PT2691413E - Compostos macrocíclicos e métodos para a sua produção - Google Patents

Info

Publication number

PT2691413E

PT2691413E PT127165397T PT12716539T PT2691413E PT 2691413 E PT2691413 E PT 2691413E PT 127165397 T PT127165397 T PT 127165397T PT 12716539 T PT12716539 T PT 12716539T PT 2691413 E PT2691413 E PT 2691413E

Authority

PT

Portugal

Prior art keywords

quot

compound

alkyl

compound according

mmol

Prior art date

2011-03-29

Links

• Espacenet
• Global Dossier
• Discuss

• 238000004519 manufacturing process Methods 0.000 title claims description 14
• 238000000034 method Methods 0.000 title description 36
• 150000002678 macrocyclic compounds Chemical class 0.000 title description 7
• 150000001875 compounds Chemical class 0.000 claims description 196
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 96
• 125000000217 alkyl group Chemical group 0.000 claims description 55
• 125000004432 carbon atom Chemical group C* 0.000 claims description 52
• 238000011282 treatment Methods 0.000 claims description 45
• -1 and R 2 is H Chemical group 0.000 claims description 40
• 125000003118 aryl group Chemical group 0.000 claims description 40
• 229910052799 carbon Inorganic materials 0.000 claims description 31
• 229910052757 nitrogen Inorganic materials 0.000 claims description 31
• 125000001072 heteroaryl group Chemical group 0.000 claims description 29
• 125000005842 heteroatom Chemical group 0.000 claims description 24
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 22
• 125000003342 alkenyl group Chemical group 0.000 claims description 20
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 229910052731 fluorine Inorganic materials 0.000 claims description 19
• 150000003839 salts Chemical class 0.000 claims description 19
• 230000001506 immunosuppresive effect Effects 0.000 claims description 17
• 125000000623 heterocyclic group Chemical group 0.000 claims description 16
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
• 229910052801 chlorine Inorganic materials 0.000 claims description 14
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 13
• 229910052760 oxygen Inorganic materials 0.000 claims description 13
• 229920006395 saturated elastomer Polymers 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
• 125000002877 alkyl aryl group Chemical group 0.000 claims description 9
• 125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 9
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
• 125000005217 alkenylheteroaryl group Chemical group 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 125000005024 alkenyl aryl group Chemical group 0.000 claims description 7
• 239000003018 immunosuppressive agent Substances 0.000 claims description 7
• 125000000468 ketone group Chemical group 0.000 claims description 7
• 208000031886 HIV Infections Diseases 0.000 claims description 6
• 208000037357 HIV infectious disease Diseases 0.000 claims description 6
• 239000003085 diluting agent Substances 0.000 claims description 6
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 6
• 239000001257 hydrogen Substances 0.000 claims description 6
• OZQGLZFAWYKKLQ-UHFFFAOYSA-N oxazinane Chemical compound C1CCONC1 OZQGLZFAWYKKLQ-UHFFFAOYSA-N 0.000 claims description 5
• 239000008194 pharmaceutical composition Substances 0.000 claims description 5
• 125000001424 substituent group Chemical group 0.000 claims description 5
• 230000009385 viral infection Effects 0.000 claims description 5
• 208000036142 Viral infection Diseases 0.000 claims description 4
• 229940125721 immunosuppressive agent Drugs 0.000 claims description 4
• 125000002757 morpholinyl group Chemical group 0.000 claims description 4
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 3
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• 229910052794 bromium Inorganic materials 0.000 claims description 3
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 3
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 203
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 123
• 239000000243 solution Substances 0.000 description 105
• 210000004027 cell Anatomy 0.000 description 87
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
• 235000019439 ethyl acetate Nutrition 0.000 description 69
• 229910001868 water Inorganic materials 0.000 description 67
• 239000000203 mixture Substances 0.000 description 64
• 241000711549 Hepacivirus C Species 0.000 description 59
• 230000002829 reductive effect Effects 0.000 description 55
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 50
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
• 239000002904 solvent Substances 0.000 description 41
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
• 230000000694 effects Effects 0.000 description 39
• 230000005764 inhibitory process Effects 0.000 description 38
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
• 238000012360 testing method Methods 0.000 description 31
• 239000011347 resin Substances 0.000 description 29
• 229920005989 resin Polymers 0.000 description 29
