WO2008018645A1 - Pesticides - Google Patents
Pesticides Download PDFInfo
- Publication number
- WO2008018645A1 WO2008018645A1 PCT/KR2006/003139 KR2006003139W WO2008018645A1 WO 2008018645 A1 WO2008018645 A1 WO 2008018645A1 KR 2006003139 W KR2006003139 W KR 2006003139W WO 2008018645 A1 WO2008018645 A1 WO 2008018645A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- insects
- compound
- chemical formula
- preparation example
- biosynthesis
- Prior art date
Links
- 239000000575 pesticide Substances 0.000 title abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 80
- 241000238631 Hexapoda Species 0.000 claims abstract description 65
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 45
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 42
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 25
- 239000000203 mixture Substances 0.000 claims abstract description 23
- 230000000361 pesticidal effect Effects 0.000 claims abstract description 18
- 150000003626 triacylglycerols Chemical class 0.000 claims abstract description 15
- 102000057234 Acyl transferases Human genes 0.000 claims abstract description 12
- 108700016155 Acyl transferases Proteins 0.000 claims abstract description 12
- 230000002147 killing effect Effects 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims description 63
- 239000003112 inhibitor Substances 0.000 claims description 19
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 239000004615 ingredient Substances 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 230000000694 effects Effects 0.000 abstract description 14
- 230000012010 growth Effects 0.000 abstract description 4
- 150000003839 salts Chemical class 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 230000003389 potentiating effect Effects 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 description 56
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 22
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 150000002632 lipids Chemical class 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 16
- 239000002917 insecticide Substances 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 14
- 108090000790 Enzymes Proteins 0.000 description 14
- 229940088598 enzyme Drugs 0.000 description 14
- 229940093499 ethyl acetate Drugs 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 235000011187 glycerol Nutrition 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 10
- 229960004373 acetylcholine Drugs 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- SWNROPPWBFHVCS-UHFFFAOYSA-N 1,4,5,8-tetramethoxynaphthalene Chemical compound C1=CC(OC)=C2C(OC)=CC=C(OC)C2=C1OC SWNROPPWBFHVCS-UHFFFAOYSA-N 0.000 description 8
- 229920002101 Chitin Polymers 0.000 description 8
- 241000018137 Trialeurodes vaporariorum Species 0.000 description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 7
- 230000000749 insecticidal effect Effects 0.000 description 7
- 239000002949 juvenile hormone Substances 0.000 description 7
- 210000005036 nerve Anatomy 0.000 description 7
- 230000001242 postsynaptic effect Effects 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 241000500437 Plutella xylostella Species 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 102000012440 Acetylcholinesterase Human genes 0.000 description 5
- 108010022752 Acetylcholinesterase Proteins 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 229940022698 acetylcholinesterase Drugs 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- -1 fatty acid esters Chemical class 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 210000000653 nervous system Anatomy 0.000 description 5
- 210000002569 neuron Anatomy 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 208000014903 transposition of the great arteries Diseases 0.000 description 5
- BOKGTLAJQHTOKE-UHFFFAOYSA-N 1,5-dihydroxynaphthalene Chemical compound C1=CC=C2C(O)=CC=CC2=C1O BOKGTLAJQHTOKE-UHFFFAOYSA-N 0.000 description 4
- ANCSPRJFGGDREM-UHFFFAOYSA-N 1,5-dimethoxynaphthalene Chemical compound C1=CC=C2C(OC)=CC=CC2=C1OC ANCSPRJFGGDREM-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000013504 Triton X-100 Substances 0.000 description 4
- 229920004890 Triton X-100 Polymers 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 235000013601 eggs Nutrition 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 229930014550 juvenile hormone Natural products 0.000 description 4
- 150000003633 juvenile hormone derivatives Chemical class 0.000 description 4
- 230000037356 lipid metabolism Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 231100000614 poison Toxicity 0.000 description 4
- 230000007096 poisonous effect Effects 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229930182558 Sterol Natural products 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 241000607479 Yersinia pestis Species 0.000 description 3
- 210000001789 adipocyte Anatomy 0.000 description 3
- 210000003050 axon Anatomy 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000004166 bioassay Methods 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 3
- 239000004927 clay Substances 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 230000036461 convulsion Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 235000020774 essential nutrients Nutrition 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 230000012447 hatching Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 230000001069 nematicidal effect Effects 0.000 description 3
- 239000005645 nematicide Substances 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000003016 pheromone Substances 0.000 description 3
- 230000003518 presynaptic effect Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 150000003432 sterols Chemical class 0.000 description 3
- 235000003702 sterols Nutrition 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 210000000225 synapse Anatomy 0.000 description 3
- 210000002504 synaptic vesicle Anatomy 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-dioxonaphthalene Natural products C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 description 2
- PMBXCGGQNSVESQ-UHFFFAOYSA-N 1-Hexanethiol Chemical compound CCCCCCS PMBXCGGQNSVESQ-UHFFFAOYSA-N 0.000 description 2
- ZRKMQKLGEQPLNS-UHFFFAOYSA-N 1-Pentanethiol Chemical compound CCCCCS ZRKMQKLGEQPLNS-UHFFFAOYSA-N 0.000 description 2
- QPUYECUOLPXSFR-UHFFFAOYSA-N 1-methylnaphthalene Chemical compound C1=CC=C2C(C)=CC=CC2=C1 QPUYECUOLPXSFR-UHFFFAOYSA-N 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- 241000905789 Lactobacillus larvae Species 0.000 description 2
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 2
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 2
- 206010033799 Paralysis Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000000895 acaricidal effect Effects 0.000 description 2
- 239000000642 acaricide Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 239000003905 agrochemical Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- WQAQPCDUOCURKW-UHFFFAOYSA-N butanethiol Chemical compound CCCCS WQAQPCDUOCURKW-UHFFFAOYSA-N 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000000919 ceramic Substances 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- QBEGYEWDTSUVHH-UHFFFAOYSA-P diazanium;cerium(3+);pentanitrate Chemical compound [NH4+].[NH4+].[Ce+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O QBEGYEWDTSUVHH-UHFFFAOYSA-P 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 239000003337 fertilizer Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 210000000087 hemolymph Anatomy 0.000 description 2
- 239000002428 insect molting hormone Substances 0.000 description 2
- 210000002490 intestinal epithelial cell Anatomy 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 239000003915 liquefied petroleum gas Substances 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- HCZKYJDFEPMADG-TXEJJXNPSA-N masoprocol Chemical compound C([C@H](C)[C@H](C)CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-TXEJJXNPSA-N 0.000 description 2
- 230000003228 microsomal effect Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 210000000063 presynaptic terminal Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- SUVIGLJNEAMWEG-UHFFFAOYSA-N propane-1-thiol Chemical compound CCCS SUVIGLJNEAMWEG-UHFFFAOYSA-N 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 210000002182 synaptic membrane Anatomy 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- DCXXMTOCNZCJGO-UHFFFAOYSA-N tristearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- AFSHUZFNMVJNKX-CLFAGFIQSA-N 1,2-dioleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCC\C=C/CCCCCCCC AFSHUZFNMVJNKX-CLFAGFIQSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- AZZZFWMZPDBLPI-UHFFFAOYSA-N 1,5-dibromo-4,8-dimethoxynaphthalene Chemical compound C1=CC(Br)=C2C(OC)=CC=C(Br)C2=C1OC AZZZFWMZPDBLPI-UHFFFAOYSA-N 0.000 description 1
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- JHWIEAWILPSRMU-UHFFFAOYSA-N 2-methyl-3-pyrimidin-4-ylpropanoic acid Chemical compound OC(=O)C(C)CC1=CC=NC=N1 JHWIEAWILPSRMU-UHFFFAOYSA-N 0.000 description 1
- IMOYOUMVYICGCA-UHFFFAOYSA-N 2-tert-butyl-4-hydroxyanisole Chemical compound COC1=CC=C(O)C=C1C(C)(C)C IMOYOUMVYICGCA-UHFFFAOYSA-N 0.000 description 1
- MRBKEAMVRSLQPH-UHFFFAOYSA-N 3-tert-butyl-4-hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1 MRBKEAMVRSLQPH-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 244000291564 Allium cepa Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 240000007124 Brassica oleracea Species 0.000 description 1
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 0 COc(c(C(C=C1S(*)=O)=O)c2C1=O)ccc2OC Chemical compound COc(c(C(C=C1S(*)=O)=O)c2C1=O)ccc2OC 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 240000004160 Capsicum annuum Species 0.000 description 1
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 1
- 235000007862 Capsicum baccatum Nutrition 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 239000004287 Dehydroacetic acid Substances 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- UXDDRFCJKNROTO-UHFFFAOYSA-N Glycerol 1,2-diacetate Chemical compound CC(=O)OCC(CO)OC(C)=O UXDDRFCJKNROTO-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000258937 Hemiptera Species 0.000 description 1
- VPIAKHNXCOTPAY-UHFFFAOYSA-N Heptane-1-thiol Chemical compound CCCCCCCS VPIAKHNXCOTPAY-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical group CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000255975 Saturniidae Species 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- LFTYTUAZOPRMMI-CFRASDGPSA-N UDP-N-acetyl-alpha-D-glucosamine Chemical compound O1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](NC(=O)C)[C@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 LFTYTUAZOPRMMI-CFRASDGPSA-N 0.000 description 1
- LFTYTUAZOPRMMI-UHFFFAOYSA-N UNPD164450 Natural products O1C(CO)C(O)C(O)C(NC(=O)C)C1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 LFTYTUAZOPRMMI-UHFFFAOYSA-N 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 150000001346 alkyl aryl ethers Chemical class 0.000 description 1
- 150000008055 alkyl aryl sulfonates Chemical class 0.000 description 1
- 150000008051 alkyl sulfates Chemical class 0.000 description 1
- 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 1
- 150000008052 alkyl sulfonates Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001728 capsicum frutescens Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000073 carbamate insecticide Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- JEQRBTDTEKWZBW-UHFFFAOYSA-N dehydroacetic acid Chemical compound CC(=O)C1=C(O)OC(C)=CC1=O JEQRBTDTEKWZBW-UHFFFAOYSA-N 0.000 description 1
- 229940061632 dehydroacetic acid Drugs 0.000 description 1
- 235000019258 dehydroacetic acid Nutrition 0.000 description 1
- PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 description 1
- 210000001787 dendrite Anatomy 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- LRCFXGAMWKDGLA-UHFFFAOYSA-N dioxosilane;hydrate Chemical compound O.O=[Si]=O LRCFXGAMWKDGLA-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- HCZKYJDFEPMADG-UHFFFAOYSA-N erythro-nordihydroguaiaretic acid Natural products C=1C=C(O)C(O)=CC=1CC(C)C(C)CC1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 150000002185 fatty acyl-CoAs Chemical class 0.000 description 1
- 150000002190 fatty acyls Chemical group 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000036540 impulse transmission Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
- QPPQHRDVPBTVEV-UHFFFAOYSA-N isopropyl dihydrogen phosphate Chemical compound CC(C)OP(O)(O)=O QPPQHRDVPBTVEV-UHFFFAOYSA-N 0.000 description 1
- 229930191400 juvenile hormones Natural products 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000003350 kerosene Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000007653 larval development Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229920005610 lignin Chemical class 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 230000013190 lipid storage Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 235000004213 low-fat Nutrition 0.000 description 1
- 229960003951 masoprocol Drugs 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 150000002759 monoacylglycerols Chemical class 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- ZVEZMVFBMOOHAT-UHFFFAOYSA-N nonane-1-thiol Chemical compound CCCCCCCCCS ZVEZMVFBMOOHAT-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- KZCOBXFFBQJQHH-UHFFFAOYSA-N octane-1-thiol Chemical compound CCCCCCCCS KZCOBXFFBQJQHH-UHFFFAOYSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000004045 organic chlorine compounds Chemical class 0.000 description 1
- 239000003986 organophosphate insecticide Substances 0.000 description 1
- MNBKLUUYKPBKDU-BBECNAHFSA-N palmitoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)CCCCCCCCCCCCCCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MNBKLUUYKPBKDU-BBECNAHFSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229960004029 silicic acid Drugs 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- KIEOKOFEPABQKJ-UHFFFAOYSA-N sodium dichromate Chemical compound [Na+].[Na+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KIEOKOFEPABQKJ-UHFFFAOYSA-N 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000010421 standard material Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 238000012032 thrombin generation assay Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N41/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom
- A01N41/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a sulfur atom bound to a hetero atom containing a sulfur-to-oxygen double bond
- A01N41/10—Sulfones; Sulfoxides
Definitions
- the present invention relates to novel derivatives having inhibitory activity against the biosynthesis of triglycerides, pesticidal compositions comprising the same as an active ingredient, and pesticidal methods using the same.
