MX2014009388A - Procedimiento para la preparacion de derivados de isoxazolina azetidina quirales como agentes antiparasitarios. - Google Patents
Procedimiento para la preparacion de derivados de isoxazolina azetidina quirales como agentes antiparasitarios.Info
- Publication number
- MX2014009388A MX2014009388A MX2014009388A MX2014009388A MX2014009388A MX 2014009388 A MX2014009388 A MX 2014009388A MX 2014009388 A MX2014009388 A MX 2014009388A MX 2014009388 A MX2014009388 A MX 2014009388A MX 2014009388 A MX2014009388 A MX 2014009388A
- Authority
- MX
- Mexico
- Prior art keywords
- phenyl
- trifluoromethyl
- carboxylate
- dichloro
- butyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 46
- 230000008569 process Effects 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims description 21
- 239000003096 antiparasitic agent Substances 0.000 title description 5
- 229940125687 antiparasitic agent Drugs 0.000 title description 4
- LZNQKPCMSCHBFF-UHFFFAOYSA-N azetidine;4,5-dihydro-1,2-oxazole Chemical class C1CNC1.C1CC=NO1 LZNQKPCMSCHBFF-UHFFFAOYSA-N 0.000 title description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- -1 = S Chemical group 0.000 claims description 178
- 150000001875 compounds Chemical class 0.000 claims description 71
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 39
- 125000001424 substituent group Chemical group 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000005843 halogen group Chemical group 0.000 claims description 20
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 125000001188 haloalkyl group Chemical group 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 12
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 235000001258 Cinchona calisaya Nutrition 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims description 9
- 238000009833 condensation Methods 0.000 claims description 9
- 230000005494 condensation Effects 0.000 claims description 9
- 239000011737 fluorine Chemical group 0.000 claims description 9
- 229910052731 fluorine Chemical group 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 9
- 229960000948 quinine Drugs 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- RERNBDGJFGBXFK-UHFFFAOYSA-N 3-[4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]phenyl]-3-hydroxyazetidine-1-carboxylic acid Chemical compound C1N(C(=O)O)CC1(O)C1=CC=C(C=2CC(ON=2)(C=2C=C(Cl)C=C(Cl)C=2)C(F)(F)F)C=C1 RERNBDGJFGBXFK-UHFFFAOYSA-N 0.000 claims description 8
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 229910003827 NRaRb Inorganic materials 0.000 claims description 8
- 125000006242 amine protecting group Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 7
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- HQOVNNDBJPCDOU-UHFFFAOYSA-N 3-[4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-1,2-oxazol-3-yl]phenyl]-3-fluoroazetidine-1-carboxylic acid Chemical compound C1N(C(=O)O)CC1(F)C1=CC=C(C=2CC(ON=2)(C=2C=C(Cl)C=C(Cl)C=2)C(F)(F)F)C=C1 HQOVNNDBJPCDOU-UHFFFAOYSA-N 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 5
- KVVMXWRFYAGASO-UHFFFAOYSA-N azetidine-1-carboxylic acid Chemical compound OC(=O)N1CCC1 KVVMXWRFYAGASO-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- TVGSMPZXTCQNAB-UHFFFAOYSA-N 1-[4-(azetidin-3-yl)phenyl]-4,4,4-trifluoro-3-phenylbut-2-en-1-one Chemical class FC(F)(F)C(=CC(=O)c1ccc(cc1)C1CNC1)c1ccccc1 TVGSMPZXTCQNAB-UHFFFAOYSA-N 0.000 claims description 4
- VOXJHBJSBBOWHS-UHFFFAOYSA-N 1-[4-(azetidin-3-yl)phenyl]ethanone Chemical class C1=CC(C(=O)C)=CC=C1C1CNC1 VOXJHBJSBBOWHS-UHFFFAOYSA-N 0.000 claims description 4
- WHOVKIMCOPXUQR-UHFFFAOYSA-N 3-[4-(azetidin-3-yl)phenyl]-5-phenyl-5-(trifluoromethyl)-4h-1,2-oxazole Chemical class N=1OC(C(F)(F)F)(C=2C=CC=CC=2)CC=1C(C=C1)=CC=C1C1CNC1 WHOVKIMCOPXUQR-UHFFFAOYSA-N 0.000 claims description 4
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 claims description 4
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- HYRBYWSCPHNZQT-UHFFFAOYSA-N tert-butyl 3-(4-acetylphenyl)-3-fluoroazetidine-1-carboxylate Chemical compound C1=CC(C(=O)C)=CC=C1C1(F)CN(C(=O)OC(C)(C)C)C1 HYRBYWSCPHNZQT-UHFFFAOYSA-N 0.000 claims description 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 3
