CA2935089C - 9,9,10,10-tetrafluoro-9,10-dihydrophenanthrene hepatitis c virus inhibitor and application thereof - Google Patents
9,9,10,10-tetrafluoro-9,10-dihydrophenanthrene hepatitis c virus inhibitor and application thereof Download PDFInfo
- Publication number
- CA2935089C CA2935089C CA2935089A CA2935089A CA2935089C CA 2935089 C CA2935089 C CA 2935089C CA 2935089 A CA2935089 A CA 2935089A CA 2935089 A CA2935089 A CA 2935089A CA 2935089 C CA2935089 C CA 2935089C
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- Canada
- Prior art keywords
- alkyl
- compound
- tetrafluoro
- imidazol
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 241000711549 Hepacivirus C Species 0.000 title claims abstract description 56
- ZTJJUXMRRLYLMS-UHFFFAOYSA-N 9,9,10,10-tetrafluorophenanthrene Chemical compound C1=CC=C2C(F)(F)C(F)(F)C3=CC=CC=C3C2=C1 ZTJJUXMRRLYLMS-UHFFFAOYSA-N 0.000 title abstract description 4
- 239000003112 inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 240
- 150000003839 salts Chemical class 0.000 claims abstract description 54
- 239000012453 solvate Substances 0.000 claims abstract description 53
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 abstract description 46
- 239000000203 mixture Substances 0.000 abstract description 45
- 239000013078 crystal Substances 0.000 abstract description 32
- 239000000651 prodrug Substances 0.000 abstract description 32
- 229940002612 prodrug Drugs 0.000 abstract description 32
- 230000000694 effects Effects 0.000 abstract description 16
- 239000003814 drug Substances 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 5
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 description 165
- -1 amino, carboxyl Chemical group 0.000 description 147
- 238000006243 chemical reaction Methods 0.000 description 110
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 73
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 68
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 239000012071 phase Substances 0.000 description 57
- 238000013519 translation Methods 0.000 description 55
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 229910052736 halogen Inorganic materials 0.000 description 50
- 150000002367 halogens Chemical class 0.000 description 50
- 238000000034 method Methods 0.000 description 50
- 125000000753 cycloalkyl group Chemical group 0.000 description 47
- 125000003545 alkoxy group Chemical group 0.000 description 46
- 125000003118 aryl group Chemical group 0.000 description 43
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 42
- 125000001072 heteroaryl group Chemical group 0.000 description 40
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 37
- 125000004093 cyano group Chemical group *C#N 0.000 description 36
- 229910052739 hydrogen Inorganic materials 0.000 description 36
- 239000007858 starting material Substances 0.000 description 36
- 239000001257 hydrogen Substances 0.000 description 35
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 34
- 239000000047 product Substances 0.000 description 25
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 24
- 125000005256 alkoxyacyl group Chemical group 0.000 description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 22
- 125000005257 alkyl acyl group Chemical group 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 19
- 238000004440 column chromatography Methods 0.000 description 19
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- 125000003282 alkyl amino group Chemical group 0.000 description 16
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 16
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 15
- 125000004663 dialkyl amino group Chemical group 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- 125000004181 carboxyalkyl group Chemical group 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 102000014150 Interferons Human genes 0.000 description 12
- 108010050904 Interferons Proteins 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 208000015181 infectious disease Diseases 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 11
- 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 11
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 11