- Insecticides are introduced into insects via various routes, including the mouth, skin and spiracles. When insecticides arrive at their targets in insects, some of them are degraded into nontoxic forms, while others are activated, become more toxic and accumulate in organs or are excreted outside the body. When an insecticide is applied to insects, not all of the insecticide that is used exerts its insecticidal activity on its target.
- Insecticides currently used around the world are classified according to their mode of action into neural transmission inhibitors, energy production inhibitors, insect growth regulators, and sex- attraction pheromones. Insect growth regulators are subgrouped into juvenile hormone inhibitors and chitin synthesis inhibitors. And there are sterol metabolism inhibitors, which are developed by the present inventors. Most of the currently used insecticides target the nervous system, which plays a critical role in sustaining life, or enzymes involved in energy production.
- a neuron the fundamental unit of the nervous system, usually has one long thin fiber, called an axon, projecting from the cell body.
- the axon makes contact with the dendrite of another neuron, thus forming a specialized structure called a synapse.
- a nerve impulse propagates along an axon.
- a neurotransmitter acetylcholine
- acetylcholine is immediately released from the synaptic vesicles into the synapse between pre-synaptic and postsynaptic membranes.
- the released acetylcholine binds to its receptor in the postsynaptic membrane, resulting in stimulation of the postsynaptic neuron. In this way, a nerve impulse is transmitted from one neuron to another.
- acetylcholine released from the synaptic vesicles is hydrolyzed by acetylcholin esterase, which is released from the postsynaptic membrane.
- Acetylcholin esterase has two functions: one is to degrade negatively charged ions and esters, and the other is to hydrolyze acetylcholine.
- acetylcholine is converted to choline and acetic acid by the action of acetylcholin esterase.
- the choline is taken into the pre-synaptic membrane for re-use, and is converted to acetylcholine in the synaptic vesicles.
- insecticides are insect growth regulators, which inhibit the construction of the exoskeleton and the biosynthesis of chitin in insects. Insects have to molt to accommodate their gradual growth, during which the biosynthesis of the exoskeleton is very important to the physiological functions of the insects.
- the insect exoskeleton is a multi-layered structure with four functional regions. The exoskeleton is roughly divided into the basal membrane and the epidermis, which is further divisible into the epicuticle and procuticle.
- the procuticle of insects is based on a polymer (chitin), consisting of units of N-acetyl glucosamine. Because this polymer does not exist in vertebrates, but is a main component of insect's exoskeleton, insects can be killed when the biosynthesis of chitin is inhibited.
- chitin synthesis inhibitors when introduced into the insect body via the mouth or stigmas, cause incomplete exoskeleton formation, incapacitating the insects from molting normally.
- the chitin synthesis inhibitors have no influence on the form ation of the epicuticle, but inhibit the synthesis of chitin in the procuticle layer.
- the chitin synthesis inhibitors although their precise mechanisms have to be proven, are known to have inhibitory activity against enzymes responsible for the polymerization of UDP-N-acetyl glucosamine.
- insecticides having inhibitory activity against functions unique to insects such as juvenile hormone inhibitors or mating disruptors are also being developed. Sex-attraction pheromones secreted from female insects are studied to capture male insects, but are not yet commercially applicable as they have failed in field tests.
- insects Many researchers have studied the physiology of insects, especially metabolism- associated enzymes or receptors, using molecular biological techniques, in an effort to develop pesticides. However, little study has been made of hormone transportation or lipid storage in insects. Because insects are unable to synthesize lipids, they require sterols as essential nutrients. Most insects convert plant lipids into suitable lipids necessary therefor.
- novel active materials were synthesized through chemical synthesis utilizing a glycerol acylation enzyme, which has been known to play an important role in the production of lipids for storage in insect lipid metabolism, as a novel concept for target- specific screening.
- the synthesized materials were evaluated for inhibitory activity toward the enzyme using the assay system of the present invention.
- the synthesized materials, identified to have inhibitory activity toward the enzyme were found to have bioactivity in various kinds of insect larvae, thereby leading to the present invention.
- FIG. 1 is a graph showing the diacyl CoA:glycerol acyltransferase inhibitory activity of compounds according to the present invention.
- the present invention pertains to a pesticidal composition
- a pesticidal composition comprising a compound that inhibits the biosynthesis of triglycerides (TGAs) in insects.
- TGAs triglycerides
- lipids show various functions. First, lipids are one of the most important energy sources. Of lipids, neutral lipids are mainly responsible for the role of energy sources and are accumulated in adipose cells. Also, lipids are used, in combination with phospholipids and sterols, as components of cell membranes. Besides, lipids are implicated in the production of molting hormones, juvenile hormones, and pheromones. However, insect lipids are almost water-insoluble, but are dissolved in organic solvents, and are classified into a chemical group the chemical properties of which are unknown.
- Lipids consisting mainly of fatty acid esters or derivatives thereof, are known to be synthesized from nutrients absorbed into the mid-intestine, including fatty acids and glycerols, amino acids, or simple carbohydrates.
- fatty acids are the most prevalent, with hemolymph most abundant in diglycerides.
- the adipose cells of male Saturniidae contain triglycerides to 95% by weight thereof with diglycerides, amounting to 65% by weight of hemolymph.
- fatty acids are, in general, provided from their diet, but some insects, especially insects which live on low-fat plants, can synthesize fatty acids in adipose cells.
- the present invention provides a pesticidal composition comprising a compound that inhibits the biosynthesis of triglycerides.
- triglycerides are synthesized from sn-l,2-diacylglycerol and fatty acyl
- ingested fats are decomposed into fatty acids and monoglycerides by lipase secreted from the pancreas, and are absorbed into intestinal epithelial cells, in which the conversion into triglyceride by DGAT occurs.
- the biosynthesis of triglycerides uses a glycerol 3-phosphate pathway (in the liver and adipose tissues) and a monoa- cylglycerol pathway (in intestinal epithelial cells).
- the present invention pertains to the inhibition of triglyceride biosynthesis in insects with an inhibitor against glycerol acylation enzymes, especially diacyl CoA: glycerol acyltransferase (DGAT), thereby killing harmful insects.
- glycerol acylation enzymes especially diacyl CoA: glycerol acyltransferase (DGAT)
- inhibition of triglyceride biosynthesis is intended to refer to the interruption of triglyceride synthesis in insects or to a decrease in the efficiency of triglyceride biosynthesis. Especially, in the preferred example, by inhibiting related enzymes activity.
- DGAT diacyl CoA: glycerol acyltransferase
- a mechanism involved in the storage or transportation of lipids within insects especially a change in biological activity upon the inhibition of triglyceride (TGA) biosynthesis in insects, is examined and used for the killing of insects.
- TGA triglyceride
- the present invention pertains to a compound having inhibitory activity against triglyceride biosynthesis, and more particularly, to a compound, represented by the following Chemical Formula 1, which inhibits the activity of diacyl CoA: glycerol acyltransferase.
- R is C ⁇ C alkyl or alkenyl.
- the present invention pertains to a method for the inhibition of triglyceride biosynthesis within insects using the compound of Chemical Formula 1.
- the inhibition of diacyl CoA: glycerol acyltransferase is effective.
- triglyceride an essential ingredient for insects, can be lessened and depleted so as to kill insects.
- Reagents and conditions (a) NaOH, (CHs) 2 SO 4 , rt 2h; (b) NBS, rt, 3h (c) CH 3 O Na, CuI, reflux 3Oh, (d) CAN, rt, "I h, (e) RSH, Na 2 Cr 2 O 7 , H 2 SO 4 , rt 4h, (f) MCPBA, 0°C , 1 h.
- This brominated compound (4,8-Dibromo-l,5-dimethoxynaphtalene) (3) is subjected to substitution reaction with sodium methoxide in the presence of copper(I) iodide to give 1,4,5,8-tetramethoxynaphthalene (4). Reaction between
- 1,4,5,8-tetramethoxynaphthalene (4) and cerium diammonium nitrate is followed by extraction with an organic solvent to yield 5,8-dimethoxy-l,4-naphthoquinone.
- sodium bicarbonate and sulfuric acid are droplet added, and then extraction with an organic solvent is carried out to produce the compound of Chemical Formula 1.
- Formula 1 in accordance with the present invention may be in its original form or as a salt thereof, with no addition of other ingredients.
