TWI423798B - Ｃ型肝炎病毒抑制劑 - Google Patents

Info

Publication number

TWI423798B

TWI423798B TW098104732A TW98104732A TWI423798B TW I423798 B TWI423798 B TW I423798B TW 098104732 A TW098104732 A TW 098104732A TW 98104732 A TW98104732 A TW 98104732A TW I423798 B TWI423798 B TW I423798B

Authority

TW

Taiwan

Prior art keywords

group

imidazol

pyrrolidinyl

methyl

alkyl

Prior art date

2008-02-13

Links

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• Global Dossier
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• 241000711549 Hepacivirus C Species 0.000 title description 54
• 239000003112 inhibitor Substances 0.000 title 1
• 239000000203 mixture Substances 0.000 claims description 207
• 150000001875 compounds Chemical class 0.000 claims description 166
• 125000000217 alkyl group Chemical group 0.000 claims description 121
• 229910052739 hydrogen Inorganic materials 0.000 claims description 82
• -1 carboxy, decyl Chemical group 0.000 claims description 68
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 62
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 61
• 125000003118 aryl group Chemical group 0.000 claims description 52
• 150000003839 salts Chemical class 0.000 claims description 50
• 125000000623 heterocyclic group Chemical group 0.000 claims description 40
• 239000001257 hydrogen Substances 0.000 claims description 34
• 125000003545 alkoxy group Chemical group 0.000 claims description 33
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 30
• GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 30
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 30
• 125000001188 haloalkyl group Chemical group 0.000 claims description 29
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 27
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 27
• 229910052757 nitrogen Inorganic materials 0.000 claims description 27
• 125000005843 halogen group Chemical group 0.000 claims description 25
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 19
• 238000011282 treatment Methods 0.000 claims description 19
• 101800001014 Non-structural protein 5A Proteins 0.000 claims description 18
• 125000001424 substituent group Chemical group 0.000 claims description 18
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 17
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 17
• 229910052717 sulfur Inorganic materials 0.000 claims description 17
• 125000003342 alkenyl group Chemical group 0.000 claims description 16
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 16
• 230000000694 effects Effects 0.000 claims description 14
• 150000002431 hydrogen Chemical class 0.000 claims description 13
• 229920006395 saturated elastomer Polymers 0.000 claims description 13
• 108010047761 Interferon-alpha Proteins 0.000 claims description 12
• 102000006992 Interferon-alpha Human genes 0.000 claims description 12
• 102000014150 Interferons Human genes 0.000 claims description 12
• 108010050904 Interferons Proteins 0.000 claims description 12
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 229940079322 interferon Drugs 0.000 claims description 12
• 239000001301 oxygen Substances 0.000 claims description 12
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 11
• 229910052799 carbon Inorganic materials 0.000 claims description 11
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
• 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 10
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
• 125000004432 carbon atom Chemical group C* 0.000 claims description 10
• 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 10
• 229960000329 ribavirin Drugs 0.000 claims description 10
• 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 9
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
• 150000001721 carbon Chemical group 0.000 claims description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
• 239000003814 drug Substances 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 8
• 208000015181 infectious disease Diseases 0.000 claims description 8
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 7
• 125000002619 bicyclic group Chemical group 0.000 claims description 7
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 7
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 claims description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
• 125000004429 atom Chemical group 0.000 claims description 6
• 125000004122 cyclic group Chemical group 0.000 claims description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
• 125000003003 spiro group Chemical group 0.000 claims description 6
• 239000011593 sulfur Substances 0.000 claims description 6
• KPPVNWGJXFMGAM-UUILKARUSA-N (e)-2-methyl-1-(6-methyl-3,4-dihydro-2h-quinolin-1-yl)but-2-en-1-one Chemical compound CC1=CC=C2N(C(=O)C(/C)=C/C)CCCC2=C1 KPPVNWGJXFMGAM-UUILKARUSA-N 0.000 claims description 5
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• 108010006035 Metalloproteases Proteins 0.000 claims description 5
• 102000005741 Metalloproteases Human genes 0.000 claims description 5
• 108060004795 Methyltransferase Proteins 0.000 claims description 5
• 101800001019 Non-structural protein 4B Proteins 0.000 claims description 5
• 108010022999 Serine Proteases Proteins 0.000 claims description 5
• 102000012479 Serine Proteases Human genes 0.000 claims description 5
• 229940079593 drug Drugs 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
• 101710200424 Inosine-5'-monophosphate dehydrogenase 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
• 230000005867 T cell response Effects 0.000 claims description 4
• IVHKZGYFKJRXBD-UHFFFAOYSA-N amino carbamate Chemical compound NOC(N)=O IVHKZGYFKJRXBD-UHFFFAOYSA-N 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
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
• 108020005544 Antisense RNA Proteins 0.000 claims description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
• 229910005965 SO 2 Inorganic materials 0.000 claims description 3
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
• 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 3
• 239000003184 complementary RNA Substances 0.000 claims description 3
• 125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 3
• 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 claims description 3
• 125000004449 heterocyclylalkenyl group Chemical group 0.000 claims description 3
• 239000002348 inosinate dehydrogenase inhibitor Substances 0.000 claims description 3
• BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 3
• WHSFCMKKZRMSEQ-UHFFFAOYSA-N 2-amino-2-iminoacetic acid Chemical compound NC(=N)C(O)=O WHSFCMKKZRMSEQ-UHFFFAOYSA-N 0.000 claims description 2