- ZQQSYPZAPHRXRY-UHFFFAOYSA-N 1-hydroxyazetidine Chemical compound ON1CCC1 ZQQSYPZAPHRXRY-UHFFFAOYSA-N 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 3
- KHNGFFOEQHPXRG-UHFFFAOYSA-N 2-bromo-1-phenylazetidine Chemical compound BrC1CCN1C1=CC=CC=C1 KHNGFFOEQHPXRG-UHFFFAOYSA-N 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 claims description 3
- 239000012025 fluorinating agent Substances 0.000 claims description 3
- 238000007363 ring formation reaction Methods 0.000 claims description 3
- 125000002053 thietanyl group Chemical group 0.000 claims description 3
- RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical class Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 claims description 2
- KHKPNKLHLOHKBG-WJOKGBTCSA-N (5r)-3-[4-(1-benzhydryl-3-fluoroazetidin-3-yl)phenyl]-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound C1=C(Cl)C(F)=C(Cl)C=C1[C@]1(C(F)(F)F)ON=C(C=2C=CC(=CC=2)C2(F)CN(C2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 KHKPNKLHLOHKBG-WJOKGBTCSA-N 0.000 claims description 2
- LFHOUJHUGJHRIO-GOSISDBHSA-N (5r)-3-[4-(3-fluoroazetidin-3-yl)phenyl]-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound C([C@](ON=1)(C(F)(F)F)C=2C=C(Cl)C(Cl)=C(Cl)C=2)C=1C(C=C1)=CC=C1C1(F)CNC1 LFHOUJHUGJHRIO-GOSISDBHSA-N 0.000 claims description 2
- QINCLOKAVIHKJZ-HKBQPEDESA-N (5s)-3-[4-(1-benzhydryl-3-fluoroazetidin-3-yl)phenyl]-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound C([C@@](ON=1)(C(F)(F)F)C=2C=C(Cl)C(Cl)=C(Cl)C=2)C=1C(C=C1)=CC=C1C(C1)(F)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 QINCLOKAVIHKJZ-HKBQPEDESA-N 0.000 claims description 2
- KHKPNKLHLOHKBG-HKBQPEDESA-N (5s)-3-[4-(1-benzhydryl-3-fluoroazetidin-3-yl)phenyl]-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound C1=C(Cl)C(F)=C(Cl)C=C1[C@@]1(C(F)(F)F)ON=C(C=2C=CC(=CC=2)C2(F)CN(C2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 KHKPNKLHLOHKBG-HKBQPEDESA-N 0.000 claims description 2
- ZPMASNYEZBXLBM-HKBQPEDESA-N (5s)-3-[4-(1-benzhydryl-3-fluoroazetidin-3-yl)phenyl]-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound C([C@@](ON=1)(C(F)(F)F)C=2C=C(Cl)C=C(Cl)C=2)C=1C(C=C1)=CC=C1C(C1)(F)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 ZPMASNYEZBXLBM-HKBQPEDESA-N 0.000 claims description 2
- LFHOUJHUGJHRIO-SFHVURJKSA-N (5s)-3-[4-(3-fluoroazetidin-3-yl)phenyl]-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound C([C@@](ON=1)(C(F)(F)F)C=2C=C(Cl)C(Cl)=C(Cl)C=2)C=1C(C=C1)=CC=C1C1(F)CNC1 LFHOUJHUGJHRIO-SFHVURJKSA-N 0.000 claims description 2
- KGWBVTDKNZMVSD-SFHVURJKSA-N (5s)-5-(3,5-dichloro-4-fluorophenyl)-3-[4-(3-fluoroazetidin-3-yl)phenyl]-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound C1=C(Cl)C(F)=C(Cl)C=C1[C@@]1(C(F)(F)F)ON=C(C=2C=CC(=CC=2)C2(F)CNC2)C1 KGWBVTDKNZMVSD-SFHVURJKSA-N 0.000 claims description 2
- DPLMQICDPYILGQ-UHFFFAOYSA-N 1-[4-(1-benzhydryl-3-fluoroazetidin-3-yl)phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C1(F)CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 DPLMQICDPYILGQ-UHFFFAOYSA-N 0.000 claims description 2
- SUZWMLMQOKJORS-UHFFFAOYSA-N 1-[4-(1-benzhydryl-3-hydroxyazetidin-3-yl)phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C1(O)CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1 SUZWMLMQOKJORS-UHFFFAOYSA-N 0.000 claims description 2
- AOZHVTFNXDMYRE-WJOKGBTCSA-N 1-benzhydryl-3-[4-[(5r)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C1C(O)(C=2C=CC(=CC=2)C=2C[C@@](ON=2)(C=2C=C(Cl)C(Cl)=C(Cl)C=2)C(F)(F)F)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 AOZHVTFNXDMYRE-WJOKGBTCSA-N 0.000 claims description 2
- WQBCZPJEJFCQOW-WJOKGBTCSA-N 1-benzhydryl-3-[4-[(5r)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C1C(O)(C=2C=CC(=CC=2)C=2C[C@@](ON=2)(C=2C=C(Cl)C=C(Cl)C=2)C(F)(F)F)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 WQBCZPJEJFCQOW-WJOKGBTCSA-N 0.000 claims description 2
- AOZHVTFNXDMYRE-HKBQPEDESA-N 1-benzhydryl-3-[4-[(5s)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C1C(O)(C=2C=CC(=CC=2)C=2C[C@](ON=2)(C=2C=C(Cl)C(Cl)=C(Cl)C=2)C(F)(F)F)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 AOZHVTFNXDMYRE-HKBQPEDESA-N 0.000 claims description 2