- the compound of Chemical Formula 1 is typically mixed with solid carriers, liquid carriers, gaseous carriers or bait, or is absorbed into base materials, for example, porous ceramic plates or nonwoven fabrics, added with surfactants and, if desired, other additives, and then formulated into a variety of forms, for example, oil sprays, emulsified concentrates, wettable powders, liquids, well-flowing granules, dusts, aerosols, fuming preparations such as fogs, evaporable preparations, combustible preparations, poisonous bait, and sheet or resin preparations for controlling mites.
- the compound of the present invention may be present as an effective ingredient in an amount of 0.01% to 95% by weight.
- solid carriers usable in the formulations include fine powders or granules of clays (e.g., kaolin clay, diatomaceous earth, synthetic hydrated silicon oxide, bentonite, fubasami clay and acid clay), talc, ceramics, other inorganic minerals (e.g., silicate, quartz, sulfur, active carbon, calcium carbonate and hydrated silica), and chemical fertilizers (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, urea and ammonium chloride).
- clays e.g., kaolin clay, diatomaceous earth, synthetic hydrated silicon oxide, bentonite, fubasami clay and acid clay
- talc ceramics
- other inorganic minerals e.g., silicate, quartz, sulfur, active carbon, calcium carbonate and hydrated silica
- chemical fertilizers e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, ure
- liquid carriers they may be exemplified by water, alcohols (e.g., methanol, ethanol, etc.), ketones (e.g., acetone and methyl ethyl ketone), aromatic hydrocarbons (e.g., benzene, toluene, xylene, ethylbenzene and methylnaphthalene), aliphatic hydrocarbons (e.g., hexane, cyclohexane, kerosene and light oil), esters (e.g., ethyl acetate and butyl acetate), nitriles (e.g., acetonitrile and isobutyronitrile), ethers (e.g., diisopropyl ether and dioxane), acid amides (e.g., N,N-dimethylformamide and N,N-dimethylacetamide), halogenated hydrocarbons (e.
- alcohols e
- Suitable as the gas carriers or propellants are Freon gas, butane gas, LPG (liquefied petroleum gas), dimethyl ether and carbon dioxide gas.
- bait components e.g., grain flour, vegetable oils, sugar, and crystalline cellulose
- antioxidants e.g., dibutylhydroxytoluene and nordihydroguaiaretic acid
- preservatives e.g., dehydroacetic acid
- agents for preventing children from eating poisonous bait by mistake e.g., red pepper powders
- attractive flavors e.g. cheese flavor or onion flavor
- alkyl sulfates, alkylsulfonates, alky- larylsulfonates, alkylaryl ethers and polyoxyethylenated derivatives thereof poly ethylenegly col ethers, polyvalent alcohol esters and sugar alcohol derivatives may be used.
- auxiliaries may be used for the formulations of the compound, and are further exemplified by casein; gelatin; polysaccharides, such as starch, gum Arabic, cellulose derivatives and alginic acid; lignin derivatives; bentonite; saccharides; and synthetic water-soluble polymers such as polyvinyl alcohol, polyvinylpyrrolidone and poly aery lie acids.
- stabilizers may include PAP (isopropyl acid phosphate), BHT
- BHA (2,6-di-tert-butyl-4-methylphenol), BHA (mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oils, mineral oils, surfactants, fatty acids and esters thereof.
- the application amount thereof typically ranges from 0.1 g to 100 g over an area of 10 acres.
- the application concentration thereof is usually in the range of 1 ppm to 1,000 ppm. Granules, dusts and the like are applied without dilution.
- the emulsified concentrates, wettable powders, well- flowing granules and other formulations thereof are applied after being diluted to 0.1 to 500 ppm with water, but the oil sprays, aerosols, fuming preparations, poisonous bait, acarid-proof sheets and the like are applied in their original form.
- the application amounts and concentrations may vary depending on the type of formulations, the time, site and method of application, the type of pests, damage, and other factors, and can be increased or decreased, rather than being limited to the above range.
- the compound of the present invention or salts thereof are used in the veterinary field in a known manner for systemic pest control, for example, by administration in the form of, for example, tablets, capsules, drenches, boli, the feed-through process or suppositories, by injections, or by administration, for example, by spraying oily or aqueous solutions, pouring-on or spotting-on; or for non-systemic pest control with the aid of formed articles such as collars, ear tags, and the like.
- the compound of the present invention may be applied in an amount of 0.01 to 100 mg per kg body weight of host animals.
- the compound of the present invention may be used in admixture with, or sequentially along with, other insecticides, nematocides, acaricides, bacteriocides, fungicides, herbicides, plant growth regulators, synergists, fertilizers, soil conditioners and/or animal feeds.
- Example 1-1 was dissolved in 160 ml of acetonitrile in a 1,000 ml round-bottom flask. A solution of 21g (0.12mol) of N-bromosuccinimide (NBS) in 180ml of acetonitrile was droplet added to the flask with stirring. After stirring at room temperature for 3 hours, the vacuum filtration of the reaction mixture formed precipitates which were washed with acetonitrile and then twice with hexane and dried to give 12.7 g of the title compound as white power. The properties of the product are as described below.
- NBS N-bromosuccinimide
- Example 1-3 was dissolved in a mixture of 450 ml of acetonitrile and 150 ml of chloroform in a 250 ml one-neck round-bottom flask, and a solution of 54g (98.5mmol) of cerium diammonium nitrate in 250 ml of water was added droplet to the flask over 30 min. After reaction for an additional 30 min, the reaction mixture was mixed with 500 ml of distilled water, extracted three times with 500 ml of chloroform, and dehydrated with sodium sulphate, followed by filtration. The filtrate was concentrated in a vacuum and the residue was re-crystallized in methanol to give 4.80 g of the title compound as a reddish brown needle-like crystal. The properties of the product are as described below.
- Example 1-4 was dissolved in 30 ml of anhydrous methanol in a 100 ml one-neck round-bottom flask, and reacted with 1.65 mmol of methylmercaptan for 4 hours with stirring. To this reaction mixture was added droplet a solution of 0.23 mmol of sodium dichromate and 0.76 mmol of sulfuric acid in solution, followed by stirring at room temperature for 3 min at room temperature. 50 ml of a saturated sodium chloride solution was added to the reaction mixture before three rounds of extraction with 50 ml of chloroform. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated in a vacuum and the residue was re-crystallized in methanol to give the title compound as a reddish brown crystal.
- Preparation Example 1-5 was dissolved at O 0 C in 20 ml of chloroform. To this solution were added five aliquots of 0.32 mmol of 77% MCPBA, followed by reaction for 4 hours. The reaction mixture was mixed with an aqueous saturated sodium bicarbonate solution and 50 ml of an aqueous sodium chloride solution and extracted three times with 50 ml of chloroform. The organic layer was dehydrated with sodium sulfate and filtered. The filtrate was concentrated in a vacuum and the residue was purified using column chromatography to give the title compound (Chemical Formula 2) as a reddish brown material. The properties of the product are as described below.
- Example 1-5 was carried out to produce the compound of Chemical Formula 7.
- the properties of the product are as described below. [186]
- EXPERIMENTAL EXAMPLE Preparation of DGAT Source [236] [237] The liver was removed from male Sprague-Dawley rats (250-300 g) washed with buffer A (0.25 M sucrose, 1.0 mM EDTA, 10 mM Tris-HCl. pH 7.4) and homogenized using a glass homogenizer equipped with a Teflon rod. The homogenate was centrifuged at 14,000 x g at 4 0 C for 15 min. The supernatant was further centrifuged at 100,000 x g at 4 0 C for 1 hour. To the pellet was added buffer B (0.25 M sucrose, 10 mM Tris-HCl.
- EXPERIMENTAL EXAMPLE 2 Assay of Compounds for Inhibitory Activity against DGAT [240]
- DGAT as follows.
- reaction solution containing 175 mM Tris-HCl (pH 8.0), 20 ⁇ l of bovine serum albumin (10 mg/ml), 8 mM MgCl , 30 ⁇ M [ 14 C]palmitoyl CoA (0.02 mCi, Amersham), and 200 ⁇ M 1,2-dioleoyl glycerol was added with 10.0 ⁇ l of a solution of a sample in methanol or DMSO and with 100-200 mg of the microsomal protein, followed by reaction for 10 min at 25 0 C.
- the reaction mixture was mixed with 1 ml of heptane and 0.5 ml of H O and vortexed.
- 0.65ml of the supernatant, containing [ C] triacyl glycerol, was measured for radioactivity using LSC (liquid scintillation counter).
- the inhibition activity of the sample against DGAT was calculated according to Equation 1, below.
- T cpm in a test reaction mixture that contains a sample (a compound of the present invention) along with an enzyme source
- the other compounds (Chemical Formulas 2 to 11) chemically synthesized according to the present invention were measured for inhibitory activity against DGAT.
- DGAT activity was inhibited by 13% at 50 ⁇ g/ml of the compound of Chemical Formula 2, by 15% at 50 ⁇ g/ml of the compound of Chemical Formula 3, by 24% at 50 ⁇ g/ml of the compound of chemical Formula 4, by 63% at 50 ⁇ g/ml of the compound of Chemical Formula 5, and by 81% and 51%, respectively, at 50 ⁇ g/ml and 25 ⁇ g/ml of the compound of Chemical Formula 6.
- the compounds of Chemical Formulas 7 to 11 were measured to inhibit 50% of DGAT activity at 18.9 ⁇ g/ml, 14.2 ⁇ g/ml, 11.8 ⁇ g/ml, 9.2 ⁇ g/ml, and 5.5 ⁇ g/ml, which were calculated as IC50 values of 53.9 ⁇ M, 39.0 ⁇ M, 31.2 ⁇ M, 23.4 ⁇ M, and 13.5 ⁇ M, because their molecular weights are 350.43, 364.43, 378.48, 392.51, and 406.54, respectively.
- inhibitory activities of the compounds of Chemical Formulas 7 to 11 toward DGAT were plotted against concentrations.
- EXPERIMENTAL EXAMPLE 3 Assay of Compounds for Toxicity against Greenhouse whitefly Larval Development and Egg Hatching
- Tomato leaves containing eggs and nymphs of greenhouse whitefly were dipped in the active compound solution for 30 sec, and were dried in the shade.
- the rate of egg hatching and mortality of whitefly nymphs were recorded every day for a period of nine days, and this test was performed in two replicates. The results are given in Table 1, below.
- the active compound-treated leaf was placed onto a Petri dish (55x20 mm) with a filter paper wet with distilled water. Then, the larvae treated with the active compound were grown in an incubator (25+1 0 C, 40-45% relative humidity, 16L:8D), and the mortality was recorded for a period of nine days.