• OLROWHGDTNFZBH-XEMWPYQTSA-N Alisporivir Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(CC)C(=O)[C@@H](C)N(C)C1=O OLROWHGDTNFZBH-XEMWPYQTSA-N 0.000 description 28
• JZKXXXDKRQWDET-QMMMGPOBSA-N L-m-tyrosine Chemical class OC(=O)[C@@H](N)CC1=CC=CC(O)=C1 JZKXXXDKRQWDET-QMMMGPOBSA-N 0.000 description 28
• 108010058359 alisporivir Proteins 0.000 description 28
• 239000000284 extract Substances 0.000 description 28
• 239000007787 solid Substances 0.000 description 28
• 235000010633 broth Nutrition 0.000 description 27
• 238000003556 assay Methods 0.000 description 26
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 26
• 239000003814 drug Substances 0.000 description 25
• 239000003112 inhibitor Substances 0.000 description 25
• 239000012074 organic phase Substances 0.000 description 25
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 24
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
• 241000725303 Human immunodeficiency virus Species 0.000 description 23
• 101150013682 sfaA gene Proteins 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• 238000002360 preparation method Methods 0.000 description 22
• 239000000758 substrate Substances 0.000 description 22
• 229910004809 Na2 SO4 Inorganic materials 0.000 description 21
• 108010078791 Carrier Proteins Proteins 0.000 description 20
• 108010068682 Cyclophilins Proteins 0.000 description 20
• 102000001493 Cyclophilins Human genes 0.000 description 20
• 239000012267 brine Substances 0.000 description 20
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
• 239000000872 buffer Substances 0.000 description 19
• 238000006243 chemical reaction Methods 0.000 description 19
• 239000002609 medium Substances 0.000 description 19
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 18
• 230000000840 anti-viral effect Effects 0.000 description 18
• 229940079593 drug Drugs 0.000 description 18
• 238000011156 evaluation Methods 0.000 description 18
• 238000000338 in vitro Methods 0.000 description 18
• 238000011081 inoculation Methods 0.000 description 18
• 238000007792 addition Methods 0.000 description 17
• 239000000134 cyclophilin inhibitor Substances 0.000 description 17
• 238000012217 deletion Methods 0.000 description 17
• 230000037430 deletion Effects 0.000 description 17
• 238000006073 displacement reaction Methods 0.000 description 16
• 238000002953 preparative HPLC Methods 0.000 description 16
• 238000003756 stirring Methods 0.000 description 16
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 15
• 108020004414 DNA Proteins 0.000 description 15
• 238000003818 flash chromatography Methods 0.000 description 15
• 208000015181 infectious disease Diseases 0.000 description 15
• 239000000047 product Substances 0.000 description 15
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 14
• 229930105110 Cyclosporin A Natural products 0.000 description 14
• 108010036949 Cyclosporine Proteins 0.000 description 14
• 238000004458 analytical method Methods 0.000 description 14
• 229960001265 ciclosporin Drugs 0.000 description 14
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
• 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 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
• 241000700721 Hepatitis B virus Species 0.000 description 13
• 229950006334 apramycin Drugs 0.000 description 13
• 238000005119 centrifugation Methods 0.000 description 13
• 235000019253 formic acid Nutrition 0.000 description 13
• 239000011541 reaction mixture Substances 0.000 description 13
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 12
• 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 12
• 229920001817 Agar Polymers 0.000 description 12
• 108010072220 Cyclophilin A Proteins 0.000 description 12
• 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 12
• 102100034539 Peptidyl-prolyl cis-trans isomerase A Human genes 0.000 description 12
• 239000008272 agar Substances 0.000 description 12
• 238000007429 general method Methods 0.000 description 12
• 239000003208 petroleum Substances 0.000 description 12
• 230000009467 reduction Effects 0.000 description 12
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 11
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
• 239000002253 acid Substances 0.000 description 11
• 239000012043 crude product Substances 0.000 description 11
• 239000012091 fetal bovine serum Substances 0.000 description 11
• 239000012634 fragment Substances 0.000 description 11
• 230000004060 metabolic process Effects 0.000 description 11
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
• 239000002243 precursor Substances 0.000 description 11
• 230000002441 reversible effect Effects 0.000 description 11
• 239000000523 sample Substances 0.000 description 11
• XZNUGFQTQHRASN-XQENGBIVSA-N apramycin Chemical compound O([C@H]1O[C@@H]2[C@H](O)[C@@H]([C@H](O[C@H]2C[C@H]1N)O[C@@H]1[C@@H]([C@@H](O)[C@H](N)[C@@H](CO)O1)O)NC)[C@@H]1[C@@H](N)C[C@@H](N)[C@H](O)[C@H]1O XZNUGFQTQHRASN-XQENGBIVSA-N 0.000 description 10