- JIBSIASZRONXMB-HKBQPEDESA-N 1-benzhydryl-3-[4-[(5s)-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C1C(O)(C=2C=CC(=CC=2)C=2C[C@](ON=2)(C=2C=C(Cl)C(F)=C(Cl)C=2)C(F)(F)F)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 JIBSIASZRONXMB-HKBQPEDESA-N 0.000 claims description 2
- WQBCZPJEJFCQOW-HKBQPEDESA-N 1-benzhydryl-3-[4-[(5s)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C1C(O)(C=2C=CC(=CC=2)C=2C[C@](ON=2)(C=2C=C(Cl)C=C(Cl)C=2)C(F)(F)F)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 WQBCZPJEJFCQOW-HKBQPEDESA-N 0.000 claims description 2
- RAXRSTOKCITCSP-UHFFFAOYSA-N 3-(4-bromophenyl)azetidin-3-ol Chemical compound C=1C=C(Br)C=CC=1C1(O)CNC1 RAXRSTOKCITCSP-UHFFFAOYSA-N 0.000 claims description 2
- FKLZLVYZEWVANK-SFHVURJKSA-N 3-[4-[(5s)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C=1C=C(C=2C[C@](ON=2)(C=2C=C(Cl)C(Cl)=C(Cl)C=2)C(F)(F)F)C=CC=1C1(O)CNC1 FKLZLVYZEWVANK-SFHVURJKSA-N 0.000 claims description 2
- AAIWBZNLKMUQJE-SFHVURJKSA-N 3-[4-[(5s)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C=1C=C(C=2C[C@](ON=2)(C=2C=C(Cl)C=C(Cl)C=2)C(F)(F)F)C=CC=1C1(O)CNC1 AAIWBZNLKMUQJE-SFHVURJKSA-N 0.000 claims description 2
- YLZSTVIVKTXQIQ-UHFFFAOYSA-N 3-[4-[3-[3,4-dichloro-5-(trifluoromethyl)phenyl]-4,4,4-trifluorobut-2-enoyl]phenyl]-3-fluoroazetidine-1-carboxylic acid Chemical compound C1N(C(=O)O)CC1(F)C1=CC=C(C(=O)C=C(C=2C=C(C(Cl)=C(Cl)C=2)C(F)(F)F)C(F)(F)F)C=C1 YLZSTVIVKTXQIQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 239000007818 Grignard reagent Substances 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 238000010640 amide synthesis reaction Methods 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 238000010915 one-step procedure Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 125000004362 3,4,5-trichlorophenyl group Chemical group [H]C1=C(Cl)C(Cl)=C(Cl)C([H])=C1* 0.000 claims 3
- GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 claims 3
- KGWBVTDKNZMVSD-GOSISDBHSA-N (5r)-5-(3,5-dichloro-4-fluorophenyl)-3-[4-(3-fluoroazetidin-3-yl)phenyl]-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound C1=C(Cl)C(F)=C(Cl)C=C1[C@]1(C(F)(F)F)ON=C(C=2C=CC(=CC=2)C2(F)CNC2)C1 KGWBVTDKNZMVSD-GOSISDBHSA-N 0.000 claims 1
- DVSSNWKOASTWTL-GOSISDBHSA-N (5r)-5-(3,5-dichlorophenyl)-3-[4-(3-fluoroazetidin-3-yl)phenyl]-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound C([C@](ON=1)(C(F)(F)F)C=2C=C(Cl)C=C(Cl)C=2)C=1C(C=C1)=CC=C1C1(F)CNC1 DVSSNWKOASTWTL-GOSISDBHSA-N 0.000 claims 1
- BZFSJRDPMCGFCY-GOSISDBHSA-N (5r)-5-[3,4-dichloro-5-(trifluoromethyl)phenyl]-3-[4-(3-fluoroazetidin-3-yl)phenyl]-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound ClC1=C(Cl)C(C(F)(F)F)=CC([C@@]2(ON=C(C2)C=2C=CC(=CC=2)C2(F)CNC2)C(F)(F)F)=C1 BZFSJRDPMCGFCY-GOSISDBHSA-N 0.000 claims 1
- JIBSIASZRONXMB-WJOKGBTCSA-N 1-benzhydryl-3-[4-[(5r)-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C1C(O)(C=2C=CC(=CC=2)C=2C[C@@](ON=2)(C=2C=C(Cl)C(F)=C(Cl)C=2)C(F)(F)F)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 JIBSIASZRONXMB-WJOKGBTCSA-N 0.000 claims 1
- UCCUXODGPMAHRL-UHFFFAOYSA-N 1-bromo-4-iodobenzene Chemical compound BrC1=CC=C(I)C=C1 UCCUXODGPMAHRL-UHFFFAOYSA-N 0.000 claims 1
- ZSALDUJSGMFZPY-UHFFFAOYSA-N 2-hydroxyazetidine-1-carboxylic acid Chemical compound OC1CCN1C(O)=O ZSALDUJSGMFZPY-UHFFFAOYSA-N 0.000 claims 1
- VFRMFIIBGUUUCE-UHFFFAOYSA-N 3,4-dichloro-4,5-dihydro-1,2-oxazole Chemical compound ClC1C(=NOC1)Cl VFRMFIIBGUUUCE-UHFFFAOYSA-N 0.000 claims 1
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 1
- XAXXTYXMWOFKLW-UHFFFAOYSA-N [C-]1=CC=[NH+]1 Chemical compound [C-]1=CC=[NH+]1 XAXXTYXMWOFKLW-UHFFFAOYSA-N 0.000 claims 1
- AKMDOVCDJPRJNC-UHFFFAOYSA-N benzyl 3-(4-acetylphenyl)-3-fluoroazetidine-1-carboxylate Chemical compound C1=CC(C(=O)C)=CC=C1C1(F)CN(C(=O)OCC=2C=CC=CC=2)C1 AKMDOVCDJPRJNC-UHFFFAOYSA-N 0.000 claims 1
- 150000004795 grignard reagents Chemical class 0.000 claims 1
- RECJKSCXHMXWQY-YBEGLDIGSA-N tert-butyl 3-[4-[(z)-3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-2-enoyl]phenyl]-3-fluoroazetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1(F)C1=CC=C(C(=O)\C=C(\C=2C=C(Cl)C(F)=C(Cl)C=2)C(F)(F)F)C=C1 RECJKSCXHMXWQY-YBEGLDIGSA-N 0.000 claims 1
