CN1479725A - N-烷氧基烷基取代的苯并咪唑化合物及其作为抗寄生原生动物活性剂的应用 - Google Patents
N-烷氧基烷基取代的苯并咪唑化合物及其作为抗寄生原生动物活性剂的应用 Download PDFInfo
- Publication number
- CN1479725A CN1479725A CNA01820225XA CN01820225A CN1479725A CN 1479725 A CN1479725 A CN 1479725A CN A01820225X A CNA01820225X A CN A01820225XA CN 01820225 A CN01820225 A CN 01820225A CN 1479725 A CN1479725 A CN 1479725A
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- eimeria
- agent
- represent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000003071 parasitic effect Effects 0.000 title claims description 12
- 239000013543 active substance Substances 0.000 title claims description 5
- 150000001556 benzimidazoles Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 239000000203 mixture Substances 0.000 claims abstract description 58
- 238000002360 preparation method Methods 0.000 claims abstract description 31
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 6
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 3
- -1 benzimidazole compound Chemical class 0.000 claims description 39
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 208000003495 Coccidiosis Diseases 0.000 claims description 19
- 206010023076 Isosporiasis Diseases 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 17
- RWVUEZAROXKXRT-VQLSFVLHSA-N maduramicin Chemical compound O1[C@@H](C)[C@H](OC)[C@@H](OC)C[C@H]1O[C@@H]1[C@H]([C@@]2(C)O[C@H](CC2)[C@@]2(C)O[C@]3(O[C@@H]([C@H](C)[C@@H](O)C3)[C@@H](C)[C@H]3[C@@H]([C@@H](OC)[C@H](C)[C@@](O)(CC(O)=O)O3)OC)CC2)O[C@@H]([C@@H]2[C@H](C[C@@H](C)[C@@](C)(O)O2)C)C1 RWVUEZAROXKXRT-VQLSFVLHSA-N 0.000 claims description 16
- 229950006915 maduramicin Drugs 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 239000004721 Polyphenylene oxide Substances 0.000 claims description 8
- 239000003242 anti bacterial agent Substances 0.000 claims description 8
- 229940088710 antibiotic agent Drugs 0.000 claims description 8
- 229920000570 polyether Polymers 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 239000002168 alkylating agent Substances 0.000 claims description 5
- 229940100198 alkylating agent Drugs 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 244000045947 parasite Species 0.000 claims description 4
- 229930191564 Monensin Natural products 0.000 claims description 3
- GAOZTHIDHYLHMS-UHFFFAOYSA-N Monensin A Natural products O1C(CC)(C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)CCC1C(O1)(C)CCC21CC(O)C(C)C(C(C)C(OC)C(C)C(O)=O)O2 GAOZTHIDHYLHMS-UHFFFAOYSA-N 0.000 claims description 3
- KQXDHUJYNAXLNZ-XQSDOZFQSA-N Salinomycin Chemical compound O1[C@@H]([C@@H](CC)C(O)=O)CC[C@H](C)[C@@H]1[C@@H](C)[C@H](O)[C@H](C)C(=O)[C@H](CC)[C@@H]1[C@@H](C)C[C@@H](C)[C@@]2(C=C[C@@H](O)[C@@]3(O[C@@](C)(CC3)[C@@H]3O[C@@H](C)[C@@](O)(CC)CC3)O2)O1 KQXDHUJYNAXLNZ-XQSDOZFQSA-N 0.000 claims description 3
- 239000004189 Salinomycin Substances 0.000 claims description 3
- 229960005358 monensin Drugs 0.000 claims description 3
- GAOZTHIDHYLHMS-KEOBGNEYSA-N monensin A Chemical compound C([C@@](O1)(C)[C@H]2CC[C@@](O2)(CC)[C@H]2[C@H](C[C@@H](O2)[C@@H]2[C@H](C[C@@H](C)[C@](O)(CO)O2)C)C)C[C@@]21C[C@H](O)[C@@H](C)[C@@H]([C@@H](C)[C@@H](OC)[C@H](C)C(O)=O)O2 GAOZTHIDHYLHMS-KEOBGNEYSA-N 0.000 claims description 3
- 229960001548 salinomycin Drugs 0.000 claims description 3
- 235000019378 salinomycin Nutrition 0.000 claims description 3
- MOOFYEJFXBSZGE-QJUDHZBZSA-N 1,2-bis[(z)-(4-chlorophenyl)methylideneamino]guanidine Chemical compound C=1C=C(Cl)C=CC=1\C=N/N=C(/N)N\N=C/C1=CC=C(Cl)C=C1 MOOFYEJFXBSZGE-QJUDHZBZSA-N 0.000 claims description 2
- OCINXEZVIIVXFU-UHFFFAOYSA-N 1-methyl-3-[3-methyl-4-[4-(trifluoromethylthio)phenoxy]phenyl]-1,3,5-triazinane-2,4,6-trione Chemical compound CC1=CC(N2C(N(C)C(=O)NC2=O)=O)=CC=C1OC1=CC=C(SC(F)(F)F)C=C1 OCINXEZVIIVXFU-UHFFFAOYSA-N 0.000 claims description 2
- WINSLRIENGBHSH-ASZYJFLUSA-N 2-[(2r,3s,4s,5r,6s)-2,4-dihydroxy-6-[(1r)-1-[(2s,5r,7s,8r,9s)-7-hydroxy-2-[(2r,5s)-5-[(2r,3s,5r)-5-[(2s,3s,5r,6s)-6-hydroxy-3,5,6-trimethyloxan-2-yl]-3-[(2s,5s,6r)-5-methoxy-6-methyloxan-2-yl]oxyoxolan-2-yl]-5-methyloxolan-2-yl]-2,8-dimethyl-1,10-dioxaspi Chemical compound O1[C@H](C)[C@@H](OC)CC[C@@H]1O[C@@H]1[C@H]([C@@]2(C)O[C@H](CC2)[C@@]2(C)O[C@]3(O[C@@H]([C@H](C)[C@@H](O)C3)[C@@H](C)[C@H]3[C@@H]([C@@H](O)[C@H](C)[C@@](O)(CC(O)=O)O3)OC)CC2)O[C@@H]([C@@H]2[C@H](C[C@@H](C)[C@@](C)(O)O2)C)C1 WINSLRIENGBHSH-ASZYJFLUSA-N 0.000 claims description 2
- VHKXXVVRRDYCIK-CWCPJSEDSA-N Narasin Chemical compound C[C@H]1C[C@H](C)[C@H]([C@@H](CC)C(O)=O)O[C@H]1[C@@H](C)[C@H](O)[C@H](C)C(=O)[C@H](CC)[C@@H]1[C@@H](C)C[C@@H](C)[C@@]2(C=C[C@@H](O)[C@@]3(O[C@@](C)(CC3)[C@@H]3O[C@@H](C)[C@@](O)(CC)CC3)O2)O1 VHKXXVVRRDYCIK-CWCPJSEDSA-N 0.000 claims description 2
- VHKXXVVRRDYCIK-UHFFFAOYSA-N Narasin Natural products CC1CC(C)C(C(CC)C(O)=O)OC1C(C)C(O)C(C)C(=O)C(CC)C1C(C)CC(C)C2(C=CC(O)C3(OC(C)(CC3)C3OC(C)C(O)(CC)CC3)O2)O1 VHKXXVVRRDYCIK-UHFFFAOYSA-N 0.000 claims description 2
- 229960003683 amprolium Drugs 0.000 claims description 2
- BBMULGJBVDDDNI-OWKLGTHSSA-N lasalocid Chemical compound C([C@@H]1[C@@]2(CC)O[C@@H]([C@H](C2)C)[C@@H](CC)C(=O)[C@@H](C)[C@@H](O)[C@H](C)CCC=2C(=C(O)C(C)=CC=2)C(O)=O)C[C@](O)(CC)[C@H](C)O1 BBMULGJBVDDDNI-OWKLGTHSSA-N 0.000 claims description 2
- 229960001851 narasin Drugs 0.000 claims description 2
- 229960004591 robenidine Drugs 0.000 claims description 2
- 229960004388 semduramicin Drugs 0.000 claims description 2
- 229960000898 toltrazuril Drugs 0.000 claims description 2
- 230000002141 anti-parasite Effects 0.000 claims 2
- 239000003096 antiparasitic agent Substances 0.000 claims 2
- 239000004606 Fillers/Extenders Substances 0.000 claims 1
- LCTXBFGHZLGBNU-UHFFFAOYSA-M amprolium Chemical compound [Cl-].NC1=NC(CCC)=NC=C1C[N+]1=CC=CC=C1C LCTXBFGHZLGBNU-UHFFFAOYSA-M 0.000 claims 1
- 230000002508 compound effect Effects 0.000 claims 1
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 abstract 2
- 229940124536 anticoccidial agent Drugs 0.000 abstract 1
- 239000003224 coccidiostatic agent Substances 0.000 abstract 1
- 239000002460 polyether antibiotic agent Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
- 239000000463 material Substances 0.000 description 28
- 241000223924 Eimeria Species 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 241001465754 Metazoa Species 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 239000002775 capsule Substances 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 11
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 241000287828 Gallus gallus Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000007868 Raney catalyst Substances 0.000 description 6