• 210000004369 blood Anatomy 0.000 description 10
• 239000008280 blood Substances 0.000 description 10
• 238000010790 dilution Methods 0.000 description 10
• 239000012895 dilution Substances 0.000 description 10
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 10
• 230000008406 drug-drug interaction Effects 0.000 description 10
• 238000000855 fermentation Methods 0.000 description 10
• 230000004151 fermentation Effects 0.000 description 10
• 238000001914 filtration Methods 0.000 description 10
• 239000007788 liquid Substances 0.000 description 10
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 10
• 239000012071 phase Substances 0.000 description 10
• 239000002953 phosphate buffered saline Substances 0.000 description 10
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 10
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 9
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
• 101100397226 Schizosaccharomyces pombe (strain 972 / ATCC 24843) isp4 gene Proteins 0.000 description 9
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
• 241000187180 Streptomyces sp. Species 0.000 description 9
• 241000700605 Viruses Species 0.000 description 9
• 239000006260 foam Substances 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 239000000543 intermediate Substances 0.000 description 9
• 239000013612 plasmid Substances 0.000 description 9
• 229910000104 sodium hydride Inorganic materials 0.000 description 9
• 238000005160 1H NMR spectroscopy Methods 0.000 description 8
• BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 8
• 241001044073 Cypa Species 0.000 description 8
• 125000002619 bicyclic group Chemical group 0.000 description 8
• 238000000605 extraction Methods 0.000 description 8
• 238000004128 high performance liquid chromatography Methods 0.000 description 8
• 238000011534 incubation Methods 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
• 238000010898 silica gel chromatography Methods 0.000 description 8
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 8
• 108091006112 ATPases Proteins 0.000 description 7
• 102000057290 Adenosine Triphosphatases Human genes 0.000 description 7
• 101100256840 Allochromatium vinosum (strain ATCC 17899 / DSM 180 / NBRC 103801 / NCIMB 10441 / D) sgpB gene Proteins 0.000 description 7
• 101100256841 Glossina morsitans morsitans sgp2 gene Proteins 0.000 description 7
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
• 150000001299 aldehydes Chemical class 0.000 description 7
• 125000004429 atom Chemical group 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 230000001684 chronic effect Effects 0.000 description 7
• 239000000287 crude extract Substances 0.000 description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 238000002474 experimental method Methods 0.000 description 7
• 230000005484 gravity Effects 0.000 description 7
• 230000012010 growth Effects 0.000 description 7
• 210000003494 hepatocyte Anatomy 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 238000002955 isolation Methods 0.000 description 7
• IXANEDBEHRGAPH-UHFFFAOYSA-N methyl 2-amino-3-(3-fluoro-5-hydroxyphenyl)propanoate Chemical compound COC(=O)C(N)CC1=CC(O)=CC(F)=C1 IXANEDBEHRGAPH-UHFFFAOYSA-N 0.000 description 7
• 125000002950 monocyclic group Chemical group 0.000 description 7
• 239000000741 silica gel Substances 0.000 description 7
• 229910002027 silica gel Inorganic materials 0.000 description 7
• 229960005322 streptomycin Drugs 0.000 description 7
• 239000006228 supernatant Substances 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 230000001225 therapeutic effect Effects 0.000 description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
• 230000003612 virological effect Effects 0.000 description 7
• 239000003643 water by type Substances 0.000 description 7
• 102100028282 Bile salt export pump Human genes 0.000 description 6
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 6
• 108010093662 Member 11 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• 229920002472 Starch Polymers 0.000 description 6
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
• 239000003443 antiviral agent Substances 0.000 description 6
• 229910002091 carbon monoxide Inorganic materials 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 238000001502 gel electrophoresis Methods 0.000 description 6
• 230000003993 interaction Effects 0.000 description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
• 229930027917 kanamycin Natural products 0.000 description 6
• 229960000318 kanamycin Drugs 0.000 description 6
• SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 6
• 229930182823 kanamycin A Natural products 0.000 description 6
• 230000035772 mutation Effects 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 239000013587 production medium Substances 0.000 description 6
• 238000011321 prophylaxis Methods 0.000 description 6
• 230000010076 replication Effects 0.000 description 6
• 239000000377 silicon dioxide Substances 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