- FDCBGRUURAPIJZ-ODLFYWEKSA-N tert-butyl 3-[4-[(z)-3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-2-enoyl]phenyl]-3-fluoroazetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1(F)C1=CC=C(C(=O)\C=C(\C=2C=C(Cl)C=C(Cl)C=2)C(F)(F)F)C=C1 FDCBGRUURAPIJZ-ODLFYWEKSA-N 0.000 claims 1
- 241001465754 Metazoa Species 0.000 abstract description 28
- 230000015572 biosynthetic process Effects 0.000 abstract description 10
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 230000000590 parasiticidal effect Effects 0.000 abstract description 2
- 239000002297 parasiticide Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 206010061217 Infestation Diseases 0.000 description 10
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 10
- 125000001931 aliphatic group Chemical group 0.000 description 10
- 244000045947 parasite Species 0.000 description 10
- 241000238631 Hexapoda Species 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 241000255925 Diptera Species 0.000 description 8
- 125000000753 cycloalkyl group Chemical group 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
- 125000001072 heteroaryl group Chemical group 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 241000251468 Actinopterygii Species 0.000 description 6
- 241001674048 Phthiraptera Species 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 244000078703 ectoparasite Species 0.000 description 6
- 235000019688 fish Nutrition 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 241000238876 Acari Species 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 241000271566 Aves Species 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 244000079386 endoparasite Species 0.000 description 5
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
- 244000144972 livestock Species 0.000 description 5
- 125000002950 monocyclic group Chemical group 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- APOYTRAZFJURPB-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)-n-(trifluoro-$l^{4}-sulfanyl)ethanamine Chemical compound COCCN(S(F)(F)F)CCOC APOYTRAZFJURPB-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 4
- 241000239250 Copepoda Species 0.000 description 4
- 241000258242 Siphonaptera Species 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000000895 acaricidal effect Effects 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 125000002837 carbocyclic group Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical compound C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 150000002547 isoxazolines Chemical class 0.000 description 4
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- DZDSQRPDUCSOQV-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone Chemical compound FC(F)(F)C(=O)C1=CC(Cl)=CC(Cl)=C1 DZDSQRPDUCSOQV-UHFFFAOYSA-N 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 241000244206 Nematoda Species 0.000 description 3
- 208000030852 Parasitic disease Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 3
- 235000005513 chalcones Nutrition 0.000 description 3
- 229940113088 dimethylacetamide Drugs 0.000 description 3
- 239000013057 ectoparasiticide Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 125000000262 haloalkenyl group Chemical group 0.000 description 3
- 125000000232 haloalkynyl group Chemical group 0.000 description 3
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 230000003071 parasitic effect Effects 0.000 description 3
- 244000144977 poultry Species 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- WFSVNYBQJYMUAK-UHFFFAOYSA-N (1-phenylazetidin-2-yl)silane Chemical compound [SiH3]C1N(CC1)C1=CC=CC=C1 WFSVNYBQJYMUAK-UHFFFAOYSA-N 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N 1-Pyrroline Chemical compound C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 2
- JNWYXXQAOGBPNL-UHFFFAOYSA-N 1-phenylazetidine Chemical group C1CCN1C1=CC=CC=C1 JNWYXXQAOGBPNL-UHFFFAOYSA-N 0.000 description 2
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- 241000239223 Arachnida Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000251730 Chondrichthyes Species 0.000 description 2
- 241001414835 Cimicidae Species 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 239000007821 HATU Substances 0.000 description 2