- a control group was grown on leaf disks, which were not treated with the present active compound but were treated merely with a mixture of 10% acetone and nine volumes of a 100 ppm Triton X-100 solution. This leaf-disk bioassay was performed in triplicate, and LC50 (50% lethal concentration) was calculated. The results are summarized in Table 2, below.
- EXPERIMENTAL EXAMPLE 3 Assay of Compounds for toxicity against Plutella xylostella L. larvae
- a control group was grown on leaf disks which were not treated with the present compound but treated merely with a mixture of 10% acetone and nine volumes of a 100 ppm Triton X-100 solution. This leaf-disk bioassay was repeated three times, and LC50 (50% lethal concentration) was calculated.
- the compounds of the present invention inhibit the biosynthesis of triglycerides in insects, particularly, the activity of diacyl CoA: glycerol acyltransferase, inducing the lack of triglycerides, essential for insects, thus leading to potent insecticidal effects. Also, the compounds of the present invention are safe for humans and may be used as environment-friendly pesticides.
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Disclosed herein are novel compounds and salts thereof having inhibitory activity against the biosynthesis of triglycerides, pesticidal compositions comprising the same as active ingredients, and a method for killing insects using the same. Functioning to inhibit the activity of diacyl CoA: glycerol acyltransferase, the novel compounds deny insects triglycerides, which are essential for their growth, thereby having a potent pesticidal effect. The compounds are safe for humans and may be used as environment- friendly pesticides.
Description
Description
PESTICIDES
Technical Field
[1] The present invention relates to novel derivatives having inhibitory activity against the biosynthesis of triglycerides, pesticidal compositions comprising the same as an active ingredient, and pesticidal methods using the same.
[2]
Background Art
[3] Agricultural chemicals have been used around the world to protect crops from diseases and harmful insects and thus to improve the production yield of crops. However, the continuous use and abuse of agricultural chemicals for several decades has resulted in many adverse effects, including residual toxicity, environmental contamination, etc., on wildlife and ecosystems. In this regard, international conferences have been held with the aim of restricting the use of highly-toxic synthetic organic chemicals to ensure the health of humans. International agreements stipulate that the use of synthetic organic chemicals, particularly those affecting humans and livestock, must be gradually reduced. It was also agreed in 2004 that the production and the domestic use of synthesized organophosphorus and organochloride pesticides should be reduced to 50% of the total amount of such pesticides consumed a decade ago, and that the amount consumed should be reduced by 50% again by the year 2010. Despite the many worldwide efforts of researchers, however, safe pesticides having activity based on novel mechanisms have not yet been developed. Thus, if safe pesticides are not developed in the near future, serious problems will be encountered due to the shortage of insecticides domestically as well as in foreign countries.
[4]
[5] Insecticides are introduced into insects via various routes, including the mouth, skin and spiracles. When insecticides arrive at their targets in insects, some of them are degraded into nontoxic forms, while others are activated, become more toxic and accumulate in organs or are excreted outside the body. When an insecticide is applied to insects, not all of the insecticide that is used exerts its insecticidal activity on its target.
[6]
[7] Various barriers which the applied insecticide encounters while being introduced into the body of the insects allow only a portion of the insecticide to arrive at its action site to then interrupt physiological and biochemical functions of the insects, eventually killing the insects. When using or developing insecticides, therefore, the sites and
mechanisms of action and the metabolism thereof, affecting their effective concentrations in the bodies of insects, should be carefully considered.
[8]
[9] Insecticides currently used around the world are classified according to their mode of action into neural transmission inhibitors, energy production inhibitors, insect growth regulators, and sex- attraction pheromones. Insect growth regulators are subgrouped into juvenile hormone inhibitors and chitin synthesis inhibitors. And there are sterol metabolism inhibitors, which are developed by the present inventors. Most of the currently used insecticides target the nervous system, which plays a critical role in sustaining life, or enzymes involved in energy production.
[10]
[11] Since insects can be killed suddenly when their nervous systems are aberrantly stimulated, excited, or suppressed, neural transmission inhibitors display toxicity targeting the nervous system.
[12]
[13] A neuron, the fundamental unit of the nervous system, usually has one long thin fiber, called an axon, projecting from the cell body. At the axon terminal, the axon makes contact with the dendrite of another neuron, thus forming a specialized structure called a synapse. A nerve impulse propagates along an axon. Upon the arrival of the nerve impulse at the axon terminal, a neurotransmitter, acetylcholine, is immediately released from the synaptic vesicles into the synapse between pre-synaptic and postsynaptic membranes. The released acetylcholine binds to its receptor in the postsynaptic membrane, resulting in stimulation of the postsynaptic neuron. In this way, a nerve impulse is transmitted from one neuron to another.
[14]
[15] Immediately after transmitting the nerve impulse from the pre-synaptic membrane to the postsynaptic membrane, the acetylcholine released from the synaptic vesicles is hydrolyzed by acetylcholin esterase, which is released from the postsynaptic membrane. Acetylcholin esterase has two functions: one is to degrade negatively charged ions and esters, and the other is to hydrolyze acetylcholine.
[16]
[17] The accumulation of acetylcholine at the postsynaptic membrane in a state of binding to its receptor after transmission of the nerve impulse to the postsynaptic neuron may cause hyper excitability and convulsions. Thus, acetylcholine is converted to choline and acetic acid by the action of acetylcholin esterase. The choline is taken into the pre-synaptic membrane for re-use, and is converted to acetylcholine in the synaptic vesicles.
[18]
[19] For the above reasons, when insecticides inhibiting the activity of acetylcholin esterase, responsible for the degradation of the neurotransmitter acetylcholine, which are mainly organophosphates and carbamates, are applied to insects, acetylcholine accumulates in the synapse to induce abnormal nerve impulse transmission, resulting in convulsions, paralysis and eventually death. Organophosphate and carbamate insecticides have been known to inhibit acetylcholine degradation mainly by acting on the active site of acetylcholin esterase. These chemicals penetrate relatively rapidly into the skin of insects and attach to the surface of the nervous system to cause abnormal nerve functioning, which is expressed as hypersensitivity, severe convulsions, paralysis and finally death after a latency period.
[20]
[21] Among insecticides are insect growth regulators, which inhibit the construction of the exoskeleton and the biosynthesis of chitin in insects. Insects have to molt to accommodate their gradual growth, during which the biosynthesis of the exoskeleton is very important to the physiological functions of the insects. The insect exoskeleton is a multi-layered structure with four functional regions. The exoskeleton is roughly divided into the basal membrane and the epidermis, which is further divisible into the epicuticle and procuticle. The procuticle of insects is based on a polymer (chitin), consisting of units of N-acetyl glucosamine. Because this polymer does not exist in vertebrates, but is a main component of insect's exoskeleton, insects can be killed when the biosynthesis of chitin is inhibited.
[22]
[23] With a mechanism different from that of neural transmission inhibitors, chitin synthesis inhibitors, when introduced into the insect body via the mouth or stigmas, cause incomplete exoskeleton formation, incapacitating the insects from molting normally. In this regard, the chitin synthesis inhibitors have no influence on the form ation of the epicuticle, but inhibit the synthesis of chitin in the procuticle layer. The chitin synthesis inhibitors, although their precise mechanisms have to be proven, are known to have inhibitory activity against enzymes responsible for the polymerization of UDP-N-acetyl glucosamine.
[24]
[25] Besides, insecticides having inhibitory activity against functions unique to insects, such as juvenile hormone inhibitors or mating disruptors are also being developed. Sex-attraction pheromones secreted from female insects are studied to capture male insects, but are not yet commercially applicable as they have failed in field tests.
[26]
[27] Many researchers have studied the physiology of insects, especially metabolism- associated enzymes or receptors, using molecular biological techniques, in an effort to
develop pesticides. However, little study has been made of hormone transportation or lipid storage in insects. Because insects are unable to synthesize lipids, they require sterols as essential nutrients. Most insects convert plant lipids into suitable lipids necessary therefor.
[28]
[29] In this regard, based on the fact that most insects require lipids as essential nutrients for their growth because of lack of de novo synthesis, decompose ingested lipids into metabolites through various metabolisms, and utilize ingested lipids as energy sources, the present inventors intended to synthesize materials having inhibitory activity toward enzymes involved in lipid metabolism in order to develop safe insecticides.
[30]
Disclosure of Invention Technical Problem
[31] In the present invention, novel active materials were synthesized through chemical synthesis utilizing a glycerol acylation enzyme, which has been known to play an important role in the production of lipids for storage in insect lipid metabolism, as a novel concept for target- specific screening. The synthesized materials were evaluated for inhibitory activity toward the enzyme using the assay system of the present invention. The synthesized materials, identified to have inhibitory activity toward the enzyme, were found to have bioactivity in various kinds of insect larvae, thereby leading to the present invention.
[32]
[33] Accordingly, it is an object of the present invention to provide a pesticidal composition comprising a compound having inhibitory activity against the biosynthesis of triglycerides in insects.
[34]
[35] It is another object of the present invention to provide a method for killing insects using the pesticidal composition to inhibit the biosynthesis of triglycerides within insects.
[36]
[37] It is a further object of the present invention to provide a compound having inhibitory activity against the biosynthesis of TGA in insects, particularly against diacylCoA: glycerol acyltransferase.
[38]
[39] It is still a further object of the present invention to provide a method for inhibiting the biosynthesis of TGA in insects using this compound.
Brief Description of the Drawings
[41] FIG. 1 is a graph showing the diacyl CoA:glycerol acyltransferase inhibitory activity of compounds according to the present invention. [42]
Best Mode for Carrying Out the Invention
[43] In one aspect, the present invention pertains to a pesticidal composition comprising a compound that inhibits the biosynthesis of triglycerides (TGAs) in insects.
[44] In insects, lipids show various functions. First, lipids are one of the most important energy sources. Of lipids, neutral lipids are mainly responsible for the role of energy sources and are accumulated in adipose cells. Also, lipids are used, in combination with phospholipids and sterols, as components of cell membranes. Besides, lipids are implicated in the production of molting hormones, juvenile hormones, and pheromones. However, insect lipids are almost water-insoluble, but are dissolved in organic solvents, and are classified into a chemical group the chemical properties of which are unknown. Lipids, consisting mainly of fatty acid esters or derivatives thereof, are known to be synthesized from nutrients absorbed into the mid-intestine, including fatty acids and glycerols, amino acids, or simple carbohydrates. Among the lipids of insects, triglycerides are the most prevalent, with hemolymph most abundant in diglycerides. For example, the adipose cells of male Saturniidae contain triglycerides to 95% by weight thereof with diglycerides, amounting to 65% by weight of hemolymph. In insects, fatty acids are, in general, provided from their diet, but some insects, especially insects which live on low-fat plants, can synthesize fatty acids in adipose cells. Since most insects require lipids as essential nutrients, lipid metabolism is very important therefor. Accordingly, based on the concept that the inhibition of triglyceride biosynthesis in insects by interrupting the lipid metabolism thereof brings about a pesticidal effect, the present invention provides a pesticidal composition comprising a compound that inhibits the biosynthesis of triglycerides.