• 238000010561 standard procedure Methods 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• 101100313763 Arabidopsis thaliana TIM22-2 gene Proteins 0.000 description 5
• 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 5
• 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 5
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
• 101000986633 Homo sapiens ATP-binding cassette sub-family C member 3 Proteins 0.000 description 5
• 108010047761 Interferon-alpha Proteins 0.000 description 5
• 102000006992 Interferon-alpha Human genes 0.000 description 5
• 229930182555 Penicillin Natural products 0.000 description 5
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 5
• 102100034943 Peptidyl-prolyl cis-trans isomerase F, mitochondrial Human genes 0.000 description 5
• 206010052779 Transplant rejections Diseases 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 208000027119 bilirubin metabolic disease Diseases 0.000 description 5
• 230000003833 cell viability Effects 0.000 description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
• 231100000135 cytotoxicity Toxicity 0.000 description 5
• 230000003013 cytotoxicity Effects 0.000 description 5
• 238000011161 development Methods 0.000 description 5
• 230000018109 developmental process Effects 0.000 description 5
• 229940125371 direct-acting antiviral drugs Drugs 0.000 description 5
• 239000000839 emulsion Substances 0.000 description 5
• 230000023611 glucuronidation Effects 0.000 description 5
• 208000036796 hyperbilirubinemia Diseases 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 239000012528 membrane Substances 0.000 description 5
• GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical compound COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 5
• 210000000056 organ Anatomy 0.000 description 5
• 239000012044 organic layer Substances 0.000 description 5
• 239000008188 pellet Substances 0.000 description 5
• 229940049954 penicillin Drugs 0.000 description 5
• 229960005190 phenylalanine Drugs 0.000 description 5
• 230000036470 plasma concentration Effects 0.000 description 5
• 230000003389 potentiating effect Effects 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 108090000623 proteins and genes Proteins 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 239000008107 starch Substances 0.000 description 5
• 229940032147 starch Drugs 0.000 description 5
• 235000019698 starch Nutrition 0.000 description 5
• 239000011550 stock solution Substances 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• 102100028162 ATP-binding cassette sub-family C member 3 Human genes 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 4
• 241000588724 Escherichia coli Species 0.000 description 4
• 241000713772 Human immunodeficiency virus 1 Species 0.000 description 4
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 4
• 101001122350 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial Proteins 0.000 description 4
• 101800001014 Non-structural protein 5A Proteins 0.000 description 4
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• 239000012980 RPMI-1640 medium Substances 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• 229940024606 amino acid Drugs 0.000 description 4
• 230000003110 anti-inflammatory effect Effects 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 235000011089 carbon dioxide Nutrition 0.000 description 4
• 238000010276 construction Methods 0.000 description 4
• 230000007423 decrease Effects 0.000 description 4
• 229940072240 direct acting antivirals Drugs 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 239000000499 gel Substances 0.000 description 4
• BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 4
• 239000008103 glucose Substances 0.000 description 4
• 239000001963 growth medium Substances 0.000 description 4
• 229910052736 halogen Inorganic materials 0.000 description 4
• 150000002367 halogens Chemical class 0.000 description 4
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical group C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 4
• 229960001571 loperamide Drugs 0.000 description 4
• 210000002540 macrophage Anatomy 0.000 description 4
• 239000003550 marker Substances 0.000 description 4
• 230000007246 mechanism Effects 0.000 description 4
• 230000001404 mediated effect Effects 0.000 description 4
• ULFJILMXAYOUAX-UHFFFAOYSA-N methyl 2-amino-3-(2-fluoro-3-hydroxyphenyl)propanoate Chemical compound COC(=O)C(N)CC1=CC=CC(O)=C1F ULFJILMXAYOUAX-UHFFFAOYSA-N 0.000 description 4
• 230000003228 microsomal effect Effects 0.000 description 4
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
• 239000002777 nucleoside Substances 0.000 description 4
• 150000003833 nucleoside derivatives Chemical class 0.000 description 4
• 125000003729 nucleotide group Chemical group 0.000 description 4
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 4
• 239000012285 osmium tetroxide Substances 0.000 description 4
• 125000004430 oxygen atom Chemical group O* 0.000 description 4