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241001481703 Rhipicephalus <genus> Species 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 241000255628 Tabanidae Species 0.000 description 2
- 241000869417 Trematodes Species 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000000642 acaricide Substances 0.000 description 2
- 125000002339 acetoacetyl group Chemical group O=C([*])C([H])([H])C(=O)C([H])([H])[H] 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 description 2
- RRIWSQXXBIFKQM-UHFFFAOYSA-N benzylcarbamic acid Chemical class OC(=O)NCC1=CC=CC=C1 RRIWSQXXBIFKQM-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 230000001055 chewing effect Effects 0.000 description 2
- 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 210000003746 feather Anatomy 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 244000000013 helminth Species 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 230000000749 insecticidal effect Effects 0.000 description 2
- 239000002917 insecticide Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 238000006263 metalation reaction Methods 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- BDJAEZRIGNCQBZ-UHFFFAOYSA-N methylcyclobutane Chemical compound CC1CCC1 BDJAEZRIGNCQBZ-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 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
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- DQFBYFPFKXHELB-VAWYXSNFSA-N trans-chalcone Chemical compound C=1C=CC=CC=1C(=O)\C=C\C1=CC=CC=C1 DQFBYFPFKXHELB-VAWYXSNFSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- UKTSSJJZFVGTCG-UHFFFAOYSA-N (4-bromophenyl)-trimethylsilane Chemical compound C[Si](C)(C)C1=CC=C(Br)C=C1 UKTSSJJZFVGTCG-UHFFFAOYSA-N 0.000 description 1
- MZVTWOSVBKAVAD-WJOKGBTCSA-N (5r)-3-[4-(1-benzhydryl-3-fluoroazetidin-3-yl)phenyl]-5-[3,4-dichloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound ClC1=C(Cl)C(C(F)(F)F)=CC([C@@]2(ON=C(C2)C=2C=CC(=CC=2)C2(F)CN(C2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C(F)(F)F)=C1 MZVTWOSVBKAVAD-WJOKGBTCSA-N 0.000 description 1
- MZVTWOSVBKAVAD-HKBQPEDESA-N (5s)-3-[4-(1-benzhydryl-3-fluoroazetidin-3-yl)phenyl]-5-[3,4-dichloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound ClC1=C(Cl)C(C(F)(F)F)=CC([C@]2(ON=C(C2)C=2C=CC(=CC=2)C2(F)CN(C2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C(F)(F)F)=C1 MZVTWOSVBKAVAD-HKBQPEDESA-N 0.000 description 1
- BZFSJRDPMCGFCY-SFHVURJKSA-N (5s)-5-[3,4-dichloro-5-(trifluoromethyl)phenyl]-3-[4-(3-fluoroazetidin-3-yl)phenyl]-5-(trifluoromethyl)-4h-1,2-oxazole Chemical compound ClC1=C(Cl)C(C(F)(F)F)=CC([C@]2(ON=C(C2)C=2C=CC(=CC=2)C2(F)CNC2)C(F)(F)F)=C1 BZFSJRDPMCGFCY-SFHVURJKSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- GWYPDXLJACEENP-UHFFFAOYSA-N 1,3-cycloheptadiene Chemical compound C1CC=CC=CC1 GWYPDXLJACEENP-UHFFFAOYSA-N 0.000 description 1
- NSWPERXXSPCRCT-UHFFFAOYSA-N 1-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethanone Chemical compound FC1=C(Cl)C=C(C(=O)C(F)(F)F)C=C1Cl NSWPERXXSPCRCT-UHFFFAOYSA-N 0.000 description 1
- HXSZEZZDGWUPCX-UHFFFAOYSA-N 1-benzhydryl-3-(4-bromophenyl)-3-fluoroazetidine Chemical compound C1C(F)(C=2C=CC(Br)=CC=2)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 HXSZEZZDGWUPCX-UHFFFAOYSA-N 0.000 description 1
- IRTAOXRAAQWMJV-UHFFFAOYSA-N 1-benzhydryl-3-(4-bromophenyl)azetidin-3-ol Chemical compound C1C(O)(C=2C=CC(Br)=CC=2)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 IRTAOXRAAQWMJV-UHFFFAOYSA-N 0.000 description 1
- YCSACLJFAAHCTA-HKBQPEDESA-N 1-benzhydryl-3-[4-[(5s)-5-[3,4-dichloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C1C(O)(C=2C=CC(=CC=2)C=2C[C@](ON=2)(C=2C=C(C(Cl)=C(Cl)C=2)C(F)(F)F)C(F)(F)F)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 YCSACLJFAAHCTA-HKBQPEDESA-N 0.000 description 1
- OIRHKGBNGGSCGS-UHFFFAOYSA-N 1-bromo-2-iodobenzene Chemical compound BrC1=CC=CC=C1I OIRHKGBNGGSCGS-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- PDQRQJVPEFGVRK-UHFFFAOYSA-N 2,1,3-benzothiadiazole Chemical compound C1=CC=CC2=NSN=C21 PDQRQJVPEFGVRK-UHFFFAOYSA-N 0.000 description 1
