JP6487547B2 - リボシドの調製のための方法 - Google Patents
リボシドの調製のための方法 Download PDFInfo
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- JP6487547B2 JP6487547B2 JP2017520934A JP2017520934A JP6487547B2 JP 6487547 B2 JP6487547 B2 JP 6487547B2 JP 2017520934 A JP2017520934 A JP 2017520934A JP 2017520934 A JP2017520934 A JP 2017520934A JP 6487547 B2 JP6487547 B2 JP 6487547B2
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- 238000000034 method Methods 0.000 title claims description 190
- 238000002360 preparation method Methods 0.000 title description 76
- 150000008223 ribosides Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 482
- 239000011541 reaction mixture Substances 0.000 claims description 207
- 239000003795 chemical substances by application Substances 0.000 claims description 85
- 239000007822 coupling agent Substances 0.000 claims description 74
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical group [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 claims description 52
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 38
- IWCVDCOJSPWGRW-UHFFFAOYSA-M magnesium;benzene;chloride Chemical group [Mg+2].[Cl-].C1=CC=[C-]C=C1 IWCVDCOJSPWGRW-UHFFFAOYSA-M 0.000 claims description 34
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical group C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 32
- 239000000654 additive Substances 0.000 claims description 31
- 230000000996 additive effect Effects 0.000 claims description 27
- 239000000126 substance Substances 0.000 claims description 25
- CQRPUKWAZPZXTO-UHFFFAOYSA-M magnesium;2-methylpropane;chloride Chemical compound [Mg+2].[Cl-].C[C-](C)C CQRPUKWAZPZXTO-UHFFFAOYSA-M 0.000 claims description 23
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 23
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 16
- DBTNVRCCIDISMV-UHFFFAOYSA-L lithium;magnesium;propane;dichloride Chemical compound [Li+].[Mg+2].[Cl-].[Cl-].C[CH-]C DBTNVRCCIDISMV-UHFFFAOYSA-L 0.000 claims description 10
- 238000011068 loading method Methods 0.000 claims description 8
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 claims description 7
- YCCXQARVHOPWFJ-UHFFFAOYSA-M magnesium;ethane;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C YCCXQARVHOPWFJ-UHFFFAOYSA-M 0.000 claims description 6
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 claims description 5
- UGVPKMAWLOMPRS-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].CC[CH2-] UGVPKMAWLOMPRS-UHFFFAOYSA-M 0.000 claims description 5
- RYEXTBOQKFUPOE-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].CC[CH2-] RYEXTBOQKFUPOE-UHFFFAOYSA-M 0.000 claims description 5
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 claims description 4
- NIXOIRLDFIPNLJ-UHFFFAOYSA-M magnesium;benzene;bromide Chemical compound [Mg+2].[Br-].C1=CC=[C-]C=C1 NIXOIRLDFIPNLJ-UHFFFAOYSA-M 0.000 claims 1
- -1 n - propyl Chemical group 0.000 description 294
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 199
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 184
- 239000000203 mixture Substances 0.000 description 158
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 137
- 239000000243 solution Substances 0.000 description 125
- 238000005481 NMR spectroscopy Methods 0.000 description 112
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 112
- 125000006239 protecting group Chemical group 0.000 description 102
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 100
- 238000006243 chemical reaction Methods 0.000 description 100
- 125000000217 alkyl group Chemical group 0.000 description 94
- 235000019439 ethyl acetate Nutrition 0.000 description 85
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 84
- 239000002904 solvent Substances 0.000 description 81
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 77
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 73
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 68
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 67
- 229910052799 carbon Inorganic materials 0.000 description 65
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 61
- 125000004432 carbon atom Chemical group C* 0.000 description 60
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
- 239000000047 product Substances 0.000 description 53
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 52
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 52
- 125000000623 heterocyclic group Chemical group 0.000 description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 47
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 45
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 45
- 239000002585 base Substances 0.000 description 44
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 42
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 42
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 42
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- 239000002841 Lewis acid Substances 0.000 description 39
- 229910052739 hydrogen Inorganic materials 0.000 description 39
- 150000007517 lewis acids Chemical class 0.000 description 39
- 239000007787 solid Substances 0.000 description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 33
- 238000004519 manufacturing process Methods 0.000 description 33
- 238000010898 silica gel chromatography Methods 0.000 description 33
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 32
- 125000003118 aryl group Chemical group 0.000 description 32
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 31
- 239000012044 organic layer Substances 0.000 description 31
- 239000002253 acid Substances 0.000 description 29
- 150000001721 carbon Chemical group 0.000 description 28
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 26
- 239000002777 nucleoside Substances 0.000 description 26
- 238000003756 stirring Methods 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 25
- 229910052757 nitrogen Inorganic materials 0.000 description 25
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 24
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 24
- 229940011051 isopropyl acetate Drugs 0.000 description 24
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 24
- 229920006395 saturated elastomer Polymers 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 22
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 22
- 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 21
- 239000007848 Bronsted acid Substances 0.000 description 21
- 229960000583 acetic acid Drugs 0.000 description 21
- 235000019253 formic acid Nutrition 0.000 description 21
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 20
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 20
- 125000000304 alkynyl group Chemical group 0.000 description 20
- 239000011780 sodium chloride Substances 0.000 description 20
- 229940125904 compound 1 Drugs 0.000 description 19
- 238000004128 high performance liquid chromatography Methods 0.000 description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 19
- 239000010410 layer Substances 0.000 description 19
- 239000011777 magnesium Substances 0.000 description 19
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 19
- 241001115402 Ebolavirus Species 0.000 description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 18
- 238000001914 filtration Methods 0.000 description 18
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 18