• 230000037050 permeability transition Effects 0.000 description 4
• 108090000765 processed proteins & peptides Proteins 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
• 238000006467 substitution reaction Methods 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 230000001988 toxicity Effects 0.000 description 4
• 231100000419 toxicity Toxicity 0.000 description 4
• 239000011573 trace mineral Substances 0.000 description 4
• 235000013619 trace mineral Nutrition 0.000 description 4
• 150000003852 triazoles Chemical class 0.000 description 4
• 239000002676 xenobiotic agent Substances 0.000 description 4
• 230000002034 xenobiotic effect Effects 0.000 description 4
• 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 description 3
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
• 108010048028 Cyclophilin D Proteins 0.000 description 3
• 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 3
• 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
• 241000238557 Decapoda Species 0.000 description 3
• 101001059719 Faecalibacterium prausnitzii (strain DSM 17677 / JCM 31915 / A2-165) Microbial anti-inflammatory molecule Proteins 0.000 description 3
• 208000005176 Hepatitis C Diseases 0.000 description 3
• 101000616435 Homo sapiens Gamma-sarcoglycan Proteins 0.000 description 3
• 101000610620 Homo sapiens Putative serine protease 29 Proteins 0.000 description 3
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
• 108010002350 Interleukin-2 Proteins 0.000 description 3
• 102000000588 Interleukin-2 Human genes 0.000 description 3
• 229930182816 L-glutamine Natural products 0.000 description 3
• 102000003855 L-lactate dehydrogenase Human genes 0.000 description 3
• 108700023483 L-lactate dehydrogenases Proteins 0.000 description 3
• 108010067028 Mitochondrial Permeability Transition Pore Proteins 0.000 description 3
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
• 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 3
• 108091034117 Oligonucleotide Proteins 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 102100040345 Putative serine protease 29 Human genes 0.000 description 3
• 108010019477 S-adenosyl-L-methionine-dependent N-methyltransferase Proteins 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 230000006052 T cell proliferation Effects 0.000 description 3
• 210000001744 T-lymphocyte Anatomy 0.000 description 3
• 239000004098 Tetracycline Substances 0.000 description 3
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 3
• 238000002835 absorbance Methods 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 239000012911 assay medium Substances 0.000 description 3
• XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 3
• 230000001580 bacterial effect Effects 0.000 description 3
• 229910000019 calcium carbonate Inorganic materials 0.000 description 3
• 229940041514 candida albicans extract Drugs 0.000 description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 230000010261 cell growth Effects 0.000 description 3
• 239000013553 cell monolayer Substances 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 229960005091 chloramphenicol Drugs 0.000 description 3
• WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 3
• 239000012230 colorless oil Substances 0.000 description 3
• 230000000295 complement effect Effects 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
• ZVTDLPBHTSMEJZ-JSZLBQEHSA-N danoprevir Chemical compound O=C([C@@]12C[C@H]1\C=C/CCCCC[C@@H](C(N1C[C@@H](C[C@H]1C(=O)N2)OC(=O)N1CC2=C(F)C=CC=C2C1)=O)NC(=O)OC(C)(C)C)NS(=O)(=O)C1CC1 ZVTDLPBHTSMEJZ-JSZLBQEHSA-N 0.000 description 3
• 238000001212 derivatisation Methods 0.000 description 3
• 230000029087 digestion Effects 0.000 description 3
• 239000003797 essential amino acid Substances 0.000 description 3
• 235000020776 essential amino acid Nutrition 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 239000005457 ice water Substances 0.000 description 3
• 208000027866 inflammatory disease Diseases 0.000 description 3
• 210000004185 liver Anatomy 0.000 description 3
• DLBFLQKQABVKGT-UHFFFAOYSA-L lucifer yellow dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(C(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N DLBFLQKQABVKGT-UHFFFAOYSA-L 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 3
• VTXPJTHDKKKDMT-UHFFFAOYSA-N methyl 2-amino-3-(2-fluoro-5-hydroxyphenyl)propanoate Chemical compound COC(=O)C(N)CC1=CC(O)=CC=C1F VTXPJTHDKKKDMT-UHFFFAOYSA-N 0.000 description 3
• 210000001589 microsome Anatomy 0.000 description 3
• 238000012544 monitoring process Methods 0.000 description 3
• 201000006938 muscular dystrophy Diseases 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
• 108010000785 non-ribosomal peptide synthase Proteins 0.000 description 3
• 239000006877 oatmeal agar Substances 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• 125000004193 piperazinyl group Chemical group 0.000 description 3
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 239000011148 porous material Substances 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 229910052938 sodium sulfate Inorganic materials 0.000 description 3