- NVMZCQYOSPFJLE-UHFFFAOYSA-N 2,2,2-trifluoro-1-(3,4,5-trichlorophenyl)ethanone Chemical compound FC(F)(F)C(=O)C1=CC(Cl)=C(Cl)C(Cl)=C1 NVMZCQYOSPFJLE-UHFFFAOYSA-N 0.000 description 1
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- DPGVNSDPGIWYQK-UHFFFAOYSA-N 2-methylheptanenitrile Chemical compound CCCCCC(C)C#N DPGVNSDPGIWYQK-UHFFFAOYSA-N 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- NTJMGOWFGQXUDY-UHFFFAOYSA-N 2H-azirine Chemical compound C1C=N1 NTJMGOWFGQXUDY-UHFFFAOYSA-N 0.000 description 1
- SIBLGQFWPWHDTF-GOSISDBHSA-N 3-[4-[(5r)-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C=1C=C(C=2C[C@@](ON=2)(C=2C=C(Cl)C(F)=C(Cl)C=2)C(F)(F)F)C=CC=1C1(O)CNC1 SIBLGQFWPWHDTF-GOSISDBHSA-N 0.000 description 1
- AAIWBZNLKMUQJE-GOSISDBHSA-N 3-[4-[(5r)-5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C=1C=C(C=2C[C@@](ON=2)(C=2C=C(Cl)C=C(Cl)C=2)C(F)(F)F)C=CC=1C1(O)CNC1 AAIWBZNLKMUQJE-GOSISDBHSA-N 0.000 description 1
- SIBLGQFWPWHDTF-SFHVURJKSA-N 3-[4-[(5s)-5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C=1C=C(C=2C[C@](ON=2)(C=2C=C(Cl)C(F)=C(Cl)C=2)C(F)(F)F)C=CC=1C1(O)CNC1 SIBLGQFWPWHDTF-SFHVURJKSA-N 0.000 description 1
- ZMMFLQAETXYDLX-SFHVURJKSA-N 3-[4-[(5s)-5-[3,4-dichloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4h-1,2-oxazol-3-yl]phenyl]azetidin-3-ol Chemical compound C=1C=C(C=2C[C@](ON=2)(C=2C=C(C(Cl)=C(Cl)C=2)C(F)(F)F)C(F)(F)F)C=CC=1C1(O)CNC1 ZMMFLQAETXYDLX-SFHVURJKSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000032484 Accidental exposure to product Diseases 0.000 description 1
- 241000282979 Alces alces Species 0.000 description 1
- 241000238679 Amblyomma Species 0.000 description 1
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- 241001465677 Ancylostomatoidea Species 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 241000272814 Anser sp. Species 0.000 description 1
- 241000238421 Arthropoda Species 0.000 description 1
- 241000244186 Ascaris Species 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 206010004194 Bed bug infestation Diseases 0.000 description 1
- 241000157302 Bison bison athabascae Species 0.000 description 1
- LKVHNWCEAZYJRS-UHFFFAOYSA-N C[Si](C)(C)[K] Chemical compound C[Si](C)(C)[K] LKVHNWCEAZYJRS-UHFFFAOYSA-N 0.000 description 1
- 241001611011 Caligus Species 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241001137901 Centropomus undecimalis Species 0.000 description 1
- 241000134426 Ceratopogonidae Species 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 241000359266 Chorioptes Species 0.000 description 1
- 241001414836 Cimex Species 0.000 description 1
- 241000251464 Coelacanthiformes Species 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 241000258922 Ctenocephalides Species 0.000 description 1
- 241000268912 Damalinia Species 0.000 description 1
- 241001128004 Demodex Species 0.000 description 1
- 241001480824 Dermacentor Species 0.000 description 1
- 241001481694 Dermanyssus Species 0.000 description 1
- 241000202813 Dermatobia Species 0.000 description 1
- 241000723298 Dicentrarchus labrax Species 0.000 description 1
- 241000251729 Elasmobranchii Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 241001480796 Haemaphysalis Species 0.000 description 1
- 241000257224 Haematobia Species 0.000 description 1
- 241001480803 Hyalomma Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241000238681 Ixodes Species 0.000 description 1
- 241000442132 Lactarius lactarius Species 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 241001247233 Lepeophtheirus Species 0.000 description 1
- 241001113970 Linognathus Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 241000238887 Ornithodoros Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000242594 Platyhelminthes Species 0.000 description 1
- 241000269980 Pleuronectidae Species 0.000 description 1
- 241001649229 Psoroptes Species 0.000 description 1
- 241000255131 Psychodidae Species 0.000 description 1
- 241000157468 Reinhardtius hippoglossoides Species 0.000 description 1
- 241000277331 Salmonidae Species 0.000 description 1
- 241000509416 Sarcoptes Species 0.000 description 1