- 125000003342 alkenyl group Chemical group 0.000 description 17
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 17
- 230000000269 nucleophilic effect Effects 0.000 description 17
- 150000003833 nucleoside derivatives Chemical class 0.000 description 17
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical group C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 16
- 239000012043 crude product Substances 0.000 description 16
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 15
- 229910052760 oxygen Inorganic materials 0.000 description 15
- 229940002612 prodrug Drugs 0.000 description 15
- 239000000651 prodrug Substances 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- KTQKOGBTMNDCFG-UHFFFAOYSA-N tert-butyl(diphenyl)silicon Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)C1=CC=CC=C1 KTQKOGBTMNDCFG-UHFFFAOYSA-N 0.000 description 15
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 14
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 14
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 14
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 239000012351 deprotecting agent Substances 0.000 description 14
- 238000002953 preparative HPLC Methods 0.000 description 14
- 239000002002 slurry Substances 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 13
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 13
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 13
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 229910052717 sulfur Inorganic materials 0.000 description 12
- 0 *C[C@]([C@@]([C@]1*)O)OC1(*)c1ccc2[n]1ncnc2N Chemical compound *C[C@]([C@@]([C@]1*)O)OC1(*)c1ccc2[n]1ncnc2N 0.000 description 11
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 11
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-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
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 11
- 150000002596 lactones Chemical class 0.000 description 11
- 229910052749 magnesium Inorganic materials 0.000 description 11
- 239000003607 modifier Substances 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- CSURKLFFMMBEFL-YDIHDLSKSA-N 2-ethylbutyl (2s)-2-[[(4-nitrophenoxy)-phenoxyphosphoryl]amino]propanoate Chemical compound C=1C=C([N+]([O-])=O)C=CC=1OP(=O)(N[C@@H](C)C(=O)OCC(CC)CC)OC1=CC=CC=C1 CSURKLFFMMBEFL-YDIHDLSKSA-N 0.000 description 10
- ZEBGLCLVPCOXIV-UHFFFAOYSA-N 7-iodopyrrolo[2,1-f][1,2,4]triazin-4-amine Chemical compound NC1=NC=NN2C(I)=CC=C12 ZEBGLCLVPCOXIV-UHFFFAOYSA-N 0.000 description 10
- 125000002947 alkylene group Chemical group 0.000 description 10
- 229910052786 argon Inorganic materials 0.000 description 10
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 10
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 10
- 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 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
- ONOZPOGRUBSLQA-UHFFFAOYSA-N 4-(2-methylbutan-2-yl)phenol;2-phenylphenol Chemical group CCC(C)(C)C1=CC=C(O)C=C1.OC1=CC=CC=C1C1=CC=CC=C1 ONOZPOGRUBSLQA-UHFFFAOYSA-N 0.000 description 9
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 9
- BRDWIEOJOWJCLU-LTGWCKQJSA-N GS-441524 Chemical compound C=1C=C2C(N)=NC=NN2C=1[C@]1(C#N)O[C@H](CO)[C@@H](O)[C@H]1O BRDWIEOJOWJCLU-LTGWCKQJSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000003710 aryl alkyl group Chemical group 0.000 description 9
- 239000012267 brine Substances 0.000 description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 125000004452 carbocyclyl group Chemical group 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- 125000004404 heteroalkyl group Chemical group 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- 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 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 239000011261 inert gas Substances 0.000 description 9
- 125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 9
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 9
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 125000001424 substituent group Chemical group 0.000 description 9
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 8
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical group COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 8
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 8
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Classifications
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/14—Pyrrolo-pyrimidine radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H7/00—Compounds containing non-saccharide radicals linked to saccharide radicals by a carbon-to-carbon bond
- C07H7/06—Heterocyclic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H9/00—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical
- C07H9/02—Compounds containing a hetero ring sharing at least two hetero atoms with a saccharide radical the hetero ring containing only oxygen as ring hetero atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
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- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Description
本発明は、一般的に、フィロウイルス科(Filoviridae)ウイルス感染症を処置するための方法および化合物、特にエボラウイルス、マールブルグウイルスおよびクエバウイルスを処置するための方法およびヌクレオシドに関する。
フィロウイルス(例えば、エボラウイルス(EBOV)およびマールブルグウイルス(MARV))は、中でも、最も致命的で、破壊性のあるウイルスである。これらのウイルスは、ヒトおよび非ヒト霊長類(例えば、サル、ゴリラ、およびチンパンジー)において、重症の、多くの場合、致死性のウイルス性出血熱を引き起こす。フィロウイルスは、これらがエアゾール剤の散布および武器化のための能力を有することから、可能な生物兵器として特に懸念されている。
フィロウイルス科感染症を処置するための新規の治療剤の重要性を考慮して、リボシド、リン酸リボシドおよびプロドラッグを生成する新規の効率的な方法が必要とされる。
一部の実施形態では、本発明は、式Vの化合物:
式Vの化合物を作製する方法は、カップリング剤、ハロシラン、式VIの化合物:
I.定義
別途述べられていない限り、以下の用語および句は、本明細書で使用する場合、以下の意味を有することを意図する:
II.化合物の調製
A.ヨード−塩基を介したヌクレオシドの調製
式Vの化合物を作製する方法は、カップリング剤、ハロシラン、式VIの化合物:
B.シアノヌクレオシドの調製
C.プロドラッグ部分の添加
一部の実施形態では、式VIIIの化合物は、
D.結晶化誘起動的分割による式X−bの調製
(実施例1)
(2S)−エチル2−(クロロ(フェノキシ)ホスホリルアミノ)プロパノエート(クロリデートA)
(実施例2)
(2S)−2−エチルブチル2−(クロロ(フェノキシ)ホスホリルアミノ)プロパノエート(クロリデートB)
(実施例3)
(2S)−イソプロピル2−(クロロ(フェノキシ)ホスホリルアミノ)プロパノエート(クロリデートC)
(実施例4)
(2R,3R,4S,5R)−2−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−3,4−ジヒドロキシ−5−(ヒドロキシメチル)テトラヒドロフラン−2−カルボニトリル(化合物1)
(実施例4−a)
(2R,3R,4S,5R)−2−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−3,4−ジヒドロキシ−5−(ヒドロキシメチル)テトラヒドロフラン−2−カルボニトリル(化合物1)
LaCl3−2LiClを使用した(3R,4R,5R)−2−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス(ベンジルオキシ)−5−((ベンジルオキシ)メチル)テトラヒドロフラン−2−オールの調製
反応を2M HCl(53mL)でクエンチし、混合物を約15℃に温めた。iPrOAc(38mL)を加え、有機相および水相を分離した。下側の水層を放出し、上側の有機層を、2.5重量%のNaHCO3(53mL)、2.5重量%のNaHCO3(53mL)、および10重量%のNaCl(53mL)で順次洗浄した。
CeCl3を使用した(3R,4R,5R)−2−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス(ベンジルオキシ)−5−((ベンジルオキシ)メチル)テトラヒドロフラン−2−オールの調製
CeCl3およびiPrMgCl−LiClを使用した(3R,4R,5R)−2−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス(ベンジルオキシ)−5−((ベンジルオキシ)メチル)テトラヒドロフラン−2−オールの調製
YCl3を使用した(3R,4R,5R)−2−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス(ベンジルオキシ)−5−((ベンジルオキシ)メチル)テトラヒドロフラン−2−オールの調製
NdCl3を使用した(3R,4R,5R)−2−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス(ベンジルオキシ)−5−((ベンジルオキシ)メチル)テトラヒドロフラン−2−オールの調製
(2R,3R,4R,5R)−2−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス(ベンジルオキシ)−5−((ベンジルオキシ)メチル)テトラヒドロフラン−2−カルボニトリルの調製
フローケミストリーを介した、(2R,3R,4R,5R)−2−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス(ベンジルオキシ)−5−((ベンジルオキシ)メチル)テトラヒドロフラン−2−カルボニトリルの調製
(2R,3R,4S,5R)−2−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−3,4−ジヒドロキシ−5−(ヒドロキシメチル)テトラヒドロフラン−2−カルボニトリルの調製
(実施例5)
(2R,3R,4R,5R)−2−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−3−フルオロ−4−ヒドロキシ−5−(ヒドロキシメチル)テトラヒドロフラン−2−カルボニトリル(化合物2)
