceptable salt or the purposes of composition as claimed in claim 5 in the compound as described in claim 1～4 any one or its pharmacy acceptable salt or Pesticide Science, it is characterized in that, for the preparation of people 5-HT2a receptors ligand or people 5-HT2a receptor stimulant.
9. the preparation method of acceptable salt in compound as claimed in claim 2 or its pharmacy acceptable salt or Pesticide Science, is characterized in that,
(a) described method comprises step: under the existence of alkali, in inert solvent, compound 7 and compound 5 are reacted, thereby obtain compound 10;
(b) described method comprises step: under the existence of alkali, in inert solvent, compound 9 and compound 5 are reacted, thereby obtain compound 10;
(c) described method comprises step: under the existence of condensing agent, in inert solvent, compound 12 and compound 5 are reacted, thereby obtain compound 10;
(d) described method comprises step: under the existence of reductive agent, in inert solvent, compound 13 and compound 5 are reacted, thereby obtain compound 10;
10. a desinsection and/or insect-prevention method, it is characterized in that, described method comprise by acceptable salt in the compound as described in claim 1～4 any one or its pharmacy acceptable salt or Pesticide Science or as claimed in claim 5 composition put in the plant materials or its soil or environment around that suffers or may insect infestation.
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CN108947978A (en) * 2017-05-22 2018-12-07 首都医科大学 Piperazine -2,5- diketone of 3R- indole methyl -6R-Tyr modification, synthesis, activity and application
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CN108948137A (en) * 2017-05-18 2018-12-07 首都医科大学 Piperazine -2,5- diketone of 3S- indolylethyl -6S- polar amino acid modification, synthesis, activity and application
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CN109196012A (en) * 2016-03-31 2019-01-11 路博润先进材料公司 Biodegradable and/or biological absorbable thermoplastic polyurethane
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CN109196012A (en) * 2016-03-31 2019-01-11 路博润先进材料公司 Biodegradable and/or biological absorbable thermoplastic polyurethane
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