- 241001417495 Serranidae Species 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical group [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 241000256103 Simuliidae Species 0.000 description 1
- 241001247231 Siphonostomatoida Species 0.000 description 1
- 241001494139 Stomoxys Species 0.000 description 1
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 241000276707 Tilapia Species 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 241001504592 Trachurus trachurus Species 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 150000001499 aryl bromides Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- UQUPQEUNHVVNKW-UHFFFAOYSA-N azetidin-1-ium-3-ol;chloride Chemical compound Cl.OC1CNC1 UQUPQEUNHVVNKW-UHFFFAOYSA-N 0.000 description 1
- 150000001539 azetidines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 241001233037 catfish Species 0.000 description 1
- 150000001789 chalcones Chemical class 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- CFBGXYDUODCMNS-UHFFFAOYSA-N cyclobutene Chemical compound C1CC=C1 CFBGXYDUODCMNS-UHFFFAOYSA-N 0.000 description 1
- ZXIJMRYMVAMXQP-UHFFFAOYSA-N cycloheptene Chemical compound C1CCC=CCC1 ZXIJMRYMVAMXQP-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- URYYVOIYTNXXBN-UPHRSURJSA-N cyclooctene Chemical compound C1CCC\C=C/CC1 URYYVOIYTNXXBN-UPHRSURJSA-N 0.000 description 1
- 239000004913 cyclooctene Substances 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- OOXWYYGXTJLWHA-UHFFFAOYSA-N cyclopropene Chemical compound C1C=C1 OOXWYYGXTJLWHA-UHFFFAOYSA-N 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- NEZRFXZYPAIZAD-UHFFFAOYSA-N ethylcyclobutane Chemical compound CCC1CCC1 NEZRFXZYPAIZAD-UHFFFAOYSA-N 0.000 description 1
- FOTXAJDDGPYIFU-UHFFFAOYSA-N ethylcyclopropane Chemical compound CCC1CC1 FOTXAJDDGPYIFU-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 210000002816 gill Anatomy 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- PIVSQSKZHIXEMK-UHFFFAOYSA-N hydron;1-hydroxyazetidine;chloride Chemical compound Cl.ON1CCC1 PIVSQSKZHIXEMK-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- 231100000225 lethality Toxicity 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- VNXBKJFUJUWOCW-UHFFFAOYSA-N methylcyclopropane Chemical compound CC1CC1 VNXBKJFUJUWOCW-UHFFFAOYSA-N 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 230000036281 parasite infection Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001846 repelling effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 150000004756 silanes Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261594614P | 2012-02-03 | 2012-02-03 | |
| PCT/US2013/023673 WO2013116236A1 (en) | 2012-02-03 | 2013-01-29 | Process for the preparation of chiral isoxazoline azetidine derivatives as antiparasitic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2014009388A true MX2014009388A (es) | 2014-08-27 |
Family
ID=47679107
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2014009388A MX2014009388A (es) | 2012-02-03 | 2013-01-29 | Procedimiento para la preparacion de derivados de isoxazolina azetidina quirales como agentes antiparasitarios. |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20140371464A1 (enExample) |
| EP (1) | EP2809667A1 (enExample) |
| JP (1) | JP2015505560A (enExample) |
| CN (1) | CN104169276A (enExample) |
| AR (1) | AR092793A1 (enExample) |
| AU (1) | AU2013215374A1 (enExample) |
| BR (1) | BR112014019212A8 (enExample) |
| CA (1) | CA2863629A1 (enExample) |
| CL (1) | CL2014002034A1 (enExample) |
| MX (1) | MX2014009388A (enExample) |
| RU (1) | RU2014131950A (enExample) |
| UY (1) | UY34612A (enExample) |
| WO (1) | WO2013116236A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2872989A1 (en) * | 2012-05-09 | 2013-11-14 | Zoetis Llc | Azetidine derivatives as antiparasitic agents |
| UY37137A (es) | 2016-02-24 | 2017-09-29 | Merial Inc | Compuestos antiparasitarios de isoxazolina, formulaciones inyectables de acción prolongada que los comprenden, métodos y usos de los mismos |
| DK3440062T3 (da) | 2016-04-06 | 2022-01-03 | Boehringer Ingelheim Animal Health Usa Inc | Fremgangsmåde til fremstillingen af enantiomerisk berigede isoxazolinforbindelser - krystallinsk toluensolvat af (s)-afoxolaner |