- 229940079322 interferon Drugs 0.000 description 11
- 125000001624 naphthyl group Chemical group 0.000 description 11
- 125000002971 oxazolyl group Chemical group 0.000 description 11
- 125000000168 pyrrolyl group Chemical group 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 125000000335 thiazolyl group Chemical group 0.000 description 11
- 125000001544 thienyl group Chemical group 0.000 description 11
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 239000012295 chemical reaction liquid Substances 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 10
- 125000001188 haloalkyl group Chemical group 0.000 description 9
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 229960004295 valine Drugs 0.000 description 9
- 239000004474 valine Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 7
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 125000002883 imidazolyl group Chemical group 0.000 description 7
- 125000001786 isothiazolyl group Chemical group 0.000 description 7
- 125000000842 isoxazolyl group Chemical group 0.000 description 7
- 125000004193 piperazinyl group Chemical group 0.000 description 7
- 125000003386 piperidinyl group Chemical group 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 125000003226 pyrazolyl group Chemical group 0.000 description 7
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 7
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 7
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 7
- 125000001425 triazolyl group Chemical group 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 208000019423 liver disease Diseases 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 125000001715 oxadiazolyl group Chemical group 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 5
- HEZJCIOLPSMDFR-UHFFFAOYSA-N 2,7-dibromo-9,9,10,10-tetrafluorophenanthrene Chemical compound C1=C(Br)C=C2C(F)(F)C(F)(F)C3=CC(Br)=CC=C3C2=C1 HEZJCIOLPSMDFR-UHFFFAOYSA-N 0.000 description 5
- HPBPNWPROCLLAA-UHFFFAOYSA-N 2-bromoethanone Chemical compound BrC[C]=O HPBPNWPROCLLAA-UHFFFAOYSA-N 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 5
- 101710172711 Structural protein Proteins 0.000 description 5
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 125000002541 furyl group Chemical group 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- NWPRXAIYBULIEI-RXMQYKEDSA-N (2s)-2-(methoxycarbonylamino)-3,3-dimethylbutanoic acid Chemical compound COC(=O)N[C@H](C(O)=O)C(C)(C)C NWPRXAIYBULIEI-RXMQYKEDSA-N 0.000 description 4
- PAISMPKJXOZRKI-UHNVWZDZSA-N (2s,3r)-3-methoxy-2-(methoxycarbonylamino)butanoic acid Chemical compound CO[C@H](C)[C@@H](C(O)=O)NC(=O)OC PAISMPKJXOZRKI-UHNVWZDZSA-N 0.000 description 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
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- 101710144111 Non-structural protein 3 Proteins 0.000 description 4
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- 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 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 125000004103 aminoalkyl group Chemical group 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000004966 cyanoalkyl group Chemical group 0.000 description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 4
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 4
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- 125000005945 imidazopyridyl group Chemical group 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 4
- 125000004971 nitroalkyl group Chemical group 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
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- 125000004076 pyridyl group Chemical group 0.000 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 description 4
- 229960000329 ribavirin Drugs 0.000 description 4
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- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
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- MYHSJJMNLDJMHK-UHFFFAOYSA-N 1-(7-bromo-9,9,10,10-tetrafluorophenanthren-2-yl)ethanone Chemical compound C(C)(=O)C1=CC=2C(C(C3=CC(=CC=C3C=2C=C1)Br)(F)F)(F)F MYHSJJMNLDJMHK-UHFFFAOYSA-N 0.000 description 2