• 235000011152 sodium sulphate Nutrition 0.000 description 3
• 235000010265 sodium sulphite Nutrition 0.000 description 3
• 239000008223 sterile water Substances 0.000 description 3
• 230000001954 sterilising effect Effects 0.000 description 3
• 238000004659 sterilization and disinfection Methods 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 229960002180 tetracycline Drugs 0.000 description 3
• 229930101283 tetracycline Natural products 0.000 description 3
• 235000019364 tetracycline Nutrition 0.000 description 3
• 150000003522 tetracyclines Chemical class 0.000 description 3
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
• 150000003536 tetrazoles Chemical class 0.000 description 3
• 229930192474 thiophene Natural products 0.000 description 3
• 206010043554 thrombocytopenia Diseases 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 230000032258 transport Effects 0.000 description 3
• 239000012138 yeast extract Substances 0.000 description 3
• UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 2
• OQANPHBRHBJGNZ-FYJGNVAPSA-N (3e)-6-oxo-3-[[4-(pyridin-2-ylsulfamoyl)phenyl]hydrazinylidene]cyclohexa-1,4-diene-1-carboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=C\C1=N\NC1=CC=C(S(=O)(=O)NC=2N=CC=CC=2)C=C1 OQANPHBRHBJGNZ-FYJGNVAPSA-N 0.000 description 2
• 108010030583 (melle-4)cyclosporin Proteins 0.000 description 2
• LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical group C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 2
• JHLKSIOJYMGSMB-UHFFFAOYSA-N 1-bromo-3,5-difluorobenzene Chemical compound FC1=CC(F)=CC(Br)=C1 JHLKSIOJYMGSMB-UHFFFAOYSA-N 0.000 description 2
• XVNQVSGOIUYOPB-UHFFFAOYSA-N 1-bromo-3-fluoro-5-methoxybenzene Chemical compound COC1=CC(F)=CC(Br)=C1 XVNQVSGOIUYOPB-UHFFFAOYSA-N 0.000 description 2
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
• SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 2
• YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
• TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 2
• VWHRYODZTDMVSS-UHFFFAOYSA-N 2-azaniumyl-3-(3-fluorophenyl)propanoate Chemical compound OC(=O)C(N)CC1=CC=CC(F)=C1 VWHRYODZTDMVSS-UHFFFAOYSA-N 0.000 description 2
• WYLRYBDGIILFIR-UHFFFAOYSA-N 2-diethoxyphosphoryl-n-methoxy-n-methylacetamide Chemical compound CCOP(=O)(OCC)CC(=O)N(C)OC WYLRYBDGIILFIR-UHFFFAOYSA-N 0.000 description 2
• 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 2
• VERWQPYQDXWOGT-LVJNJWHOSA-N 4-amino-5-fluoro-1-[(2r,5s)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one;[[(2r)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethyl-(propan-2-yloxycarbonyloxymethoxy)phosphoryl]oxymethyl propan-2-yl carbonate;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VERWQPYQDXWOGT-LVJNJWHOSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• 208000006820 Arthralgia Diseases 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 2
• 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 2
• 102000004631 Calcineurin Human genes 0.000 description 2
• 108010042955 Calcineurin Proteins 0.000 description 2
• 101000870191 Catharanthus roseus Peptidyl-prolyl cis-trans isomerase Proteins 0.000 description 2
• 108090000317 Chymotrypsin Proteins 0.000 description 2
• 102000003780 Clusterin Human genes 0.000 description 2
• 108090000197 Clusterin Proteins 0.000 description 2
• 229920002785 Croscarmellose sodium Polymers 0.000 description 2
• 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
• 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 206010019851 Hepatotoxicity Diseases 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 101000878213 Homo sapiens Inactive peptidyl-prolyl cis-trans isomerase FKBP6 Proteins 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
• 102100036984 Inactive peptidyl-prolyl cis-trans isomerase FKBP6 Human genes 0.000 description 2
• 108010050904 Interferons Proteins 0.000 description 2
• 102000014150 Interferons Human genes 0.000 description 2
• UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 2
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
• 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
• QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
• JOCBASBOOFNAJA-UHFFFAOYSA-N N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid Chemical compound OCC(CO)(CO)NCCS(O)(=O)=O JOCBASBOOFNAJA-UHFFFAOYSA-N 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• 101710191011 Peptidyl-prolyl cis-trans isomerase F, mitochondrial Proteins 0.000 description 2
• 108010030975 Polyketide Synthases Proteins 0.000 description 2
• 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 description 2
• 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• 206010037660 Pyrexia Diseases 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
• 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 2
• IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 2
• 108091006731 SLCO1B1 Proteins 0.000 description 2
