CN103641825A - Naphthalimide derivative and application thereof as enzyme inhibitor and pesticide - Google Patents

Naphthalimide derivative and application thereof as enzyme inhibitor and pesticide Download PDF

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Publication number
CN103641825A
CN103641825A CN201310539176.XA CN201310539176A CN103641825A CN 103641825 A CN103641825 A CN 103641825A CN 201310539176 A CN201310539176 A CN 201310539176A CN 103641825 A CN103641825 A CN 103641825A
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naphthalimide derivative
insect
compound
pesticide
hydrogen
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杨青
刘田
钱旭红
郭朋
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Dalian University of Technology
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Dalian University of Technology
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    • 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
    • C07D417/02—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 two hetero rings
    • C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

The invention provides a naphthalimide derivative and application thereof as enzyme inhibitor and pesticide, and the invention belongs to the field of chemical biology and agricultural insect control technology. In the formula of naphthalimide derivative, R1 is hydrogen, C1-C4 is alkoxy, C1-C4 is alkyl substituted amino or halogen; R2 is hydrogen, C1-C4 is alkyl, C1-C4 is alkoxy substituted phenyl or halogen substituted phenyl; X, Y and Z respectively and independently selected from one of O, S, N and C, which are identical or different; n is 0 or 1. The compound can be used as insect chitinase and n-acetyl hexosamine enzyme inhibitor and pesticide. The invention provides a non-glycosyl novel naphthalimide derivative, which can be used as insect n-acetyl hexosamine enzyme selective inhibitor and pesticide, and has the advantages of simple synthetic method, low cost and good application prospect.

Description

A kind of naphthalimide derivative and as enzyme inhibitors, sterilant
Technical field
The invention belongs to chemicobiology and agricultural insect pests control technical field, relate to a kind of naphthalimide derivative and as the purposes of inhibitor and the sterilant of insect chitinase and N-acetylmuramic glycanchydrolase.
Background technology
Most glycosyl hydrolase enzyme inhibitors is all based on glycosyl precursor structure, has building-up process complexity, high in cost of production problem.
2006, Canada doctor Mahuran seminar of children's hospital has found that by the method for high flux screening a kind of compound-bisnaphthalimides M31850 of non-glycosyl structure is mankind's N-acetylmuramic glycanchydrolase inhibitor (Chem.Biol., 14,153-164), its structure is as follows:
2012, the derivative of the synthetic a series of M31850 of the inventor and as the purposes of mankind's N-acetylmuramic glycanchydrolase inhibitor, and applied for national inventing patent, and publication number is CN102911117A, its general structure is as follows:
Figure BDA0000407024750000012
Chitinase and N-acetylmuramic glycanchydrolase are one of key enzymes of insect chitin hydrolytic process, most important for growing of insect.Therefore, insect chitinase and N-acetylmuramic glycanchydrolase inhibitor have the application prospect as sterilant.Yet the naphthalimide derivative of having reported is at present effective to mankind's N-acetylmuramic glycanchydrolase, invalid to insect chitinase and N-acetylmuramic glycanchydrolase.Therefore, the inhibitor for insect chitinase and N-acetylmuramic glycanchydrolase of exploitation based on naphthalimide precursor structure just seems very necessary.
Summary of the invention
The invention provides a kind of naphthalimide derivative, described naphthalimide derivative is compound shown in formula I or it is at pharmacologically acceptable salts.
In formula,
R 1for hydrogen, C 1～C 4alkoxyl group, C 1～C 4amino or halogen that alkyl replaces; C 1～C 4the amino that alkyl replaces, molecular formula is
Figure BDA0000407024750000022
r 3and R 4independently be selected from respectively C 1～C 4a kind of in alkyl, identical or different;
R 2for hydrogen, C 1～C 4alkyl, C 1～C 4the phenyl that the phenyl that alkoxyl group replaces or halogen replace;
X, Y, Z are independently selected from respectively a kind of, identical or different in O, S, N, C;
N is 0 or 1.