- ULUNQYODBKLBOE-UHFFFAOYSA-N 2-(1h-pyrrol-2-yl)-1h-pyrrole Chemical compound C1=CNC(C=2NC=CC=2)=C1 ULUNQYODBKLBOE-UHFFFAOYSA-N 0.000 description 2
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C25/00—Compounds containing at least one halogen atom bound to a six-membered aromatic ring
- C07C25/18—Polycyclic aromatic halogenated hydrocarbons
- C07C25/22—Polycyclic aromatic halogenated hydrocarbons with condensed rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epidemiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310754318.4 | 2013-12-31 | ||
| CN201310754318 | 2013-12-31 | ||
| PCT/CN2014/095043 WO2015101215A1 (zh) | 2013-12-31 | 2014-12-26 | 9,9,10,10-四氟-9,10二氢菲类丙型肝炎病毒抑制剂及其应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2935089A1 CA2935089A1 (en) | 2015-07-09 |
| CA2935089C true CA2935089C (en) | 2018-11-27 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2935089A Expired - Fee Related CA2935089C (en) | 2013-12-31 | 2014-12-26 | 9,9,10,10-tetrafluoro-9,10-dihydrophenanthrene hepatitis c virus inhibitor and application thereof |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US9512108B2 (enExample) |
| EP (1) | EP3091010A4 (enExample) |
| JP (1) | JP2017536329A (enExample) |
| KR (1) | KR101857689B1 (enExample) |
| CN (2) | CN105873922B (enExample) |
| AU (1) | AU2014375584B2 (enExample) |
| CA (1) | CA2935089C (enExample) |
| TW (1) | TWI532735B (enExample) |
| WO (1) | WO2015101215A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107266424A (zh) * | 2016-04-07 | 2017-10-20 | 南京圣和药业股份有限公司 | 二氢菲类化合物及其制备方法 |
| CN108623569A (zh) * | 2017-03-21 | 2018-10-09 | 南京圣和药业股份有限公司 | 9,10-二氢菲类化合物的制备方法 |
| CN108623570A (zh) * | 2017-03-21 | 2018-10-09 | 南京圣和药业股份有限公司 | 9,10-二氢菲类化合物、其制备方法及用途 |
| CN108619102A (zh) * | 2017-03-21 | 2018-10-09 | 南京圣和药业股份有限公司 | 一种包含丙型肝炎病毒抑制剂的药物组合物及其制备方法 |
| CN108623568B (zh) * | 2017-03-21 | 2022-04-19 | 南京汇诚制药有限公司 | 9,10二氢菲类丙型肝炎病毒抑制剂的盐型及其制备 |
| CN109419806B (zh) * | 2017-08-23 | 2023-06-20 | 南京圣和药业股份有限公司 | 抗病毒组合物及其应用 |
| CN114890916A (zh) * | 2022-04-25 | 2022-08-12 | 常州吉恩药业有限公司 | 一种n-甲氧羰基-l-叔亮氨酸的制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19524230A1 (de) * | 1995-07-04 | 1997-01-09 | Hoechst Ag | Fluorierte Phenanthren-Derivate und ihre Verwendung in flüssigkristallinen Mischungen |
| US6455744B1 (en) * | 2001-01-23 | 2002-09-24 | Air Products And Chemicals, Inc. | Synthesis of vicinal difluoro aromatics and intermediates thereof |
| MX363732B (es) * | 2009-05-13 | 2019-04-01 | Gilead Pharmasset Llc Star | Compuestos antivirales. |
| TWI548629B (zh) * | 2010-11-17 | 2016-09-11 | 吉李德製藥公司 | 抗病毒化合物 |
| CA2845321A1 (en) * | 2011-08-24 | 2013-02-28 | Glaxosmithkline Llc | Combination treatments for hepatitis c |
-
2014
- 2014-12-26 CA CA2935089A patent/CA2935089C/en not_active Expired - Fee Related
- 2014-12-26 KR KR1020167011524A patent/KR101857689B1/ko not_active Expired - Fee Related
- 2014-12-26 WO PCT/CN2014/095043 patent/WO2015101215A1/zh not_active Ceased
- 2014-12-26 EP EP14876481.4A patent/EP3091010A4/en not_active Withdrawn
- 2014-12-26 AU AU2014375584A patent/AU2014375584B2/en not_active Ceased
- 2014-12-26 CN CN201480071487.0A patent/CN105873922B/zh active Active
- 2014-12-26 JP JP2016531709A patent/JP2017536329A/ja active Pending
- 2014-12-26 US US15/030,990 patent/US9512108B2/en not_active Expired - Fee Related
- 2014-12-29 CN CN201410835606.7A patent/CN104744444B/zh active Active
- 2014-12-31 TW TW103146591A patent/TWI532735B/zh not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CN105873922B (zh) | 2018-08-14 |
| CN105873922A (zh) | 2016-08-17 |
| KR20160058187A (ko) | 2016-05-24 |
| JP2017536329A (ja) | 2017-12-07 |
| CA2935089A1 (en) | 2015-07-09 |
| TW201524973A (zh) | 2015-07-01 |
| CN104744444B (zh) | 2019-02-26 |
| KR101857689B1 (ko) | 2018-05-14 |
| AU2014375584B2 (en) | 2017-11-09 |
| US9512108B2 (en) | 2016-12-06 |
| TWI532735B (zh) | 2016-05-11 |
| EP3091010A1 (en) | 2016-11-09 |
| CN104744444A (zh) | 2015-07-01 |
| EP3091010A4 (en) | 2017-10-04 |
| US20160297804A1 (en) | 2016-10-13 |
| WO2015101215A1 (zh) | 2015-07-09 |
| AU2014375584A1 (en) | 2016-07-07 |
| HK1222845A1 (zh) | 2017-07-14 |
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