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
- 229910000564 Raney nickel Inorganic materials 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 239000003963 antioxidant agent Substances 0.000 description 6
- 230000003078 antioxidant effect Effects 0.000 description 6
- 235000006708 antioxidants Nutrition 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 235000019688 fish Nutrition 0.000 description 6
- 210000004215 spore Anatomy 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
- 241000251468 Actinopterygii Species 0.000 description 5
- 241000224483 Coccidia Species 0.000 description 5
- 241000223934 Eimeria maxima Species 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000002191 fatty alcohols Chemical class 0.000 description 5
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 230000008719 thickening Effects 0.000 description 5
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 5
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
- 241000223932 Eimeria tenella Species 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 241000630524 Taractes rubescens Species 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 240000008042 Zea mays Species 0.000 description 4
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 4
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 235000005822 corn Nutrition 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 244000144977 poultry Species 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 229960001866 silicon dioxide Drugs 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- 210000003046 sporozoite Anatomy 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000271566 Aves Species 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000252233 Cyprinus carpio Species 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000223931 Eimeria acervulina Species 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 241000238631 Hexapoda Species 0.000 description 3
- 241000243190 Microsporidia Species 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 241001126829 Nosema Species 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 241000224003 Sarcocystis Species 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 229960004217 benzyl alcohol Drugs 0.000 description 3
- 230000031709 bromination Effects 0.000 description 3
- 238000005893 bromination reaction Methods 0.000 description 3
- 238000005660 chlorination reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000008119 colloidal silica Substances 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- 210000003608 fece Anatomy 0.000 description 3
- 235000013312 flour Nutrition 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 210000000582 semen Anatomy 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000003549 soybean oil Substances 0.000 description 3
- 235000012424 soybean oil Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 239000008399 tap water Substances 0.000 description 3
- 235000020679 tap water Nutrition 0.000 description 3
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- NFDXQGNDWIPXQL-UHFFFAOYSA-N 1-cyclooctyldiazocane Chemical compound C1CCCCCCC1N1NCCCCCC1 NFDXQGNDWIPXQL-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 2
- LZILFXHGPBJADI-UHFFFAOYSA-N 2-(2-hydroxypropoxy)propan-1-ol;nonanoic acid Chemical compound CC(O)COC(C)CO.CCCCCCCCC(O)=O LZILFXHGPBJADI-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QDFXRVAOBHEBGJ-UHFFFAOYSA-N 3-(cyclononen-1-yl)-4,5,6,7,8,9-hexahydro-1h-diazonine Chemical compound C1CCCCCCC=C1C1=NNCCCCCC1 QDFXRVAOBHEBGJ-UHFFFAOYSA-N 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical class O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 208000000230 African Trypanosomiasis Diseases 0.000 description 2
- 241000272525 Anas platyrhynchos Species 0.000 description 2
- 241001056488 Anatis Species 0.000 description 2
- 241000252082 Anguilla anguilla Species 0.000 description 2
- 241000252087 Anguilla japonica Species 0.000 description 2
- 241000272814 Anser sp. Species 0.000 description 2
- 241000223836 Babesia Species 0.000 description 2
- 241000223838 Babesia bovis Species 0.000 description 2
- 241000223846 Babesia canis Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000223782 Ciliophora Species 0.000 description 2
- 241000994379 Eimeria anseris Species 0.000 description 2
- 241001043461 Eimeria arloingi Species 0.000 description 2
- 241000223933 Eimeria bovis Species 0.000 description 2
- 241000013739 Eimeria faurei Species 0.000 description 2
- 244000309702 Eimeria hagani Species 0.000 description 2
- 241001485866 Eimeria intestinalis Species 0.000 description 2
- 241000221513 Eimeria irresidua Species 0.000 description 2
- 241001452550 Eimeria meleagridis Species 0.000 description 2
- 241001485851 Eimeria perforans Species 0.000 description 2
- 241000886136 Eimeria scabra Species 0.000 description 2
- 241001464848 Entamoebidae Species 0.000 description 2
- 241000011458 Epistylis Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 241000224466 Giardia Species 0.000 description 2
- 241001508494 Glugea Species 0.000 description 2
- 241000149124 Hepatozoon canis Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 241000222727 Leishmania donovani Species 0.000 description 2
- 241001375804 Mastigophora Species 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 229920000881 Modified starch Polymers 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 241001492486 Nosema apis Species 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 241000223960 Plasmodium falciparum Species 0.000 description 2
- 241001505293 Plasmodium ovale Species 0.000 description 2
- 241000223810 Plasmodium vivax Species 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 241000881767 Sarcocystis hominis Species 0.000 description 2
- 241000555745 Sciuridae Species 0.000 description 2
- 241000269796 Seriola quinqueradiata Species 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 241000276707 Tilapia Species 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- 241000223104 Trypanosoma Species 0.000 description 2
- 241000223095 Trypanosoma evansi Species 0.000 description 2
- 241000223091 Trypanosoma lewisi Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 201000008680 babesiosis Diseases 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical group O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-O benzylaminium Chemical compound [NH3+]CC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-O 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 235000013339 cereals Nutrition 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- FCYRSDMGOLYDHL-UHFFFAOYSA-N chloromethoxyethane Chemical compound CCOCCl FCYRSDMGOLYDHL-UHFFFAOYSA-N 0.000 description 2