The present invention also provides naphthalimide derivative shown in a kind of preparation formula I or its method at pharmacologically acceptable salts, its key step (synthesis strategy) is: with 2-(2-amino-ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone or 6-position are containing substituent 2-(2-amino-ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone are raw material, under alkaline condition, alkane amination reaction obtains target compound with corresponding muriate; Or 2-(1,3-diketone-1H-benzo [de] isoquinoline 99.9-2 (3H)-yl) acetaldehyde and a series of five-membered ring aminated compounds are formed to azomethine, through reduction, obtain target compound.
Table 1: the compounds of this invention of part as shown in general formula I
Compound R1 R2 X Y Z n
1 Hydrogen Methyl S N N 1
2 Hydrogen Methyl O N N 1
3 Dimethylamino Methyl S N N 1
4 Hydrogen Phenyl O N N 1
5 Hydrogen Chloro-phenyl- O N N 1
6 Hydrogen P-methoxy-phenyl O N N 1
7 Hydrogen Fluorophenyl O N N 1
8 Hydrogen Hydrogen S N N 0
9 Hydrogen Hydrogen S N C 0
The invention provides naphthalimide derivative shown in formula I or its application as insect chitinase and N-acetylmuramic glycanchydrolase inhibitor at pharmacologically acceptable salts.Experiment shows: the naphthalimide analog derivative that the present invention designs and invents has to insect chitinase OfCht-h and N-acetylmuramic glycanchydrolase OfHex1 the activity of inhibition.The 3 couples of insect chitinase OfCht-h of compound that wherein mention in table 1 and the inhibition activity of N-acetylmuramic glycanchydrolase OfHex1 are best, and it suppresses constant is 0.25 μ M and 0.31 μ M.
The invention provides naphthalimide derivative shown in formula I or its application as selectivity insect N-acetylmuramic glycanchydrolase inhibitor at pharmacologically acceptable salts.The compound 3 of wherein mentioning in table 1 does not suppress the N-acetylmuramic glycanchydrolase HsHexA/B in Mammals source and the N-acetylmuramic glycanchydrolase CeHex of plant origin under 100 μ M concentration.
The invention provides naphthalimide derivative shown in formula I or its application as sterilant at pharmacologically acceptable salts.
Effect of the present invention and benefit have been to provide the novel naphthalimide derivative of non-glycosyl as insect N-acetylmuramic glycanchydrolase selective depressant and sterilant, and it is synthetic simple, and with low cost, application prospect is better.
Embodiment
Below in conjunction with technical scheme, describe the specific embodiment of the present invention in detail.These embodiment are only for illustrating the present invention and understanding better content of the present invention, the protection domain that it does not limit the present invention in any way.
Embodiment 1
2-(2-(((5-methyl isophthalic acid, 3,4-thiadiazoles-2-yl) methyl) amino) ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (1) synthetic
Figure BDA0000407024750000041
Salt of wormwood (383mg, 2.77mmol) join 2-(2-amino-ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (500mg, 2.08mmol) with 2-chloromethyl-5-methyl isophthalic acid, in the 20mL acetonitrile solution of 3,4-thiadiazoles (206mg, 1.39mmol), it is complete that reflux is stirred to TLC monitoring raw material reaction, approximately 12 hours.Reaction solution suction filtration is removed insolubles.Filtrate decompression evaporate to dryness, the separated (CH of residue silica gel column chromatography 2cl 2/ CH 3oH (30:1)), obtain white solid (250mg, 0.71mmol, 51%).
1h NMR (400MHz, CDCl 3): δ=8.59 (d, J=7.2Hz, 2H), 8.23 (d; J=8.0Hz, 2H), 7.76 (dd, J=8.0; 7.2Hz, 2H), 4.37 (t, J=6.0Hz; 2H), 4.22 (s, 2H), 3.10 (t; J=6.0Hz, 2H), 2.63 (s; 3H), 1.96ppm (br, 1H); 13c NMR (100MHz, CDCl 3): δ=172.0,165.7,164.4,134.1,131.6,131.3,128.2,127.0,122.5,47.9,47.2,39.6,15.6ppm; HRMS-ESI (m/z): calculated value C 18h 17n 4o 2s[M+H] +, 353.1072; Experimental value, 353.1078.
