UA124184C2 - 3-ЗАМІЩЕНІ 5-АМІНО-6H-ТІАЗОЛО[4,5-d]ПІРИМІДИН-2,7-ДІОНОВІ СПОЛУКИ ДЛЯ ЛІКУВАННЯ І ПРОФІЛАКТИКИ ВІРУСНИХ ІНФЕКЦІЙ - Google Patents

Info

Publication number

UA124184C2

UA124184C2 UAA201706823A UAA201706823A UA124184C2 UA 124184 C2 UA124184 C2 UA 124184C2 UA A201706823 A UAA201706823 A UA A201706823A UA A201706823 A UAA201706823 A UA A201706823A UA 124184 C2 UA124184 C2 UA 124184C2

Authority

UA

Ukraine

Prior art keywords

amino

compound

hydroxy

pyrimidine

tetrahydrofuran

Prior art date

2014-12-08

Links

• Espacenet
• Global Dossier
• Discuss

• -1 3-SUBSTITUTED 5-AMINO-6H-THIAZOLO [4,5-d] PYRIMIDINE-2,7-DIONE COMPOUNDS Chemical class 0.000 title claims description 56
• 238000011282 treatment Methods 0.000 title claims description 36
• 230000002265 prevention Effects 0.000 title claims description 6
• 208000036142 Viral infection Diseases 0.000 title description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 455
• 150000003839 salts Chemical class 0.000 claims abstract description 54
• 238000000034 method Methods 0.000 claims abstract description 20
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 12
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 125
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 98
• 229910052739 hydrogen Inorganic materials 0.000 claims description 58
• 239000001257 hydrogen Substances 0.000 claims description 57
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 47
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 44
• 238000006243 chemical reaction Methods 0.000 claims description 40
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• 239000003153 chemical reaction reagent Substances 0.000 claims description 16
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
• 125000001544 thienyl group Chemical group 0.000 claims description 13
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims description 9
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 7
• 208000002672 hepatitis B Diseases 0.000 claims description 7
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 6
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
• OANDNNNKGULGJK-UHFFFAOYSA-N oxolane-3-carbonitrile Chemical compound N#CC1CCOC1 OANDNNNKGULGJK-UHFFFAOYSA-N 0.000 claims description 6
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 5
• 150000008065 acid anhydrides Chemical class 0.000 claims description 5
• 125000002252 acyl group Chemical group 0.000 claims description 5
• 238000004458 analytical method Methods 0.000 claims description 5
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
• 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 5
• 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 4
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 4
• YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 3
• 229940090181 propyl acetate Drugs 0.000 claims description 3
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 3
• 239000013543 active substance Substances 0.000 claims description 2
• 229910052702 rhenium Inorganic materials 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 10
• 239000000203 mixture Substances 0.000 abstract description 92
• 239000000651 prodrug Substances 0.000 abstract description 32
• 229940002612 prodrug Drugs 0.000 abstract description 32
• 239000000243 solution Substances 0.000 description 167
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 140
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 107
• 238000002360 preparation method Methods 0.000 description 106
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
• 239000002244 precipitate Substances 0.000 description 96
• 238000005481 NMR spectroscopy Methods 0.000 description 93
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 75
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 73
• 239000012044 organic layer Substances 0.000 description 71
• 235000019439 ethyl acetate Nutrition 0.000 description 69
• 239000007787 solid Substances 0.000 description 62
• 239000011541 reaction mixture Substances 0.000 description 56
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 53
• 239000003208 petroleum Substances 0.000 description 52
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 46
• WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 46
• 239000000741 silica gel Substances 0.000 description 46
• 229910002027 silica gel Inorganic materials 0.000 description 46
• 238000004440 column chromatography Methods 0.000 description 42
• 238000002953 preparative HPLC Methods 0.000 description 41
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 37
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 35
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 35
• 229940095102 methyl benzoate Drugs 0.000 description 32
• 239000012043 crude product Substances 0.000 description 29
• 239000012047 saturated solution Substances 0.000 description 29
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
• 238000000746 purification Methods 0.000 description 27
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 25
• MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 24
• 239000003921 oil Substances 0.000 description 24
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
• 229910052770 Uranium Inorganic materials 0.000 description 23
• 238000003756 stirring Methods 0.000 description 23
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 22
• 239000011572 manganese Substances 0.000 description 21
• 239000000556 agonist Substances 0.000 description 20
• 239000012300 argon atmosphere Substances 0.000 description 20
• 238000010898 silica gel chromatography Methods 0.000 description 20
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
• 229920006395 saturated elastomer Polymers 0.000 description 19
• YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 18
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 18
• 239000002904 solvent Substances 0.000 description 18
• 210000004027 cell Anatomy 0.000 description 17
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 16
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
• 239000008346 aqueous phase Substances 0.000 description 16
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 235000011054 acetic acid Nutrition 0.000 description 15
• 150000002431 hydrogen Chemical class 0.000 description 15
• FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 15
• 239000000725 suspension Substances 0.000 description 15
• 238000001816 cooling Methods 0.000 description 14
• 241000282414 Homo sapiens Species 0.000 description 13
• 239000012230 colorless oil Substances 0.000 description 13
• 239000000706 filtrate Substances 0.000 description 13
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
• 125000004093 cyano group Chemical group *C#N 0.000 description 12
• 239000003814 drug Substances 0.000 description 12
• 238000010438 heat treatment Methods 0.000 description 12
• 210000003494 hepatocyte Anatomy 0.000 description 12
• 229910052740 iodine Inorganic materials 0.000 description 12
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 10
• MCNQUWLLXZZZAC-UHFFFAOYSA-N 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C#N)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl MCNQUWLLXZZZAC-UHFFFAOYSA-N 0.000 description 10
• 108020004414 DNA Proteins 0.000 description 10
• 229910004373 HOAc Inorganic materials 0.000 description 10
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
• 241000699670 Mus sp. Species 0.000 description 10
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 10
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
• 229940079593 drug Drugs 0.000 description 10
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 10
• 108020003175 receptors Proteins 0.000 description 10
• 102000005962 receptors Human genes 0.000 description 10
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 10
• 229920002554 vinyl polymer Polymers 0.000 description 10
• 239000002253 acid Substances 0.000 description 9
• 238000004128 high performance liquid chromatography Methods 0.000 description 9
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
• 230000004913 activation Effects 0.000 description 8
• 230000000840 anti-viral effect Effects 0.000 description 8
• 239000012298 atmosphere Substances 0.000 description 8
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 102000004127 Cytokines Human genes 0.000 description 7
• 108090000695 Cytokines Proteins 0.000 description 7
• 241000699666 Mus <mouse, genus> Species 0.000 description 7
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 238000010511 deprotection reaction Methods 0.000 description 7
• 125000000623 heterocyclic group Chemical group 0.000 description 7
• 239000013067 intermediate product Substances 0.000 description 7
• 238000007912 intraperitoneal administration Methods 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• 238000002560 therapeutic procedure Methods 0.000 description 7
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
• 241000700721 Hepatitis B virus Species 0.000 description 6
• 241001529936 Murinae Species 0.000 description 6
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 6
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 230000001684 chronic effect Effects 0.000 description 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 238000011534 incubation Methods 0.000 description 6
• 208000015181 infectious disease Diseases 0.000 description 6
• 239000002609 medium Substances 0.000 description 6
• 230000002503 metabolic effect Effects 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 125000002757 morpholinyl group Chemical group 0.000 description 6
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
• 125000003729 nucleotide group Chemical group 0.000 description 6
• 125000003386 piperidinyl group Chemical group 0.000 description 6
• 210000002966 serum Anatomy 0.000 description 6
• 230000000638 stimulation Effects 0.000 description 6
• 230000001225 therapeutic effect Effects 0.000 description 6
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 6
• IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 5
• 241000711549 Hepacivirus C Species 0.000 description 5
• 125000000217 alkyl group Chemical group 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 125000004432 carbon atom Chemical group C* 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 125000005394 methallyl group Chemical group 0.000 description 5
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 5
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 5
• 239000002773 nucleotide Substances 0.000 description 5
• 239000000546 pharmaceutical excipient Substances 0.000 description 5
• 230000009467 reduction Effects 0.000 description 5
• 239000006228 supernatant Substances 0.000 description 5
• MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 5
• OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical class [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 4
• 241000700605 Viruses Species 0.000 description 4
• YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 4
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
• 230000001270 agonistic effect Effects 0.000 description 4
• 238000013459 approach Methods 0.000 description 4
• UDEWPOVQBGFNGE-UHFFFAOYSA-N benzoic acid n-propyl ester Natural products CCCOC(=O)C1=CC=CC=C1 UDEWPOVQBGFNGE-UHFFFAOYSA-N 0.000 description 4
• 239000000969 carrier Substances 0.000 description 4
• 238000004140 cleaning Methods 0.000 description 4
• 239000012091 fetal bovine serum Substances 0.000 description 4
• 208000010710 hepatitis C virus infection Diseases 0.000 description 4
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
• 150000002576 ketones Chemical class 0.000 description 4
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
• 239000003446 ligand Substances 0.000 description 4
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 4
• 239000002207 metabolite Substances 0.000 description 4
• OLXYLDUSSBULGU-UHFFFAOYSA-N methyl pyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC=C1 OLXYLDUSSBULGU-UHFFFAOYSA-N 0.000 description 4
• 239000012434 nucleophilic reagent Substances 0.000 description 4
• KOSYAAIZOGNATQ-UHFFFAOYSA-N o-phenyl chloromethanethioate Chemical compound ClC(=S)OC1=CC=CC=C1 KOSYAAIZOGNATQ-UHFFFAOYSA-N 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 108090000623 proteins and genes Proteins 0.000 description 4
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• CYIUFVYZGOCGEV-UHFFFAOYSA-N tributyl(2-methylprop-2-enyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)CC(C)=C CYIUFVYZGOCGEV-UHFFFAOYSA-N 0.000 description 1
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