- 239000012973 diazabicyclooctane Substances 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000428 dust Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- MVLVMROFTAUDAG-UHFFFAOYSA-N ethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC MVLVMROFTAUDAG-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 235000013372 meat Nutrition 0.000 description 2
- 229940043265 methyl isobutyl ketone Drugs 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 235000019426 modified starch Nutrition 0.000 description 2
- LMZGUSUROCCNQU-UHFFFAOYSA-N n-[2-amino-4-(trifluoromethoxy)-5-(trifluoromethyl)phenyl]-2,2,2-trifluoroacetamide Chemical compound NC1=CC(OC(F)(F)F)=C(C(F)(F)F)C=C1NC(=O)C(F)(F)F LMZGUSUROCCNQU-UHFFFAOYSA-N 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- 229920000151 polyglycol Polymers 0.000 description 2
- 239000010695 polyglycol Substances 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229920002545 silicone oil Polymers 0.000 description 2
- 239000002689 soil Substances 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- AGEBJYJJWHBPJT-UHFFFAOYSA-N $l^{1}-oxidanylsulfonylmethane Chemical compound CS([O])(=O)=O AGEBJYJJWHBPJT-UHFFFAOYSA-N 0.000 description 1
- MEIRRNXMZYDVDW-MQQKCMAXSA-N (2E,4E)-2,4-hexadien-1-ol Chemical compound C\C=C\C=C\CO MEIRRNXMZYDVDW-MQQKCMAXSA-N 0.000 description 1
- HTZOGMBRKCPHSZ-UHFFFAOYSA-N (3-ethylphenyl)methanamine;hydrochloride Chemical compound Cl.CCC1=CC=CC(CN)=C1 HTZOGMBRKCPHSZ-UHFFFAOYSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 1
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
- SJBBXFLOLUTGCW-UHFFFAOYSA-N 1,3-bis(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(C(F)(F)F)=C1 SJBBXFLOLUTGCW-UHFFFAOYSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
- HRMGYAZODUDKFX-UHFFFAOYSA-N 1-$l^{1}-oxidanylsulfonyl-4-methylbenzene Chemical compound CC1=CC=C(S([O])(=O)=O)C=C1 HRMGYAZODUDKFX-UHFFFAOYSA-N 0.000 description 1
- XFRVVPUIAFSTFO-UHFFFAOYSA-N 1-Tridecanol Chemical compound CCCCCCCCCCCCCO XFRVVPUIAFSTFO-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- NBMFWYCEILUASN-UHFFFAOYSA-N 2,2,2-trifluoro-n-[2-nitro-4-(trifluoromethoxy)-5-(trifluoromethyl)phenyl]acetamide Chemical compound [O-][N+](=O)C1=CC(OC(F)(F)F)=C(C(F)(F)F)C=C1NC(=O)C(F)(F)F NBMFWYCEILUASN-UHFFFAOYSA-N 0.000 description 1
- JAYGZAXTTXFYJJ-UHFFFAOYSA-N 2,2,2-trifluoro-n-[4-(trifluoromethoxy)-3-(trifluoromethyl)phenyl]acetamide Chemical compound FC(F)(F)OC1=CC=C(NC(=O)C(F)(F)F)C=C1C(F)(F)F JAYGZAXTTXFYJJ-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 description 1
- OAYXUHPQHDHDDZ-UHFFFAOYSA-N 2-(2-butoxyethoxy)ethanol Chemical compound CCCCOCCOCCO OAYXUHPQHDHDDZ-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
- QCAHUFWKIQLBNB-UHFFFAOYSA-N 3-(3-methoxypropoxy)propan-1-ol Chemical compound COCCCOCCCO QCAHUFWKIQLBNB-UHFFFAOYSA-N 0.000 description 1
- XKTYXVDYIKIYJP-UHFFFAOYSA-N 3h-dioxole Chemical compound C1OOC=C1 XKTYXVDYIKIYJP-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000224422 Acanthamoeba Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000224489 Amoeba Species 0.000 description 1
- 241001492423 Amoebidae Species 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- 241000224482 Apicomplexa Species 0.000 description 1
- 241000256844 Apis mellifera Species 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 241001235572 Balantioides coli Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241000191796 Calyptosphaeria tropica Species 0.000 description 1
- 241000282836 Camelus dromedarius Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 241000272201 Columbiformes Species 0.000 description 1
- 241000222716 Crithidia Species 0.000 description 1
- 235000019750 Crude protein Nutrition 0.000 description 1
- 241000223935 Cryptosporidium Species 0.000 description 1
- 241000303991 Cystoisospora canis Species 0.000 description 1
- 241000205706 Cystoisospora felis Species 0.000 description 1
- 241000495917 Cystoisospora ohioensis Species 0.000 description 1
- 241000209630 Cystoisospora suis Species 0.000 description 1
- 241000283014 Dama Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- XTJFFFGAUHQWII-UHFFFAOYSA-N Dibutyl adipate Chemical compound CCCCOC(=O)CCCCC(=O)OCCCC XTJFFFGAUHQWII-UHFFFAOYSA-N 0.000 description 1
- 241000723298 Dicentrarchus labrax Species 0.000 description 1
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-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
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 241001098070 Echinorhynchus truttae Species 0.000 description 1
- 241000289819 Eimeria adenoeides Species 0.000 description 1
- 241001218115 Eimeria auburnensis Species 0.000 description 1
- 241000499566 Eimeria brunetti Species 0.000 description 1
- 241000646177 Eimeria chinchillae Species 0.000 description 1
- 241000146358 Eimeria crandallis Species 0.000 description 1
- 241001327860 Eimeria dispersa Species 0.000 description 1
- 241001662550 Eimeria falciformis Species 0.000 description 1
- 241001327857 Eimeria gallopavonis Species 0.000 description 1
- 241001485852 Eimeria magna Species 0.000 description 1
- 241001485868 Eimeria media Species 0.000 description 1
- 241001278028 Eimeria meleagrimitis Species 0.000 description 1
- 241000179199 Eimeria mitis Species 0.000 description 1
- 241000499563 Eimeria necatrix Species 0.000 description 1
- 241000059291 Eimeria ninakohlyakimovae Species 0.000 description 1
- 241000999134 Eimeria pavonina Species 0.000 description 1
- 241001485850 Eimeria piriformis Species 0.000 description 1
- 241000886137 Eimeria porci Species 0.000 description 1
- 241000499544 Eimeria praecox Species 0.000 description 1
- 241001485873 Eimeria stiedai Species 0.000 description 1
- 241001218082 Eimeria zuernii Species 0.000 description 1
- 241000224484 Eimeriidae Species 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000224431 Entamoeba Species 0.000 description 1
- 241000224432 Entamoeba histolytica Species 0.000 description 1
- 241001133637 Entamoeba suis Species 0.000 description 1
- 241001584862 Enterococcus canis Species 0.000 description 1
- 241000194028 Enterococcus columbae Species 0.000 description 1
- 241000321429 Epinephelus itajara Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241001245650 Eragrostis truncata Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 241000356197 Euphorbia contorta Species 0.000 description 1