(実施例6)
(2R,3R,4R,5S)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−4−フルオロ−2−(ヒドロキシメチル)−5−メチルテトラヒドロフラン−3−オール(化合物3)
(実施例7)
(2S)−イソプロピル2−(((((2R,3R,4R,5S)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−4−フルオロ−3−ヒドロキシ−5−メチルテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(化合物4)
(実施例8)
(2S)−エチル2−(((((2R,3R,4R,5S)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−4−フルオロ−3−ヒドロキシ−5−メチルテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(化合物5)
(実施例9)
((2R,3R,4R,5S)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−4−フルオロ−3−ヒドロキシ−5−メチルテトラヒドロフラン−2−イル)メチル四水素トリホスフェート(化合物6)
(実施例10)
(2R,3R,5S)−2−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−3−ヒドロキシ−5−(ヒドロキシメチル)−テトラヒドロフラン−2−カルボニトリル(化合物7)
(実施例11)
(2S)−イソプロピル2−((((2R,3S,4R,5R)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)−ホスホリルアミノ)プロパノエート(化合物8)
(実施例12)
(2S)−2−エチルブチル2−((((2R,3S,4R,5R)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリルアミノ)プロパノエート(化合物9)
手順2
(S)と(R)ジアステレオマーの分離
(実施例13)
(2S)−エチル2−((((2R,3S,4R,5R)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリルアミノ)プロパノエート(化合物10)
手順1。クロリデートAを介した調製
手順2。ニトロ−ベンゼン化合物Lを介した調製
(実施例14)
(2S)−エチル2−((((2R,3R,4R,5R)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−5−シアノ−4−フルオロ−3−ヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリルアミノ)プロパノエート(化合物11)
(実施例15)
(2S,2’S)−ジエチル2,2’−((((2R,3S,4R,5R)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)ホスホリル)ビス(アザンジイル)ジプロパノエート(化合物12)
(実施例16)
(2S,3R,4S,5R)−2−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−2−エチニル−5−(ヒドロキシメチル)テトラヒドロフラン−3,4−ジオール(化合物13)
(実施例17)
(2R,3R,4R)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−1,3,4−トリス(ベンジルオキシ)ヘキサン−2,5−ジオール(化合物14)
(実施例18)
S,S’−2,2’−((((2R,3S,4R,5R)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)ホスホリル)ビス(オキシ)ビス(エタン−2,1−ジイル)ビス(2,2−ジメチルプロパンチオエート)(化合物15)
(実施例19)
S,S’−2,2’−((((2R,3S,4R,5S)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−5−エチニル−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)ホスホリル)ビス(オキシ)ビス(エタン−2,1−ジイル)ビス(2,2−ジメチルプロパンチオエート)(化合物16)
(実施例20)
((2R,3S,4R,5R)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メチル四水素トリホスフェート(化合物17)
(実施例21)
((2R,3S,4R,5S)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−5−エチニル−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メチル四水素トリホスフェート(化合物18)
(実施例22)
((2R,3S,4R,5S)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−3,4−ジヒドロキシ−5−メチルテトラヒドロフラン−2−イル)メチル四水素トリホスフェート(化合物19)
(実施例23)
((2R,3R,4R,5R)−5−(4−アミノピロロ[1,2−f][1,2,4]トリアジン−7−イル)−5−シアノ−4−フルオロ−3−ヒドロキシテトラヒドロフラン−2−イル)メチル四水素トリホスフェート(化合物20)
(実施例24)
(2S)−エチル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)−3−フェニルプロパノエート(21)
(S)−エチル2−アミノ−3−フェニルプロパノエート塩酸塩の調製。
(2S)−エチル2−(((4−ニトロフェノキシ)(フェノキシ)ホスホリル)アミノ)−3−フェニルプロパノエート(化合物D)の調製
(2S)−エチル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)−3−フェニルプロパノエート(化合物21)の調製
(実施例25)
(2S)−エチル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)−3−メチルブタノエート(22)
(2S)−エチル3−メチル−2−(((4−ニトロフェノキシ)(フェノキシ)ホスホリル)アミノ)ブタノエート(化合物E)の調製
(2S)−エチル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)−3−メチルブタノエート(化合物22)の調製
(実施例26)
(S)−イソプロピル2−(((R)−(((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(23)
(実施例27)
(2S)−シクロブチル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(24)
(2S)−シクロブチル2−(((4−ニトロフェノキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(化合物G)の調製
(2S)−シクロブチル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(化合物24)の調製
(実施例28)
(2S)−イソプロピル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)−3−フェニルプロパノエート(25)
(2S)−イソプロピル2−(((4−ニトロフェノキシ)(フェノキシ)ホスホリル)アミノ)−3−フェニルプロパノエート(化合物H)の調製
(2S)−イソプロピル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)−3−フェニルプロパノエート(化合物25)の調製
(実施例29)
(S)−メチル2−(((S)−(((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(26)
(実施例30)
(S)−ネオペンチル2−(((S)−(((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(27)
(実施例31)
(2S)−シクロペンチル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(28)
(実施例32)
(2S)−シクロヘキシル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(29)
(実施例33)
エチル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)−2−メチルプロパノエート(30)
エチル2−((tert−ブトキシカルボニル)アミノ)−2−メチルプロパノエートの調製
エチル2−アミノ−2−メチルプロパノエート塩酸塩の調製
エチル2−メチル−2−(((4−ニトロフェノキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(化合物N)の調製
エチル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)−2−メチルプロパノエート(化合物30)の調製
(実施例34)
イソプロピル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)−2−メチルプロパノエート(31)
イソプロピル2−((tert−ブトキシカルボニル)アミノ)−2−メチルプロパノエートの調製
イソプロピル2−アミノ−2−メチルプロパノエート塩酸塩の調製
イソプロピル2−メチル−2−(((4−ニトロフェノキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(化合物O)の調製
イソプロピル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)−2−メチルプロパノエート(化合物31)の調製
(実施例35)
(S)−2−エチルブチル2−(((S)−(((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(32)
(3R,4R,5R)−3,4−ビス(ベンジルオキシ)−5−((ベンジルオキシ)メチル)ジヒドロフラン−2(3H)−オンの調製。
(4−アミノ−7−ヨードピロロ[2,1−f][1,2,4]トリアジン)の調製
(4−アミノ−7−ヨードピロロ[2,1−f][1,2,4]トリアジン)を介した(3R,4R,5R)−2−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス(ベンジルオキシ)−5−((ベンジルオキシ)メチル)テトラヒドロフラン−2−オールの調製
((2S)−2−エチルブチル2−(((ペルフルオロフェノキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート)(SpとRpの混合物)の調製:
((2S)−2−エチルブチル2−(((ペルフルオロフェノキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート)の調製:
2−エチルブチル((S)−(4−ニトロフェノキシ)(フェノキシ)ホスホリル)−L−アラニネートの調製:
表題化合物(SpとRpの混合物)の調製:
(3aR,4R,6R,6aR)−4−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−6−(ヒドロキシメチル)−2,2−ジメチルテトラヒドロフロ[3,4−d][1,3]ジオキソール−4−カルボニトリルの調製:
(3aR,4R,6R,6aR)−4−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−6−(ヒドロキシメチル)−2,2−ジメチルテトラヒドロフロ[3,4−d][1,3]ジオキソール−4−カルボニトリルTsOH塩の調製:
(3aR,4R,6R,6aR)−4−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−6−(ヒドロキシメチル)−2,2−ジメチルテトラヒドロフロ[3,4−d][1,3]ジオキソール−4−カルボニトリルの調製:
(2S)−2−エチルブチル2−(((((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエートの調製:
(S)−2−エチルブチル2−(((S)−(((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(化合物32)の調製
(S)−2−エチルブチル2−(((S)−(((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(化合物32)の調製
直接カップリングを介した(S)−2−エチルブチル2−(((S)−(((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエート(化合物32)の調製
(3R,4R,5R)−2−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス((tert−ブチルジメチルシリル)オキシ)−5−(((tert−ブチルジメチルシリル)オキシ)メチル)テトラヒドロフラン−2−オールの調製
(2R,3R,4R,5R)−2−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス((tert−ブチルジメチルシリル)オキシ)−5−(ヒドロキシメチル)テトラヒドロフラン−2−カルボニトリルの調製
(S)−2−エチルブチル2−(((S)−(((2R,3R,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−3,4−ビス((tert−ブチルジメチルシリル)オキシ)−5−シアノテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエートの調製
(S)−2−エチルブチル2−(((S)−(((2R,3S,4R,5R)−5−(4−アミノピロロ[2,1−f][1,2,4]トリアジン−7−イル)−5−シアノ−3,4−ジヒドロキシテトラヒドロフラン−2−イル)メトキシ)(フェノキシ)ホスホリル)アミノ)プロパノエートの調製
本発明の好ましい実施形態によれば、例えば、以下が提供される。
(項1)
式Vの化合物:
を調製する方法であって、
カップリング剤、ハロシラン、式VIの化合物:
および式VIIの化合物:
を含む反応混合物を、式Vの化合物を調製するのに適切な条件下で形成すること
を含み、式中、
各PGは、独立して、ヒドロキシ保護基であるか、
あるいは、隣接する炭素上の2つのPG基が合わされて、−C(R 19 ) 2 −基を形成し
ていてもよく、
R 10 は、Hまたはシリル基であり、
R 19 は、H、C 1 〜C 8 アルキル、フェニルまたは置換フェニルである、方法。
(項2)
前記カップリング剤が、リチウムカップリング剤またはマグネシウムカップリング剤で
あり、
前記ハロシランが、Cl−Si(CH 3 ) 3 、またはCl−Si(CH 3 ) 2 CH 2 CH
2 Si(CH 3 ) 2 −Clであり、
前記ヒドロキシ保護基が、トリメチルシラン(TMS)、t−ブチルジメチルシラン(T
BDMS)、t−ブチルジフェニルシラン(TBDPS)、メチル−メトキシ(MOM)
、テトラヒドロピラン(THP)、t−ブチル、アリル、ベンジル、アセチル、ピバロイ
ル、またはベンゾイルである、上記項1に記載の方法。
(項3)
前記カップリング剤がPhMgClおよびiPrMgClであり、
前記ハロシランがTMS−Clであり、
前記ヒドロキシ保護基がベンジルである、上記項1に記載の方法。
(項4)
前記式Vの化合物:
を調製する方法であって、
TMS−Cl、PhMgCl、iPrMgCl、前記式VIの化合物:
および前記式VIIの化合物:
を含む前記反応混合物を、前記式Vの化合物を調製するのに適切な条件下で形成すること
を含む、上記項1に記載の方法。
(項5)
式V−aまたはV−bの化合物:
を調製する方法であって、
脱プロトン化剤、シリル化剤、カップリング剤、添加物質、式VI−aの化合物:
および式VIIの化合物:
を含む反応混合物を、前記式V−aまたはV−bの化合物を調製するのに適切な条件下で
形成すること
を含み、式中、
各R b は、独立して、ヒドロキシ保護基であるか、
あるいは、隣接する炭素上の2つのR b 基が合わされて、−C(R 19 ) 2 −基を形成し
ていてもよく、
R 10 は、Hまたはシリル基であり、
R 19 は、H、C 1 〜C 8 アルキル、フェニルまたは置換フェニルである、方法。
(項6)
前記脱プロトン化剤がリチウムカップリング剤またはマグネシウムカップリング剤であ
り、前記シリル化剤がクロロシランであり、前記カップリング剤がマグネシウムベースの
カップリング剤であり、前記添加物質が、LaCl 3 −2LiCl、YCl 3 、CeCl
3 、NdCl 3 、またはLaCl 3 である、上記項5に記載の方法。
(項7)
前記脱プロトン化剤がPhMgClであり、
前記シリル化剤がTMSClであり、
前記カップリング剤がiPrMgClであり、
前記添加物質がLaCl 3 −2LiCl、YCl 3 、CeCl 3 、NdCl 3 、またはL
aCl 3 であり、
前記ヒドロキシ保護基がベンジルである、上記項5に記載の方法。
(項8)
前記式V−aまたは式V−bの化合物:
を調製する方法であって、
TMSCl、PhMgCl、iPrMgCl、添加物質、前記式VI−aの化合物:
および前記式VIIの化合物:
を含む前記反応混合物を、前記式V−aまたは式V−bの化合物を調製するのに適切な条
件下で形成すること
を含み、前記添加物質がLaCl 3 −2LiCl、LaCl 3 、CeCl 3 、NdCl 3
、またはYCl 3 である、上記項5に記載の方法。
(項9)
前記式V−aの化合物:
を調製する方法であって、
TMSCl、PhMgCl、iPrMgCl−LiCl、添加物質、前記式VI−aの化
合物:
および前記式VIIの化合物:
を含む前記反応混合物を、前記式V−aの化合物を調製するのに適切な条件下で形成する
こと
を含み、前記添加物質がLaCl 3 −2LiCl、LaCl 3 、CeCl 3 、NdCl 3
、またはYCl 3 である、上記項5に記載の方法。
(項10)
式XI−aの化合物
を調製する方法であって、
シアン化剤、ルイス酸、ブレンステッド酸、溶媒、および式V−aまたはV−bの化合物
:
を含む反応混合物を、前記式XI−aの化合物を調製するのに適切な条件下で形成するこ
と
を含み、式中、
各R b は、独立して、ヒドロキシ保護基であるか、
あるいは、隣接する炭素上の2つのR b 基が合わされて、−C(R 19 ) 2 −基を形成し
ていてもよく、
R 10 は、Hまたはシリル基であり、
R 19 は、H、C 1 〜C 8 アルキル、フェニルまたは置換フェニルである、方法。
(項11)
前記シアン化剤がTMSCNであり、
前記ルイス酸がTMSOTfであり、
前記ブレンステッド酸がTFAであり、
前記溶媒がDCMであり、
前記ヒドロキシ保護基がベンジルである、上記項10に記載の方法。
(項12)
前記式XI−aの化合物:
を調製する方法であって、
TFA、TMSCN、TMSOTfおよび前記式Vaまたは式V−bの化合物:
を含む前記反応混合物を、前記式XI−aの化合物を調製するのに適切な条件下で形成す
ること
を含む、上記項10に記載の方法。
(項13)
式XI−a 2 の化合物
を調製する方法であって、
シアン化剤、ルイス酸、ブレンステッド酸、溶媒、および式V−aの化合物:
を含む反応混合物を、前記式XI−a 2 の化合物を調製するのに適切な条件下で形成する
こと
を含み、式中、
各R b は、独立して、ヒドロキシ保護基であるか、
あるいは、隣接する炭素上の2つのR b 基が合わされて、−C(R 19 ) 2 −基を形成し
ていてもよく、
R 10 はHまたはシリル基であり、
R 19 は、H、C 1 〜C 8 アルキル、フェニルまたは置換フェニルである、方法。
(項14)
前記シアン化剤がTMSCNであり、
前記ルイス酸がTMSOTfであり、
前記ブレンステッド酸がTFAであり、
前記溶媒がDCMであり、
前記ヒドロキシ保護基がTBSである、上記項13に記載の方法。
(項15)
前記式XI−a 2 の化合物:
を調製する方法であって、
TFA、TMSCN、TMSOTfおよび前記式Vaの化合物:
を含む前記反応混合物を、前記式XI−aの化合物を調製するのに適切な条件下で形成す
ること
を含む、上記項13に記載の方法。
(項16)
式XI−bの化合物
を調製する方法であって、
ルイス酸、塩基、溶媒、濾過剤、および式XI−aの化合物:
を含む反応混合物を、前記式XI−bの化合物を調製するのに適切な条件下で形成するこ
と
を含む、方法。
(項17)
前記ルイス酸がBCL 3 であり、
前記塩基がEt 3 Nであり、
前記溶媒がMeOHであり、
前記濾過剤がCelite(登録商標)である、上記項16に記載の方法。
(項18)
前記式XI−bの化合物:
を調製する方法であって、
BCL3、Et2N、MeOH、Celite(登録商標)、および:
の化合物を含む前記反応混合物を、前記式XI−bの化合物を調製するのに適切な条件下
で形成すること
を含む、上記項16に記載の方法。
(項19)
式XI−cの化合物
を調製する方法であって、
溶媒、試薬、酸、および式XI−bの化合物:
を含む反応混合物を、前記式XI−bの化合物を調製するのに適切な条件下で形成するこ
と
を含む、方法。
(項20)
前記溶媒がアセトンであり、
前記試薬が2,2−ジメトキシプロパンであり、
前記酸が硫酸である、上記項19に記載の方法。
(項21)
前記式XI−cの化合物:
を調製する方法であって、
アセトン、2,2−ジメトキシプロパン、硫酸、および:
の化合物を含む前記反応混合物を、前記式XI−cの化合物を調製するのに適切な条件下
で形成すること
を含む、上記項19に記載の方法。
(項22)
式VIIIの化合物:
を調製する方法であって、カップリング剤、非求核性塩基、式IXの化合物:
および式Xの化合物:
を含む反応混合物を、前記式VIIIの化合物を形成するのに適切な条件下で形成するこ
とを含み、式中、
各R a はHまたはPGであり、
各PG基はヒドロキシ保護基であるか、または両方のPG基が合わされて、−C(R 19
) 2 −を形成し、
R e1 およびR e2 は、それぞれ独立して、H、C 1 〜C 6 アルキルまたはベンジルであ
り、
R f は、H、C 1 〜C 8 アルキル、ベンジル、C 3 〜C 6 シクロアルキル、または−CH
2 −C 3 〜C 6 シクロアルキルであり、
R 19 は、H、C 1 〜C 8 アルキル、フェニルまたは置換フェニルであり、
LGは脱離基である、方法。
(項23)
各R a がPGであり、前記PG基が合わされて、−C(R 19 ) 2 −を形成し、
R f がC 1 〜C 8 アルキルであり、
R 19 がC 1 〜C 8 アルキルであり、
前記脱離基LGが4−ニトロフェノキシまたはペンタフルオロフェノキシである、上記項
22に記載の方法。
(項24)
前記カップリング剤がMgCl 2 であり、
前記非求核性塩基がジ−イソプロピルエチルアミンである、上記項22に記載の方法。
(項25)
前記式VIIIの化合物が、
である、上記項22に記載の方法。
(項26)
前記式VIIIの化合物が、
である、上記項22に記載の方法。
(項27)
前記式VIIIの化合物が、
である、上記項22に記載の方法。
(項28)
MgCl 2 、DIPEA、前記式IXの化合物:
および前記式Xの化合物:
を含む前記反応混合物を、前記式VIIIの化合物:
を形成するのに適切な条件下で形成することを含む、上記項22に記載の方法。
(項29)
脱保護剤と、各R a 基が前記保護基PGである前記式VIIIの化合物を含む第2の反
応混合物を、各R a がHである前記式VIIIの化合物を形成するのに適切な条件下で形
成することをさらに含む、上記項22に記載の方法。
(項30)
式VIIIの化合物:
を調製する方法であって、カップリング剤、非求核性塩基、式IX−aの化合物:
および式Xの化合物:
を含む反応混合物を、前記式VIIIの化合物を形成するのに適切な条件下で形成するこ
とを含み、式中、
各R a はHまたはヒドロキシ保護基であり、
各R 35 は、独立して、Hまたはヒドロキシ保護基であるか、あるいは両方のR 35 基が
合わされて、−C(R 19 ) 2 −を形成し、
R e1 およびR e2 は、それぞれ独立して、H、C 1 〜C 6 アルキルまたはベンジルであ
り、
R f は、H、C 1 〜C 8 アルキル、ベンジル、C 3 〜C 6 シクロアルキル、または−CH
2 −C 3 〜C 6 シクロアルキルであり、
R 19 は、H、C 1 〜C 8 アルキル、フェニルまたは置換フェニルであり、
LGは脱離基である、方法。
(項31)
各R 35 が合わされて、−C(R 19 ) 2 −を形成し、
R f がC 1 〜C 8 アルキルであり、
R 19 がC 1 〜C 8 アルキルであり、
前記脱離基LGが4−ニトロフェノキシまたはペンタフルオロフェノキシである、上記項
30に記載の方法。
(項32)
前記カップリング剤がMgCl 2 であり、
前記非求核性塩基がジ−イソプロピルエチルアミンである、上記項30に記載の方法。
(項33)
前記式VIIIの化合物が、
である、上記項30に記載の方法。
(項34)
前記式VIIIの化合物が、
である、上記項30に記載の方法。
(項35)
前記式VIIIの化合物が、
である、上記項30に記載の方法。
(項36)
前記式VIIIの化合物が、
である、上記項30に記載の方法。
(項37)
MgCl 2 、DIPEA、前記式IXの化合物:
および前記式Xの化合物:
を含む前記反応混合物を、前記式VIIIの化合物:
を形成するのに適切な条件下で形成すること
を含む、上記項30に記載の方法。
(項38)
MgCl 2 、DIPEA、式IX−a 2 の化合物:
および前記式Xの化合物:
を含む前記反応混合物を、前記式VIIIの化合物:
を形成するのに適切な条件下で形成すること
を含む、上記項30に記載の方法。
(項39)
脱保護剤と、各R 35 基がヒドロキシ保護基である前記式VIIIの化合物とを含む第
2の反応混合物を、各R a がHである前記式VIIIの化合物を形成するのに適切な条件
下で形成することをさらに含む、上記項30に記載の方法。
(項40)
式X−bの化合物:
を調製する方法であって、
適切な溶媒、適切な塩基、および式X−aの化合物:
ならびに、任意選択で、1つまたは複数の式X−bの種結晶を含む反応混合物を、
前記式X−bの化合物を形成するのに適切な条件下で形成すること
を含む、方法。
(項41)
前記適切な溶媒がアセトニトリルであり、
前記適切な塩基がDBUである、上記項40に記載の方法。
(項42)
式
の化合物またはその薬学的に許容される塩、水和物またはエステル。
Claims (5)
- 式V−aまたはV−bの化合物:
を調製する方法であって、
脱プロトン化剤、シリル化剤、カップリング剤、添加物質、式VI−aの化合物:
および式VIIの化合物:
を含む反応混合物を形成して、前記式V−aまたはV−bの化合物を調製すること
を含み、式中、
各Rbは、独立して、ベンジル(Bn)またはtert−ブチルジメチルシリル(TBS)であるか、
あるいは、隣接する炭素上の2つのRb基が合わされて、−C(Me)2−基を形成していてもよく、そして
R10は、Hまたはシリル基であり、
ここで、
前記脱プロトン化剤がPhMgClまたはPhMgBrであり、
前記シリル化剤がTMSClであり、
前記カップリング剤がiPrMgCl、iPrMgCl−LiCl、tBuMgCl、MeMgCl、MeMgBr、EtMgBr、EtMgCl、PrMgBrまたはPrMgClであり、そして
前記添加物質が、LaCl3−2LiCl、LaCl3、CeCl3、NdCl3、またはYCl3である、
方法。 - 前記脱プロトン化剤がPhMgClであり、そして
前記カップリング剤がiPrMgClまたはiPrMgCl−LiClである、
請求項1に記載の方法。 - 前記脱プロトン化剤がPhMgClであり、
前記シリル化剤がTMSClであり、
前記カップリング剤がiPrMgClであり、そして
R b がベンジルである、
請求項1に記載の方法。
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Country Status (45)
Families Citing this family (102)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK2480559T3 (da) | 2009-09-21 | 2013-08-05 | Gilead Sciences Inc | Fremgangsmåder og mellemprodukter til fremstillingen af 1'-cyano-carbanukleosid-analoger |
CR20170278A (es) | 2010-07-22 | 2017-09-29 | Gilead Sciences Inc | Métodos y compuestos para tratar infecciones virales por paramyxoviridae |
TWI740546B (zh) * | 2014-10-29 | 2021-09-21 | 美商基利科學股份有限公司 | 製備核糖苷的方法 |
SG10202001878WA (en) | 2015-09-16 | 2020-04-29 | Gilead Sciences Inc | Methods for treating arenaviridae and coronaviridae virus infections |
WO2018089306A1 (en) * | 2016-11-10 | 2018-05-17 | Oyagen, Inc. | Methods of treating and inhibiting ebola virus infection |
KR20190085976A (ko) * | 2016-11-18 | 2019-07-19 | 뉴로바이브 파마슈티컬 에이비 | 미토콘드리아 프로톤 이오노포어의 간 프로드러그 |
KR102460968B1 (ko) * | 2017-03-14 | 2022-11-01 | 길리애드 사이언시즈, 인코포레이티드 | 고양이 코로나바이러스 감염의 치료 방법 |
JP6923112B2 (ja) * | 2017-03-31 | 2021-08-18 | 国立大学法人北海道大学 | フィロウイルスの細胞侵入阻害活性を有するビアリールスルフォンアミド誘導体 |
WO2018204198A1 (en) | 2017-05-01 | 2018-11-08 | Gilead Sciences, Inc. | Crystalline forms of (s) 2 ethylbutyl 2 (((s) (((2r,3s,4r,5r) 5 (4 aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2 yl)methoxy)(phenoxy) phosphoryl)amino)propanoate |
CA3077489A1 (en) | 2017-07-11 | 2019-01-17 | Gilead Sciences, Inc. | Compositions comprising an rna polymerase inhibitor and cyclodextrin for treating viral infections |
CR20200126A (es) * | 2017-09-18 | 2020-07-11 | Janssen Biopharma Inc | Nucleósidos sustituidos, nucleótidos y análogos de estos |
CN109535200A (zh) * | 2017-09-21 | 2019-03-29 | 杭州和正医药有限公司 | 一种核苷类似物的磷酰胺酯前药、药物组合物及其应用 |
CN109748943A (zh) * | 2017-11-03 | 2019-05-14 | 中国科学院上海药物研究所 | 2’-c-甲基取代核苷类化合物及其制备与用途 |
CN109748944B (zh) * | 2017-11-03 | 2021-12-10 | 中国科学院上海药物研究所 | 5’-脱氧-5’-异丙基取代氨基核苷类化合物、其制备方法和用途 |
CN110330540A (zh) * | 2019-08-08 | 2019-10-15 | 木天(济南)生物科技有限公司 | 核苷盐及其制备方法 |