Embodiment 2
2-(2-(((5-methyl isophthalic acid, 3,4-oxadiazole-2-yl) methyl) amino) ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (2) synthetic
Figure BDA0000407024750000051
Divided by 2-chloromethyl-5-methyl isophthalic acid, the 2-chloromethyl-5-methyl isophthalic acid in 3,4-oxadiazole alternative embodiment 1, outside 3,4-thiadiazoles, other condition and step are identical with embodiment 1, obtain compound 2, white solid, productive rate 50%.
1h NMR (400MHz, CDCl 3): δ=8.59 (d, J=7.2Hz, 2H), 8.23 (d; J=8.0Hz, 2H), 7.76 (dd, J=8.0; 7.2Hz, 2H), 4.37 (t, J=6.0Hz; 2H), 4.05 (s, 2H), 3.10 (t; J=6.0Hz, 2H), 2.47 (s; 3H), 1.96ppm (br, 1H); 13c NMR (100MHz, CDCl 3): δ=172.0,165.4,164.1,134.1,131.6,131.3,128.2,127.0,122.5,47.1,43.4,39.5,11.0ppm; HRMS-ESI (m/z): calculated value C 18h 17n 4o 3[M+H] +, 337.1301; Experimental value, 337.1300.
Embodiment 3
6-(dimethylamino)-2-(2-(((5-methyl isophthalic acid, 3,4-thiadiazoles-2-yl) methyl) amino) ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (3) synthetic
Figure BDA0000407024750000052
Divided by 2-(2-amino-ethyl)-6-(dimethylamino)-1H-benzo [de] isoquinoline 99.9-1,2-(2-amino-ethyl)-1H-benzo [de] isoquinoline 99.9-1 in 3 (2H)-diketone alternative embodiments 1, outside 3 (2H)-diketone, other condition and step are identical with embodiment 1, obtain compound 3, yellow oil, productive rate 50%.
1h NMR (400MHz, CDCl 3): δ=8.54 (dd, J=7.2,0.8Hz, 1H), 8.47-8.40 (m; 2H), 7.64 (dd, J=8.4,7.2Hz, 1H); 7.10 (d, J=8.4Hz, 1H), 4.33 (t, J=6.4Hz; 2H), 4.21 (s, 2H), 3.10 (s; 6H), 3.07 (t, J=6.4Hz, 2H); 2.62 (s, J=3H), 2.16ppm (br, 1H); 13c NMR (100MHz, CDCl 3): δ=172.1,165.6,164.8,164.2,157.0,132.7,131.3,131.1,130.3,125.2,124.8,122.9,114.7,113.2,47.8,47.3,44.7,39.4,15.5ppm; HRMS-ESI (m/z): calculated value, C 20h 22n 5o 2s[M+H] +, 396.1494; Experimental value, 396.1494.
Embodiment 4
2-(2-(((5-phenyl-1,3,4-oxadiazole-2-yl) methyl) amino) ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (4) synthetic
Divided by 2-chloromethyl-5-phenyl-1, the 2-chloromethyl-5-methyl isophthalic acid in 3,4-oxadiazole alternative embodiment 1, outside 3,4-thiadiazoles, other condition and step are identical with embodiment 1, obtain compound 4, white solid, fusing point: 166-168 ℃, productive rate 60%.