[45] In insects, triglycerides are synthesized from sn-l,2-diacylglycerol and fatty acyl
CoA with the aid of diacyl CoA: glycerol acyltransferase.
[46] Diacyl CoA:glycerol acyltransferase catalyzes the final step of the glycerol
3-phosphate pathway, functioning to synthesize triglycerides by using sn- 1,2-diacylglycerol and fatty acyl CoA as substrates. In greater detail, ingested fats are decomposed into fatty acids and monoglycerides by lipase secreted from the pancreas, and are absorbed into intestinal epithelial cells, in which the conversion into triglyceride by DGAT occurs. Generally, the biosynthesis of triglycerides uses a glycerol 3-phosphate pathway (in the liver and adipose tissues) and a monoa- cylglycerol pathway (in intestinal epithelial cells).
[47] In an embodiment thereof, thus, the present invention pertains to the inhibition of triglyceride biosynthesis in insects with an inhibitor against glycerol acylation enzymes, especially diacyl CoA: glycerol acyltransferase (DGAT), thereby killing harmful insects.
[48] The term inhibition of triglyceride biosynthesis, as used herein, is intended to refer to the interruption of triglyceride synthesis in insects or to a decrease in the efficiency of triglyceride biosynthesis. Especially, in the preferred example, by inhibiting related enzymes activity.
[49] The term "inhibition of diacyl CoA: glycerol acyltransferase (DGAT)", as used herein, is intended to refer to interrupting the enzymatic reaction of triglyceride synthesis or decreasing the efficiency of triglyceride biosynthesis. The inhibition of the enzymatic activity induces various cellular reactions in insect cells. For example, when DGAT activity is inhibited, molting hormone or juvenile hormone is not produced, thus leading to the inhibition of insect growth and finally to the death of the insects.
[50] Accordingly, in this invention, a mechanism involved in the storage or transportation of lipids within insects, especially a change in biological activity upon the inhibition of triglyceride (TGA) biosynthesis in insects, is examined and used for the killing of insects.
[51] In accordance with another embodiment thereof, the present invention pertains to a compound having inhibitory activity against triglyceride biosynthesis, and more particularly, to a compound, represented by the following Chemical Formula 1, which inhibits the activity of diacyl CoA: glycerol acyltransferase.
[52] [Chemical Formula 1]
[53]
[54] Wherein R is C ~C alkyl or alkenyl.
[55]
[56] In the practice of the present invention, even a low concentration of the compound of Chemical Formula 1 was found to inhibit DGAT activity. Also, the compound of Chemical Formula 1 displayed sustained insecticidal effects on greenhouse whitefly larvae and Plutella xylostella L. larvae in a dose-dependent manner over time. Thus, the compound of Chemical Formula 1 inhibits the activity of DGAT to block TGA biosynthesis, showing pesticidal effects.
[57]
[58] In accordance with another embodiment thereof, the present invention pertains to a method for the inhibition of triglyceride biosynthesis within insects using the compound of Chemical Formula 1. As a way of inhibiting triglyceride biosynthesis, the inhibition of diacyl CoA: glycerol acyltransferase is effective. In this way, triglyceride, an essential ingredient for insects, can be lessened and depleted so as to kill insects.
[59] The compound of Chemical Formula 1 may be prepared as illustrated in the following Reaction Scheme 1.
[60] [61] [Reaction Scheme 1] [62]
Reagents and conditions, (a) NaOH, (CHs)2SO4, rt 2h; (b) NBS, rt, 3h (c) CH3O Na, CuI, reflux 3Oh, (d) CAN, rt, "I h, (e) RSH, Na2Cr2O7, H2SO4, rt 4h, (f) MCPBA, 0°C , 1 h.
[63] [64] The processes of Reaction Route 1 are elucidated as follows. [65] First, 1,5-dihydroxynaphthalene (1) is reacted with dimethyl sulfate to yield 1,5-dimethoxynaphthalene (2), which is in turn brominated in the presence of NBS (N-bromosuccinimide) to give 4,8-dibromo-l,5-dimethoxynaphtalene (3). This brominated compound (4,8-Dibromo-l,5-dimethoxynaphtalene) (3) is subjected to substitution reaction with sodium methoxide in the presence of copper(I) iodide to give 1,4,5,8-tetramethoxynaphthalene (4). Reaction between
1,4,5,8-tetramethoxynaphthalene (4) and cerium diammonium nitrate is followed by extraction with an organic solvent to yield 5,8-dimethoxy-l,4-naphthoquinone. After the reaction of 5,8-dimethoxy-l,4-naphthoquinone with alkyl mercaptan, sodium bicarbonate and sulfuric acid are droplet added, and then extraction with an organic solvent is carried out to produce the compound of Chemical Formula 1.
[66]
[67] However, the method according to Reaction Scheme 1 is only one of many possible ways of preparing the compound of Chemical Formula 1. The reaction conditions, such as solvent, base, reactant amounts, etc., are not limited to those described above. In addition to the method of Reaction Scheme 1, various methods known to those who are skilled in the art can be used to synthesize the compound of Chemical Formula 1.
[68]
[69] For use as an effective ingredient of an insecticide, the compound of Chemical
Formula 1 in accordance with the present invention may be in its original form or as a salt thereof, with no addition of other ingredients. However, the compound of Chemical Formula 1 is typically mixed with solid carriers, liquid carriers, gaseous carriers or bait, or is absorbed into base materials, for example, porous ceramic plates or nonwoven fabrics, added with surfactants and, if desired, other additives, and then formulated into a variety of forms, for example, oil sprays, emulsified concentrates, wettable powders, liquids, well-flowing granules, dusts, aerosols, fuming preparations such as fogs, evaporable preparations, combustible preparations, poisonous bait, and sheet or resin preparations for controlling mites.
[70]
[71] In each of the above formulations, the compound of the present invention may be present as an effective ingredient in an amount of 0.01% to 95% by weight.
[72]
[73] Examples of solid carriers usable in the formulations include fine powders or granules of clays (e.g., kaolin clay, diatomaceous earth, synthetic hydrated silicon oxide, bentonite, fubasami clay and acid clay), talc, ceramics, other inorganic minerals (e.g., silicate, quartz, sulfur, active carbon, calcium carbonate and hydrated silica), and chemical fertilizers (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, urea and ammonium chloride).
[74]
[75] As for the liquid carriers, they may be exemplified by water, alcohols (e.g., methanol, ethanol, etc.), ketones (e.g., acetone and methyl ethyl ketone), aromatic hydrocarbons (e.g., benzene, toluene, xylene, ethylbenzene and methylnaphthalene), aliphatic hydrocarbons (e.g., hexane, cyclohexane, kerosene and light oil), esters (e.g., ethyl acetate and butyl acetate), nitriles (e.g., acetonitrile and isobutyronitrile), ethers (e.g., diisopropyl ether and dioxane), acid amides (e.g., N,N-dimethylformamide and N,N-dimethylacetamide), halogenated hydrocarbons (e.g., dichloromethane, trichloroethane and carbon tetrachloride), dimethyl sulfoxide, and vegetable oils (e.g., soybean oil and cottonseed oil).
[76]
[77] Suitable as the gas carriers or propellants are Freon gas, butane gas, LPG (liquefied
petroleum gas), dimethyl ether and carbon dioxide gas.
[78]
[79] For use as base materials for the poisonous bait, there are examples including bait components (e.g., grain flour, vegetable oils, sugar, and crystalline cellulose), antioxidants (e.g., dibutylhydroxytoluene and nordihydroguaiaretic acid), preservatives (e.g., dehydroacetic acid), agents for preventing children from eating poisonous bait by mistake (e.g., red pepper powders), and attractive flavors (e.g. cheese flavor or onion flavor).
[80] As the surfactants suitable for the formulations, alkyl sulfates, alkylsulfonates, alky- larylsulfonates, alkylaryl ethers and polyoxyethylenated derivatives thereof, poly ethylenegly col ethers, polyvalent alcohol esters and sugar alcohol derivatives may be used.
[81]
[82] Like adhesive agents and dispersants, auxiliaries may be used for the formulations of the compound, and are further exemplified by casein; gelatin; polysaccharides, such as starch, gum Arabic, cellulose derivatives and alginic acid; lignin derivatives; bentonite; saccharides; and synthetic water-soluble polymers such as polyvinyl alcohol, polyvinylpyrrolidone and poly aery lie acids.
[83]
[84] Examples of stabilizers may include PAP (isopropyl acid phosphate), BHT
(2,6-di-tert-butyl-4-methylphenol), BHA (mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol), vegetable oils, mineral oils, surfactants, fatty acids and esters thereof.
[85]
[86] When the compound of the present invention is used as an agricultural pesticide, acarid killer or nematocide, the application amount thereof typically ranges from 0.1 g to 100 g over an area of 10 acres. In the case in which preparations such as emulsified concentrates, wettable powders or well-flowing granules are used after being diluted with water, the application concentration thereof is usually in the range of 1 ppm to 1,000 ppm. Granules, dusts and the like are applied without dilution. When the compound of the present invention is used as a pesticide, acarid killer or nematocide for the prevention of epidemics, the emulsified concentrates, wettable powders, well- flowing granules and other formulations thereof are applied after being diluted to 0.1 to 500 ppm with water, but the oil sprays, aerosols, fuming preparations, poisonous bait, acarid-proof sheets and the like are applied in their original form. The application amounts and concentrations may vary depending on the type of formulations, the time, site and method of application, the type of pests, damage, and other factors, and can be increased or decreased, rather than being limited to the above range.
[87]
[88] Upon application as a pesticide or acaricide for controlling parasites of animals, including livestock, such as cattle and pigs, and pets, such as cats and dogs, the compound of the present invention or salts thereof are used in the veterinary field in a known manner for systemic pest control, for example, by administration in the form of, for example, tablets, capsules, drenches, boli, the feed-through process or suppositories, by injections, or by administration, for example, by spraying oily or aqueous solutions, pouring-on or spotting-on; or for non-systemic pest control with the aid of formed articles such as collars, ear tags, and the like. In these cases, the compound of the present invention may be applied in an amount of 0.01 to 100 mg per kg body weight of host animals.