CN110613726B (zh) * | 2019-09-25 | 2020-10-16 | 广州六顺生物科技股份有限公司 | 核苷化合物的应用 |
WO2021095091A1 (ja) * | 2019-11-11 | 2021-05-20 | 藤本化学製品株式会社 | アミノアリール誘導体及びその中間体、並びにそれらの製造方法 |
CN110776512A (zh) * | 2019-11-28 | 2020-02-11 | 成都傲飞生物化学品有限责任公司 | 一种核苷类似物的制备方法 |
CA3163424A1 (en) | 2020-01-27 | 2021-08-05 | Gilead Sciences, Inc. | Methods for treating sars cov-2 infections |
WO2021158248A1 (en) | 2020-02-04 | 2021-08-12 | Oyagen, Inc. | Method for treating coronavirus infections |
CN113214263B (zh) * | 2020-02-06 | 2022-09-30 | 北京桦冠医药科技有限公司 | 瑞德西韦关键中间体的一种合成方法 |
US20210244705A1 (en) * | 2020-02-07 | 2021-08-12 | Centre For Digestive Diseases | Therapeutic compositions, products of manufacture and methods for ameliorating or preventing coronavirus infection |
CN111205327B (zh) * | 2020-02-17 | 2022-05-31 | 南京法恩化学有限公司 | 一种瑞德西韦的制备方法 |
TWI775313B (zh) * | 2020-02-18 | 2022-08-21 | 美商基利科學股份有限公司 | 抗病毒化合物 |
TWI791193B (zh) | 2020-02-18 | 2023-02-01 | 美商基利科學股份有限公司 | 抗病毒化合物 |
TWI794742B (zh) | 2020-02-18 | 2023-03-01 | 美商基利科學股份有限公司 | 抗病毒化合物 |
CN113292565B (zh) * | 2020-02-24 | 2023-01-31 | 浙江森科建设有限公司 | 核苷类化合物及其制备方法和应用 |
CN111205294B (zh) * | 2020-02-27 | 2021-10-01 | 江苏阿尔法药业股份有限公司 | 一种瑞德西韦中间体的制备方法 |
CN111171078B (zh) * | 2020-02-27 | 2022-04-22 | 江苏阿尔法药业股份有限公司 | 一种瑞德西韦的合成方法 |
CN111187269A (zh) * | 2020-02-27 | 2020-05-22 | 江苏阿尔法药业有限公司 | 一种瑞德西韦中间体的合成方法 |
CN111233930B (zh) * | 2020-03-04 | 2022-05-13 | 江苏阿尔法药业股份有限公司 | 一种瑞德西韦的制备方法 |
CN113354699B (zh) * | 2020-03-04 | 2023-07-18 | 中国科学院上海药物研究所 | 瑞德西韦的中间体及其制备方法 |
CN111269248A (zh) * | 2020-03-05 | 2020-06-12 | 江苏福瑞康泰药业有限公司 | 一种核苷氨基磷酸酯类药物母液回收的新方法 |
CN111269263A (zh) * | 2020-03-09 | 2020-06-12 | 上海龙翔生物医药开发有限公司 | 一种瑞德西韦侧链中间体及其制备方法 |
CN113387954B (zh) * | 2020-03-11 | 2024-03-19 | 上海特化医药科技有限公司 | 一种瑞德西韦中间体的制备方法 |
CN111233870A (zh) * | 2020-03-11 | 2020-06-05 | 中国科学技术大学 | 用于快速制备瑞德西韦药物中间体的方法 |
CN111233869B (zh) * | 2020-03-12 | 2022-09-16 | 杭州新博思生物医药有限公司 | 用于制备瑞德西韦关键中间体的新化合物及其制备方法 |
JP2023516087A (ja) | 2020-03-12 | 2023-04-17 | ギリアード サイエンシーズ, インコーポレイテッド | 1’-シアノヌクレオシドを調製する方法 |
WO2021194860A1 (en) | 2020-03-23 | 2021-09-30 | Genentech, Inc. | Tocilizumab and remdesivir combination therapy for covid-19 pneumonia |
EP4107185A1 (en) | 2020-03-23 | 2022-12-28 | Genentech, Inc. | Biomarkers for predicting response to il-6 antagonist in covid-19 pneumonia |
CN111233931B (zh) * | 2020-03-26 | 2022-03-22 | 宿迁盛基医药科技有限公司 | 一种瑞德西韦的合成方法 |
CN111398464B (zh) * | 2020-04-02 | 2022-03-08 | 广州隽沐生物科技股份有限公司 | 2-乙基丁基((全氟苯氧基)(苯氧基)磷酰基)-l-丙氨酸酯的检测方法 |
CN111423443A (zh) * | 2020-04-03 | 2020-07-17 | 广州科锐特生物科技有限公司 | 一种4-氨基-7-碘吡咯并[2,1-f][1,2,4]三嗪的制备方法 |
KR20220164784A (ko) | 2020-04-06 | 2022-12-13 | 길리애드 사이언시즈, 인코포레이티드 | 1'-시아노 치환된 카르바뉴클레오시드 유사체의 흡입 제형 |
WO2021207386A1 (en) * | 2020-04-07 | 2021-10-14 | Biocryst Pharmaceuticals, Inc. | Methods, compositions, and dosing regimens for treatment of sars-cov-2 infections |
WO2021208910A1 (zh) * | 2020-04-13 | 2021-10-21 | 山东华铂凯盛生物科技有限公司 | 用于治疗病毒感染的聚合物制剂及制备方法和用途 |
CN111393494A (zh) * | 2020-04-17 | 2020-07-10 | 广东帕派恩生物科技有限公司 | 基于核苷酸结构的化合物、制备方法、用途 |
CN112778310A (zh) * | 2020-04-20 | 2021-05-11 | 中国科学院上海药物研究所 | 核苷类似物或含有核苷类似物的组合制剂在抗病毒中的应用 |
CN111471070B (zh) * | 2020-04-26 | 2022-05-13 | 江苏阿尔法药业股份有限公司 | 瑞德西韦的合成方法 |
WO2021217685A1 (zh) * | 2020-04-27 | 2021-11-04 | 南通伟顺生物科技有限公司 | 一种含六元环的核苷类化合物及其制备方法 |
CN111440176B (zh) * | 2020-04-28 | 2022-04-26 | 江苏大学 | 金属配合物促进的瑞德西韦中间体的合成方法 |
US10988503B1 (en) * | 2020-05-06 | 2021-04-27 | Nantong Weishun Biotechnology Co., Ltd | Six-membered ring-containing nucleoside compound and preparation method thereof |
CN113637041B (zh) * | 2020-05-11 | 2024-02-27 | 上海科胜药物研发有限公司 | 一种核糖核苷的制备方法 |
RU2740660C1 (ru) * | 2020-05-20 | 2021-01-19 | Общество С Ограниченной Ответственностью "Промомед Рус" | Противовирусная композиция |
WO2021237109A1 (en) | 2020-05-22 | 2021-11-25 | Trailhead Biosystems Inc. | Combination therapy for treatment of viral infections |
CN111961057A (zh) * | 2020-05-26 | 2020-11-20 | 李小冬 | 一种α构型核苷及其在治疗猫冠状病毒感染的应用 |
TW202203941A (zh) | 2020-05-29 | 2022-02-01 | 美商基利科學股份有限公司 | 瑞德西韋之治療方法 |
IN202011022634A (ja) | 2020-05-29 | 2020-10-09 | Jubilant Generics Limited | |
EP3915548A1 (en) | 2020-05-29 | 2021-12-01 | Jubilant Generics Limited | Transmucosal pharmaceutical compositions of antiviral drugs |
CN113754694B (zh) * | 2020-06-03 | 2022-10-25 | 上海交通大学 | 一种不对称催化无保护基核苷合成瑞德西韦的方法 |
CN113754693B (zh) * | 2020-06-03 | 2022-09-09 | 上海交通大学 | 一种磷手性核苷衍生物的不对称催化合成方法及催化剂 |
CN113754692B (zh) * | 2020-06-03 | 2022-06-10 | 上海交通大学 | 瑞德西韦中间体(s,s)-氨基磷酸酯的不对称催化合成方法 |
WO2021257569A1 (en) * | 2020-06-15 | 2021-12-23 | Metro International Biotech, Llc | Anti-viral compounds and methods of use |
US20230241225A1 (en) | 2020-06-15 | 2023-08-03 | Metro International Biotech, Llc | Anti-viral compounds and methods of use |
CN111620903A (zh) * | 2020-06-17 | 2020-09-04 | 安徽贝克联合制药有限公司 | C-核苷类似物以及用于合成瑞德西韦合成的含腈c-核苷类化合物的制备方法及其应用 |
US20210393663A1 (en) * | 2020-06-23 | 2021-12-23 | Cai Gu Huang | Pharmaceutical formulation containing active metabolites of remdesivir or its analog for inhalation |
CR20220675A (es) | 2020-06-24 | 2023-02-15 | Gilead Sciences Inc | Análogos de nucleósido de 1´- ciano y usos de los mismos |
CN111732618A (zh) * | 2020-07-03 | 2020-10-02 | 镇江巨杰新材料技术研发中心(有限合伙) | 瑞德西韦关键片段的合成方法 |
CN111961079A (zh) * | 2020-07-17 | 2020-11-20 | 南京正济医药研究有限公司 | 一种瑞德西韦有关物质及其制备方法和应用 |
WO2022020793A1 (en) * | 2020-07-24 | 2022-01-27 | The Regents Of The University Of California | Antiviral prodrugs, pharmaceutical formulations, and methods |
WO2022029704A1 (en) | 2020-08-06 | 2022-02-10 | Richter Gedeon Nyrt. | Remdesivir intermediates |
CN113004330A (zh) * | 2020-08-22 | 2021-06-22 | 齐鲁制药有限公司 | 一种高纯度瑞德西韦的制备方法 |
KR20230057411A (ko) * | 2020-08-27 | 2023-04-28 | 길리애드 사이언시즈, 인코포레이티드 | 바이러스 감염 치료를 위한 화합물 및 방법 |
CN114105989A (zh) * | 2020-08-31 | 2022-03-01 | 中国科学院大连化学物理研究所 | 一种碘代吡咯并三嗪胺类化合物的制备方法和应用 |
US20230357418A1 (en) | 2020-09-17 | 2023-11-09 | Genentech, Inc. | Results of empacta: a randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of tocilizumab in hospitalized patients with covid-19 pneumonia |
CN112321642A (zh) * | 2020-09-28 | 2021-02-05 | 南京正济医药研究有限公司 | 一种瑞德西韦有关物质及其制备方法和用途 |
WO2022074630A1 (en) * | 2020-10-09 | 2022-04-14 | Auxilla Pharmaceuticals And Research Llp | Liquid oral suspension of favipiravir |
CN112194661B (zh) * | 2020-10-22 | 2021-06-08 | 威海同丰海洋生物科技有限公司 | 一种4-氨基-7-碘吡咯并[2,l-f][l,2,4]三嗪的制备方法 |
RU2756921C1 (ru) * | 2020-11-20 | 2021-10-07 | Общество С Ограниченной Ответственностью "Технология Лекарств" | Способ получения ремдесивира и фосфорамидаты |
MX2023005878A (es) | 2020-11-23 | 2023-06-05 | Genentech Inc | Metodos para modular las interacciones de la superficie de la celula huesped con sars-cov-2. |
CN112358513A (zh) * | 2020-12-02 | 2021-02-12 | 上海朴颐化学科技有限公司 | 一种利用连续流反应器制备瑞德西韦中间体的方法 |
CN114621229A (zh) * | 2020-12-11 | 2022-06-14 | 嘉兴金派特生物科技有限公司 | 治疗或预防猫传染性腹膜炎的化合物或组合物 |
CN114685558A (zh) * | 2020-12-28 | 2022-07-01 | 尚科生物医药(上海)有限公司 | 一种瑞德西韦中间体的制备方法 |
CN116874490A (zh) * | 2020-12-30 | 2023-10-13 | 南方科技大学 | 化合物atv014或其药学可接受的盐及其药物组合物 |
CN113754665B (zh) * | 2020-12-30 | 2022-08-19 | 南方科技大学 | 一种核苷类化合物的制备方法 |
WO2022166581A1 (zh) * | 2021-02-07 | 2022-08-11 | 石家庄迪斯凯威医药科技有限公司 | 一种核苷酸衍生物及其药物组合物和用途 |
WO2022174779A1 (zh) * | 2021-02-19 | 2022-08-25 | 南京赛弗斯医药科技有限公司 | 一种具有抗肿瘤活性的核苷酸衍生物及其药物组合物和用途 |
CN112979736B (zh) * | 2021-03-04 | 2022-03-25 | 南京欧信医药技术有限公司 | 一种瑞德西韦的制备方法 |