1h NMR (400MHz, CDCl 3): δ=8.51 (d, J=7.2Hz, 2H), 8.13 (d, J=7.6Hz, 2H); 7.93 (dt, J=6.8,1.6Hz, 2H), 7.67 (dd, J=7.6; 7.2Hz, 2H), 7.47 (tt, J=7.2,2.4Hz; 1H), 7.41 (tt, J=7.2,1.6Hz, 2H); 4.35 (t, J=6.4Hz, 2H), 4.14 (s, 2H); 3.13 (t, J=6.4Hz, 2H), 1.97ppm (s, 1H); 13c NMR (100MHz, CDCl 3): δ=165.0,164.8,164.2,133.8,131.4,131.3,131.0,128.7,127.9,126.7,126.6,123.6,122.2,46.9,43.2,39.3ppm; HRMS-ESI (m/z): calculated value C 23h 19n 4o 3[M+H] +, 399.1457; Experimental value, 399.1457.
Embodiment 5
2-(2-(((5-(4-chloro-phenyl-)-1,3,4-oxadiazole-2-yl) methyl) amino) ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (5) synthetic
Figure BDA0000407024750000071
Divided by 2-chloromethyl-5-(4-chloro-phenyl-)-1,3, the 2-chloromethyl-5-methyl isophthalic acid in 4-oxadiazole alternative embodiment 1,3, outside 4-thiadiazoles, other condition and step are identical with embodiment 1, obtain compound 5, white solid, fusing point: 147-149 ℃, productive rate 80%.
1h NMR (400MHz, CDCl 3): δ=8.52 (d, J=7.2Hz, 2H), 8.15 (d, J=8.0Hz; 2H), 7.86 (d, J=8.0Hz, 2H), 7.69 (dd; J=8.0,7.6Hz, 2H), 7.38 (d; J=8.0Hz, 2H), 4.35 (t, J=6.4Hz; 2H), 4.14 (s, 2H), 3.13 (t; J=6.4Hz, 2H), 1.91ppm (s, 1H); 13cNMR (100MHz, CDCl 3): δ=165.4,164.3,164.1,137.7,133.9,131.4,131.2,129.2,128.0,126.8,122.4,122.2,47.0,43.3,39.4ppm; HRMS-ESI (m/z): calculated value C 23h 18n 4o 3cl[M+H] +, 433.1067; Experimental value, 433.1047.
Embodiment 6
2-(2-(((5-(4-p-methoxy-phenyl)-1,3,4-oxadiazole-2-yl) methyl) amino) ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (6) synthetic
Figure BDA0000407024750000072
Divided by 2-chloromethyl-5-(4-p-methoxy-phenyl)-1,3, the 2-chloromethyl-5-methyl isophthalic acid in 4-oxadiazole alternative embodiment 1,3, outside 4-thiadiazoles, other condition and step are identical with embodiment 1, obtain compound 6, white solid, fusing point: 145-146 ℃, productive rate 80%.
1h NMR (400MHz, CDCl 3): δ=8.54 (d, J=7.2Hz, 2H), 8.16 (d, J=8.0Hz; 2H), 7.88 (d, J=8.0Hz, 2H), 7.70 (dd; J=8.0,7.6Hz, 2H), 6.92 (d, J=8.0Hz; 2H), 4.36 (t, J=6.4Hz, 2H), 4.12 (s; 2H), 3.84 (s, 3H), 3.13 (t; J=6.4Hz, 2H), 1.90ppm (s, 1H); 13c NMR (100MHz, CDCl 3): δ=164.8,164.4,164.3,162.1,133.9,131.4,131.2,128.5,128.1,126.8,122.4,116.2,114.3,55.4,47.0,43.3,39.5ppm; HRMS-ESI (m/z): calculated value C 24h 21n 4o 4[M+H] +, 429.1563; Experimental value, 429.1564.
Embodiment 7
2-(2-(((5-(3-fluorophenyl)-1,3,4-oxadiazole-2-yl) methyl) amino) ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (7) synthetic
Figure BDA0000407024750000081
Divided by 2-chloromethyl-5-(3-fluorophenyl)-1,3, the 2-chloromethyl-5-methyl isophthalic acid in 4-oxadiazole alternative embodiment 1,3, outside 4-thiadiazoles, other condition and step are identical with embodiment 1, obtain compound 7, white solid, fusing point: 144-146 ℃, productive rate 80%.