[89]
[90] The compound of the present invention may be used in admixture with, or sequentially along with, other insecticides, nematocides, acaricides, bacteriocides, fungicides, herbicides, plant growth regulators, synergists, fertilizers, soil conditioners and/or animal feeds.
[91]
[92] A better understanding of the present invention may be obtained through the following examples, which are set forth to illustrate, but are not to be construed as the limit of the present invention.
[93]
Mode for the Invention
[94] PREPARATION EXAMPLES
[95] Chemical Synthesis of DGAT Inhibitors
[96]
[97] PREPARATION EXAMPLE 1: Preparation of
2-Methylsulfinyl-5,8-dimethoxy-l,4-naphthoquinone (Chemical Formula 2)
[98] [Chemical Formula 2]
[99]
[100]
[101] Preparation Example 1-1 : Synthesis of 1,5-Dimethoxynaphthalene
[103] lOOg (0.62 mol) of 1,5-dihydroxynaphthalene) (1) was dissolved in 500ml
(1.25mol) of 10% NaOH in the presence of nitrogen gas in a 2L two-neck round- bottom flask, followed by the slow addition of 156g (1.24 mol) of dimethyl sulfate over 1 hour. After reaction for 2 hours, the precipitates thus formed were filtered in a vacuum, washed twice with 200 ml of 5% KOH and then three times with 200 ml of distilled water and dried. The resulting residue was completely dissolved at 8O0C in 1.5 L of benzene, containing 300 g of active carbon, and the hot solution was filtered and left, thus yielding 73 g of the title compound as a white crystal. The properties of the product are as described below.
[104]
[105] Yield : 63%, m.p.: 181.9-182.3 0C
[106] Rf: 0.49 [hexane:ethylacetate(5:l)]
[107] IH-NMR (CDCl , 400MHz): δ 7.70(d, J=8.8Hz, 2H), 7.38(t, J=8.0Hz, 2H), 6.98(d,
J=8.0Hz, 2H), 3.94(s, 6H)
[108]
[109] Preparation Example 1-2: Synthesis of
4,8-Dibromo-l,5-dimethoxynaphthalene
[HO]
[111] 1Og (0.05mol) of the 1,5-dimethoxynaphthalene, synthesized in Preparation
Example 1-1, was dissolved in 160 ml of acetonitrile in a 1,000 ml round-bottom flask. A solution of 21g (0.12mol) of N-bromosuccinimide (NBS) in 180ml of acetonitrile was droplet added to the flask with stirring. After stirring at room temperature for 3 hours, the vacuum filtration of the reaction mixture formed precipitates which were washed with acetonitrile and then twice with hexane and dried to give 12.7 g of the title compound as white power. The properties of the product are as described below.
[112]
[113] Yield: 69.02%, m.p.: 187-188 0C
[114] Rf: 0.20 [hexane:ethylacetate(50: 1)]
[115] IH-NMR (CDCl , 400MHz): δ 7.68(d, J=8.4Hz, 2H), 6.72(d, J=8.4Hz, 2H), 3.91(s,
6H)
[116]
[117] Preparation Example 1-3: Synthesis of 1,4,5,8-Tetramethoxynaphthalene
[118]
[119] 14.5g (0.04mol) of the 4,8-dibromo- 1,5-dimethoxynaphthalene was dissolved, along with 7.5g (0.14mol) of sodium methoxide and 26.3g (0.14mol) copper(I) iodide, in 700 ml of a solvent mixture of dimethylformamide 50% and methanol 50% and fluxed for 30 hours. The reaction mixture was cooled and added to 1 L of ice water to form precipitates which were then filtered and washed. These precipitates were
dissolved in 1 L of methylene chloride, followed by filtration to remove insoluble material. The filtrate was concentrated in a vacuum and the residue was re-crystallized in benzene to produce 6.5 g of the title compound as a white needle-like crystal. The properties of the product are as described below.
[120]
[121] Yield: 62.5%, m.p.: 168-169 0C
[122] Rf: 0.14 [hexane : methylene chloride (1:4)]
[123] IH-NMR (CDCl , 400MHz): δ 6.85(s, 4H), 3.90(s, 12H)
[124]
[125] Preparation Example 1-4: Synthesis of 5,8-Dimethoxy-l,4-naphthoquinone
[126]
[127] 10 g (40.28 mmol) of the 1,4,5,8-tetramethoxynaphthalene, prepared in Preparation
Example 1-3, was dissolved in a mixture of 450 ml of acetonitrile and 150 ml of chloroform in a 250 ml one-neck round-bottom flask, and a solution of 54g (98.5mmol) of cerium diammonium nitrate in 250 ml of water was added droplet to the flask over 30 min. After reaction for an additional 30 min, the reaction mixture was mixed with 500 ml of distilled water, extracted three times with 500 ml of chloroform, and dehydrated with sodium sulphate, followed by filtration. The filtrate was concentrated in a vacuum and the residue was re-crystallized in methanol to give 4.80 g of the title compound as a reddish brown needle-like crystal. The properties of the product are as described below.
[128]
[129] Yield : 54.6%, m.p.: 122-123 0C
[ 130] Rf: 0.22 [hexane : ethylacetate (1:2)]
[131] IH-NMR (CDCl , 400MHz): δ 7.33(s, 2H), 6.79(s, 2H), 3.97(s, 6H)
[132]
[133] Preparation Example 1-5: Synthesis of
2-Methylthio-5,8-dimethoxy-l,4-naphthoquinones
[134]
[135] 1.38 mmol of the 5,8-dimethoxy-l,4-naphthoquinone prepared in Preparation
Example 1-4 was dissolved in 30 ml of anhydrous methanol in a 100 ml one-neck round-bottom flask, and reacted with 1.65 mmol of methylmercaptan for 4 hours with stirring. To this reaction mixture was added droplet a solution of 0.23 mmol of sodium dichromate and 0.76 mmol of sulfuric acid in solution, followed by stirring at room temperature for 3 min at room temperature. 50 ml of a saturated sodium chloride solution was added to the reaction mixture before three rounds of extraction with 50 ml of chloroform. The organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated in a vacuum and the residue was re-crystallized in methanol
to give the title compound as a reddish brown crystal.
[136]
[137] Preparation Example 1-6: Synthesis of
2-Methylsulfinyl-5,8-dimethoxy-l,4-naphthoquinones (Chemical Formula 2)
[138]
[139] 0.21 mmol of the 2-methylthio-5,8-dimethoxy-l,4-naphthoquinone prepared in
Preparation Example 1-5 was dissolved at O0C in 20 ml of chloroform. To this solution were added five aliquots of 0.32 mmol of 77% MCPBA, followed by reaction for 4 hours. The reaction mixture was mixed with an aqueous saturated sodium bicarbonate solution and 50 ml of an aqueous sodium chloride solution and extracted three times with 50 ml of chloroform. The organic layer was dehydrated with sodium sulfate and filtered. The filtrate was concentrated in a vacuum and the residue was purified using column chromatography to give the title compound (Chemical Formula 2) as a reddish brown material. The properties of the product are as described below.
[140]
[141] Yield: 66.2%, m.p.: 222-223 0C
[142] Rf: 0.06 [hexane : ethyl acetate ( 1 :4)]
[143] IH-NMR (CDCl , 400MHz): δ 7.42(d, J=9.2Hz, IH), 7.34(d, J=9.2Hz, IH), 7.35(s,
IH), 3.99(s, 6H), 2.95(s, 3H)
[144]
[145] Preparation Example 2: Preparation of
2-Ethylsulfinyl-5,8-dimethoxy-l,4-naphthoquinone (Chemical Formula 3)
[146]
[147] The same procedure as in Preparation Example 1, with the exception that ethylmercaptan was used instead of methylmercaptan, which was used in Preparation Example 1-5, was carried out to produce the compound of Chemical Formula 3. The properties of the product are as described below.
[148] [Chemical Formula 3]
[149]
[150] Yield: 71.1%, m.p.: 145-146 0C
[151] Rf : 0.09 [hexane : ethylacetate( 1 :4)]
[152] IH-NMR (CDCl , 400MHz): δ 7.42(d, J=9.6Hz, IH), 7.37(d, J=9.2Hz, IH), 7.28(s,
IH), 3.99(s, 6H), 3.32~3.23(m, IH), 3.03~2.95(m, IH), 1.31(t, J=7.2Hz, 3H)
[153] [154] Preparation Example 3: Preparation of 2-Propylsulfinyl- 5,8-dimethoxy-l,4-naphthoquinone) (Chemical Formula 4)
[155] [156] The same procedure as in Preparation Example 1, with the exception that propy- lmercaptan was used instead of methylmercaptan, which was used in Preparation Example 1-5, was carried out to produce the compound of Chemical Formula 4. The properties of the product are as described below.
[157] [Chemical Formula 4] [158]
[159] Yield: 41.9%, m.p.: 120-121 0C [160] Rf: 0.18 [hexane : ethylacetate(l:4)] [161] IH-NMR (CDCl , 400MHz): δ 7.35(d, J=9.2Hz, IH), 7.30(d, J=9.6Hz, IH), 7.22(s, IH), 3.92(s, 3H), 3.91(s, 3H), 3.18~3.10(m, IH), 2.86~2.79(m, IH), 1.94-1.84(m, IH), 1.71~1.63(m, IH), 1.01(t, J=7.2Hz, 3H)
[162] [163] PREPARATION EXAMPLE 4: Preparation of 2-Butylsulfinyl-5,8-dimethoxy-l,4-naphthoquinone) (Chemical Formula 5)
[164] [165] The same procedure as in Preparation Example 1, with the exception that butylmercaptan was used instead of methylmercaptan, which was used in Preparation Example 1-5, was carried out to produce the compound of Chemical Formula 5. The properties of the product are as described below.
[166] [chemical Formula 5] [167]
[168] [169] Yield: 81.6%, m.p.: 127-128 0C [170] Rf: 0.18 [hexane : ethylacetate(l:4)]
[171] IH-NMR (CDCl , 400MHz): δ 7.41(d, J=9.6Hz, IH), 7.37(d, J=9.6Hz, IH), 7.31(s,
IH), 3.99(s, 6H), 3.28~3.20(m, IH), 2.95~2.88(m, IH), 1.95~1.85(m, IH), 1.70~1.60(m, IH), 1.54~1.42(m, 2H), 0.95(t, J=7.2Hz, 3H)
[172]
[173] PREPARATION EXAMPLE 5: Preparation of
2-Pentylsulfinyl-5,8-dimethoxy-l,4-naphthoquinone) (Chemical Formula 6)
[174]
[175] The same procedure as in Preparation Example 1, with the exception that pentylmercaptan was used instead of methylmercaptan, which was used in Preparation Example 1-5, was carried out to produce the compound of Chemical Formula 6. The properties of the product are as described below.