EP4323361A1 (en) | 2021-04-16 | 2024-02-21 | Gilead Sciences, Inc. | Methods of preparing carbanucleosides using amides |
WO2022221514A1 (en) | 2021-04-16 | 2022-10-20 | Gilead Sciences, Inc. | Methods of preparing carbanucleosides using amides |
US20230000873A1 (en) | 2021-05-26 | 2023-01-05 | Gilead Sciences, Inc. | Phospholipid formulations of 1'-cyano substituted carba-nucleoside analogs |
CN113683640A (zh) * | 2021-08-10 | 2021-11-23 | 浙江华海药业股份有限公司 | 一种丁基瑞德西韦的制备方法 |
KR20240050362A (ko) | 2021-08-20 | 2024-04-18 | 시오노기 앤드 컴파니, 리미티드 | 바이러스 증식 억제 작용을 갖는 뉴클레오사이드 유도체 및 그들의 프로드러그 |
CN113999237B (zh) * | 2021-10-29 | 2023-08-08 | 润佳(苏州)医药科技有限公司 | 一种核苷类前药及其用途 |
KR20230063790A (ko) | 2021-11-02 | 2023-05-09 | 충남대학교산학협력단 | 렘데시비르를 함유하는 나노지질담체, 이의 제조방법 및 이를 포함하는 약학적 조성물 |
CN114409655A (zh) * | 2022-01-26 | 2022-04-29 | 郑州大学 | 3′,4′-不饱和核糖c-核苷类似物及其制备方法 |
TW202400185A (zh) | 2022-03-02 | 2024-01-01 | 美商基利科學股份有限公司 | 用於治療病毒感染的化合物及方法 |
CN115028672A (zh) * | 2022-06-14 | 2022-09-09 | 南京正济医药研究有限公司 | 瑞德西韦中间体晶体及其制备方法 |
US11655255B2 (en) | 2022-10-17 | 2023-05-23 | Sph No.1 Biochemical & Pharmaceutical Co., Ltd. | Method for catalytic asymmetric synthesis of phosphorus-stereogenic (P-stereogenic) nucleoside derivative and catalyst used therein |
CN115737675B (zh) * | 2022-11-28 | 2024-03-08 | 安徽农业大学 | 氧化型硒代硫酸钠的制备及其在治疗冠状病毒感染中的应用 |
CN116284135A (zh) * | 2023-05-04 | 2023-06-23 | 南京颐媛生物医学研究院有限公司 | 抗冠状病毒核苷类化合物的制备方法及其应用 |
CN116332996A (zh) * | 2023-05-04 | 2023-06-27 | 南京颐媛生物医学研究院有限公司 | 抗冠状病毒化合物及其制备方法和应用 |
Family Cites Families (154)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4816570A (en) | 1982-11-30 | 1989-03-28 | The Board Of Regents Of The University Of Texas System | Biologically reversible phosphate and phosphonate protective groups |
US4968788A (en) | 1986-04-04 | 1990-11-06 | Board Of Regents, The University Of Texas System | Biologically reversible phosphate and phosphonate protective gruops |
DK0533833T3 (da) | 1990-06-13 | 1996-04-22 | Arnold Glazier | Phosphorprolægemidler |
ATE167679T1 (de) | 1990-09-14 | 1998-07-15 | Acad Of Science Czech Republic | Wirkstoffvorläufer von phosphonaten |
JPH1017629A (ja) | 1996-07-04 | 1998-01-20 | Kayaku Akzo Kk | ハードコート用樹脂組成物及びその硬化方法 |
US6887707B2 (en) | 1996-10-28 | 2005-05-03 | University Of Washington | Induction of viral mutation by incorporation of miscoding ribonucleoside analogs into viral RNA |
JP2002505340A (ja) | 1998-03-03 | 2002-02-19 | ノボ ノルディスク アクティーゼルスカブ | (2e)−5−アミノ−5−メチルヘキセ−2−エン酸n−メチル−n−((1r)−1−(n−メチル−n−((1r)−1−(メチルカルバモイル)−2−フェニルエチル)カルバモイル)−2−(2−ナフチル)エチル)アミドの新規な塩 |
US6312662B1 (en) | 1998-03-06 | 2001-11-06 | Metabasis Therapeutics, Inc. | Prodrugs phosphorus-containing compounds |
CA2326535A1 (en) | 1998-03-27 | 1999-10-07 | Regents Of The University Of Minnesota | Nucleosides with antiviral and anticancer activity |
DE69936998T2 (de) | 1998-10-16 | 2008-05-21 | Merck Sharp & Dohme Ltd., Hoddesdon | Pyrazolotriazinderivate als gaba-rezeptorliganden |
DE19912636A1 (de) | 1999-03-20 | 2000-09-21 | Aventis Cropscience Gmbh | Bicyclische Heterocyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Herbizide und pharmazeutische Mittel |
DE60029314T2 (de) * | 1999-03-24 | 2007-07-12 | Exiqon A/S | Verbesserte Synthese für -2.2.1. I Bicyclo-Nukleoside |
CA2376016A1 (en) * | 1999-06-03 | 2000-12-14 | Abbott Laboratories | Oligonucleotide synthesis with lewis acids as activators |
AUPQ105499A0 (en) | 1999-06-18 | 1999-07-08 | Biota Scientific Management Pty Ltd | Antiviral agents |
AU7490600A (en) | 1999-09-15 | 2001-04-17 | Biocryst Pharmaceuticals, Inc. | Inhibiting t-cell proliferation |
EP1225899A2 (en) | 1999-11-04 | 2002-07-31 | Virochem Pharma Inc. | Method for the treatment or prevention of flaviviridae viral infection using nucleoside analogues |
CN1427722A (zh) | 2000-02-18 | 2003-07-02 | 希拉生物化学股份有限公司 | 用核苷类似物治疗或预防黄病毒感染的方法 |
MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
EA200601591A1 (ru) | 2000-05-26 | 2007-02-27 | Айденикс (Кайман) Лимитед | Применение рибонуклеозидных соединений для лечения флавивирусных и пестивирусных инфекций |
HRP20160074B1 (hr) | 2000-07-21 | 2021-09-03 | Gilead Sciences, Inc. | Prolijekovi koji su fosfonatni analozi nukleotida i metode njihovog odabira te njihova priprava |
US20030008841A1 (en) | 2000-08-30 | 2003-01-09 | Rene Devos | Anti-HCV nucleoside derivatives |
BR0114837A (pt) | 2000-10-18 | 2006-05-09 | Pharmasset Ltd | nucleosìdeos modificados para tratamento de infecções viróticas e proliferação celular anormal |
AUPR213700A0 (en) | 2000-12-18 | 2001-01-25 | Biota Scientific Management Pty Ltd | Antiviral agents |
WO2002057287A2 (en) | 2001-01-22 | 2002-07-25 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
DE10145223A1 (de) | 2001-09-13 | 2003-04-03 | Basf Ag | Verfahren zur Herstellung von meso-Zeaxanthin |
WO2003026675A1 (en) | 2001-09-28 | 2003-04-03 | Idenix (Cayman) Limited | Methods and compositions for treating flaviviruses and pestiviruses using 4'-modified nucleoside |
AT410792B (de) | 2001-12-28 | 2003-07-25 | Dsm Fine Chem Austria Gmbh | Verfahren zur herstellung von geschützten, enantiomeren-angereicherten cyanhydrinen durch in-situ-derivatisierung |
WO2003073989A2 (en) | 2002-02-28 | 2003-09-12 | Biota, Inc. | Nucleoside 5'-monophosphate mimics and their prodrugs |
CA2477741A1 (en) | 2002-02-28 | 2003-09-04 | Biota, Inc. | Nucleotide mimics and their prodrugs |
US20040138170A1 (en) | 2002-03-06 | 2004-07-15 | Montgomery John A. | Nucleosides, preparation thereof and use as inhibitors of rna viral polymerases |
GB0210127D0 (en) | 2002-05-02 | 2002-06-12 | Merck Sharp & Dohme | Therapeutic agents |
GB0210124D0 (en) | 2002-05-02 | 2002-06-12 | Merck Sharp & Dohme | Therapeutic agents |
CA2484921A1 (en) | 2002-05-06 | 2003-11-13 | Genelabs Technologies, Inc. | Nucleoside derivatives for treating hepatitis c virus infection |
US20050250728A1 (en) | 2002-05-23 | 2005-11-10 | Shanta Bantia | Enhancing the efficacy of reverse transcriptase and dna polymerase inhibitors (nucleoside analogs) using pnp inhibitors and/or 2'-deoxyguanosine and/or prodrug thereof |
EP1576138B1 (en) | 2002-11-15 | 2017-02-01 | Idenix Pharmaceuticals LLC. | 2'-methyl nucleosides in combination with interferon and flaviviridae mutation |
DK1628685T3 (da) | 2003-04-25 | 2011-03-21 | Gilead Sciences Inc | Antivirale phosphonatanaloge |
WO2004112687A2 (en) | 2003-06-26 | 2004-12-29 | Biotron Limited | Antiviral acylguanidine compounds and methods |
GB0317009D0 (en) | 2003-07-21 | 2003-08-27 | Univ Cardiff | Chemical compounds |
BRPI0412849A (pt) | 2003-07-25 | 2006-09-26 | Idenix Cayman Ltd | compostos, composições e usos de análogos de nucleosìdeo de purina para o tratamento de flaviviridae, incluindo hepatite c |
JP2007504152A (ja) | 2003-08-27 | 2007-03-01 | ビオタ, インコーポレイテッド | 治療剤としての新規三環ヌクレオシドまたはヌクレオチド |
JP2005185235A (ja) * | 2003-12-26 | 2005-07-14 | Univ Of Tokyo | ウイルス感染に対する感受性診断のための方法およびキット。 |
JP2005187428A (ja) * | 2003-12-26 | 2005-07-14 | Univ Of Tokyo | 抗mgl抗体によるフィロウイルス治療薬 |
RS52365B (en) | 2004-03-16 | 2012-12-31 | Boehringer Ingelheim International Gmbh | BENZOL DERIVATIVES SUBSTITUTED BY GLUCOPYRANOSIL, MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS, THEIR USE AND THE PROCEDURE FOR THEIR PRODUCTION |
AU2005254057B2 (en) | 2004-06-15 | 2011-02-17 | Isis Pharmaceuticals, Inc. | C-purine nucleoside analogs as inhibitors of RNA-dependent RNA viral polymerase |