- 241000073845 Eysarcoris aeneus Species 0.000 description 1
- 235000019733 Fish meal Nutrition 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 241000224467 Giardia intestinalis Species 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000224492 Hartmannella Species 0.000 description 1
- 241001278020 Hepatozoon Species 0.000 description 1
- CMBYOWLFQAFZCP-UHFFFAOYSA-N Hexyl dodecanoate Chemical group CCCCCCCCCCCC(=O)OCCCCCC CMBYOWLFQAFZCP-UHFFFAOYSA-N 0.000 description 1
- 241000567229 Isospora Species 0.000 description 1
- 241000624722 Isospora rivolta Species 0.000 description 1
- 241000442132 Lactarius lactarius Species 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- 241000222740 Leishmania braziliensis Species 0.000 description 1
- 208000004554 Leishmaniasis Diseases 0.000 description 1
- 241001593519 Liza affinis Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000693084 Mycoplasma ovis Species 0.000 description 1
- 241001494184 Myxozoa Species 0.000 description 1
- CMEWLCATCRTSGF-UHFFFAOYSA-N N,N-dimethyl-4-nitrosoaniline Chemical compound CN(C)C1=CC=C(N=O)C=C1 CMEWLCATCRTSGF-UHFFFAOYSA-N 0.000 description 1
- 241001147660 Neospora Species 0.000 description 1
- 241000772415 Neovison vison Species 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000238127 Pagurus Species 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000269799 Perca fluviatilis Species 0.000 description 1
- 241000021737 Pezicula sp. 1-40 Species 0.000 description 1
- 241000223834 Piroplasmida Species 0.000 description 1
- 241001364006 Plagioscion Species 0.000 description 1
- 241000963804 Plasmodiidae Species 0.000 description 1
- 241000224017 Plasmodium berghei Species 0.000 description 1
- 206010035500 Plasmodium falciparum infection Diseases 0.000 description 1
- 241000223821 Plasmodium malariae Species 0.000 description 1
- 206010035501 Plasmodium malariae infection Diseases 0.000 description 1
- 206010035502 Plasmodium ovale infection Diseases 0.000 description 1
- 206010035503 Plasmodium vivax infection Diseases 0.000 description 1
- 241000269980 Pleuronectidae Species 0.000 description 1
- 241000233872 Pneumocystis carinii Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical group CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241000146987 Sarcocystis neurona Species 0.000 description 1
- 241001473628 Sarcocystis suihominis Species 0.000 description 1
- 241000269821 Scombridae Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical group [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Polymers CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 241000269809 Sparus aurata Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 241000921519 Syrrhopodon sp. Species 0.000 description 1
- 241000223777 Theileria Species 0.000 description 1
- 241000223779 Theileria parva Species 0.000 description 1
- 241000223997 Toxoplasma gondii Species 0.000 description 1
- 201000005485 Toxoplasmosis Diseases 0.000 description 1
- 241001500087 Trichodina Species 0.000 description 1
- 241001061558 Trichomonadidae Species 0.000 description 1
- 241000893962 Trichophyton equinum Species 0.000 description 1
- 241000219793 Trifolium Species 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- 241001442399 Trypanosoma brucei gambiense Species 0.000 description 1
- 241001442397 Trypanosoma brucei rhodesiense Species 0.000 description 1
- 241000223107 Trypanosoma congolense Species 0.000 description 1
- 241000557167 Trypanosoma percae Species 0.000 description 1
- 241000224553 Trypanosoma simiae Species 0.000 description 1
- 241000223099 Trypanosoma vivax Species 0.000 description 1
- 241000222714 Trypanosomatidae Species 0.000 description 1
- 206010047505 Visceral leishmaniasis Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 235000019742 Vitamins premix Nutrition 0.000 description 1
- 239000005862 Whey Substances 0.000 description 1
- 102000007544 Whey Proteins Human genes 0.000 description 1
- 108010046377 Whey Proteins Proteins 0.000 description 1
- 239000011358 absorbing material Substances 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 210000002534 adenoid Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 150000001335 aliphatic alkanes Chemical group 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 229940124339 anthelmintic agent Drugs 0.000 description 1
- 239000000921 anthelmintic agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 208000007456 balantidiasis Diseases 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- 235000013405 beer Nutrition 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical group C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 1
- 229910052790 beryllium Inorganic materials 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 235000019846 buffering salt Nutrition 0.000 description 1
- 229940043232 butyl acetate Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- RLGQACBPNDBWTB-UHFFFAOYSA-N cetyltrimethylammonium ion Chemical compound CCCCCCCCCCCCCCCC[N+](C)(C)C RLGQACBPNDBWTB-UHFFFAOYSA-N 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- ALSTYHKOOCGGFT-UHFFFAOYSA-N cis-oleyl alcohol Natural products CCCCCCCCC=CCCCCCCCCO ALSTYHKOOCGGFT-UHFFFAOYSA-N 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- BLHUAXIDWCQEPL-UHFFFAOYSA-M dibenzyl(dimethyl)azanium;methyl sulfate Chemical compound COS([O-])(=O)=O.C=1C=CC=CC=1C[N+](C)(C)CC1=CC=CC=C1 BLHUAXIDWCQEPL-UHFFFAOYSA-M 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 229940007078 entamoeba histolytica Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 229940116333 ethyl lactate Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000004467 fishmeal Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000003502 gasoline Substances 0.000 description 1
- 229940085435 giardia lamblia Drugs 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- PJBQYZZKGNOKNJ-UHFFFAOYSA-M hydron;5-[(2-methylpyridin-1-ium-1-yl)methyl]-2-propylpyrimidin-4-amine;dichloride Chemical compound Cl.[Cl-].NC1=NC(CCC)=NC=C1C[N+]1=CC=CC=C1C PJBQYZZKGNOKNJ-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001524 infective effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940089456 isopropyl stearate Drugs 0.000 description 1
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Polymers [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 235000012204 lemonade/lime carbonate Nutrition 0.000 description 1
