TW201722965A - 用於抗菌應用之化合物 - Google Patents

Info

Publication number

TW201722965A

TW201722965A TW105125824A TW105125824A TW201722965A TW 201722965 A TW201722965 A TW 201722965A TW 105125824 A TW105125824 A TW 105125824A TW 105125824 A TW105125824 A TW 105125824A TW 201722965 A TW201722965 A TW 201722965A

Authority

TW

Taiwan

Prior art keywords

methyl

amino

pyrazino

fluoro

thiazin

Prior art date

2015-08-16

Links

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• Global Dossier
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 192
• 230000000844 anti-bacterial effect Effects 0.000 title abstract description 6
• 150000003839 salts Chemical class 0.000 claims abstract description 86
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
• 208000035143 Bacterial infection Diseases 0.000 claims abstract description 19
• 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 19
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 509
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 358
• -1 (6-fluoro-3-methoxyquinoxalin-5-yl)methyl Chemical group 0.000 claims description 191
• 239000000203 mixture Substances 0.000 claims description 155
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 122
• 229910052736 halogen Inorganic materials 0.000 claims description 100
• 150000002367 halogens Chemical class 0.000 claims description 98
• VUHWWMUKMLLBIC-UHFFFAOYSA-N 4H-pyrazino[2,3-b][1,4]thiazin-3-one Chemical compound O=C1CSc2nccnc2N1 VUHWWMUKMLLBIC-UHFFFAOYSA-N 0.000 claims description 92
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 76
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 68
• QQWWDSRPZBNPEE-UHFFFAOYSA-N 4H-pyrazino[2,3-b][1,4]oxazin-3-one Chemical compound C1=CN=C2NC(=O)COC2=N1 QQWWDSRPZBNPEE-UHFFFAOYSA-N 0.000 claims description 64
• 238000009472 formulation Methods 0.000 claims description 39
• 229910052757 nitrogen Inorganic materials 0.000 claims description 38
• FBXGQDUVJBKEAJ-UHFFFAOYSA-N 4h-oxazin-3-one Chemical compound O=C1CC=CON1 FBXGQDUVJBKEAJ-UHFFFAOYSA-N 0.000 claims description 30
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 29
• GAGAICHLGQDUTL-UHFFFAOYSA-N 4h-thiazin-3-one Chemical compound O=C1CC=CSN1 GAGAICHLGQDUTL-UHFFFAOYSA-N 0.000 claims description 29
• 125000001072 heteroaryl group Chemical group 0.000 claims description 27
• 239000003814 drug Substances 0.000 claims description 25
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 25
• 125000000217 alkyl group Chemical group 0.000 claims description 23
• 125000003118 aryl group Chemical group 0.000 claims description 23
• 125000000623 heterocyclic group Chemical group 0.000 claims description 23
• 229910052799 carbon Inorganic materials 0.000 claims description 22
• 229910052717 sulfur Inorganic materials 0.000 claims description 22
• 239000002502 liposome Substances 0.000 claims description 21
• 125000005842 heteroatom Chemical group 0.000 claims description 20
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 150000001412 amines Chemical class 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 18
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 16
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
• 241000124008 Mammalia Species 0.000 claims description 14
• XEKAWZARUWARND-UHFFFAOYSA-N 6h-oxazin-3-one Chemical compound O=C1NOCC=C1 XEKAWZARUWARND-UHFFFAOYSA-N 0.000 claims description 12