WO2006002231A1 (en) | 2004-06-22 | 2006-01-05 | Biocryst Pharmaceuticals, Inc. | Aza nucleosides, preparation thereof and use as inhibitors of rna viral polymerases |
PT3109244T (pt) | 2004-09-14 | 2019-06-04 | Gilead Pharmasset Llc | ¿preparação de ribofuranosil pirimidinas e purinas 2¿-fluoro-2¿-alquil substituídas ou outras opcionalmente substituídas e os seus derivados |
CN101043893A (zh) | 2004-10-21 | 2007-09-26 | 默克公司 | 治疗RNA-依赖性RNA病毒感染的氟化吡咯并[2,3-d]嘧啶核苷 |
CA2584367A1 (en) | 2004-10-21 | 2006-06-22 | Merck & Co., Inc. | Fluorinated pyrrolo[2,3-d]pyrimidine nucleosides for the treatment of rna-dependent rna viral infection |
WO2006050161A2 (en) | 2004-10-29 | 2006-05-11 | Biocryst Pharmaceuticals, Inc. | Therapeutic furopyrimidines and thienopyrimidines |
ATE407938T1 (de) | 2004-12-16 | 2008-09-15 | Boehringer Ingelheim Int | Glucopyranosyl-substituierte benzen-derivate, medikamente mit solchen verbindungen, ihre verwendung und herstellungsverfahren dafür |
EP1858889A1 (en) | 2005-03-08 | 2007-11-28 | Biota Scientific Management Pty. Ltd. | Bicyclic nucleosides and nucleotides as therapeutic agents |
WO2006104945A2 (en) | 2005-03-29 | 2006-10-05 | Biocryst Pharmaceuticals, Inc. | Hepatitis c therapies |
US7405204B2 (en) | 2005-04-25 | 2008-07-29 | Genelabs Technologies, Inc. | Nucleoside compounds for treating viral infections |
WO2006121820A1 (en) | 2005-05-05 | 2006-11-16 | Valeant Research & Development | Phosphoramidate prodrugs for treatment of viral infection |
WO2007027248A2 (en) | 2005-05-16 | 2007-03-08 | Valeant Research & Development | 3', 5' - cyclic nucleoside analogues for treatment of hcv |
DK1902017T3 (da) | 2005-06-24 | 2014-06-30 | Biotron Ltd | Antivirale acylguanidinforbindelser |
CN101321775B (zh) | 2005-10-03 | 2012-05-23 | 大学健康网络 | 用于治疗疟疾的odcase抑制剂 |
US8431695B2 (en) | 2005-11-02 | 2013-04-30 | Bayer Intellectual Property Gmbh | Pyrrolo[2,1-f][1,2,4]triazin-4-ylamines IGF-1R kinase inhibitors for the treatment of cancer and other hyperproliferative diseases |
JP5329969B2 (ja) | 2005-12-01 | 2013-10-30 | バジリア ファルマスーチカ アーゲー | エポキシブタノール中間体の製造方法 |
CN101466710B (zh) | 2005-12-02 | 2013-05-29 | 拜尔健康护理有限责任公司 | 用于治疗与血管生成有关的过度增殖性病症和疾病的取代的4-氨基-吡咯并三嗪衍生物 |
PE20070855A1 (es) | 2005-12-02 | 2007-10-14 | Bayer Pharmaceuticals Corp | Derivados de 4-amino-pirrolotriazina sustituida como inhibidores de quinasas |
EP1971331A2 (en) | 2005-12-09 | 2008-09-24 | Basilea Pharmaceutica AG | 4-oxo-(iso)tretinoin for the topical treatment of severe dermatological disorders |
KR101238461B1 (ko) | 2005-12-09 | 2013-03-05 | 길리어드 파마셋 엘엘씨 | 항바이러스성 뉴클레오시드 |
WO2007097991A2 (en) | 2006-02-16 | 2007-08-30 | Pharmasset, Inc. | Methods and kits for dosing of antiviral agents |
DE102006015378A1 (de) | 2006-04-03 | 2007-10-04 | Ludwig-Maximilians-Universität München | Verfahren zur Synthese von Organoelementverbindungen |
AR061024A1 (es) | 2006-05-22 | 2008-07-30 | Novartis Ag | Maleato de 5-amino-3- (2'3'-di-o-acetil-beta-d-ribofuranosil)-3h-tiazolo[4,5-d] pirimidin-2-ona. |
WO2008005542A2 (en) | 2006-07-07 | 2008-01-10 | Gilead Sciences, Inc., | Antiviral phosphinate compounds |
US20080161324A1 (en) | 2006-09-14 | 2008-07-03 | Johansen Lisa M | Compositions and methods for treatment of viral diseases |
JP2010508371A (ja) * | 2006-11-06 | 2010-03-18 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | グルコピラノシル置換フェニル誘導体、該化合物を含有する医薬品及びその使用と製造方法 |
JP2010513484A (ja) | 2006-12-20 | 2010-04-30 | メルク・シャープ・エンド・ドーム・コーポレイション | Rna依存性rnaウイルス感染治療用ヌクレオシド環状ホスホロアミデート |
US20080261913A1 (en) | 2006-12-28 | 2008-10-23 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of liver disorders |
EP2124555B1 (en) | 2007-01-05 | 2015-07-08 | Merck Sharp & Dohme Corp. | Nucleoside aryl phosphoramidates for the treatment of rna-dependent rna viral infection |
MX2009007333A (es) * | 2007-01-12 | 2009-08-31 | Biocryst Pharm Inc | Analogos de nucleosidos antivirales. |
EP2125819B1 (en) | 2007-03-21 | 2014-10-22 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful for the treatment of proliferative, allergic, autoimmune or inflammatory diseases |
US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
DK2155758T3 (da) | 2007-05-10 | 2012-11-05 | Biocryst Pharm Inc | Tetrahydrofuro[3,4-d]dioxolanforbindelser til anvendelse i behandlingen af virusinfektioner og cancer |
CN100532388C (zh) | 2007-07-16 | 2009-08-26 | 郑州大学 | 2’-氟-4’-取代-核苷类似物、其制备方法及应用 |
ES2563477T3 (es) | 2007-08-03 | 2016-03-15 | Biotron Limited | Composiciones antivirales para tratar la hepatitis C a base de 5-(1-metilpirazol-4-il)2-naftoilguanidina y 2'-C-metiladenosina o 2'-C-metilcitidina |
KR101502533B1 (ko) | 2007-11-22 | 2015-03-13 | 에스케이케미칼주식회사 | 우수한 안정성을 갖는 택산 유도체 함유 주사제용동결건조 조성물 및 이의 제조방법 |
TW200942243A (en) | 2008-03-05 | 2009-10-16 | Biocryst Pharm Inc | Antiviral therapeutic agents |
US8227431B2 (en) | 2008-03-17 | 2012-07-24 | Hetero Drugs Limited | Nucleoside derivatives |
WO2009132135A1 (en) | 2008-04-23 | 2009-10-29 | Gilead Sciences, Inc. | 1' -substituted carba-nucleoside analogs for antiviral treatment |
US7863291B2 (en) | 2008-04-23 | 2011-01-04 | Bristol-Myers Squibb Company | Quinuclidine compounds as alpha-7 nicotinic acetylcholine receptor ligands |
WO2010036407A2 (en) | 2008-05-15 | 2010-04-01 | Biocryst Pharmaceuticals, Inc. | Antiviral nucleoside analogs |
EP2313102A2 (en) | 2008-07-03 | 2011-04-27 | Biota Scientific Management | Bycyclic nucleosides and nucleotides as therapeutic agents |
CA2751277C (en) | 2009-02-10 | 2018-10-30 | Gilead Sciences, Inc. | Carba-nucleoside analogs for antiviral treatment |
AR075584A1 (es) | 2009-02-27 | 2011-04-20 | Intermune Inc | COMPOSICIONES TERAPEUTICAS QUE COMPRENDEN beta-D-2'-DESOXI-2'-FLUORO-2'-C-METILCITIDINA Y UN DERIVADO DE ACIDO ISOINDOL CARBOXILICO Y SUS USOS. COMPUESTO. |
AU2010226466A1 (en) | 2009-03-20 | 2011-10-20 | Alios Biopharma, Inc. | Substituted nucleoside and nucleotide analogs |
JP5766687B2 (ja) | 2009-03-24 | 2015-08-19 | バイオクリスト ファーマスーティカルズ,インコーポレイテッドBiocryst Pharmaceuticals,Inc. | 7−[(3r,4r)−3−ヒドロキシ−4−ヒドロキシメチル−ピロリジン−1−イルメチル]−3,5−ジヒドロ−ピロロ[3,2−d]ピリミジン−4−オンの有用な医薬塩 |
TWI598358B (zh) | 2009-05-20 | 2017-09-11 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
SG177709A1 (en) | 2009-07-21 | 2012-02-28 | Gilead Sciences Inc | Inhibitors of flaviviridae viruses |
US8455451B2 (en) | 2009-09-21 | 2013-06-04 | Gilead Sciences, Inc. | 2'-fluoro substituted carba-nucleoside analogs for antiviral treatment |
NZ599402A (en) | 2009-09-21 | 2014-02-28 | Gilead Sciences Inc | 2’ -fluoro substituted carba-nucleoside analogs for antiviral treatment |
DK2480559T3 (da) | 2009-09-21 | 2013-08-05 | Gilead Sciences Inc | Fremgangsmåder og mellemprodukter til fremstillingen af 1'-cyano-carbanukleosid-analoger |
US7973013B2 (en) | 2009-09-21 | 2011-07-05 | Gilead Sciences, Inc. | 2'-fluoro substituted carba-nucleoside analogs for antiviral treatment |
CN105859689A (zh) | 2009-12-28 | 2016-08-17 | 财团法人生物技术开发中心 | 作为mTOR和PI3K抑制剂的新颖嘧啶化合物 |
JP5872539B2 (ja) | 2010-03-31 | 2016-03-01 | ギリアド ファーマセット エルエルシー | プリンヌクレオシドホスホルアミダート |
CN102858790A (zh) | 2010-03-31 | 2013-01-02 | 吉利德制药有限责任公司 | 核苷氨基磷酸酯 |
TW201201815A (en) | 2010-05-28 | 2012-01-16 | Gilead Sciences Inc | 1'-substituted-carba-nucleoside prodrugs for antiviral treatment |
BR112013001267A2 (pt) * | 2010-07-19 | 2016-05-17 | Gilead Sciences Inc | métodos para a preparação de pró-fármacos de fosforamidato diasteromericamente puro |