- AHNJTQYTRPXLLG-UHFFFAOYSA-N lithium;diethylazanide Chemical compound [Li+].CC[N-]CC AHNJTQYTRPXLLG-UHFFFAOYSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000020640 mackerel Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 125000005397 methacrylic acid ester group Chemical group 0.000 description 1
- 125000005395 methacrylic acid group Chemical group 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 230000003641 microbiacidal effect Effects 0.000 description 1
- 229940124561 microbicide Drugs 0.000 description 1
- 239000002855 microbicide agent Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229940031815 mycocide Drugs 0.000 description 1
- OKDQKPLMQBXTNH-UHFFFAOYSA-N n,n-dimethyl-2h-pyridin-1-amine Chemical compound CN(C)N1CC=CC=C1 OKDQKPLMQBXTNH-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N n-octadecyl alcohol Natural products CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002900 organolithium compounds Chemical class 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 description 1
- 235000010263 potassium metabisulphite Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- ZPWFUIUNWDIYCJ-UHFFFAOYSA-N propan-2-yl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(C)C ZPWFUIUNWDIYCJ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- WFITUPFQQAGOBI-UHFFFAOYSA-M sodium;carbonochloridate Chemical compound [Na+].[O-]C(Cl)=O WFITUPFQQAGOBI-UHFFFAOYSA-M 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical group [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000012747 synergistic agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229940118701 toxoplasma gondii Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 description 1
- 229940087291 tridecyl alcohol Drugs 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- UCRLQOPRDMGYOA-DFTDUNEMSA-L zinc;(4r)-4-[[(2s)-2-[[(4r)-2-[(1s,2s)-1-amino-2-methylbutyl]-4,5-dihydro-1,3-thiazole-4-carbonyl]amino]-4-methylpentanoyl]amino]-5-[[(2s,3s)-1-[[(3s,6r,9s,12r,15s,18r,21s)-3-(2-amino-2-oxoethyl)-18-(3-aminopropyl)-12-benzyl-15-[(2s)-butan-2-yl]-6-(carbox Chemical compound [Zn+2].C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC([O-])=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2NC=NC=2)C(=O)N[C@H](CC([O-])=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 UCRLQOPRDMGYOA-DFTDUNEMSA-L 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/10—Radicals substituted by halogen atoms or nitro radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及式(I)新的N-烷氧基烷基取代的苯并咪唑化合物,其中R1代表氟代烷基,R2代表氢或烷基,R3代表烷基,X1代表三氟甲基,且X2代表三氟甲氧基。本发明还涉及式(I)化合物的制备及其作为抗寄生原生动物的活性剂的应用。
Description
本发明涉及N-烷氧基烷基取代的苯并咪唑化合物、其制备及其作为抗寄生原生动物活性剂的应用。
本发明还涉及这些化合物与聚醚类抗生素或合成制得的抗球虫病剂在用于防治寄生原生动物、特别是球虫的组合物中的混合物。
取代的苯并咪唑化合物及其作为杀虫剂、杀真菌剂和除草剂的应用已经被公开过(EP-OS 87375、152360、181826、239508、260744、266984、US-P 3418318、3472865、3576818、3728994)。
卤代苯并咪唑化合物及其作为驱肠虫剂、抗球虫病剂和杀虫剂的作用已经被公开过(DE-OS 2047369、DE-OS 4237617)。已经公开了用作抗球虫病剂的硝基取代的苯并咪唑化合物与聚醚类抗生素的混合物(US-P 5331003、US-P 5670485)。其它取代的苯并咪唑化合物与聚醚类抗生素或合成的抗球虫病剂的混合物是已知的(WO 96/38140、WO00/04022)。
球虫病是由单细胞寄生虫(原生动物)引起的病症。其可引起严重损失,特别是当饲养家禽时更是如此。为了避免这些损失,用抗球虫病剂来预防性地治疗牲畜。由于对所用的治疗剂发展成抗药性,在引入抗球虫病剂很短时间后就发生了严重问题。另一方面,通过使用在化学上全新的抗球虫病剂、特别是治疗剂组合,能够防治甚至是多抗药性的寄生虫。
因此,在防治由寄生原生动物引起的疾病中仍然需要具有改善性质的新的活性化合物和组合物。
本发明涉及表现出优良的抗球虫病活性的式(I)新的苯并咪唑化合物其中R1代表氟代烷基,R2代表氢或烷基,R3代表烷基,X1代表三氟甲基,且X2代表三氟甲氧基。式(I)的苯并咪唑化合物其中R1、R2、R3、X1和X2具有上文给出的含义,是这样制得的:将式(II)的1H-苯并咪唑化合物其中R1、X1和X2具有上文给出的含义,与式(III)的烷化剂反应,其中A代表合适的离去基团,R2和R3具有上文给出的含义,所述反应任选在稀释剂和/或反应助剂存在下进行。
根据取代基的性质和数目,式(I)化合物可任选作为几何和/或旋光异构体或区域异构体或不同组成的其异构体的混合物存在。这些异物体可任选通过本身已知的方法,例如结晶或色谱法来分离。纯的异构体和异构体混合物都在本发明范围内。
本发明化合物还可以作为盐存在。在本发明范围内,生理可接受盐是优选的。
生理可接受盐可以是本发明化合物与无机酸或有机酸形成的盐。优选与无机酸例如盐酸、氢溴酸、磷酸或硫酸形成的盐,或者与有机羧酸或磺酸例如下列酸形成的盐:乙酸、丙酸、马来酸、富马酸、苹果酸、柠檬酸、酒石酸、乳酸、苯甲酸、或甲磺酸、乙磺酸、苯磺酸、甲苯磺酸或萘二磺酸。
式(I)提供了本发明取代的苯并咪唑化合物的一般定义。定义如下的式(I)化合物是优选的,其中R1代表C1-C4-氟烷基,R2代表氢或C1-C4-烷基,R3代表C1-C8-烷基,X1代表三氟甲基,且X2代表三氟甲氧基。
定义如下的式(I)化合物是特别优选的,其中R1代表CF3、CHF2、CH2F,R2代表氢、甲基、乙基、正丙基或异丙基,R3代表C1-C6-烷基,X1代表三氟甲基,且X2代表三氟甲氧基。
定义如下的式(I)化合物是非常特别优选的,其中R1代表CF3,R2代表氢、R3代表甲基、乙基、丙基、异丙基、丁基、异丁基或仲丁基,X1代表三氟甲基,且X2代表三氟甲氧基。
烷基一般代表具有优选最高达8个、特别优选最高达6个、非常特别优选最高达4个碳原子的直链或支链烷基。实例是:甲基、乙基、正丙基、异丙基、正丁基、异丁基(=仲丁基)。
氟代烷基一般代表具有优选最高达6个、特别优选最高达4个、非常特别优选最高达3个碳原子,并且其中至少一个、优选一个以上、特别优选所有氢被氟取代的直链或支链烷基。其实例是:三氟甲基、二氟甲基、五氟乙基等。
如果使用例如5-三氟甲氧基-2,6-二(三氟甲基)苯并咪唑来进行制备式(I)化合物的本发明方法,则该制备方法的反应过程可通过下述反应式代表:
式(II)提供了需要用作进行该制备方法的原料的1H-苯并咪唑化合物的一般定义。在式(II)中,R1-R3与X1和X2优选代表在描述本发明式(I)化合物时所提及的关于这些取代基的优选基团。
式(II)的1H-苯并咪唑化合物是已知的,或者可通过类似于已知方法的方法获得(参见例如J.Amer.Chem.Soc.75,1292[1953],US专利3576818)。
式(III)提供了也需要用作进行该制备方法的原料的烷化剂的一般定义。在式(III)中,R2和R3优选代表在描述本发明式(I)化合物时所提及的关于这些取代基的优选基团。
A代表烷化剂中的常规离去基团,优选卤素,特别是氯、溴或碘,或代表分别任选被取代的烷基磺酰基氧基、烷氧基磺酰基氧基或芳基磺酰基氧基,例如特别是甲磺酰基氧基、三氟甲磺酰基氧基、甲氧基磺酰基氧基、乙氧基磺酰基氧基或对甲苯磺酰基氧基。
式(III)化合物是已知的,或者可通过类似于已知方法的方法获得(参见例如J.Amer.Chem.Soc.93,5725-5731,Synthesis 1982,942-944)。
适于进行该制备方法的稀释剂是惰性有机溶剂。这些稀释剂特别包括脂族、脂环族或芳族任选卤代的烃,例如汽油、苯、甲苯、二甲苯、氯苯、二氯苯、石油醚、己烷、环己烷、二氯甲烷、氯仿或四氯化碳;醚例如乙醚、二异丙基醚、二噁烷、四氢呋喃或乙二醇二甲醚或乙二醇二乙醚;酮例如丙酮、丁酮或甲基异丁基酮;腈例如乙腈、丙腈或苯甲腈;酰胺例如N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基-N-甲酰苯胺、N-甲基吡咯烷酮或六甲基磷酸三酰胺;酯例如乙酸甲酯或乙酸乙酯,或碱例如吡啶。
该反应方法优选在合适的反应助剂存在下进行。合适的反应助剂是所有常规无机碱或有机碱。这些碱包括例如碱土金属或碱金属氢化物、氢氧化物、氨化物、醇化物、乙酸盐、碳酸盐或碳酸氢盐,例如氢化钠、氨基钠、二乙基氨基锂、甲醇钠、乙醇钠、叔丁醇钾、氢氧化钠、氢氧化钾、氢氧化铵、乙酸钠、乙酸钾、乙酸钙、乙酸铵、碳酸钠、碳酸钾、碳酸氢钾、碳酸氢钠或碳酸铵,有机锂化合物例如正丁基锂,以及叔胺例如三甲胺、三乙胺、三丁胺、二异丙基乙胺、四甲基胍、N,N-二甲基苯胺、吡啶、哌啶、N-甲基哌啶、N,N-二甲基氨基吡啶、二氮杂二环辛烷(DABCO)、二氮杂二环壬烯(DBN)或二氮杂二环十一碳烯(DBU)。
该制备方法还任选在两相系统例如水/甲苯或水/二氯甲烷中,任选在合适的相转移催化剂存在下进行。可提及的这样的催化剂的实例有:碘化四丁基铵、溴化四丁基铵、氯化四丁基铵、溴化三丁基甲基鏻、氯化三甲基-C13/C15-烷基铵、溴化三甲基-C13/C15-烷基铵、甲基硫酸二苄基二甲基铵、氯化二甲基-C12/C14-烷基-苄基铵、溴化二甲基-C12/C14-烷基-苄基铵、氢氧化四丁基铵、氯化三乙基苄基铵、氯化甲基三辛基铵、氯化三甲基苄基铵、15-冠-5、18-冠-6或三-[2-(2-甲氧基乙氧基)-乙基]-胺。
当进行该制备方法时,反应温度可在较宽的范围内改变。该反应一般在-70℃-+200℃、优选0℃-130℃的温度下进行。
该制备方法一般在常压下进行。然而,该制备方法也可以在高压或减压下进行。
为了进行该制备方法,相对于每摩尔式(II)的1H-苯并咪唑化合物,一般使用1.0-5.0mol、优选1.0-2.5mol式(III)的烷化剂,并任选应用0.01-5.0mol、优选1.0-3.0mol反应助剂。
依据已知方法进行反应和后处理以及分离反应产物(还参见制备
实施例)。
借助于常规方法,例如通过柱色谱法或重结晶来纯化式(I)终产物。
用熔点,或者对于非结晶化合物,特别是对于区域异构体混合物,用质子核磁共振色谱(1H-NMR)进行化合物的表征。
本发明活性化合物在具有有利的温血动物毒性的情况下适合用于防治寄生原生动物,所述寄生原生动物是在有用动物、饲养动物、动物园动物、实验室动物和试验动物和宠物的饲养和繁殖中发生的。对此,它们对所有或个别发育阶段的害虫以及抗性和通常敏感的害虫有效。通过防治寄生原生动物,疾病、死亡以及产量下降(例如肉、奶、羊毛、兽皮、蛋、蜂蜜等)应当被降低,这样通过使用活性化合物能更经济且更容易地饲养动物。
寄生的原生动物包括:
鞭毛纲(Mastigophora)(鞭毛虫类(Flagellata))如锥虫科,例如布鲁斯锥虫(Trypanosoma brucei),冈比锥虫(T.gambiense),罗德森锥虫(T.rhodesiense),刚果锥虫(T.congolense),克鲁兹锥虫(T.Cruzi),伊氏锥虫(T.evansi),马锥虫(T.equinum),路氏锥虫(T.lewisi),鲈鱼锥虫(T.percae),T.simiae,活跃锥虫(T.vivax),巴西利什曼原虫(Leishmania brasililensis),杜氏利什曼原虫(L.donovani),热带利什曼原虫(L.tropica),如毛滴虫科,例如吸吮贾弟虫(Giardia lamblia),犬贾弟虫(G.canis)。
肉足鞭毛亚门(Sarcomastigophora)(根足亚纲(Rhizopoda)),如内阿米巴科(Entamoebidae),例如痢疾内变形虫(Entamoebahistolytica),哈氏阿米巴科,例如棘阿米巴属(Acanthamoebasp.),哈氏阿米巴属(Hartmanella sp)。
