NZ576817A - Hepatitis c virus inhibitors - Google Patents

Info

Publication number

NZ576817A

NZ576817A NZ576817A NZ57681707A NZ576817A NZ 576817 A NZ576817 A NZ 576817A NZ 576817 A NZ576817 A NZ 576817A NZ 57681707 A NZ57681707 A NZ 57681707A NZ 576817 A NZ576817 A NZ 576817A

Authority

NZ

New Zealand

Prior art keywords

methoxy

oxy

methyl

cyclopropylsulfonyl

carbamoyl

Prior art date

2006-11-09

Links

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• Global Dossier
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• 239000003112 inhibitor Substances 0.000 title claims description 23
• 241000711549 Hepacivirus C Species 0.000 title abstract description 51
• 150000001875 compounds Chemical class 0.000 claims abstract description 397
• 238000011282 treatment Methods 0.000 claims abstract description 24
• 208000015181 infectious disease Diseases 0.000 claims abstract description 11
• 239000000203 mixture Substances 0.000 claims description 291
• 238000002360 preparation method Methods 0.000 claims description 130
• 125000000217 alkyl group Chemical group 0.000 claims description 99
• -1 (NRH^sulfonyl Chemical group 0.000 claims description 75
• 150000003839 salts Chemical class 0.000 claims description 48
• 125000003118 aryl group Chemical group 0.000 claims description 46
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
• 125000003545 alkoxy group Chemical group 0.000 claims description 43
• 125000005843 halogen group Chemical group 0.000 claims description 38
• 125000001188 haloalkyl group Chemical group 0.000 claims description 34
• 108010050904 Interferons Proteins 0.000 claims description 32
• 102000014150 Interferons Human genes 0.000 claims description 32
• 229940079322 interferon Drugs 0.000 claims description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 239000001257 hydrogen Substances 0.000 claims description 30
• 229910052757 nitrogen Inorganic materials 0.000 claims description 30
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 29
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 29
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 28
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
• 125000000623 heterocyclic group Chemical group 0.000 claims description 28
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 27
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 26
• 125000003342 alkenyl group Chemical group 0.000 claims description 23
• 230000000694 effects Effects 0.000 claims description 23
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 20
• 229960000329 ribavirin Drugs 0.000 claims description 19
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 19
• 125000005842 heteroatom Chemical group 0.000 claims description 17
• 229910052717 sulfur Chemical group 0.000 claims description 16
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 15
• 229910052760 oxygen Inorganic materials 0.000 claims description 15
• 239000001301 oxygen Chemical group 0.000 claims description 15
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
• 239000011593 sulfur Chemical group 0.000 claims description 15
• 125000004432 carbon atom Chemical group C* 0.000 claims description 14
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 13
• 125000001153 fluoro group Chemical group F* 0.000 claims description 12
• 108010047761 Interferon-alpha Proteins 0.000 claims description 11
• 102000006992 Interferon-alpha Human genes 0.000 claims description 11
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
• 239000003937 drug carrier Substances 0.000 claims description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 10
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 8
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 229910052702 rhenium Inorganic materials 0.000 claims description 8
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 7
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 6
• 101710200424 Inosine-5'-monophosphate dehydrogenase Proteins 0.000 claims description 6
• VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 claims description 6
• 101800001019 Non-structural protein 4B Proteins 0.000 claims description 6
• 102000012479 Serine Proteases Human genes 0.000 claims description 6
• 108010022999 Serine Proteases Proteins 0.000 claims description 6
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
• 108060004795 Methyltransferase Proteins 0.000 claims description 5
• 125000004414 alkyl thio group Chemical group 0.000 claims description 5
• 238000011161 development Methods 0.000 claims description 5
• 108090000623 proteins and genes Proteins 0.000 claims description 5
• UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 claims description 4
• 108020005544 Antisense RNA Proteins 0.000 claims description 4
• 102100040018 Interferon alpha-2 Human genes 0.000 claims description 4
• 108010079944 Interferon-alpha2b Proteins 0.000 claims description 4
• 102000013462 Interleukin-12 Human genes 0.000 claims description 4
• 108010065805 Interleukin-12 Proteins 0.000 claims description 4
• 102000000588 Interleukin-2 Human genes 0.000 claims description 4
• 108010002350 Interleukin-2 Proteins 0.000 claims description 4
• 102000004889 Interleukin-6 Human genes 0.000 claims description 4
• 108090001005 Interleukin-6 Proteins 0.000 claims description 4
• 108010006035 Metalloproteases Proteins 0.000 claims description 4
• 102000005741 Metalloproteases Human genes 0.000 claims description 4
• 101800001014 Non-structural protein 5A Proteins 0.000 claims description 4
• 230000005867 T cell response Effects 0.000 claims description 4
• DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 4
• 229960003805 amantadine Drugs 0.000 claims description 4
• 239000003184 complementary RNA Substances 0.000 claims description 4
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
• 210000002443 helper t lymphocyte Anatomy 0.000 claims description 4
• 230000002452 interceptive effect Effects 0.000 claims description 4
• 108700027921 interferon tau Proteins 0.000 claims description 4
• 229940117681 interleukin-12 Drugs 0.000 claims description 4
• 229940100601 interleukin-6 Drugs 0.000 claims description 4
• 229960000888 rimantadine Drugs 0.000 claims description 4
• HAEJPQIATWHALX-KQYNXXCUSA-N ITP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CNC2=O)=C2N=C1 HAEJPQIATWHALX-KQYNXXCUSA-N 0.000 claims description 3
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
• 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
• 102000004169 proteins and genes Human genes 0.000 claims description 3
• 101710088194 Dehydrogenase Proteins 0.000 claims description 2
• 229940124186 Dehydrogenase inhibitor Drugs 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• 229920002554 vinyl polymer Polymers 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 406
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 354
• 239000000047 product Substances 0.000 description 248
• 239000000243 solution Substances 0.000 description 189