CR20170278A (es) | 2010-07-22 | 2017-09-29 | Gilead Sciences Inc | Métodos y compuestos para tratar infecciones virales por paramyxoviridae |
TW201305185A (zh) | 2010-09-13 | 2013-02-01 | Gilead Sciences Inc | 用於抗病毒治療之2’-氟取代之碳-核苷類似物 |
KR101879887B1 (ko) | 2010-09-20 | 2018-07-18 | 길리애드 사이언시즈, 인코포레이티드 | 항바이러스 치료용 2'-플루오로 치환된 카바-누클레오시드 유사체 |
CA2810928A1 (en) | 2010-09-22 | 2012-03-29 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
CA2813783C (en) | 2010-10-15 | 2019-01-22 | Shanta Bantia | Methods and compositions for inhibition of polymerase |
PT3042910T (pt) | 2010-11-30 | 2019-04-16 | Gilead Pharmasset Llc | 2'-espiro-nucleósidos para utilização na terapia da hepatite c |
CA2822037A1 (en) | 2010-12-20 | 2012-06-28 | Gilead Sciences, Inc. | Methods for treating hcv |
WO2012142523A2 (en) | 2011-04-13 | 2012-10-18 | Gilead Sciences, Inc. | 1'-substituted pyrimidine n-nucleoside analogs for antiviral treatment |
EP2696681B1 (en) | 2011-04-13 | 2018-10-03 | Merck Sharp & Dohme Corp. | 2'-substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
AU2012256000B2 (en) | 2011-05-13 | 2017-05-11 | Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Hendra and Nipah virus G glycoprotein immunogenic compositions |
EP3384938A1 (en) * | 2011-09-12 | 2018-10-10 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
SG10201602044WA (en) | 2011-09-16 | 2016-04-28 | Gilead Pharmassett Llc | Methods For Treating HCV |
US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
WO2013084165A1 (en) | 2011-12-05 | 2013-06-13 | Medivir Ab | Hcv polymerase inhibitors |
US20130143835A1 (en) * | 2011-12-05 | 2013-06-06 | Medivir Ab | HCV Polymerase Inhibitors |
CA2860234A1 (en) * | 2011-12-22 | 2013-06-27 | Alios Biopharma, Inc. | Substituted phosphorothioate nucleotide analogs |
AU2013266393B2 (en) | 2012-05-22 | 2017-09-28 | Idenix Pharmaceuticals Llc | D-amino acid compounds for liver disease |
ES2671478T3 (es) | 2012-08-31 | 2018-06-06 | Novartis Ag | Derivados de 2'-etinil nucleósidos para el tratamiento de infecciones virales |
PE20150776A1 (es) | 2012-09-10 | 2015-05-21 | Hoffmann La Roche | 6-aminoacido-heteroarildihidropirimidinas para el tratamiento y profilaxis de la infeccion del virus de la hepatitis b |
WO2014042433A2 (en) * | 2012-09-14 | 2014-03-20 | Kainos Medicine, Inc. | Compounds and compositions for modulating adenosine a3 receptor activity |
EP3251674A3 (en) | 2012-11-16 | 2018-02-21 | BioCryst Pharmaceuticals, Inc. | Antiviral azasugar-containing nucleosides |
US9732111B2 (en) | 2012-11-19 | 2017-08-15 | Merck Sharp & Dohme Corp. | 2′-alkynyl substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
EP3421482A1 (en) * | 2012-12-21 | 2019-01-02 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
US9283242B2 (en) | 2013-01-22 | 2016-03-15 | Massachusetts Institute Of Technology | Uses of dihydro bases |
US10034893B2 (en) | 2013-02-01 | 2018-07-31 | Enanta Pharmaceuticals, Inc. | 5, 6-D2 uridine nucleoside/tide derivatives |
BR112015025716A2 (pt) | 2013-04-12 | 2017-07-18 | Achillion Pharmaceuticals Inc | pró-fármacos de nucleosídeo submetidos a deutério úteis para o tratamento de hcv |
US9542154B2 (en) | 2013-06-25 | 2017-01-10 | Intel Corporation | Fused multiply add operations using bit masks |
UA117375C2 (uk) * | 2013-09-04 | 2018-07-25 | Медівір Аб | Інгібітори полімерази hcv |
BR112016005507B1 (pt) | 2013-09-11 | 2023-02-07 | Centre National De La Recherche Scientifique (Cnrs) | Uso de um agonista do receptor farnesoide x (fxr) |
UA119050C2 (uk) * | 2013-11-11 | 2019-04-25 | Ґілеад Саєнсиз, Інк. | ПІРОЛО[1.2-f][1.2.4]ТРИАЗИНИ, ЯКІ ВИКОРИСТОВУЮТЬСЯ ДЛЯ ЛІКУВАННЯ РЕСПІРАТОРНО-СИНЦИТІАЛЬНИХ ВІРУСНИХ ІНФЕКЦІЙ |
CN105899508B (zh) | 2014-01-30 | 2017-07-04 | 豪夫迈·罗氏有限公司 | 用于治疗和预防乙型肝炎病毒感染的新型二氢喹嗪酮类化合物 |
NZ721520A (en) | 2014-03-07 | 2023-03-31 | Hoffmann La Roche | Novel 6-fused heteroaryldihydropyrimidines for the treatment and prophylaxis of hepatitis b virus infection |
CN106459032B (zh) | 2014-05-13 | 2019-04-05 | 豪夫迈·罗氏有限公司 | 治疗和预防乙型肝炎病毒感染的新的二氢喹嗪酮类 |
US9504701B2 (en) | 2014-06-02 | 2016-11-29 | The Board Of Regents Of The University Of Texas System | Methods for treating viral infections using hydrogen sulfide donors |
US9616076B2 (en) * | 2014-06-02 | 2017-04-11 | The Board Of Regents Of The University Of Texas Systems | Methods for treating viral infections using hydrogen sulfide donors |
WO2016012470A1 (en) | 2014-07-25 | 2016-01-28 | F. Hoffmann-La Roche Ag | New amorphous and crystalline forms of (3s)-4-[[(4r)-4-(2-chloro-4-fluoro-phenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1, 4-dihydropyrimidin-6-yl]methyl]morpholine-3-carboxylic acid |
EP3180319B1 (en) | 2014-08-14 | 2018-10-03 | F.Hoffmann-La Roche Ag | Novel pyridazones and triazinones for the treatment and prophylaxis of hepatitis b virus infection |
TWI740546B (zh) | 2014-10-29 | 2021-09-21 | 美商基利科學股份有限公司 | 製備核糖苷的方法 |
US9637485B2 (en) | 2014-11-03 | 2017-05-02 | Hoffmann-La Roche Inc. | 6,7-dihydrobenzo[a]quinolizin-2-one derivatives for the treatment and prophylaxis of hepatitis B virus infection |
WO2016102438A1 (en) | 2014-12-23 | 2016-06-30 | F. Hoffmann-La Roche Ag | Process for the preparation of 4-phenyl-5-alkoxycarbonyl-2-thiazol-2-yl-1,4-dihydropyrimidine analogues |
US9676793B2 (en) | 2014-12-23 | 2017-06-13 | Hoffmann-Laroche Inc. | Co-crystals of 5-amino-2-oxothiazolo[4,5-d]pyrimidin-3(2H)-yl-5-hydroxymethyl tetrahydrofuran-3-yl acetate and methods for preparing and using the same |
EP3240537B1 (en) | 2014-12-30 | 2020-09-09 | F. Hoffmann-La Roche AG | Novel tetrahydropyridopyrimidines and tetrahydropyridopyridines for the treatment and prophylaxis of hepatitis b virus infection |
EP3240913A1 (en) | 2014-12-31 | 2017-11-08 | F. Hoffmann-La Roche AG | A novel high-throughput method for quantification of hbv cccdna from cell lysate by real-time pcr |
MA41338B1 (fr) | 2015-01-16 | 2019-07-31 | Hoffmann La Roche | Composés de pyrazine pour le traitement de maladies infectieuses |
EP3250685A1 (en) | 2015-01-27 | 2017-12-06 | F. Hoffmann-La Roche AG | Recombinant hbv cccdna, the method to generate thereof and the use thereof |
CN107207505B (zh) | 2015-02-11 | 2018-12-14 | 豪夫迈·罗氏有限公司 | 治疗和预防乙型肝炎病毒感染的 2-氧代-6,7-二氢苯并[a]喹嗪-3-甲酸衍生物 |
SG10202001878WA (en) | 2015-09-16 | 2020-04-29 | Gilead Sciences Inc | Methods for treating arenaviridae and coronaviridae virus infections |
WO2017184668A1 (en) | 2016-04-20 | 2017-10-26 | Gilead Sciences, Inc. | Methods for treating flaviviridae virus infections |
KR102607599B1 (ko) | 2017-02-08 | 2023-11-28 | 바이오트론 리미티드 | 인플루엔자의 치료 방법 |
KR102460968B1 (ko) | 2017-03-14 | 2022-11-01 | 길리애드 사이언시즈, 인코포레이티드 | 고양이 코로나바이러스 감염의 치료 방법 |
WO2018204198A1 (en) | 2017-05-01 | 2018-11-08 | Gilead Sciences, Inc. | Crystalline forms of (s) 2 ethylbutyl 2 (((s) (((2r,3s,4r,5r) 5 (4 aminopyrrolo[2,1-f] [1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2 yl)methoxy)(phenoxy) phosphoryl)amino)propanoate |
CA3077489A1 (en) | 2017-07-11 | 2019-01-17 | Gilead Sciences, Inc. | Compositions comprising an rna polymerase inhibitor and cyclodextrin for treating viral infections |
CN111265532A (zh) | 2020-01-21 | 2020-06-12 | 中国人民解放军军事科学院军事医学研究院 | 取代氨基丙酸酯类化合物在治疗2019-nCoV感染中的应用 |
CA3163424A1 (en) | 2020-01-27 | 2021-08-05 | Gilead Sciences, Inc. | Methods for treating sars cov-2 infections |
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