顶复门(Apicomplexa)(孢子虫纲(Sporozoa)),如艾美虫科,例如堆形艾美球虫(Eimeria acervulina),腺样艾美球虫(E.adenoids),阿州艾美球虫(E.alabahmensis),鸭艾美球虫(E.anatis),鹅艾美球虫(E.anseris),阿氏艾美球虫(E.arloingi),E.ashata,奥本艾美球虫(E.auburnensis),牛艾美球虫(E.bovis),波氏艾美球虫(E.brunetti),犬艾美球虫(E.canis),E.chinchillae,鱼艾美球虫(E.clupearum),鸽艾美球虫(E.columbae),E.contorta,槌状艾美球虫(E.crandalis),德氏艾美球虫(E.debliecki),散布艾美球虫(E.dispersa),椭圆艾美球虫(E.ellipsoidales),镰刀形艾美球虫(E.falciformis),福氏艾美球虫(E.faurei),E,flavescens,E.gallopavonis,哈氏艾美球虫(E.hagani),肠艾美球虫(E.intestinalis),E.iroquoina,无残艾美球虫(E.irresidua),唇艾美球虫(E.labbeana),勒氏艾美球虫(E.leucarti),大艾美球虫(E.magna),巨型艾美球虫(E.maxima),中型艾美球虫(E.media),珠鸡艾美球虫(E.meleagridis),E.meleagrimitis,和缓艾美球虫(E.mitis),尼氏艾美球虫(E.necatrix),尼纳艾美球虫(E.ninakohlyakimovae),E.ovis,小艾美球虫(E.parva),孔雀艾美球虫(E.pavonis),穿孔艾美球虫(E.perforans),E.phasani,梨形艾美球虫(E.pikriformis),塞前艾美球虫(E.praecox),E.residua,粗糙艾美球虫(E.scabra),艾美球虫属(E.spec.),兔肝艾美球虫(E.stiedai),猪艾美球虫(E.suis),柔嫩艾美球虫(E.tenella),树艾美球虫(E.truncata),E.truttae,邱氏艾美球虫(E.zuernii),球孢子虫属(Globidium spec.),贝氏等孢子虫(Isospora belii),犬等孢子虫(I.canis),猫等孢子虫(I.felis),I.ohioensis,I.rivolta,等孢子属(I.spec.),猪等孢子虫(I.suis),Neospora carinum,N.Hugesi,Cystisospora属,隐孢子属(Cryptosporidium spec.),如弓浆虫科,例如鼠弓浆虫(Toxopla smagondii),如肉孢子虫科,例如牛犬肉孢子虫(Sarcocystis bovicanis),牛人肉孢子虫(S.bovihominis),S.neurona,S.ovicanis,S.ovifelis,肉孢子虫属(S.spec.),猪人肉孢子虫(S.suihominis),如Leucozoidae,例如Leucozytozoonsimondi,如疟虫科,例如柏氏疟虫(Plasmodium berghei),恶性疟原虫(P.falciparum),三日疟原虫(P.malariae),卵形疟原虫(P.ovale),间日疟原虫(P.vivax),疟虫属(P.spec.),如焦虫目,例如Babesia argentina,牛巴贝虫(B.bovis),犬巴贝虫(B.canis),巴贝虫属(B.spec.),小泰来虫(Theileria parva),泰来虫属(T.spec.),如阿德尔球虫目(Adeleina),例如犬肝簇虫(Hepatozooncanis),肝簇虫属(H.spec)。
此外还有粘孢子门(Myxospora)和微孢子门(Microspora),例如格留虫属(Glugea spec.),微粒子虫属(Nosema spec.)。
此外还有卡氏肺囊虫,以及纤毛门(Ciliata)如结肠肠袋虫(Balantidium coli),Ichthiophthirius属,车轮虫属(Trichodinaspec.),累枝虫属(Epistylis spec.)。
本发明的化合物在防治昆虫的寄生原虫时也是有效的。可能提到的这类寄生原虫包括小孢子虫门,特别是小孢子虫属(Nosema),特别提到的是蜜蜂的蜂小孢子虫(Nosema apis)。
有用和饲养的动物包括哺乳类的如牛,马,绵羊,猪,山羊,骆驼,水牛,驴,兔,黇鹿,驯鹿,皮毛动物如水貂,灰鼠,浣熊,鸟类如鸡,鹅,火鸡,鸭,鸽子,家养和动物园饲养的鸟类。还包括有用的和观赏的鱼类。
实验和试验动物包括小鼠,大鼠,豚鼠,金花鼠,犬和猫。
宠物包括犬和猫。
鱼类包括生活在淡水和咸水中各年龄段的有用的、养殖的、水族箱饲养的和观赏用的鱼类。有用的和养殖的鱼类包括鲤鱼,鳗鲡,鲑鱼,白鱼,大麻哈鱼,乌鲂,拟鲤,红眼鱼,鲐鱼(Dbel),鳎鱼,鲽鱼,大比目鱼,日本黄尾鱼(Seriola quinqueradiata),日本鳗鲡(Anguilla japonica),红海乌鲂(Pagurus major),海鲈(Dicentrarchus labrax),灰梭鱼(Mugilus cephalus),小斑鲳,隆颈海乌鲂(Sparus aurata),罗非鱼属(Tilapia spp.),观赏用的种类包括斜纹鱼(plagioscion),海峡猫鱼。本发明的组合物特别适用于处理鱼苗,例如体长2~4cm的鲤鱼鱼苗。该组合物也特别适合于鳗鲡的生长。
给药既可以是出于预防目的进行,也可以是出于治疗目的进行。
本发明活性化合物的给药可直接进行,或者以合适的制剂形式经肠、非胃肠道、经皮或经鼻进行。
本发明活性化合物的经肠给药能够以例如粉剂、栓剂、片剂、胶囊、糊剂、饮用剂、粒剂、兽用顿服药、大丸剂、加有药物的饲料或饮用水的形式口服给药。经皮给药能够以例如浸泡、喷雾、沐浴、洗涤、倾注和点缀以及撒布的形式进行。非胃肠道给药以例如注射(肌内、皮下、静脉内、腹膜内)的形式进行,或者通过植入进行。
合适的制剂是:
溶液,例如注射溶液、口服溶液、用于稀释后口服给药的浓缩物、用在皮肤上或体腔中的溶液,倾注制剂;凝胶;
用于经口或经皮给药的乳剂和悬浮液;半固体制剂;
其中活性化合物掺入在软膏基质或在水包油或油包水乳液基质中的制剂;
固体制剂例如粉剂、预混剂或浓缩物、粒剂、丸剂、片剂、大丸剂、胶囊;气雾剂和吸入剂,含有活性化合物的有形制品。
注射溶液是通过静脉内、肌内和皮下途径给药。
注射溶液是这样制得的:将活性化合物溶解在合适的溶剂中,并且可以加入添加剂例如助溶剂、酸、碱、缓冲盐、抗氧化剂、防腐剂。将溶液无菌过滤和灌装。
可提及的溶剂有:生理可耐受溶剂例如水,醇例如乙醇、丁醇、苯甲醇、甘油、烃、丙二醇、聚乙二醇,N-甲基吡咯烷酮及其混合物。
还可以任选将活性化合物溶解在适于注射的生理可耐受植物油或合成油中。
可提及的助溶剂有:促进活性化合物在主要溶剂中溶解或防止其沉淀的溶剂。实例有聚乙烯吡咯烷酮、聚乙氧基化蓖麻油、聚乙氧基化脱水山梨醇酯。
防腐剂有:苯甲醇、三氯丁醇、对羟基苯甲酸酯、正丁醇。
口服溶液是直接施用。浓缩物是预先稀释至使用浓度后口服使用。口服溶液和浓缩物是按照上述制备注射溶液的方法制得的,其中省去无菌操作。
用于皮肤上的溶液是通过点缀、涂敷、擦、喷射或喷雾来使用,或者通过浸泡、沐浴或洗涤来施用。这些溶液是按照上述制备注射溶液的方法制得的。
在制备期间加入增稠剂是有利的。增稠剂有:无机增稠剂例如膨润土、胶态二氧化硅、一硬脂酸铝,有机增稠剂例如纤维素衍生物、聚乙烯醇及其共聚物、丙烯酸酯和异丁烯酸酯。
凝胶是涂敷在皮肤上或引入到体腔内。凝胶是这样制得的:将按照上述制备注射溶液的方法制得的溶液与足量的增稠剂混合,以形成具有软膏样稠度的澄清组合物。所用的增稠剂是上述增稠剂。
倾注制剂是倾注或喷雾在皮肤的有限区域上,在这种情况下,活性化合物渗透入皮肤,并具有全身作用或分布在身体表面上。
倾注制剂是通过将活性化合物在与皮肤相容的合适的溶剂或溶剂混合物中溶解、悬浮或乳化而制得的。可任选加入另外的辅助剂例如着色剂、吸收促进物质、抗氧化剂、光稳定剂和/或粘合剂。
可提及的溶剂有:水、链烷醇,二醇,聚乙二醇,聚丙二醇,甘油,芳族醇例如苯甲醇、苯乙醇、苯氧基乙醇,酯例如乙酸乙酯、乙酸丁酯、苯甲酸苄酯,醚例如烷二醇烷基醚例如二丙二醇一甲醚、二甘醇一丁醚,酮例如丙酮、甲基乙基酮,芳烃和/或脂族烃,植物油或合成油,DMF,二甲基乙酰胺,N-甲基吡咯烷酮,2-二甲基-4-羟基亚甲基-1,3-二氧杂环戊烷(2-Dimethy1-4-oxy-methylen-1,3-dioxolan)。
着色剂是被批准用于动物并且可溶解或悬浮的所有着色剂。
促进吸收物质是例如DMSO、涂布油例如肉豆蔻酸异丙酯、二丙二醇壬酸酯、硅油、脂肪酸酯、甘油三酯、脂肪醇。
抗氧化剂是亚硫酸盐或焦亚硫酸盐例如焦亚硫酸钾、抗坏血酸、丁基羟基甲苯、丁化羟基茴香醚、生育酚。
光稳定剂的实例是二苯甲酮或novantisolic acid类物质。
粘合剂的实例是纤维素衍生物、淀粉衍生物、聚丙烯酸酯、天然聚合物例如藻酸酯(盐)、明胶。
乳剂可通过口服、经皮或注射来使用。
乳剂是油包水或水包油型。
乳剂一般是这样制得的:将活性化合物溶解在疏水或亲水相中,借助于合适的乳化剂和任选另外的辅助剂例如着色剂、吸收促进物质、防腐剂、抗氧化剂、光稳定剂和/或提高粘度的物质将这个相与其它相的溶剂均化。
可提及的疏水相(油)如下:石蜡油,硅油,天然植物油例如芝麻油、杏仁油、蓖麻油,合成甘油三酯例如辛酸/癸酸甘油二酯,具有链长为C8-12的植物脂肪酸或其它特定选择的天然脂肪酸的甘油三酯混合物,饱和或不饱和、可能还含有羟基的脂肪酸的部分甘油酯混合物,C8/C10脂肪酸的甘油单酯和甘油二酯。
脂肪酸酯例如硬脂酸乙酯、己二酸二正丁酯(Di-n-butyryl-adipat)、月桂酸己酯、二丙二醇壬酸酯、中等链长的支链脂肪酸与链长为C16-C18的饱和脂肪醇的酯、肉豆蔻酸异丙酯、棕榈酸异丙酯、链长为C12-C18的饱和脂肪醇的辛酸/癸酸酯、硬脂酸异丙酯、油酸油醇酯、油酸癸酯、油酸乙酯、乳酸乙酯、蜡状脂肪酸酯例如邻苯二甲酸二丁酯、己二酸二异丙酯、关于己二酸二异丙酯的酯混合物,尤其是脂肪醇例如异十三烷醇、2-辛基十二烷醇、鲸蜡基硬脂醇、油醇。
脂肪酸例如油酸及其混合物。
可提及的亲水相如下:水,醇例如丙二醇、甘油、山梨醇及其混合物。
可提及的乳化剂如下:非离子表面活性剂,例如聚乙氧基化蓖麻油、聚乙氧基化脱水山梨醇一油酸酯、脱水山梨醇一硬脂酸酯、甘油一硬脂酸酯、聚氧乙烯硬脂酸酯(Polyoxyethyl-Stearat)、烷基苯基聚乙二醇醚;两性表面活性剂例如N-月桂基-β-亚氨基二丙酸二钠或卵磷脂;阴离子表面活性剂例如十二烷基硫酸钠、脂肪醇醚硫酸盐、一/二烷基聚乙二醇醚正磷酸酯一乙醇胺盐;阳离子表面活性剂例如氯化鲸蜡基三甲基铵。
可提及的其它辅助剂是:增加粘度和稳定乳液的物质,例如羧甲基纤维素、甲基纤维素和其它纤维素以及淀粉衍生物、聚丙烯酸酯、藻酸酯(盐)、明胶、阿拉伯胶、聚乙烯吡咯烷酮、聚乙烯醇、甲基乙烯醚和马来酸酐的共聚物、聚乙二醇、蜡、胶态二氧化硅或所述物质的混合物。
悬浮剂可通过口服、经皮或注射来使用。它们可通过将活性化合物悬浮在悬浮剂中来制得,任选加入另外的辅助剂例如润湿剂、着色剂、吸收促进物质、防腐剂、抗氧化剂、光稳定剂。
可提及的悬浮剂是所有均质溶剂以及溶剂混合物。
可提及的润湿剂(分散剂)是上述表面活性剂。
可提及的其它辅助剂是如上所述的那些。
半固体制剂可口服或经皮给药。它们与上述悬浮液和乳液的差异仅在于其具有较高的粘度。
为了制备固体制剂,将活性化合物与合适的赋形剂混合,任选加入辅助剂,并转化成所需形式。
可提及的载体是所有生理可耐受固体惰性物质。可使用的有无机物和有机物。无机物是例如氯化钠、碳酸盐例如碳酸钙、碳酸氢盐、氧化铝、二氧化硅、矾土、沉淀的或胶态二氧化硅、磷酸盐。
有机物的实例是糖、纤维素、人和动物食品例如奶粉、动物饲料、谷类粗粉或碎粉、淀粉。
辅助剂是上述防腐剂、抗氧化剂、着色剂。
其它合适的辅助剂是润滑剂和助流剂,例如硬脂酸镁、硬脂酸、滑石粉、膨润土,崩解促进物质例如淀粉或交联聚乙烯吡咯烷酮,粘合剂例如淀粉、明胶或直链聚乙烯吡咯烷酮,和干的粘合剂例如微晶纤维素。
本发明活性化合物可以作为与增效剂或其它活性化合物的混合物存在于制剂中。
特别重要的是本发明化合物与聚醚类抗生素或合成的抗球虫病剂的混合物。
可优选用于本发明混合物中的合成的抗球虫病剂或聚醚类抗生素是:安普罗铵,在某些情况下是与叶酸拮抗剂的组合,罗贝胍,托曲珠利,莫能星,沙利霉素,马度米星,拉沙洛西,甲基盐霉素,生度米星。
其中莫能星、沙利霉素和马度米星是优选的。与马度米星的混合物是特别重要的。
即用型制剂含有浓度为10ppm-20重量%、优选为0.1-10重量%的活性化合物。
在使用前稀释的制剂含有浓度为0.5-90重量%、优选为1-50重量%的活性化合物。
一般情况下,已证实,施用约0.5-约50mg、优选1-20mg活性化合物/kg体重/天的量能有利地获得有效结果。
在与其它抗球虫病剂或聚醚类抗生素的混合物中,本发明活性化合物的比例为1∶0.1-10到1∶1-10。1∶5的比例是优选的。
本发明活性化合物还可以与饲料或饮用水一起对动物给药。
饲料和食品含有0.01-250ppm、优选0.5-100ppm本发明活性化合物,其中活性化合物与合适的可食用材料混合在一起。
这样的饲料和食品既可以出于治疗目的使用,也可以出于预防目的使用。
这样的饲料和食品是通过将作为与可食用有机或无机载体的混合物的含有0.5-30%、优选1-20重量%的活性化合物的浓缩物或预混合物与常规饲料混合而制得的。可食用载体是例如玉米粉或玉米与大豆粉或无机盐,其中优选含有少量可食用防粉尘油例如玉米油或大豆油。之后可将以该方式获得的预混合物加到完全饲料中,然后喂给动物。
可提及的在球虫病中的应用的实例是:
为了治疗和预防例如家禽,特别是母鸡、鸭子、鹅和火鸡中的球虫病,将0.1-100ppm、优选0.5-100ppm的活性化合物与合适的的可食用材料例如营养饲料混合。如果需要的话,特别是如果接受治疗者对活性化合物良好耐受的话,可提高活性化合物的用量。相应地,可经由饮用水进行给药。
为了治疗动物个体,例如当治疗哺乳动物中的球虫病或弓形体病时,优选每天施用0.5-100mg/kg体重的活性化合物以获得所需结果。尽管如此,但是有时可能需要背离所述的量,这特别取决于实验动物的体重或给药方法的类型,但是也取决于动物的种类及其对活性化合物的个体反应或制剂的性质及其给药时间或间隔。因此,在一些情况下,用低于上述最小量的量可能就足以实现防治作用,而在其它情况下,必须超过所述的上限。当施用较大量时,最好还是将它们分成几份,以在一天的期间内分几次给药。
本发明化合物的效力可在例如具有下述实验安排的笼子实验中证实,其中是用各单独组分以及单独组分的混合物来治疗动物。
含有活性化合物的饲料是这样制备,将所需量的活性化合物与营养平衡的动物饲料例如下述小鸡饲料充分混合。
如果要制备最后在饲料中稀释至实验所述的值的浓缩物或预混合物,一般将大约1-30%、优选大约10-20重量%的活性化合物与可食用有机或无机载体例如含有少量食用防粉尘油例如玉米油或大豆油的玉米与大豆粉或无机盐混合。然后在施用前将由此获得的预混合物加到完全家禽饲料中。