• 108091006730 SLCO1B3 Proteins 0.000 description 2
• 101100397225 Schizosaccharomyces pombe (strain 972 / ATCC 24843) isp3 gene Proteins 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• 102100027239 Solute carrier organic anion transporter family member 1B3 Human genes 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• 239000007994 TES buffer Substances 0.000 description 2
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 2
• RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
• LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 2
• ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 2
• WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 description 2
• 229960003205 adefovir dipivoxil Drugs 0.000 description 2
• 230000002411 adverse Effects 0.000 description 2
• 238000013019 agitation Methods 0.000 description 2
• 229950004789 alisporivir Drugs 0.000 description 2
• 230000004075 alteration Effects 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 230000003321 amplification Effects 0.000 description 2
• 230000001399 anti-metabolic effect Effects 0.000 description 2
• 238000002832 anti-viral assay Methods 0.000 description 2
• 239000002518 antifoaming agent Substances 0.000 description 2
• 238000011225 antiretroviral therapy Methods 0.000 description 2
• 230000001363 autoimmune Effects 0.000 description 2
• 210000003719 b-lymphocyte Anatomy 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 2
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
• 210000000941 bile Anatomy 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 229960000517 boceprevir Drugs 0.000 description 2
• LHHCSNFAOIFYRV-DOVBMPENSA-N boceprevir Chemical compound O=C([C@@H]1[C@@H]2[C@@H](C2(C)C)CN1C(=O)[C@@H](NC(=O)NC(C)(C)C)C(C)(C)C)NC(C(=O)C(N)=O)CC1CCC1 LHHCSNFAOIFYRV-DOVBMPENSA-N 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 229960002376 chymotrypsin Drugs 0.000 description 2
• 229940125833 compound 23 Drugs 0.000 description 2
• 229940125961 compound 24 Drugs 0.000 description 2
• 229940125846 compound 25 Drugs 0.000 description 2
• 229940125851 compound 27 Drugs 0.000 description 2
• 229940127204 compound 29 Drugs 0.000 description 2
• 230000021615 conjugation Effects 0.000 description 2
• 238000013270 controlled release Methods 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 230000000875 corresponding effect Effects 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 125000004093 cyano group Chemical group *C#N 0.000 description 2
• 125000006165 cyclic alkyl group Chemical group 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 2
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 238000005906 dihydroxylation reaction Methods 0.000 description 2
• 238000007865 diluting Methods 0.000 description 2
• 231100000676 disease causative agent Toxicity 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 239000012153 distilled water Substances 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 239000000890 drug combination Substances 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 229960000980 entecavir Drugs 0.000 description 2
• YXPVEXCTPGULBZ-WQYNNSOESA-N entecavir hydrate Chemical compound O.C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)C1=C YXPVEXCTPGULBZ-WQYNNSOESA-N 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 206010016256 fatigue Diseases 0.000 description 2
• SLVAPEZTBDBAPI-GDLZYMKVSA-N filibuvir Chemical compound CCC1=NC(CC)=CC(CC[C@]2(OC(=O)C(CC3=NN4C(C)=CC(C)=NC4=N3)=C(O)C2)C2CCCC2)=C1 SLVAPEZTBDBAPI-GDLZYMKVSA-N 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 239000012737 fresh medium Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 208000002672 hepatitis B Diseases 0.000 description 2
• 108700008776 hepatitis C virus NS-5 Proteins 0.000 description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 2
• 231100000304 hepatotoxicity Toxicity 0.000 description 2
• 230000007686 hepatotoxicity Effects 0.000 description 2
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
• 229960003444 immunosuppressant agent Drugs 0.000 description 2
• 238000000099 in vitro assay Methods 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 239000012499 inoculation medium Substances 0.000 description 2
• 229940124524 integrase inhibitor Drugs 0.000 description 2
• 239000002850 integrase inhibitor Substances 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 229960001627 lamivudine Drugs 0.000 description 2
• JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 2
• 238000012417 linear regression Methods 0.000 description 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• 208000019423 liver disease Diseases 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 238000004020 luminiscence type Methods 0.000 description 2
• 210000004698 lymphocyte Anatomy 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• JZKXXXDKRQWDET-UHFFFAOYSA-N meta-tyrosine Natural products OC(=O)C(N)CC1=CC=CC(O)=C1 JZKXXXDKRQWDET-UHFFFAOYSA-N 0.000 description 2