[176] [Chemical Formula
[177]
[178]
[179] Yield: 40.2%, m.p.: 125-126 0C
[180] Rf: 0.24 [hexane: ethylacetate(l:4)]
[181] IH-NMR (CDCl , 400MHz): δ 7.41(d, J=9.6Hz, IH), 7.36(d, J=9.6Hz, IH), 7.31(s,
IH), 3.99(s, 6H), 3.27~3.20(m, IH), 2.94~2.87(m, IH), 1.94~1.89(m, IH),
1.71~1.66(m, IH), 1.51~1.29(m, 6H), 0.90(t, J=7.6Hz, 3H) [182] [183] PREPARATION EXAMPLE 6: Preparation of
2-Hexylsulfinyl-5,8-dimethoxy-l,4-naphthoquinone) (Chemical Formula 7) [184] [185] The same procedure as in Preparation Example 1, with the exception that hexylmercaptan was used instead of methylmercaptan, which was used in Preparation
Example 1-5, was carried out to produce the compound of Chemical Formula 7. The properties of the product are as described below. [186]
[187] [Chemical Formula 7]
[189] [190] Yield: 76.7%, m.p.: 120-121 0C [191] Rf: 0.18 [hexane: ethylacetate(l:4)] [192] IH-NMR (CDCl , 400MHz): δ 7.42(d, J=9.6Hz, IH), 7.37(d, J=9.6Hz, IH), 7.30(s, IH), 4.00(s, 3H), 3.99(s, 3H), 3.27~3.20(m, IH), 2.95~2.88(m, IH), 1.96-1.88(m, IH), 1.71~1.65(m, IH), 1.49-1.37 (m, 2H), 1.33-1.27 (m, 4H), 0.87(t, J=7.2Hz, 3H)
[193] [194] PREPARATION EXAMPLE 7: Preparation of 2-Heptylsulfinyl-5,8-dimethoxy-l,4-naphthoquinone (Chemical Formula 8)
[195] [196] The same procedure as in Preparation Example 1, with the exception that hep- tylmercaptan was used instead of methylmercaptan, which was used in Preparation Example 1-5, was carried out to produce the compound of Chemical Formula 8. The properties of the product are as described below.
[197] [198] [Chemical Formula 8] [199]
[200] [201] Yield: 46.9%, m.p.: 106-107 0C [202] Rf: 0.27 [hexane: ethylacetate(l:4)] [203] IH-NMR (CDCl , 400MHz): δ 7.42(d, J=9.6Hz, IH), 7.37(d, J=9.2Hz, IH), 7.30(s, IH), 3.99(s, 6H), 3.27~3.20(m, IH), 2.94~2.87(m, IH), 1.96~1.86(m, IH), 1.49~1.37(m, 2H), 1.35~1.27(m, 6H), 0.87(t, J=6.8Hz, 3H)
[204] [205] PREPARATION EXAMPLE 8: Preparation of 2-Octylsulfinyl-5,8-dimethoxy-l,4-naphthoquinone (Chemical Formula 9)
[206] [207] The same procedure as in Preparation Example 1, with the exception that
octylmercaptan was used instead of methylmercaptan, which was used in Preparation Example 1-5, was carried out to produce the compound of Chemical Formula 9. The properties of the product are as described below.
[208] [209] [Chemical Formula 9] [210]
[211] Yield: 63.2%, m.p.: 110-111 0C [212] Rf: 0.26 [hexane: ethylacetate(l:4)] [213] IH-NMR (CDCl , 400MHz): δ 7.41(d, J=9.2Hz, IH), 7.36(d, J=9.6Hz, IH), 7.23(s, IH), 3.99(s, 6H), 3.27~3.20(m, IH), 2.94~2.87(m, IH), 1.93~1.88(m, IH), 1.73~1.60(m, 2H), 1.50-1.88(m, 9H), 0.87(t, J=7.2Hz, 3H)
[214] [215] PREPARATION EXAMPLE 9: Preparation of 2-Nonylsulfinyl-5,8-dimethoxy-l,4-naphthoquinone (Chemical Formula 10)
[216] [217] The same procedure as in Preparation Example 1, with the exception that nonylmercaptan was used instead of methylmercaptan, which was used in Preparation Example 1-5, was carried out to produce the compound of Chemical Formula 10. The properties of the product are as described below.
[218] [219] [Chemical Formula 10] [220]
[221] Yield: 74%, m.p.: 100-101 0C [222] Rf: 0.26 [hexane: ethylacetate(l:4)] [223] IH-NMR (CDCl3, 400MHz): δ 7.42(d, J=9.6Hz, IH), 7.37(d, J=9.6Hz, IH), 7.31(s, IH), 4.00(s, 3H), 3.99(s, 3H), 3.27~3.20(m, IH), 2.94~2.87(m, IH), 1.97-1.86(m, IH), 1.71~1.61(m, 2H), 1.49~1.25(m, HH), 0.87(t, J=7.2Hz, 3H)
[224] [225] PREPARATION 10: Preparation of 2-Decylsulfinyl-5,8-dimethoxy-l,4-naphthoquinone (Chemical Formula 11)
[226] [227] The same procedure as in Preparation Example 1, with the exception that de- cylmercaptan was used instead of methylmercaptan, which was used in Preparation Example 1-5, was carried out to produce the compound of Chemical Formula 11. The properties of the product are as described below.
[228] [229] [Chemical Formula 11] [230]
[231] Yield: 92.4%, m.p.: 127-128 0C [232] Rf: 0.27 [hexane: ethylacetate(l:4)] [233] IH-NMR (CDCl , 400MHz): δ 7.41(d, J=9.6Hz, IH), 7.37(d, J=9.2Hz, IH), 7.30(s, IH), 3.99(s, 6H), 3.28~3.18(m, IH), 2.94~2.84(m, IH), 1.95~1.85(m, IH), 1.70~1.58(m, 2H), 1.45~1.20(m, 13H), 0.87(t, J=7.6Hz, 3H)
[234] [235] EXPERIMENTAL EXAMPLE: Preparation of DGAT Source [236] [237] The liver was removed from male Sprague-Dawley rats (250-300 g) washed with buffer A (0.25 M sucrose, 1.0 mM EDTA, 10 mM Tris-HCl. pH 7.4) and homogenized using a glass homogenizer equipped with a Teflon rod. The homogenate was centrifuged at 14,000 x g at 4 0C for 15 min. The supernatant was further centrifuged at 100,000 x g at 4 0C for 1 hour. To the pellet was added buffer B (0.25 M sucrose, 10 mM Tris-HCl. pH 7.4), followed by centrifugation at 100,000 x g at 4 0C for 1 hour to isolate microsomes containing DGAT. The pellet was dissolved again in buffer B (4 ml) and analyzed for protein concentration with bovine serum albumin, serving as a standard material. The enzyme source solution thus obtained was diluted to a protein concentration of 10 mg/ml and divided in vials which were stored at -70 0C until use in assay for DGAT activity.
[238] [239] EXPERIMENTAL EXAMPLE 2: Assay of Compounds for Inhibitory Activity against DGAT
[240]
[241] The compounds of the present invention were assayed for inhibitory activity against
DGAT as follows. The [ C] triacylglycerol, which was synthesized from 1,2-diacylglycerol and [ C] palmitoyl-CoA, with the rat microsomal protein serving as an enzyme source, was measured for radioactivity. In detail, a reaction solution containing 175 mM Tris-HCl (pH 8.0), 20 μl of bovine serum albumin (10 mg/ml), 8 mM MgCl , 30 μM [14C]palmitoyl CoA (0.02 mCi, Amersham), and 200 μM 1,2-dioleoyl glycerol was added with 10.0 μl of a solution of a sample in methanol or DMSO and with 100-200 mg of the microsomal protein, followed by reaction for 10 min at 250C. The reaction was terminated with the addition of 1.5 ml of a solution (2-propanol / heptane / water = 80 / 20 / 2, v/v/v). The reaction mixture was mixed with 1 ml of heptane and 0.5 ml of H O and vortexed. To 1 ml of the supernatant was added 2 ml of an alkaline ethanol solution (ethanol / 0.5 N sodium hydroxide / water = 50 / 10 / 40, v/v/v) before vortexing. 0.65ml of the supernatant, containing [ C] triacyl glycerol, was measured for radioactivity using LSC (liquid scintillation counter). The inhibition activity of the sample against DGAT was calculated according to Equation 1, below.
[242]
[243] [Equation 1]
[244]
[245] (T: cpm in a test reaction mixture that contains a sample (a compound of the present invention) along with an enzyme source
[246] C: cpm in a control reaction mixture that does not contain a sample but contains the enzyme source
[247] B: cpm in another control reaction mixture that contains a sample but does not contain the enzyme source)
[248]
[249] Also, the other compounds (Chemical Formulas 2 to 11) chemically synthesized according to the present invention were measured for inhibitory activity against DGAT. As a result, DGAT activity was inhibited by 13% at 50 μg/ml of the compound of Chemical Formula 2, by 15% at 50 μg/ml of the compound of Chemical Formula 3, by 24% at 50 μg/ml of the compound of chemical Formula 4, by 63% at 50 μg/ml of the compound of Chemical Formula 5, and by 81% and 51%, respectively, at 50 μg/ml and 25 μg/ml of the compound of Chemical Formula 6. The compounds of Chemical
Formulas 7 to 11 were measured to inhibit 50% of DGAT activity at 18.9 μg/ml, 14.2 μg/ml, 11.8 μg/ml, 9.2 μg/ml, and 5.5 μg/ml, which were calculated as IC50 values of 53.9 μM, 39.0 μM, 31.2 μM, 23.4 μM, and 13.5 μM, because their molecular weights are 350.43, 364.43, 378.48, 392.51, and 406.54, respectively. In FIG. 1, inhibitory activities of the compounds of Chemical Formulas 7 to 11 toward DGAT were plotted against concentrations.
[250] [251] EXPERIMENTAL EXAMPLE 3: Assay of Compounds for Toxicity against Greenhouse whitefly Larval Development and Egg Hatching
[252] [253] The compounds according to the present invention were tested for their insecticidal effects on greenhouse whitefly larvae (Trialeurodes vaporariorum) on May 2006 in the Agrobiology Department, Agrobiological Environment College, Chungbuk National University, Cheongju city, Chung-cheong-buk-do. After the compounds of the present invention, identified as having inhibitory activity against DGAT, were weighed precisely, a suitable amount of each compound was dissolved in acetone, mixed with nine volumes of a 100 ppm Triton X-100 solution, and serially diluted in order to obtain active compound solutions.