• 125000003545 alkoxy group Chemical group 0.000 claims description 12
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 9
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 9
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 8
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 6
• KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 229910052731 fluorine Inorganic materials 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 claims description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
• 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 claims description 4
• APSYYKGWNWKKOC-UHFFFAOYSA-N quinoxaline-5-carboxamide Chemical compound C1=CN=C2C(C(=O)N)=CC=CC2=N1 APSYYKGWNWKKOC-UHFFFAOYSA-N 0.000 claims description 4
• 238000006467 substitution reaction Methods 0.000 claims description 4
• NWJPHMZRFXIYDZ-UHFFFAOYSA-N 4H-pyrazino[2,3-b][1,4]thiazine Chemical compound N1C=CSc2nccnc12 NWJPHMZRFXIYDZ-UHFFFAOYSA-N 0.000 claims description 3
• HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 claims description 2
• MAXWBIKKKHOPJK-UHFFFAOYSA-N 6-[[2-[5-(6-fluoro-3-methoxyquinoxalin-5-yl)pyrimidin-2-yl]ethylamino]methyl]-4H-pyrazino[2,3-b][1,4]oxazin-3-one Chemical compound COC1=NC2=C(C(F)=CC=C2N=C1)C1=CN=C(CCNCC2=CN=C3OCC(=O)NC3=N2)N=C1 MAXWBIKKKHOPJK-UHFFFAOYSA-N 0.000 claims description 2
• HIKVNNMXGRTOOU-UHFFFAOYSA-N 6-[[2-[5-(6-fluoro-3-methoxyquinoxalin-5-yl)pyrimidin-2-yl]ethylamino]methyl]-4H-pyrazino[2,3-b][1,4]thiazin-3-one Chemical compound COC1=NC2=C(C(F)=CC=C2N=C1)C1=CN=C(CCNCC2=CN=C3SCC(=O)NC3=N2)N=C1 HIKVNNMXGRTOOU-UHFFFAOYSA-N 0.000 claims description 2
• BJKLLLMPABHQKY-PGRDOPGGSA-N 6-[[[(3S,4S)-1-[2-[2-[2-(dimethylamino)ethoxy]-7-fluoroquinolin-8-yl]ethyl]-4-hydroxypyrrolidin-3-yl]methylamino]methyl]-4H-pyrazino[2,3-b][1,4]thiazin-3-one Chemical compound CN(C)CCOC1=NC2=C(CCN3C[C@@H](O)[C@@H](CNCC4=CN=C5SCC(=O)NC5=N4)C3)C(F)=CC=C2C=C1 BJKLLLMPABHQKY-PGRDOPGGSA-N 0.000 claims description 2
• RGTAMOMTYXYTEV-UHFFFAOYSA-N 7-fluoro-2-methoxyquinoline Chemical compound C1=CC(F)=CC2=NC(OC)=CC=C21 RGTAMOMTYXYTEV-UHFFFAOYSA-N 0.000 claims description 2
• XUGPJEFJSYQHII-ULFGMLNVSA-N COC1=NC2=C(CN[C@H]3CC[C@@H](C[C@H]3O)NCC3=CN=C4OCC(=O)NC4=N3)C(Cl)=CC=C2N=C1 Chemical compound COC1=NC2=C(CN[C@H]3CC[C@@H](C[C@H]3O)NCC3=CN=C4OCC(=O)NC4=N3)C(Cl)=CC=C2N=C1 XUGPJEFJSYQHII-ULFGMLNVSA-N 0.000 claims description 2
• 229930192474 thiophene Natural products 0.000 claims description 2
• UIRSLBDCOYTZPH-UHFFFAOYSA-N 4h-1,4-thiazin-3-one Chemical compound O=C1CSC=CN1 UIRSLBDCOYTZPH-UHFFFAOYSA-N 0.000 claims 2
• 125000006693 (C2-C9) heterocyclyl group Chemical group 0.000 claims 1
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
• LAQJGAKLLZAETL-UHFFFAOYSA-N 2h-pyrazin-3-one Chemical compound O=C1CN=CC=N1 LAQJGAKLLZAETL-UHFFFAOYSA-N 0.000 claims 1
• ALAWSALYSPGPLF-UHFFFAOYSA-N 6-[[2-[5-(6-fluoro-3-methoxyquinoxalin-5-yl)-1,3-thiazol-2-yl]ethylamino]methyl]-4H-pyrazino[2,3-b][1,4]thiazin-3-one Chemical compound COC1=NC2=C(C3=CN=C(CCNCC4=CN=C5SCC(=O)NC5=N4)S3)C(F)=CC=C2N=C1 ALAWSALYSPGPLF-UHFFFAOYSA-N 0.000 claims 1
• JSICMVAYZHKUJL-IFXJQAMLSA-N 6-[[[(3S,4S)-1-[2-(8-chloro-2-methyl-[1,3]oxazolo[4,5-f]quinolin-9-yl)ethyl]-4-hydroxypyrrolidin-3-yl]methylamino]methyl]-4H-pyrazino[2,3-b][1,4]oxazin-3-one Chemical compound CC1=NC2=C(O1)C=CC1=NC=C(Cl)C(CCN3C[C@@H](O)[C@@H](CNCC4=CN=C5OCC(=O)NC5=N4)C3)=C21 JSICMVAYZHKUJL-IFXJQAMLSA-N 0.000 claims 1