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
• 229910020008 S(O) Inorganic materials 0.000 claims description 2
• 125000002252 acyl group Chemical group 0.000 claims description 2
• DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 2
• 229960003805 amantadine Drugs 0.000 claims description 2
• 229960002751 imiquimod Drugs 0.000 claims description 2
• DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• WFJRIDQGVSJLLH-UHFFFAOYSA-N methyl n-aminocarbamate Chemical compound COC(=O)NN WFJRIDQGVSJLLH-UHFFFAOYSA-N 0.000 claims description 2
• 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 claims 4
• UMPWFNPLHSVRAN-UHFFFAOYSA-N 2-(diethylamino)-2-phenylacetaldehyde Chemical compound CCN(CC)C(C=O)C1=CC=CC=C1 UMPWFNPLHSVRAN-UHFFFAOYSA-N 0.000 claims 2
• 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims 1
• 150000001336 alkenes Chemical class 0.000 claims 1
• TZIHFWKZFHZASV-UHFFFAOYSA-N anhydrous methyl formate Natural products COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 claims 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
• PQJFJRGZSZKPTF-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O.COC(N)=O PQJFJRGZSZKPTF-UHFFFAOYSA-N 0.000 claims 1
• VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 claims 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
• BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 360
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 320
• 238000005481 NMR spectroscopy Methods 0.000 description 166
• 235000019439 ethyl acetate Nutrition 0.000 description 139
• 239000000243 solution Substances 0.000 description 125
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 106
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 105
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 105
• 238000004458 analytical method Methods 0.000 description 103
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 93
• 239000007787 solid Substances 0.000 description 81
• 238000000034 method Methods 0.000 description 78
• 239000011541 reaction mixture Substances 0.000 description 74
• 239000002904 solvent Substances 0.000 description 66
• 239000000460 chlorine Substances 0.000 description 57
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
• 238000003756 stirring Methods 0.000 description 41
• 239000003921 oil Substances 0.000 description 39
• 235000019198 oils Nutrition 0.000 description 38
• 239000000047 product Substances 0.000 description 38
• 239000011734 sodium Substances 0.000 description 38
• 239000012074 organic phase Substances 0.000 description 37
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 35
• 239000000725 suspension Substances 0.000 description 35
• 239000012267 brine Substances 0.000 description 34
• 238000006243 chemical reaction Methods 0.000 description 34
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 33
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• 238000000746 purification Methods 0.000 description 33
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
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• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• 150000001412 amines Chemical class 0.000 description 24
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• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
• 239000002585 base Substances 0.000 description 20
• 238000004128 high performance liquid chromatography Methods 0.000 description 20
• 238000002953 preparative HPLC Methods 0.000 description 20
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• 239000005909 Kieselgur Substances 0.000 description 19
• 238000001816 cooling Methods 0.000 description 19
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
• 239000000706 filtrate Substances 0.000 description 17
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 16
• 239000000543 intermediate Substances 0.000 description 16
• 230000002829 reductive effect Effects 0.000 description 16
• 238000004007 reversed phase HPLC Methods 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 15
• 239000010410 layer Substances 0.000 description 15
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• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 14
• 150000002148 esters Chemical class 0.000 description 14
• 239000008194 pharmaceutical composition Substances 0.000 description 14
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• 239000006260 foam Substances 0.000 description 13
• 239000005457 ice water Substances 0.000 description 12
• 229910052763 palladium Inorganic materials 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• 239000000741 silica gel Substances 0.000 description 12
• 229910002027 silica gel Inorganic materials 0.000 description 12
• 239000007821 HATU Substances 0.000 description 11
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 11
• 238000003818 flash chromatography Methods 0.000 description 11
• 238000009472 formulation Methods 0.000 description 11
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
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• 239000000126 substance Substances 0.000 description 10
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• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
• 150000005331 phenylglycines Chemical class 0.000 description 9
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• 125000002102 aryl alkyloxo group Chemical group 0.000 description 8
• 201000010099 disease Diseases 0.000 description 8
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• 239000000499 gel Substances 0.000 description 8
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• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
• 125000004430 oxygen atom Chemical group O* 0.000 description 8
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• VONGZNXBKCOUHB-UHFFFAOYSA-N Phenylmethyl butanoate Chemical compound CCCC(=O)OCC1=CC=CC=C1 VONGZNXBKCOUHB-UHFFFAOYSA-N 0.000 description 7
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 230000002441 reversible effect Effects 0.000 description 7
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• 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 6
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
• 101710144111 Non-structural protein 3 Proteins 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• 235000001014 amino acid Nutrition 0.000 description 6
• 125000005129 aryl carbonyl group Chemical group 0.000 description 6
• DDKMFOUTRRODRE-UHFFFAOYSA-N chloromethanone Chemical compound Cl[C]=O DDKMFOUTRRODRE-UHFFFAOYSA-N 0.000 description 6
• 238000002347 injection Methods 0.000 description 6
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