在家禽饲料中使用本发明化合物的合适实例是下述组合物。52.00% 谷类碎粉饲料,也就是:40%玉米,12%小麦17.00% 优等大豆碎粉5.00% 玉米麸质饲料5.00% 小麦粗粉饲料3.00% 鱼粉3.00% 无机混合物3.00% 苜蓿绿草粉2.50% 维生素预混合物2.00% 粉碎的小麦胚芽2.00% 大豆油2.00% 肉骨粉1.50% 乳清粉1.00% 糖蜜1.00% 用于生产啤酒的啤酒酵母100.00%
这样的饲料含有18%的粗蛋白、5%粗制纤维、1%Ca、0.7%P和每千克1200i.U.维生素A、1200i.U.维生素D3、10mg维生素E、20mg杆菌肽锌。
将活性化合物以例如1-20ppm(w/w)的量加到饲料中。活性化合物的合适的剂量是例如1ppm;2.5ppm;5ppm(在每种情况下都是重量份“(w/w)”)。
首先将0.85g(2.5mmol)5-三氟甲氧基-2,6-二(三氟甲基)-苯并咪唑置于25ml无水二氯甲烷中,并在20℃加入0.45ml(0.32g)(3.15mmol)三乙胺。然后在20℃滴加在2.5ml无水二氯甲烷中的0.30g(3.15mmol)氯甲基乙基醚,并将该混合物回流24小时。将有机相用水洗涤3次,用氯化钠水溶液洗涤,用硫酸钠干燥并浓缩。通过硅胶(35-70μm)色谱纯化残余物,使用环己烷/乙酸乙酯(5∶1)洗脱。产量:0.54g(产率为54%),油状物。RF=0.47[TLC:环己烷/乙酸乙酯(5∶1)],区域异构体的混合物(比例1∶1)。实施例2
首先将1.7g(5mmol)5-三氟甲氧基-2,6-二(三氟甲基)-苯并咪唑置于50ml无水二氯甲烷中,在20℃加入0.9ml(0.64g)(6.3mmol)三乙胺。然后在20℃滴加在5ml无水二氯甲烷中的0.65g(6.3mmol)氯甲基-2-甲基异丙基醚,并回流16小时。将有机相用水洗涤2次,用氯化钠水溶液洗涤,用硫酸钠干燥并浓缩。通过硅胶(35-70μm)色谱纯化残余物,使用环己烷/乙酸乙酯(10∶1)洗脱。产量:1.0g(产率为47%),油状物。RF=0.48[TLC:环己烷/乙酸乙酯(5∶1)],区域异构体的混合物(比例1∶1)。实施例3
首先将0.68g(2mmol)6-三氟甲氧基-2,4-二(三氟甲基)-苯并咪唑置于20ml二氯甲烷中,在20℃加入0.35ml(0.25g)(2.5mmol)三乙胺。然后在20℃滴加在2.5ml无水二氯甲烷中的0.19g(2.5mmol)氯甲基乙基醚,并将该混合物回流16小时。将有机相用水洗涤3次,用氯化钠水溶液洗涤,用硫酸钠干燥并浓缩。通过硅胶(35-70μm)色谱纯化残余物,使用环己烷/乙酸乙酯(5∶1)洗脱。产量:0.63g(产率为76%),油状物。RF=0.5[TLC:环己烷/乙酸乙酯(5∶1)]。制备用于实施例1和2的原料 实施例a
首先在室温下将122g(0.5mol)4-三氟甲氧基-3-三氟甲基苯胺置于500ml甲苯和5ml吡啶中,滴加112g(1.1mol)三氟乙酸,使用水分离器将该混合物加热回流3小时。将该混合物浓缩,将残余物与水混合,用二氯甲烷萃取,并使用硫酸钠干燥有机相。将该有机相浓缩并减压蒸馏。产量:109g(产率为64%),b.p0.1:120-125℃,GC:95.8%。实施例b
在冷却下将110g(0.32mol)N-(4-三氟甲氧基-3-三氟甲基-苯基)-三氟乙酰胺溶解在180ml浓硫酸中。在冰冷却下,于5℃用5小时缓慢地加入180ml浓硫酸与30ml浓硝酸的混合物。然后将该混合物倒入冰上,并用二氯甲烷萃取,将有机相用水洗涤直至呈中性,用硫酸钠干燥。将有机相浓缩,并减压干燥。将粗产物用于进一步反应。产量:95g(产率为77%),GC:>99%。实施例c
在高压釜中,使用8g阮内镍,将35g(0.09mol)N-(2-硝基-4-三氟甲氧基-5-三氟甲基-苯基)-三氟乙酰胺在200ml甲醇中于100巴的氢气压下氢化22小时。然后过滤出阮内镍,用甲醇洗涤,并将母液浓缩。将残余物与二氯甲烷混合,用少量水洗涤2次,并用硫酸钠干燥。残余物仍然含有N-(2-氨基-4-三氟甲氧基-5-三氟甲基-苯基)-三氟乙酰胺(GC)。因此将有机相用150ml三氟乙酸和20ml三氟乙酸酐处理,并加热回流14小时。将该混合物冷却,依次使用200ml20%的氢氧化钠溶液和50ml浓的氢氧化钠溶液将其调节至pH8。用二氯甲烷萃取该混合物,用水洗涤有机相直至呈中性,用硫酸钠干燥并浓缩。产量:10g(产率为32%),GC:64%。制备用于实施例3的原料 实施例d
在冷却下将115g(0.5mol)3-三氟甲基三氟甲苯溶解在180ml浓硫酸中。在冰冷却下,于5℃用5小时缓慢地滴加180ml浓硫酸与30ml浓硝酸的混合物,然后将该混合物倒入冰上,并用叔丁基甲基醚萃取,将有机相用水洗涤直至呈中性,用硫酸钠干燥。将有机相浓缩,并减压干燥。产量:90g(产率为65%),GC:>98%。实施例e
在高压釜中,使用2g阮内镍,将30g(0.19mol)4-三氟甲氧基-2-三氟甲基-硝基苯在200ml甲醇中于100巴的氢气压下氢化。然后过滤出阮内镍,用甲醇洗涤,并将有机相浓缩。将残余物与二氯甲烷混合,用少量水洗涤2次,并用硫酸钠干燥。产量:23.7g(产率为89%),GC:>96%。实施例f
首先将23.7g(0.97mol)4-三氟甲氧基-2-三氟甲基苯胺置于400ml二氯甲烷中,并加入58.6g(0.58mol)三乙胺。然后在20℃加入61g(0.29mol)三氟乙酸酐,将该混合物在室温搅拌1小时。将有机相用水洗涤,用硫酸钠干燥并浓缩。将残余物减压浓缩。产量:17.8g(产率为54%),b.p.0.5:68℃,GC:93.7%。实施例g
在冷却下,将18g(0.53mol)N-(4-三氟甲氧基-2-三氟甲基)-三氟乙酰胺溶解在50ml浓硫酸中。在冰冷却下,于5℃用2小时缓慢地滴加50ml浓硫酸与10ml浓硝酸的混合物。然后将该混合物倒入冰上,并用叔丁基甲基醚萃取,将有机相用水和氯化钠溶液洗涤直至呈中性,并用硫酸钠干燥。将有机相浓缩,并减压干燥。从乙醇中重结晶。产量:13.2g(产率为65%),GC:96%。实施例h
在高压釜中,使用1g阮内镍,将5g(12.9mmol)N-(2-硝基-4-三氟甲氧基-6-三氟甲基)-三氟乙酰胺在50ml甲醇中于100巴的氢气压下氢化8小时。然后过滤出阮内镍,用甲醇洗涤,并将有机相浓缩。将残余物与二氯甲烷混合,用少量水洗涤2次,并用硫酸钠干燥。残余物仍然含有N-(2-氨基-4-三氟甲氧基-6-三氟甲基)-三氟乙酰胺(GC)。因此将有机相用25ml三氟乙酸和5ml三氟乙酸酐处理,并加热回流5小时。将该混合物冷却,使用20%的氢氧化钠溶液将其调节至pH8。用二氯甲烷萃取该混合物,用水洗涤有机相直至呈中性,用硫酸钠干燥并浓缩。将残余物减压干燥。产量:4.1g(产率为94%),GC:85.6%。生物实施例 关于球虫病/小鸡的笼子实验
让在没有球虫的情况下饲养的8-12天大小的雄性小鸡(例如LSLBrinkschulte/Senden)接受本发明化合物(测试物),测试物的浓度以ppm表示,是用饲料从感染前(=a.i.)3天(-3天)开始直至感染后(=p.i.)8(9)天进行施用。每个笼子里放3只动物。每个剂量采用一个或多个这类组。感染是通过将含有大约100000个形成孢子的堆形艾美球虫卵囊和包含30000个巨型艾美球虫卵囊与40000形成孢子的禽艾美球虫卵囊的胃管直接插到膆囊内来进行感染。这些球虫是高度有毒的球虫株。调节精确的感染剂量,尽可能使3只实验感染的小鸡当中有1只由于感染而死亡。为了评价效力,使用下述标准:从实验开始到实验结束时的体重增加,由于感染所导致的死亡率,在感染后第5天和第7天用肉眼评价粪便在腹泻和排泄血液方面的特征(评定的分数0-6),用肉眼评价肠粘膜,特别是阑尾(评定的分数0-6),和卵囊排泄以及在24小时期间卵囊形成孢子的比例(%)。借助于McMaster计数室测定粪便中卵囊的数目(参见Engelbrecht及其合作者的“Parasitologische Arbeitsmethoden in Medizin undVeterinrmedizin”[医疗和兽医中的寄生物学工作方法],Akademie-Verlag,Berlin(1965))。将个体实验结果与未治疗的未感染对照组比较,并计算总的分数(参见A.Haberkorn(1986),第263-270页,Research in Avian Coccidiosis ed L.R.McDougald,L.P.Joyner,P.L.Long Proceedings of the Georgia CoccidiosisConference Nov,18.-20.1985 Athens/Georgia USA)。
使用本发明组合的实验结果作为实例显示在下表中。与单独的组分相比,组合的协同活性在减少卵囊排泄以及切片结果、体重增加和更好的耐受性方面特别显著。
在下表中,在“治疗”这栏中,信息表示:n.inf.contr.=未感染的对照组inf.contr.=感染的对照组1=苯并咪唑实施例序号。
在“ppm”栏中,以ppm给出了所用的活性化合物在饲料中的浓度。
在“死亡率”栏中,死亡动物的百分比是在%下面给出的,并且死亡动物数目/在实验中使用的动物数目是在n下面给出。
在“未感染对照的重量%”栏中,给出了治疗动物的体重与未感染对照组体重的比值。
在“下降(dropping)分数”、“损害分数”和“卵囊对照”栏中给出了作用的个体详细数据。
在“%效力”栏中,评价了总分数;%表示没有作用,100%表示完全作用。
本发明化合物的效力的实验结果总结在下表中。表1抗堆形艾美球虫、巨型艾美球虫和柔嫩艾美球虫的效力
评价标准:2=完全作用1=轻微作用0=没有活性D=死亡NT=未测试表2用抗堆形艾美球虫、巨型艾美球虫和柔嫩艾美球虫感染小鸡的实验。实施例2化合物与马度米星(MAD)的组合
化合物 | 50ppm | 25ppm | 10ppm | 7.5ppm | 5ppm | 2.5ppm | 1ppm |
实施例1 | NT | NT | 221 | 222 | 222 | 222 | 011 |
实施例2 | 222 | 222 | 121 | 111 | 010 | 111 | 111 |
实施例3 | NT | NT | 111 | 222 | 222 | 221 | 000 |
治疗 | ppm | 死亡率 | 未感染对照的重量% | 下降分数 | 损害分数 | 感染对照的卵囊% | %总效力 | ||||
% | n | ac. | max. | ten. | tot. | ||||||
n.inf.contr. | 0 | 0 | 0/6 | 100 | 0 | 0 | 0 | 0 | 0 | 0 | 100 |
inf.contr. | 0 | 0 | 0/6 | 46 | 6 | 6 | 100 | 100 | 100 | 100 | 0 |
MAD | 1 | 67 | 2/3 | 17 | 6 | 6 | >100 | >100 | 85 | >100 | 0 |
MAD | 2 | 0 | 0/3 | 82 | 2 | 6 | >100 | >100 | >100 | >100 | 29 |
MAD | 3 | 0 | 0/3 | 98 | 0 | 1 | >100 | >100 | 75 | >100 | 44 |
实施例2 | 2.5 | 33 | 1/3 | 33 | 6 | 6 | >100 | >100 | >100 | >100 | 2 |
实施例2 | 5 | 33 | 1/3 | 65 | 6 | 6 | 54 | 0 | 98 | 73 | 37 |
实施例2 | 7.5 | 33 | 1/3 | 74 | 6 | 6 | 56 | 0 | 23 | 41 | 36 |
实施例2 | 10 | 0 | 0/3 | 69 | 6 | 6 | 93 | >100 | 65 | 83 | 17 |
实施例2+MAD | 10+1 | 0 | 0/3 | 118 | 0 | 1 | 0 | 0 | 0 | 0 | 98 |
实施例2+MAD | 7.5+2 | 0 | 0/3 | 103 | 0 | 1 | 4 | 0 | 1 | 3 | 93 |
实施例2+MAD | 10+2 | 0 | 0/3 | 113 | 0 | 0 | 0 | 0 | 0 | 0 | 100 |
实施例2+MAD | 2.5+3 | 0 | 0/3 | 115 | 0 | 2 | 1 | 30 | 3 | 2 | 78 |
实施例2+MAD | 5+3 | 0 | 0/3 | 135 | 0 | 0 | 0 | 0 | 0 | 0 | 100 |
实施例2+MAD | 7.5+3 | 0 | 0/3 | 99 | 0 | 0 | 0 | 0 | 0 | 0 | 100 |
实施例2+MAD | 10+3 | 0 | 0/3 | 85 | 0 | 0 | 0 | 0 | 0 | 0 | 91 |
Claims (9)
1.式(I)的苯并咪唑化合物其中R1代表氟代烷基,R2代表氢或烷基,R3代表烷基,X1代表三氟甲基,且X2代表三氟甲氧基。
3.组合物,其特征在于,所述组合物包含至少一种如权利要求1所述的式(I)化合物。
4.权利要求3的组合物,其特征在于,所述组合物包含聚醚类抗生素或合成的抗球虫病剂作为另外的活性化合物。
5.权利要求4的组合物,其特征在于,所述聚醚类抗生素或合成的抗球虫病剂选自安普罗铵、罗贝胍、托曲珠利、莫能星、沙利霉素、马度米星、拉沙洛西、甲基盐霉素、生度米星。
6.如权利要求1所述的式(I)化合物在防治寄生虫中的应用。
7.防治寄生虫的方法,其特征在于,使权利要求1所述的式(I)化合物作用于寄生虫。
8.制备抗寄生虫组合物的方法,其特征在于,将如权利要求1所述的式(I)化合物与增量剂和/或表面活性剂混合。
9.如权利要求1所述的式(I)化合物在制备抗寄生虫组合物中的应用。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10049468.4 | 2000-10-06 | ||
DE10049468A DE10049468A1 (de) | 2000-10-06 | 2000-10-06 | N-Alkoxyalkyl-substituierte Benzimidazole, ihre Herstellung und ihre Verwendung als Mittel gegen parasitäre Protozoen |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1479725A true CN1479725A (zh) | 2004-03-03 |
CN1234695C CN1234695C (zh) | 2006-01-04 |
Family
ID=7658860
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB01820225XA Expired - Fee Related CN1234695C (zh) | 2000-10-06 | 2001-09-24 | N-烷氧基烷基取代的苯并咪唑化合物及其作为抗寄生原生动物活性剂的应用 |
Country Status (17)
Country | Link |