• WQKHERPPDYPMNX-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(Cl)=CC=C21 WQKHERPPDYPMNX-UHFFFAOYSA-N 0.000 claims 1
• GARYIHNTRVDSMG-DPMMWBKBSA-N COC1=NC2=C(CN[C@@H]3CC[C@@H](NCC4=CN=C5OCC(=O)NC5=N4)[C@@H](O)C3)C(Cl)=CC(F)=C2C=C1 Chemical compound COC1=NC2=C(CN[C@@H]3CC[C@@H](NCC4=CN=C5OCC(=O)NC5=N4)[C@@H](O)C3)C(Cl)=CC(F)=C2C=C1 GARYIHNTRVDSMG-DPMMWBKBSA-N 0.000 claims 1
• JXMBXMUOPSOMTL-KEQGGVEFSA-N COC1=NC2=C(CN[C@@H]3CC[C@H](CNCC4=CN=C5OCC(=O)NC5=N4)[C@@H]3O)C(F)=CC=C2C=C1 Chemical compound COC1=NC2=C(CN[C@@H]3CC[C@H](CNCC4=CN=C5OCC(=O)NC5=N4)[C@@H]3O)C(F)=CC=C2C=C1 JXMBXMUOPSOMTL-KEQGGVEFSA-N 0.000 claims 1
• SWVCBDOUOYDFFF-ZOCIIQOWSA-N COC1=NC2=C(CN[C@H]3CC[C@@H](C[C@H]3O)NCC3=CN=C4OCC(=O)NC4=N3)C(Cl)=CC=C2C=C1 Chemical compound COC1=NC2=C(CN[C@H]3CC[C@@H](C[C@H]3O)NCC3=CN=C4OCC(=O)NC4=N3)C(Cl)=CC=C2C=C1 SWVCBDOUOYDFFF-ZOCIIQOWSA-N 0.000 claims 1
• WHEYYJDDQCYFPA-FASAQXTFSA-N COC1=NC2=C(CN[C@H]3CC[C@@H](C[C@H]3O)NCC3=CN=C4OCC(=O)NC4=N3)C(F)=CC(OC)=C2C=C1 Chemical compound COC1=NC2=C(CN[C@H]3CC[C@@H](C[C@H]3O)NCC3=CN=C4OCC(=O)NC4=N3)C(F)=CC(OC)=C2C=C1 WHEYYJDDQCYFPA-FASAQXTFSA-N 0.000 claims 1
• PYKPDIXAWFORPI-XZOAIXRZSA-N COC1=NC2=C(CO[C@H]3CC[C@@H](C[C@H]3N)NCC3=CN=C4SCC(=O)NC4=N3)C(F)=CC=C2N=C1 Chemical compound COC1=NC2=C(CO[C@H]3CC[C@@H](C[C@H]3N)NCC3=CN=C4SCC(=O)NC4=N3)C(F)=CC=C2N=C1 PYKPDIXAWFORPI-XZOAIXRZSA-N 0.000 claims 1
• GTDCPPVUYLTVLZ-HNNXBMFYSA-N O=C1CSC2=NC=C(CNC[C@@H]3CCN(CCN4C(=O)C=NC5=C4C4=C(OCCO4)C=C5)C3)N=C2N1 Chemical compound O=C1CSC2=NC=C(CNC[C@@H]3CCN(CCN4C(=O)C=NC5=C4C4=C(OCCO4)C=C5)C3)N=C2N1 GTDCPPVUYLTVLZ-HNNXBMFYSA-N 0.000 claims 1
• MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 claims 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 49
• 229940088710 antibiotic agent Drugs 0.000 abstract description 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 344
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 201
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 174
• 239000000243 solution Substances 0.000 description 167
• 239000007787 solid Substances 0.000 description 148
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 109
• 238000006243 chemical reaction Methods 0.000 description 97
• 235000019439 ethyl acetate Nutrition 0.000 description 96
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 83
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 82
• 239000000047 product Substances 0.000 description 66
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 60
• 239000011541 reaction mixture Substances 0.000 description 59
• 238000005160 1H NMR spectroscopy Methods 0.000 description 56
• 239000007858 starting material Substances 0.000 description 55
• 238000005481 NMR spectroscopy Methods 0.000 description 54
• 238000001914 filtration Methods 0.000 description 45
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 41
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 40
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 36
• 239000012044 organic layer Substances 0.000 description 36
• 150000001204 N-oxides Chemical class 0.000 description 35
• 239000012453 solvate Substances 0.000 description 35
• 239000000706 filtrate Substances 0.000 description 33