1h NMR (400MHz, CDCl 3): δ=8.52 (d, J=7.2Hz, 2H), 8.15 (d; J=8.0Hz, 2H), 7.78-7.58 (m, 4H); 7.46-7.34 (m, 1H), 7.24-7.12 (m, 1H); 4.36 (t, J=6.4Hz, 2H), 4.15 (s; 2H), 3.13 (t, J=6.4Hz; 2H), 1.97ppm (s, 1H); 13c NMR (100MHz, CDCl 3): δ=165.5,164.3,163.8,162.7 (d; J=257.1Hz), 133.9,131.4,131.2; 130.7 (d, J=8.1Hz), 128.0,126.8; 125.6 (d, J=8.7Hz), 122.4 (d, J=19.6Hz); 118.5 (d, J=21.2Hz), 113.8 (d, J=24.2Hz); 47.0,43.3,39.4ppm; HRMS-ESI (m/z): calculated value C 23h 18n 4o 3f[M+H] +, 417.1363; Experimental value, 417.1371.
Embodiment 8
2-(2-((1,3,4-thiadiazoles-2-yl) amino) ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (8) synthetic
Figure BDA0000407024750000091
In 100mL round-bottomed flask, add 2-(2-amino-ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (500mg, 2.09mmol), 2-amido-1,3,4-thiadiazoles (211mg, 2.09mmol) and 50mL ethanol.This mixture is heated to return stirring and spends the night, suction filtration, and filter cake IR bake is dry, obtains white solid.
Again sodium borohydride (158mg, 4.18mmol) is joined to the 50mL alcohol suspending liquid of above-mentioned solid.Suction filtration after being heated to return stirring and spending the night, removes insolubles.Filtrate is poured in 50mL water, and methylene dichloride (50mL) extraction three times, merges organic phase, and dry organic phase, removes organic solvent under reduced pressure, and resistates is through the separated (CH of silica gel column chromatography 2cl 2/ CH 3oH, 20:1, v/v) obtain pale solid (compound 8) 200mg, productive rate 30%.
1h NMR (400MHz, DMSO-d 6): δ=8.58 (s, 1H), 8.46 (t, J=8.4Hz, 4H), 7.90-7.80 (m, 3H), 4.30 (t, J=6.0Hz, 2H), 3.65ppm (q, J=6.0Hz, 2H); 13c NMR (100MHz, DMSO-d 6): δ=168.6,163.5,142.1,134.1,131.2,130.6,127.4,127.1,122.1,42.5,38.6ppm; HRMS-ESI (m/z): calculated value C 16h 12n 4o 2sNa[M+Na] +, 347.0579; Experimental value, 347.0572.
Embodiment 9
2-(2-((1,3-thiazoles-2-yl) amino) ethyl)-1H-benzo [de] isoquinoline 99.9-1,3 (2H)-diketone (9) synthetic
Figure BDA0000407024750000092
Outside the 2-amido-1,3,4-thiadiazoles in 2-amino-1,3-thiazoles alternative embodiment 8, other condition and step are identical with embodiment 8, obtain compound 9, white solid, productive rate 20%.
1h NMR (400MHz, CDCl 3): δ=8.59 (d, J=7.2Hz, 2H), 8.21 (d; J=8.0Hz, 2H), 7.75 (dd, J=8.0; 7.2Hz, 2H), 7.03 (d, J=3.6Hz; 1H), 6.40 (d, J=3.6Hz, 1H); 5.82 (br, 1H), 4.54 (t, J=6.0Hz; 2H), 3.72ppm (t, J=6.0Hz, 2H); 13c NMR (100MHz, CDCl 3): δ=169.9,164.7,139.1,134.2,131.5,128.2,126.9,122.2,106.5,45.0,39.3ppm; HRMS-ESI (m/z): calculated value C 17h 14n 3o 2[M+H] +, 324.0807; Experimental value, 324.0802.