---|---|
US (1) | US20040044055A1 (zh) |
EP (1) | EP1326845B1 (zh) |
JP (1) | JP2004511471A (zh) |
KR (1) | KR20030031194A (zh) |
CN (1) | CN1234695C (zh) |
AR (1) | AR031720A1 (zh) |
AT (1) | ATE312825T1 (zh) |
AU (1) | AU2001291877A1 (zh) |
BR (1) | BR0114419A (zh) |
DE (2) | DE10049468A1 (zh) |
DK (1) | DK1326845T3 (zh) |
ES (1) | ES2253424T3 (zh) |
HK (1) | HK1063469A1 (zh) |
MX (1) | MXPA03002937A (zh) |
MY (1) | MY141606A (zh) |
TW (1) | TWI242556B (zh) |
WO (1) | WO2002030909A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101282723B (zh) * | 2005-09-03 | 2012-06-13 | 莫沃斯技术有限公司 | 采他子卡的用途以及含有其的药物组合物 |
CN108883095A (zh) * | 2016-03-31 | 2018-11-23 | 玛鲁哈日鲁株式会社 | 鳞介类的微孢子虫的防除用组合物、及使用了该组合物的鳞介类的微孢子虫的防除方法 |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060034978A1 (en) * | 2004-08-16 | 2006-02-16 | Grain Processing Corporation | Aerosol compositions, devices and methods |
DE102004042958A1 (de) * | 2004-09-02 | 2006-03-09 | Bayer Healthcare Ag | Neue antiparasitäre Kombination von Wirkstoffen |
GB0526552D0 (en) | 2005-12-29 | 2006-02-08 | Morvus Technology Ltd | New use |
DE102007025908A1 (de) | 2007-06-01 | 2008-12-04 | Bayer Healthcare Ag | Formulierungen enthaltend Triazinone und Eisen |
WO2017170970A1 (ja) * | 2016-03-31 | 2017-10-05 | マルハニチロ株式会社 | 魚介類の微胞子虫の防除用組成物及びそれを用いた魚介類の微胞子虫の防除方法 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1122988A (en) * | 1964-10-22 | 1968-08-07 | Fisons Pest Control Ltd | Benzimidazole derivatives |
GB1163711A (en) * | 1966-01-13 | 1969-09-10 | Fisons Pest Control Ltd | Substituted Benzimidazoles and Biocidally-Active Compositions |
AU413408B2 (en) * | 1966-09-19 | 1971-05-19 | 2-cyanobenzimidazoles | |
US3728994A (en) * | 1970-08-18 | 1973-04-24 | Teledyne Ind | Exhaust port structure |
FR2521141A1 (fr) * | 1982-02-09 | 1983-08-12 | Rhone Poulenc Agrochimie | Nouveaux derives du cyano-2 benzimidazole, leur preparation et leur utilisation comme fongicides |
FR2559150B1 (fr) * | 1984-02-06 | 1986-06-27 | Rhone Poulenc Agrochimie | Nouveaux derives du cyano-2 benzimidazole, leur preparation et leur utilisation comme fongicides |
DE4237557A1 (de) * | 1992-11-06 | 1994-05-11 | Bayer Ag | Substituierte Benzimidazole |
DE4237617A1 (de) * | 1992-11-06 | 1994-05-11 | Bayer Ag | Verwendung von substituierten Benzimidazolen |
DE4242183A1 (de) * | 1992-12-15 | 1994-06-16 | Bayer Ag | Verwendung von CN-substituierten Benzimidazolen |
US5331003A (en) * | 1993-03-26 | 1994-07-19 | Eli Lilly And Company | Anticoccidial methods |
DE19519821A1 (de) * | 1995-05-31 | 1996-12-05 | Bayer Ag | Mittel gegen parasitäre Protozoen |
DE19831985A1 (de) * | 1998-07-16 | 2000-01-20 | Bayer Ag | Substituierte Benzimidazole, ihre Herstellung und ihre Verwendung als Mittel gegen parasitäre Protozoen |
DE19920551A1 (de) * | 1999-05-05 | 2000-11-09 | Bayer Ag | Substituierte Benzimidazole, ihre Herstellung und ihre Verwendung als Mittel gegen parasitäre Protozoen |
-
2000
- 2000-10-06 DE DE10049468A patent/DE10049468A1/de not_active Withdrawn
-
2001
- 2001-09-24 US US10/398,295 patent/US20040044055A1/en not_active Abandoned
- 2001-09-24 DK DK01972078T patent/DK1326845T3/da active
- 2001-09-24 JP JP2002534295A patent/JP2004511471A/ja active Pending
- 2001-09-24 BR BR0114419-7A patent/BR0114419A/pt not_active IP Right Cessation
- 2001-09-24 DE DE50108402T patent/DE50108402D1/de not_active Expired - Fee Related
- 2001-09-24 AT AT01972078T patent/ATE312825T1/de not_active IP Right Cessation
- 2001-09-24 EP EP01972078A patent/EP1326845B1/de not_active Expired - Lifetime
- 2001-09-24 ES ES01972078T patent/ES2253424T3/es not_active Expired - Lifetime
- 2001-09-24 WO PCT/EP2001/011010 patent/WO2002030909A1/de active IP Right Grant
- 2001-09-24 CN CNB01820225XA patent/CN1234695C/zh not_active Expired - Fee Related
- 2001-09-24 AU AU2001291877A patent/AU2001291877A1/en not_active Abandoned
- 2001-09-24 MX MXPA03002937A patent/MXPA03002937A/es active IP Right Grant
- 2001-09-24 KR KR10-2003-7004421A patent/KR20030031194A/ko active IP Right Grant
- 2001-09-27 AR ARP010104564A patent/AR031720A1/es not_active Application Discontinuation
- 2001-10-04 TW TW090124458A patent/TWI242556B/zh not_active IP Right Cessation
- 2001-10-04 MY MYPI20014630A patent/MY141606A/en unknown
-
2004
- 2004-08-19 HK HK04106217A patent/HK1063469A1/xx not_active IP Right Cessation
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101282723B (zh) * | 2005-09-03 | 2012-06-13 | 莫沃斯技术有限公司 | 采他子卡的用途以及含有其的药物组合物 |
CN108883095A (zh) * | 2016-03-31 | 2018-11-23 | 玛鲁哈日鲁株式会社 | 鳞介类的微孢子虫的防除用组合物、及使用了该组合物的鳞介类的微孢子虫的防除方法 |
CN108883095B (zh) * | 2016-03-31 | 2020-02-18 | 玛鲁哈日鲁株式会社 | 鳞介类的微孢子虫的防除用组合物、及使用了该组合物的鳞介类的微孢子虫的防除方法 |
US10813914B2 (en) | 2016-03-31 | 2020-10-27 | Maruha Nichiro Corporation | Composition for controlling microsporidia in fishes and method for controlling microsporidia in fishes using same |
Also Published As
Publication number | Publication date |
---|---|
AR031720A1 (es) | 2003-10-01 |
HK1063469A1 (en) | 2004-12-31 |
TWI242556B (en) | 2005-11-01 |
JP2004511471A (ja) | 2004-04-15 |
ATE312825T1 (de) | 2005-12-15 |
BR0114419A (pt) | 2003-08-26 |
CN1234695C (zh) | 2006-01-04 |
US20040044055A1 (en) | 2004-03-04 |
AU2001291877A1 (en) | 2002-04-22 |
EP1326845A1 (de) | 2003-07-16 |
KR20030031194A (ko) | 2003-04-18 |
DK1326845T3 (da) | 2006-05-08 |
DE10049468A1 (de) | 2002-04-11 |
EP1326845B1 (de) | 2005-12-14 |
WO2002030909A1 (de) | 2002-04-18 |
ES2253424T3 (es) | 2006-06-01 |
MY141606A (en) | 2010-05-31 |
MXPA03002937A (es) | 2004-05-04 |
DE50108402D1 (de) | 2006-01-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5141938A (en) | Parasiticidal substituted 1,2,4-triazinediones | |
CN1196485C (zh) | 防治寄生性原生动物的组合物 | |
JPH051047A (ja) | 置換1,2,4−トリアジンジオン、その製法、その中間体およびその使用 | |
CN1479725A (zh) | N-烷氧基烷基取代的苯并咪唑化合物及其作为抗寄生原生动物活性剂的应用 | |
CN1469868A (zh) | 三嗪三酮砜在控制球虫病中的应用 | |
CN1130359C (zh) | 取代的苯并咪唑类、其制备和作为抗寄生原生动物剂的用途 | |
US20070066671A1 (en) | Substituted benzimidazoles, production and use thereof as agents for combating parasitic protozoas | |
CN1469747A (zh) | 三嗪三酮亚砜类在防治球虫病中的应用 | |
JP2008511567A (ja) | 抗寄生虫作用を有する置換ベンゾイミダゾール類およびトリアジン誘導体の組合せ | |
CZ273493A3 (en) | The use of cn-substituted benzimidazoles | |
CN1215332A (zh) | 取代的芳基咪唑类化合物的应用 | |
DE102009038950A1 (de) | Neue antiparasitäre Kombination von Wirkstoffen |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1063469 Country of ref document: HK |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C19 | Lapse of patent right due to non-payment of the annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |