KR20200023034A - 이속사졸 유도체 및 그의 제조방법 - Google Patents
이속사졸 유도체 및 그의 제조방법 Download PDFInfo
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- KR20200023034A KR20200023034A KR1020180099378A KR20180099378A KR20200023034A KR 20200023034 A KR20200023034 A KR 20200023034A KR 1020180099378 A KR1020180099378 A KR 1020180099378A KR 20180099378 A KR20180099378 A KR 20180099378A KR 20200023034 A KR20200023034 A KR 20200023034A
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- halogen
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- 238000002360 preparation method Methods 0.000 title description 18
- 150000002545 isoxazoles Chemical class 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 168
- -1 isoxazole derivative compound Chemical class 0.000 claims abstract description 56
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 claims abstract description 39
- 241000711573 Coronaviridae Species 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 208000001528 Coronaviridae Infections Diseases 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical group 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 28
- 150000002431 hydrogen Chemical class 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 230000002265 prevention Effects 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- WTDHULULXKLSOZ-UHFFFAOYSA-N hydroxylamine hydrochloride Substances Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 102000014150 Interferons Human genes 0.000 claims description 4
- 108010050904 Interferons Proteins 0.000 claims description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003242 anti bacterial agent Substances 0.000 claims description 4
- 229940088710 antibiotic agent Drugs 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229940079322 interferon Drugs 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 229960000329 ribavirin Drugs 0.000 claims description 4
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 4
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 claims description 4
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 claims description 4
- OFFWOVJBSQMVPI-RMLGOCCBSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O.N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 OFFWOVJBSQMVPI-RMLGOCCBSA-N 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- WCYJQVALWQMJGE-UHFFFAOYSA-M hydroxylammonium chloride Chemical compound [Cl-].O[NH3+] WCYJQVALWQMJGE-UHFFFAOYSA-M 0.000 claims description 3
- 229940113983 lopinavir / ritonavir Drugs 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 238000007363 ring formation reaction Methods 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- OEPAPHUXCPDJQJ-UHFFFAOYSA-N 3-(3-fluorophenyl)-4-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]-5-methyl-1,2-oxazole Chemical compound FC=1C=C(C=CC=1)C1=NOC(=C1CN1CCN(CC1)C1=C(C=CC=C1)OC)C OEPAPHUXCPDJQJ-UHFFFAOYSA-N 0.000 claims description 2
- ZQTIAFMHNKQESJ-UHFFFAOYSA-N 3-(3-fluorophenyl)-4-[[4-(3-methoxyphenyl)piperazin-1-yl]methyl]-5-methyl-1,2-oxazole Chemical compound FC=1C=C(C=CC=1)C1=NOC(=C1CN1CCN(CC1)C1=CC(=CC=C1)OC)C ZQTIAFMHNKQESJ-UHFFFAOYSA-N 0.000 claims description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 2
- ZUWWBGDJYNVVQE-UHFFFAOYSA-N 4-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]-5-methyl-3-[2-(trifluoromethyl)phenyl]-1,2-oxazole Chemical compound COC1=C(C=CC=C1)N1CCN(CC1)CC=1C(=NOC=1C)C1=C(C=CC=C1)C(F)(F)F ZUWWBGDJYNVVQE-UHFFFAOYSA-N 0.000 claims description 2
- UODBOBJWWSNXKQ-UHFFFAOYSA-N 4-[[4-(3,4-dichlorophenyl)piperazin-1-yl]methyl]-5-methyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazole Chemical compound ClC=1C=C(C=CC=1Cl)N1CCN(CC1)CC=1C(=NOC=1C)C1=C(C=CC=C1)OC(F)(F)F UODBOBJWWSNXKQ-UHFFFAOYSA-N 0.000 claims description 2
- UMGSBUVBYSKHRT-UHFFFAOYSA-N 4-[[4-(3,4-dichlorophenyl)piperazin-1-yl]methyl]-5-methyl-3-[2-(trifluoromethyl)phenyl]-1,2-oxazole Chemical compound ClC=1C=C(C=CC=1Cl)N1CCN(CC1)CC=1C(=NOC=1C)C1=C(C=CC=C1)C(F)(F)F UMGSBUVBYSKHRT-UHFFFAOYSA-N 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 239000012448 Lithium borohydride Substances 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- 239000004317 sodium nitrate Substances 0.000 claims description 2
- 235000010344 sodium nitrate Nutrition 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 229940102001 zinc bromide Drugs 0.000 claims description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims 2
- IARUJFTVLFXWHG-UHFFFAOYSA-N 4-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]-5-methyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazole Chemical compound COC1=C(C=CC=C1)N1CCN(CC1)CC=1C(=NOC=1C)C1=C(C=CC=C1)OC(F)(F)F IARUJFTVLFXWHG-UHFFFAOYSA-N 0.000 claims 1
- MFMAUOLXNQFJDX-UHFFFAOYSA-N 4-[[4-(3,4-dichlorophenyl)piperazin-1-yl]methyl]-3-(3-fluorophenyl)-5-methyl-1,2-oxazole Chemical compound ClC=1C=C(C=CC=1Cl)N1CCN(CC1)CC=1C(=NOC=1C)C1=CC(=CC=C1)F MFMAUOLXNQFJDX-UHFFFAOYSA-N 0.000 claims 1
- JIXUPVVVKGHXQW-UHFFFAOYSA-N 4-[[4-(3-methoxyphenyl)piperazin-1-yl]methyl]-5-methyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazole Chemical compound COC=1C=C(C=CC=1)N1CCN(CC1)CC=1C(=NOC=1C)C1=C(C=CC=C1)OC(F)(F)F JIXUPVVVKGHXQW-UHFFFAOYSA-N 0.000 claims 1
- YZXFFQIKXGQKPI-UHFFFAOYSA-N 4-[[4-(3-methoxyphenyl)piperazin-1-yl]methyl]-5-methyl-3-[2-(trifluoromethyl)phenyl]-1,2-oxazole Chemical compound COC=1C=C(C=CC=1)N1CCN(CC1)CC=1C(=NOC=1C)C1=C(C=CC=C1)C(F)(F)F YZXFFQIKXGQKPI-UHFFFAOYSA-N 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 17
- 239000000126 substance Substances 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 206010062106 Respiratory tract infection viral Diseases 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 description 35
- 238000003786 synthesis reaction Methods 0.000 description 34
- 238000005160 1H NMR spectroscopy Methods 0.000 description 33
- 239000007787 solid Substances 0.000 description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 230000000840 anti-viral effect Effects 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 13
- 208000015181 infectious disease Diseases 0.000 description 13
- 241000700605 Viruses Species 0.000 description 12
- 239000000651 prodrug Substances 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- 238000012360 testing method Methods 0.000 description 10
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 230000000241 respiratory effect Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 6
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 6
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- 241000315672 SARS coronavirus Species 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 description 6
- 230000003833 cell viability Effects 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
- 230000003013 cytotoxicity Effects 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000007505 plaque formation Effects 0.000 description 6
- 210000003501 vero cell Anatomy 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 5
- 125000000217 alkyl group Chemical group 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000011156 evaluation Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
- 208000023504 respiratory system disease Diseases 0.000 description 5
- CUWBQOYKGKOIBX-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-methyl-1,2-oxazole-4-carbaldehyde Chemical compound FC=1C=C(C=CC=1)C1=NOC(=C1C=O)C CUWBQOYKGKOIBX-UHFFFAOYSA-N 0.000 description 4
- 241000004176 Alphacoronavirus Species 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 231100000517 death Toxicity 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000002962 plaque-reduction assay Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- CSNRRHDXCFAEBP-UHFFFAOYSA-N 5-methyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazole-4-carbaldehyde Chemical compound CC1=C(C(=NO1)C1=C(C=CC=C1)OC(F)(F)F)C=O CSNRRHDXCFAEBP-UHFFFAOYSA-N 0.000 description 3
- WYFGOURWVGFDCJ-UHFFFAOYSA-N 5-methyl-3-[2-(trifluoromethyl)phenyl]-1,2-oxazole-4-carbaldehyde Chemical compound O=CC1=C(C)ON=C1C1=CC=CC=C1C(F)(F)F WYFGOURWVGFDCJ-UHFFFAOYSA-N 0.000 description 3
- 241000271566 Aves Species 0.000 description 3
- 241000008904 Betacoronavirus Species 0.000 description 3
- 241000288673 Chiroptera Species 0.000 description 3
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 3
- 208000025370 Middle East respiratory syndrome Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 241001493065 dsRNA viruses Species 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 3
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020180099378A KR20200023034A (ko) | 2018-08-24 | 2018-08-24 | 이속사졸 유도체 및 그의 제조방법 |
| PCT/KR2018/010557 WO2020040343A1 (fr) | 2018-08-24 | 2018-09-10 | Dérivés d'isoxazole et leurs procédés de préparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020180099378A KR20200023034A (ko) | 2018-08-24 | 2018-08-24 | 이속사졸 유도체 및 그의 제조방법 |
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| KR20200023034A true KR20200023034A (ko) | 2020-03-04 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR1020180099378A KR20200023034A (ko) | 2018-08-24 | 2018-08-24 | 이속사졸 유도체 및 그의 제조방법 |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR20200023034A (fr) |
| WO (1) | WO2020040343A1 (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112618547B (zh) * | 2020-12-23 | 2022-02-11 | 中国医学科学院医药生物技术研究所 | 一种喹啉类化合物在制备抗冠状病毒制剂中的应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3819037A1 (de) * | 1988-06-04 | 1989-12-14 | Hoechst Ag | 2,4-disubstituierte oxazol-derivate, verfahren zu ihrer herstellung sowie ihre verwendung als therapiemittel gegen krankheiten, die durch rhinoviren verursacht werden |
| US6319937B1 (en) * | 1998-11-18 | 2001-11-20 | Dupont Pharmaceuticals Company | Isoxazoline fibrinogen receptor antagonists |
| RU2243226C2 (ru) * | 1999-06-22 | 2004-12-27 | НьюроСёрч А/С | Новые производные бензимидазола и содержащие эти соединения фармацевтические композиции |
| KR101007469B1 (ko) * | 2006-12-22 | 2011-01-12 | 성균관대학교산학협력단 | 사스 코로나 바이러스의 ｒｎａ 유사매듭구조에 결합하여 리보솜 틀 이동을 억제하는 호모피페라진계 화합물 |
| CA2951924A1 (fr) * | 2014-06-12 | 2015-12-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Composes heterocycliques et leurs methodes d'utilisation |
| US10844051B2 (en) * | 2015-07-22 | 2020-11-24 | The Royal Institution For The Advancement Of Learning/Mcgill University | Substituted oxazoles for the treatment of cancer |
-
2018
- 2018-08-24 KR KR1020180099378A patent/KR20200023034A/ko unknown
- 2018-09-10 WO PCT/KR2018/010557 patent/WO2020040343A1/fr active Application Filing
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| Publication number | Publication date |
|---|---|
| WO2020040343A1 (fr) | 2020-02-27 |
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