Embodiment 10
The inhibition active testing of compound provided by the invention to chitinase:
Enzyme: Ostrinia furnacalis chitinase OfCht-h is prepared by recombinant expression method for the inventor.
Substrate: p-NP chitobiose (p-nitrophenyl-β-chitobiose, pNP-β-(GlcNAc) 2), purchased from Sigma-Aldrich company.
Activity determination method: by enzyme and survey enzyme damping fluid (20mM NaH alive 2pO 4, pH6.8) in 96 orifice plates, being mixed to final volume is 54 μ l, adds 6 μ l5mM pNP-β--(GlcNAc) 2initial action, 25 ℃ of incubation 5min, add 60 μ l0.5M Na 2cO 3termination reaction, measures absorption value in 405nm.
Compound suppresses activity determination method: the inhibitor of enzyme and different concns, at room temperature incubation 10min, and is measured to enzyme work with aforesaid method respectively under the concentration of substrate of 0.1mM and 0.2mM.Suppressing constant (Ki) utilizes Dixon plots linear regression data fitting to obtain.Compound sees the following form 2 to the inhibition activity of insect chitinase OfCht-h:
Table 2 compound is active to the inhibition of insect chitinase OfCht-h
Compound Inhibition percentage under 50 μ M
1 75
2 70
3 98
4 53
5 60
6 66
7 70
8 33
9 40
Embodiment 11
The inhibition active testing of compound provided by the invention to N-acetylmuramic glycanchydrolase:
Enzyme: Ostrinia furnacalis N-acetylmuramic glycanchydrolase OfHex1 is prepared by recombinant expression method for the inventor; Viride N-acetylmuramic glycanchydrolase TvHex, sword bean N-acetylmuramic glycanchydrolase CeHex and mankind's N-acetylmuramic glycanchydrolase HsHexA/B are purchased from Sigma-Aldrich company.
Substrate: p-NP-N-Acetyl-D-glucosamine (p-nitrophenyl2-acetamido-2-deoxy-β-D-glucopyranoside, pNP-β-GlcNAc), purchased from Sigma-Aldrich company.
Activity determination method: by enzyme and survey enzyme damping fluid (20mM NaH alive 2pO 4, pH6.8) in 96 orifice plates, being mixed to final volume is 54 μ l, adds 6 μ l5mM pNP-β-GlcNAc initial actions, 25 ℃ of incubation 5min, add 60 μ l0.5M Na 2cO 3termination reaction, measures absorption value in 405nm.
Compound suppresses activity determination method: the inhibitor of enzyme and different concns, at room temperature incubation 10min, and is measured to enzyme work with aforesaid method respectively under the concentration of substrate of 0.1mM and 0.2mM.Suppress constant (K i) utilize Dixon plots linear regression data fitting to obtain.Compound sees the following form 3 to the inhibition activity of insect N-acetylmuramic glycanchydrolase OfHex1:
Table 3 compound is active to the inhibition of insect N-acetylmuramic glycanchydrolase OfHex1
Compound Inhibition percentage under 20 μ M
1 67
2 63
3 92
4 10
5 14
6 12
7 10
8 16
9 19
Embodiment 12
Compound insecticidal activity test provided by the invention:
Kill armyworm determination of activity
Mythimna separata is the normal population of indoor feeding.Experimental technique: leaf dipping method.By leaf of Semen Maydis, impregnated in the liquid of acetone preparation (500ppm), after liquid is dry, access 3 instar larvaes, be mainly stomach toxicity, action of contace poison, observe larval feeding phenomenon simultaneously.Within 72 hours, check mortality ratio.Compound sees the following form 4 to the insecticidal activity of armyworm:
The insecticidal activity of table 4 compound to armyworm
Compound (500ppm) Mortality ratio (%)
1 70
2 40
3 100
4 90
5 80
6 100
7 80
8 60
9 50

Claims (5)

1. a naphthalimide derivative, is characterized in that having compound shown in formula I:
Figure FDA0000407024740000011
In formula,
R 1for hydrogen, C 1～C 4alkoxyl group, C 1～C 4amino or halogen that alkyl replaces; C 1～C 4the amino that alkyl replaces, molecular formula is
Figure FDA0000407024740000012
r 3and R 4independently be selected from respectively C 1～C 4a kind of in alkyl, identical or different;
R 2for hydrogen, C 1～C 4alkyl, C 1～C 4the phenyl that the phenyl that alkoxyl group replaces or halogen replace;
X, Y, Z are independently selected from respectively a kind of, identical or different in O, S, N, C;
N is 0 or 1.