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 30
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 30
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 30
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
• 239000011734 sodium Substances 0.000 description 30
• 239000000460 chlorine Substances 0.000 description 26
• 239000012043 crude product Substances 0.000 description 25
• 229920006395 saturated elastomer Polymers 0.000 description 23
• 239000002904 solvent Substances 0.000 description 23
• 230000000694 effects Effects 0.000 description 22
• 239000000463 material Substances 0.000 description 22
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
• 125000004432 carbon atom Chemical group C* 0.000 description 20
• 239000012535 impurity Substances 0.000 description 20
• 238000003756 stirring Methods 0.000 description 19
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 19
• 239000000725 suspension Substances 0.000 description 18
• 229940079593 drug Drugs 0.000 description 17
• 239000004094 surface-active agent Substances 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• 239000012267 brine Substances 0.000 description 16
• 150000002632 lipids Chemical class 0.000 description 16
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 238000004458 analytical method Methods 0.000 description 15
• 230000008569 process Effects 0.000 description 15
• 239000004698 Polyethylene Substances 0.000 description 14
• 239000012074 organic phase Substances 0.000 description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• 239000012458 free base Substances 0.000 description 12
• 239000001257 hydrogen Substances 0.000 description 12
• 239000010410 layer Substances 0.000 description 12
• BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 description 12
• 230000002829 reductive effect Effects 0.000 description 12
• 239000002002 slurry Substances 0.000 description 12
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 11
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
• 229910000420 cerium oxide Inorganic materials 0.000 description 11
• 244000005700 microbiome Species 0.000 description 11
• 239000002245 particle Substances 0.000 description 11
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 10
• 230000015572 biosynthetic process Effects 0.000 description 10
• WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Substances O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
• 150000003904 phospholipids Chemical class 0.000 description 10
• 238000002360 preparation method Methods 0.000 description 10
• 206010057190 Respiratory tract infections Diseases 0.000 description 9
• 239000003242 anti bacterial agent Substances 0.000 description 9
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 9
• 239000000843 powder Substances 0.000 description 9
• 238000010898 silica gel chromatography Methods 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
• 239000007864 aqueous solution Substances 0.000 description 8
• 239000002585 base Substances 0.000 description 8
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 8
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 8
• 238000004440 column chromatography Methods 0.000 description 8
• 239000013058 crude material Substances 0.000 description 8
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