[254] Tomato leaves containing eggs and nymphs of greenhouse whitefly were dipped in the active compound solution for 30 sec, and were dried in the shade. The rate of egg hatching and mortality of whitefly nymphs were recorded every day for a period of nine days, and this test was performed in two replicates. The results are given in Table 1, below.
[255] The active compound-treated leaf was placed onto a Petri dish (55x20 mm) with a filter paper wet with distilled water. Then, the larvae treated with the active compound were grown in an incubator (25+10C, 40-45% relative humidity, 16L:8D), and the mortality was recorded for a period of nine days. A control group was grown on leaf disks, which were not treated with the present active compound but were treated merely with a mixture of 10% acetone and nine volumes of a 100 ppm Triton X-100 solution. This leaf-disk bioassay was performed in triplicate, and LC50 (50% lethal concentration) was calculated. The results are summarized in Table 2, below.
[256] [257] Table 1 Inhibitory Activity against Egg Hatching of Greenhouse whitefly
[258] Table 2
Pesticidal Activity on Greenhouse Whitefly Nymphs
[259] [260] It is apparent from the data of Tables 1 and 2 that the DGAT inhibitor of Chemical Formula 9 sustained insecticidal effects over time in a dose-dependent manner compared to the control as measured for mortality at regular intervals of one day after it was applied to greenhouse whitefly at concentrations of 1, 10 and 100 ppm.
[261] [262] EXPERIMENTAL EXAMPLE 3: Assay of Compounds for toxicity against Plutella xylostella L. larvae
[263] [264] The compounds of the present invention were evaluated for insecticidal effects on larvae of Plutella xylostella L. A leaf-disk bioassay was conducted on May 2006 in the
Agrobiology Department, Agrobiological Environment College, Chungbuk National University, Cheongju city, Chung-cheong-buk-do. After the compounds, identified as DGAT inhibitors, were weighed accurately, a suitable amount of each compound was dissolved in acetone, mixed with nine volumes of a 100 ppm Triton X-100 solution and serially diluted in order to obtain active compound solutions. Leaves of uniformly grown cabbages, as feed for the larvae, were cut into leaf disks (3.0 cm in diameter), dipped in the active compound solution for 30 sec, and dried under a hood for 60 min. Each of the active compound-treated leaf disks was placed onto a Petri dish (55x20 mm) with a wet filter paper. Then, ten P. xylostella larvae in the second instars were placed on each leaf disc using a soft brush, taking care not to damage the larvae. Each sample was prepared in triplicate. The larvae were grown in an incubator (25+1 0C, 40-45% relative humidity, 16L:8D), and mortality was recorded after 24 and 48 hrs. A control group was grown on leaf disks which were not treated with the present compound but treated merely with a mixture of 10% acetone and nine volumes of a 100 ppm Triton X-100 solution. This leaf-disk bioassay was repeated three times, and LC50 (50% lethal concentration) was calculated.
[265] The results are given in Table 3, below.
[266]
[267]
[268] [Table 3]
[269] Pesticidal Activity on P. xylostella larvae
[270]
[271] [272] It is apparent from the data of Table 3 that the DGAT inhibitors of Chemical Formulas 8 to 10 sustained insecticidal effects over time in a dose-dependent manner, compared to the control, as measured for mortality at regular intervals of one day after they were applied in amounts of 1, 10 and 100 ppm to P. xylostella larvae. Also, it was observed that the larvae were more reluctant to eat the feed treated with the compounds of the present invention as compared to the control.
[273]
Industrial Applicability The compounds of the present invention, as described hitherto, inhibit the biosynthesis of triglycerides in insects, particularly, the activity of diacyl CoA: glycerol acyltransferase, inducing the lack of triglycerides, essential for insects, thus leading to potent insecticidal effects. Also, the compounds of the present invention are safe for humans and may be used as environment-friendly pesticides.
Claims
[1] A pesticidal composition, comprising a compound an inhibitor against biosynthesis of triglycerides in insects as an effective ingredient.
[2] The pesticidal composition according to claim 1, wherein the inhibitor has inhibitory activity against diacyl CoA: glycerol acyltransferase.
[3] The pesticidal composition according to claim 1, wherein the inhibitor is a compound represented by the following Chemical Formula 1 : [Chemical Formula 1]
Wherein R is a C ~ C alkyl or alkenyl.
[4] The pesticidal composition according to claim 3, wherein R is C ~ C alkyl.
[5] The pesticidal composition according to claim 1, further comprising a carrier.
[6] A method for killing insects, using the pesticidal composition of one of claims 1 to 5.
[7] The method according to claim 6, wherein the composition is sprayed or administered to insects.
[8] A compound, represented by the following Chemical Formula 1 : Chemical Formula 1
Wherein R is a C ~ C alkyl or alkenyl.
[9] The compound according to claim 8, wherein R is C ~ C alkyl. [10] A method of inhibiting triglyceride biosynthesis in insects, using the compound of claim 8.
[H] The method according to claim 10, wherein the inhibiting triglyceride biosynthesis results from inhibiting diacyl CoA: glycerol acyltransferase.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/KR2006/003139 WO2008018645A1 (en) | 2006-08-10 | 2006-08-10 | Pesticides |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/KR2006/003139 WO2008018645A1 (en) | 2006-08-10 | 2006-08-10 | Pesticides |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2008018645A1 true WO2008018645A1 (en) | 2008-02-14 |
Family
ID=39033155
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/KR2006/003139 WO2008018645A1 (en) | 2006-08-10 | 2006-08-10 | Pesticides |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2008018645A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20180007907A1 (en) * | 2015-01-23 | 2018-01-11 | Syngenta Participations Ag | Pesticidally active semi-carbazones and thiosemicarbazones derivatives |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4148918A (en) * | 1974-05-10 | 1979-04-10 | E. I. Du Pont De Nemours And Company | Substituted 2-higher alkyl-3-hydroxy-1,4-naphthoquinone carboxylic acid esters and their use as miticides |
WO1995032176A1 (en) * | 1994-05-20 | 1995-11-30 | British Technology Group Limited | Naphthoquinone derivatives |
WO1996021354A1 (en) * | 1995-01-10 | 1996-07-18 | British Technology Group Limited | Pesticidal compounds |
-
2006
- 2006-08-10 WO PCT/KR2006/003139 patent/WO2008018645A1/en active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4148918A (en) * | 1974-05-10 | 1979-04-10 | E. I. Du Pont De Nemours And Company | Substituted 2-higher alkyl-3-hydroxy-1,4-naphthoquinone carboxylic acid esters and their use as miticides |
WO1995032176A1 (en) * | 1994-05-20 | 1995-11-30 | British Technology Group Limited | Naphthoquinone derivatives |
WO1996021354A1 (en) * | 1995-01-10 | 1996-07-18 | British Technology Group Limited | Pesticidal compounds |
Non-Patent Citations (2)
Title |
---|
CARRENO M.C. ET AL.: "Tautomeric Equilibrium of Naphthazarin Thioderivatives", TETRAHEDRON, vol. 50, no. 17, 1994, pages 5013 - 5020 * |
JEWESS P.J. ET AL.: "Insecticidal 2-hydroxy-3-alkyl-1,4-naphthoquinones: correlation of inhibition of ubiquinol cytochrome c oxidoreductase (complex III) with insecticidal activity", PEST MANAGEMENT SCIENCE, vol. 58, no. 3, 2002, pages 243 - 247 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20180007907A1 (en) * | 2015-01-23 | 2018-01-11 | Syngenta Participations Ag | Pesticidally active semi-carbazones and thiosemicarbazones derivatives |
US10721933B2 (en) * | 2015-01-23 | 2020-07-28 | Syngenta Participations Ag | Pesticidally active semi-carbazones and thiosemicarbazones derivatives |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2003303489B2 (en) | Insecticidal compositions comprising compounds having inhibitory activity versus acyl CoA: cholesterol acyltransferase or salts thereof as effective ingredients | |
DE69215393T2 (en) | Hydrazine derivative and this derivative as an active ingredient containing pesticidal composition | |
KR100371071B1 (en) | Use of 2-{(dihydro)pyrazolyl-3'-oxymethylene}-anilides as pest-control agents and fungicides | |
KR940011908B1 (en) | Benzoylurea compounds, process for their production and pesticides containing them | |
KR100943983B1 (en) | Pyripyropene derivatives and insecticidal compositions comprising them | |
KR101074212B1 (en) | An insecticidal composition comprising 4-quinolinone derivative compound for tree insecticide and the method for killing the insect using thereby | |
WO2008018645A1 (en) | Pesticides | |
KR100769708B1 (en) | Chemical synthetic method for sulfonyl naphthoquinone compounds having pesticide and comprising their compounds | |
PL95242B1 (en) | ||
KR100836172B1 (en) | The composition for killing insects comprising azol compounds as an effective ingredients | |
KR100758371B1 (en) | Pesticides | |
KR101614095B1 (en) | Parthenocissus tricuspidata PLANCH extracts for killing insects thereof | |
US20080103205A1 (en) | Pesticidal compositions and methods of use | |
IE840345L (en) | 2-nitromethylene-1-formyl tetrahydro 1,3-thiazine | |
KR101067196B1 (en) | An ACYL-CoA: choloesterol acyltransferase inhibitor and a therapeutic agent containing pheophorbide A methyl ester, porphyrin-type compound or extracts of Diospyros kaki as an effective ingredient for the treatment of larvicide | |
KR900003276B1 (en) | Process for preparing thiazinge phosphonic acid derivatives | |
WO2007050867A2 (en) | Pesticidal compositions and methods of use | |
EP1827097A2 (en) | Insecticidal and nematicidal compositions and methods of use | |
Emara | Effect of 6-methyl-5-hepten-2-one on acetylcholinesterase activity, growth and development of Spodoptera littoralis | |
KR101542843B1 (en) | An insecticide comprising ursolic acid | |
JPS59155376A (en) | Agricultural nitromethylene derivtive | |
Moharil et al. | Detection of a carboxylesterase-mediated resistance mechanism in Plutella xyloestella (L.) by diagnostic microplate assay | |
KR100928867B1 (en) | Insecticide Containing Bokbunja Extract | |
JPH04288052A (en) | New phenylthiourea derivative and insecticidal miticidal composition containing the derivative as active component | |
JPH01146870A (en) | Benzoylurea derivative, its production, use and intermediate and production of said intermediate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 06783563 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
NENP | Non-entry into the national phase |
Ref country code: RU |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 06783563 Country of ref document: EP Kind code of ref document: A1 |