2. a kind of naphthalimide derivative described in claim 1, as enzyme inhibitors, is characterized in that, this naphthalimide derivative is as insect chitin enzyme inhibitors.
3. a kind of naphthalimide derivative described in claim 1, as enzyme inhibitors, is characterized in that, this naphthalimide derivative is as insect β-N-acetylmuramic glycanchydrolase inhibitor.
4. a kind of naphthalimide derivative described in claim 1, as enzyme inhibitors, is characterized in that, this naphthalimide derivative is as selectivity β-N-acetylmuramic glycanchydrolase inhibitor.
5. a kind of naphthalimide derivative described in claim 1, as sterilant, is characterized in that, this naphthalimide derivative is as sterilant.
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CN107094780A (en) * 2017-03-31 2017-08-29 大连理工大学 Jamaicin and its derivative as hexosaminidase inhibitor application
CN107383120A (en) * 2017-07-31 2017-11-24 中国农业大学 A kind of glycosyl naphthalimide derivative and preparation method and application
CN107513083A (en) * 2017-09-07 2017-12-26 大连理工大学 The preparation method of glycosyl naphthoyl imide compounds and application
CN107832577A (en) * 2017-10-30 2018-03-23 中国农业大学 A kind of method for screening the inhibitor of chitinase OfCht I
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Publication number Priority date Publication date Assignee Title
CN107094780A (en) * 2017-03-31 2017-08-29 大连理工大学 Jamaicin and its derivative as hexosaminidase inhibitor application
CN107383120A (en) * 2017-07-31 2017-11-24 中国农业大学 A kind of glycosyl naphthalimide derivative and preparation method and application
CN107383120B (en) * 2017-07-31 2019-08-20 中国农业大学 A kind of glycosyl naphthalimide derivative and the preparation method and application thereof
CN107513083A (en) * 2017-09-07 2017-12-26 大连理工大学 The preparation method of glycosyl naphthoyl imide compounds and application
CN107513083B (en) * 2017-09-07 2020-09-29 大连理工大学 Preparation method and application of glycosyl naphthalimide compound
CN107832577B (en) * 2017-10-30 2021-07-13 中国农业大学 Method for screening chitinase OfChtI inhibitor
CN107832577A (en) * 2017-10-30 2018-03-23 中国农业大学 A kind of method for screening the inhibitor of chitinase OfCht I
CN108467395A (en) * 2018-05-09 2018-08-31 大连理工大学 A kind of chitinase inhibitors and its application
CN108467395B (en) * 2018-05-09 2020-12-11 大连理工大学 Chitinase inhibitor and application thereof
CN110540571A (en) * 2019-08-08 2019-12-06 云南农业大学 Notoginsenoside R1 derivative and application thereof
CN110540571B (en) * 2019-08-08 2021-07-06 云南农业大学 Notoginsenoside R1 derivative and application thereof
US20220034808A1 (en) * 2020-07-29 2022-02-03 Robert Bosch Gmbh Sensing devices and chemosensors and compositions relating thereto
CN114249697A (en) * 2021-12-31 2022-03-29 中国农业大学 Nitrogen heterocyclic macrolide compound containing methylguanidinyl urea and preparation method and application thereof

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