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 169
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 150
• 239000007787 solid Substances 0.000 description 139
• 235000019439 ethyl acetate Nutrition 0.000 description 131
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 130
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 125
• 238000000034 method Methods 0.000 description 109
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 94
• 239000012071 phase Substances 0.000 description 86
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
• 238000002953 preparative HPLC Methods 0.000 description 78
• 229910001868 water Inorganic materials 0.000 description 74
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 73
• 238000006243 chemical reaction Methods 0.000 description 73
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 72
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 69
• 230000002441 reversible effect Effects 0.000 description 66
• 239000011541 reaction mixture Substances 0.000 description 63
• 239000007821 HATU Substances 0.000 description 60
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 55
• 239000012267 brine Substances 0.000 description 53
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 53
• 239000002904 solvent Substances 0.000 description 52
• ZHGNHOOVYPHPNJ-UHFFFAOYSA-N Amigdalin Chemical compound FC(F)(F)C(=O)OCC1OC(OCC2OC(OC(C#N)C3=CC=CC=C3)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C2OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C(OC(=O)C(F)(F)F)C1OC(=O)C(F)(F)F ZHGNHOOVYPHPNJ-UHFFFAOYSA-N 0.000 description 47
• 239000000543 intermediate Substances 0.000 description 47
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 46
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• 239000000843 powder Substances 0.000 description 42
• 238000000746 purification Methods 0.000 description 40
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
• 239000003921 oil Substances 0.000 description 39
• GPKDGVXBXQTHRY-UHFFFAOYSA-N 3-chloropropane-1-sulfonyl chloride Chemical compound ClCCCS(Cl)(=O)=O GPKDGVXBXQTHRY-UHFFFAOYSA-N 0.000 description 38
• 235000019198 oils Nutrition 0.000 description 38
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 37
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
• 230000008569 process Effects 0.000 description 34
• 239000002253 acid Substances 0.000 description 33
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 33
• 230000015572 biosynthetic process Effects 0.000 description 32
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 27
• 230000000840 anti-viral effect Effects 0.000 description 26
• 239000000725 suspension Substances 0.000 description 26
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 25
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 24
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 23
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 23
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 22
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• 238000010992 reflux Methods 0.000 description 20
• 238000010898 silica gel chromatography Methods 0.000 description 20
• 150000002431 hydrogen Chemical group 0.000 description 19
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• 239000008346 aqueous phase Substances 0.000 description 17
• 238000010168 coupling process Methods 0.000 description 17
• 239000000706 filtrate Substances 0.000 description 17
• VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 17
• 239000000463 material Substances 0.000 description 17
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• BRGZEQXWZWBPJH-UHFFFAOYSA-N 1,3-dichloroisoquinoline Chemical compound C1=CC=C2C(Cl)=NC(Cl)=CC2=C1 BRGZEQXWZWBPJH-UHFFFAOYSA-N 0.000 description 16
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 16
• 229940124530 sulfonamide Drugs 0.000 description 16
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 15
• 230000008878 coupling Effects 0.000 description 15
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 15
• 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 14
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• 239000012044 organic layer Substances 0.000 description 14
• 239000011734 sodium Substances 0.000 description 14
• 239000000872 buffer Substances 0.000 description 13
• 239000006260 foam Substances 0.000 description 13
• 229920006395 saturated elastomer Polymers 0.000 description 13
• 229910000029 sodium carbonate Inorganic materials 0.000 description 13
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
• 239000004480 active ingredient Substances 0.000 description 12
• 239000012043 crude product Substances 0.000 description 12
• WMSPXQIQBQAWLL-UHFFFAOYSA-N cyclopropanesulfonamide Chemical compound NS(=O)(=O)C1CC1 WMSPXQIQBQAWLL-UHFFFAOYSA-N 0.000 description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
• 238000009472 formulation Methods 0.000 description 12
• 229960005235 piperonyl butoxide Drugs 0.000 description 12
• 229910052708 sodium Inorganic materials 0.000 description 12
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 11
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• QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 11
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• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
• 239000013078 crystal Substances 0.000 description 10
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• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 10
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• 238000003818 flash chromatography Methods 0.000 description 9
• AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 9
• 239000011591 potassium Substances 0.000 description 9
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• 239000003826 tablet Substances 0.000 description 9
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
• 241000287219 Serinus canaria Species 0.000 description 8
• 239000013058 crude material Substances 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• 229910052763 palladium Inorganic materials 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• RLJWTAURUFQFJP-UHFFFAOYSA-N propan-2-ol;titanium Chemical compound [Ti].CC(C)O.CC(C)O.CC(C)O.CC(C)O RLJWTAURUFQFJP-UHFFFAOYSA-N 0.000 description 8
• NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 8
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• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
• OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 7
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 7
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
• 101710144111 Non-structural protein 3 Proteins 0.000 description 7
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
• 230000005587 bubbling Effects 0.000 description 7
• 238000003776 cleavage reaction Methods 0.000 description 7
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• 230000007017 scission Effects 0.000 description 7
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