| MX380497B (es) | 2016-10-14 | 2025-03-11 | Boehringer Ingelheim Animal Health Usa Inc | Compuestos de vinil isoxazolina pesticidas y parasiticidas. |
| MX2020001724A (es) | 2017-08-14 | 2020-07-29 | Boehringer Ingelheim Animal Health Usa Inc | Compuestos de pirazol-isoxazolina plaguicidas y parasiticidas. |
| EP3986878B1 (en) * | 2019-06-19 | 2024-09-25 | NMD Pharma A/S | Process for the preparation of clc-1 chloride channel inhibitors |
| KR20230043904A (ko) | 2020-07-24 | 2023-03-31 | 엘랑코 유에스 인코포레이티드 | 이속사졸린 화합물 및 이의 중간체의 제조 공정 |
| MX2023014962A (es) | 2021-08-11 | 2024-02-13 | Elanco Us Inc | Proceso para elaborar derivado de diaril isoxazolina. |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200803740A (en) | 2005-12-16 | 2008-01-16 | Du Pont | 5-aryl isoxazolines for controlling invertebrate pests |
| CN101331127B (zh) * | 2005-12-16 | 2012-05-23 | 杜邦公司 | 用于防治无脊椎害虫的5-芳基异噁唑啉 |
| WO2007105814A1 (ja) | 2006-03-10 | 2007-09-20 | Nissan Chemical Industries, Ltd. | 置換イソキサゾリン化合物及び有害生物防除剤 |
| JP2008044880A (ja) * | 2006-08-15 | 2008-02-28 | Bayer Cropscience Ag | 殺虫性イソオキサゾリン類 |
| US8303622B2 (en) | 2007-03-14 | 2012-11-06 | St. Jude Medical, Inc. | Heart valve chordae replacement methods and apparatus |
| JP2008260691A (ja) * | 2007-04-10 | 2008-10-30 | Bayer Cropscience Ag | 殺虫性アリールイソオキサゾリン誘導体 |
| JP5365806B2 (ja) | 2007-09-10 | 2013-12-11 | 日産化学工業株式会社 | 置換イソキサゾリン化合物及び有害生物防除剤 |
| WO2009063910A1 (ja) | 2007-11-12 | 2009-05-22 | Nissan Chemical Industries, Ltd. | 光学活性イソキサゾリン化合物の触媒的不斉合成方法 |
| BRPI0923009B1 (pt) * | 2008-12-19 | 2018-07-17 | Elanco Tiergesundheit Ag | compostos de isoxazolina, composição para o controle de parasitas e uso de compostos de isoxazolina para o preparo de composição para o controle de parasitas |
| CN102822168B (zh) | 2010-02-25 | 2016-10-26 | 先正达参股股份有限公司 | 制备异恶唑啉衍生物的方法 |
| PH12013500164A1 (en) * | 2010-08-05 | 2015-07-08 | Zoetis Services Llc | Isoxazoline derivatives as antiparasitic agents |
-
2013
- 2013-01-29 WO PCT/US2013/023673 patent/WO2013116236A1/en not_active Ceased
- 2013-01-29 CN CN201380014566.3A patent/CN104169276A/zh active Pending
- 2013-01-29 JP JP2014555626A patent/JP2015505560A/ja active Pending
- 2013-01-29 AU AU2013215374A patent/AU2013215374A1/en not_active Abandoned
- 2013-01-29 CA CA2863629A patent/CA2863629A1/en not_active Abandoned
- 2013-01-29 US US14/375,056 patent/US20140371464A1/en not_active Abandoned
- 2013-01-29 BR BR112014019212A patent/BR112014019212A8/pt not_active IP Right Cessation
- 2013-01-29 RU RU2014131950A patent/RU2014131950A/ru unknown
- 2013-01-29 MX MX2014009388A patent/MX2014009388A/es unknown
- 2013-01-29 EP EP13703287.6A patent/EP2809667A1/en not_active Withdrawn
- 2013-02-01 AR ARP130100321A patent/AR092793A1/es unknown
- 2013-02-04 UY UY0001034612A patent/UY34612A/es not_active Application Discontinuation
-
2014
- 2014-07-30 CL CL2014002034A patent/CL2014002034A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20140371464A1 (en) | 2014-12-18 |
| AU2013215374A1 (en) | 2014-08-21 |
| BR112014019212A8 (pt) | 2017-07-11 |
| UY34612A (es) | 2013-09-30 |
| AR092793A1 (es) | 2015-05-06 |
| RU2014131950A (ru) | 2016-03-27 |
| WO2013116236A1 (en) | 2013-08-08 |
| CL2014002034A1 (es) | 2014-11-14 |
| JP2015505560A (ja) | 2015-02-23 |
| CA2863629A1 (en) | 2013-08-08 |
| CN104169276A (zh) | 2014-11-26 |
| EP2809667A1 (en) | 2014-12-10 |
| BR112014019212A2 (enExample) | 2017-06-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2566083C2 (ru) | Спироциклические производные изоксазолина в качестве противопаразитарных агентов | |
| MX2014009388A (es) | Procedimiento para la preparacion de derivados de isoxazolina azetidina quirales como agentes antiparasitarios. | |
| CA2881844A1 (en) | Spirocyclic derivatives as antiparasitic agents | |
| JP6049866B2 (ja) | 駆虫剤としてのアゼチジン誘導体 | |
| CA2863625C (en) | Dihydrofuran azetidine derivatives as antiparasitic agents | |
| HK1190393B (en) | Spirocyclic isoxazoline derivatives as antiparasitic agents | |
| TW201249838A (en) | Organic compounds | |
| NZ614547B2 (en) | Spirocyclic isoxazoline derivatives as antiparasitic agents | |
| HK1190392A (en) | Isoxazoline derivatives as antiparasitic agents |