• VSAZMHNTMFFKPW-UHFFFAOYSA-N methyl 2-amino-3-(2,6-difluoro-3-hydroxyphenyl)propanoate Chemical compound COC(=O)C(N)CC1=C(F)C=CC(O)=C1F VSAZMHNTMFFKPW-UHFFFAOYSA-N 0.000 description 2
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 230000002438 mitochondrial effect Effects 0.000 description 2
• 238000007799 mixed lymphocyte reaction assay Methods 0.000 description 2
• 210000001616 monocyte Anatomy 0.000 description 2
• 208000010125 myocardial infarction Diseases 0.000 description 2
• 125000003136 n-heptyl 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])* 0.000 description 2
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 229960000210 nalidixic acid Drugs 0.000 description 2
• MHWLWQUZZRMNGJ-UHFFFAOYSA-N nalidixic acid Chemical compound C1=C(C)N=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 MHWLWQUZZRMNGJ-UHFFFAOYSA-N 0.000 description 2
• RPJPZDVUUKWPGT-FOIHOXPVSA-N nim811 Chemical compound CC[C@H](C)[C@@H]1N(C)C(=O)CN(C)C(=O)[C@H](CC)NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC1=O RPJPZDVUUKWPGT-FOIHOXPVSA-N 0.000 description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
• 238000003199 nucleic acid amplification method Methods 0.000 description 2
• 239000002773 nucleotide Substances 0.000 description 2
• 231100000822 oral exposure Toxicity 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 230000001590 oxidative effect Effects 0.000 description 2
• 230000035699 permeability Effects 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
• 239000004033 plastic Substances 0.000 description 2
• 229920003023 plastic Polymers 0.000 description 2
• 229930001119 polyketide Natural products 0.000 description 2
• 229940069328 povidone Drugs 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical group N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
• 238000003753 real-time PCR Methods 0.000 description 2
• 230000006798 recombination Effects 0.000 description 2
• 238000005215 recombination Methods 0.000 description 2
• 238000011084 recovery Methods 0.000 description 2
• 208000023504 respiratory system disease Diseases 0.000 description 2
• 229960000329 ribavirin Drugs 0.000 description 2
• HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 2
• 108020004418 ribosomal RNA Proteins 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
• 229960002930 sirolimus Drugs 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229940054269 sodium pyruvate Drugs 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 2
• 229960001940 sulfasalazine Drugs 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 230000001839 systemic circulation Effects 0.000 description 2
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
• IQFYYKKMVGJFEH-CSMHCCOUSA-N telbivudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1O[C@@H](CO)[C@H](O)C1 IQFYYKKMVGJFEH-CSMHCCOUSA-N 0.000 description 2
• 229960005311 telbivudine Drugs 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 231100001274 therapeutic index Toxicity 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• 238000003569 transporter assay Methods 0.000 description 2
• BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 2
• LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 2
• 229960001722 verapamil Drugs 0.000 description 2
• 239000011782 vitamin Substances 0.000 description 2
• 229940088594 vitamin Drugs 0.000 description 2
• 239000011534 wash buffer Substances 0.000 description 2
• AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
• OTXAMWFYPMNDME-OPUYQWCOSA-N (1r,2r)-1-[[(2s,4r)-1-[(2s)-2-[[(1r,5s)-3-bicyclo[3.1.0]hexanyl]oxycarbonylamino]-3,3-dimethylbutanoyl]-4-[8-chloro-7-(2-morpholin-4-ylethoxy)-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl]oxypyrrolidine-2-carbonyl]amino]-2-ethylcyclopropane-1-ca Chemical compound CC[C@@H]1C[C@@]1(C(O)=O)NC(=O)[C@H]1N(C(=O)[C@@H](NC(=O)OC2C[C@H]3C[C@H]3C2)C(C)(C)C)C[C@H](OC=2C3=CC=C(OCCN4CCOCC4)C(Cl)=C3N=C(C=2)C=2N=C(NC(C)C)SC=2)C1 OTXAMWFYPMNDME-OPUYQWCOSA-N 0.000 description 1
• SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
• XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
• PASOFFRBGIVJET-YRKGHMEHSA-N (2r,3r,4r,5r)-2-(6-aminopurin-9-yl)-5-(hydroxymethyl)-3-methyloxolane-3,4-diol Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N)=C2N=C1 PASOFFRBGIVJET-YRKGHMEHSA-N 0.000 description 1
• TWYYFYNJOJGNFP-CUXYNZQBSA-N (2s,4r,5s,6s)-2-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-2-carbamoyl-4-[[(e,4s,6s)-4,6-dimethyloct-2-enoyl]oxymethyl]-5-hydroxy-1,3-dioxane-4,5,6-tricarboxylic acid Chemical compound O1[C@H](C(O)=O)[C@](C(O)=O)(O)[C@](COC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)(C(O)=O)O[C@]1(C(N)=O)CCC(=C)[C@@H](OC(C)=O)[C@H](C)CC1=CC=CC=C1 TWYYFYNJOJGNFP-CUXYNZQBSA-N 0.000 description 1
• BZIBRGSBQKLEDC-BYPYZUCNSA-N (3S)-1,2-diazinane-3-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCNN1 BZIBRGSBQKLEDC-BYPYZUCNSA-N 0.000 description 1
• 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 1
• AQHMBDAHQGYLIU-XNFHFXFQSA-N (3s,6s,9s,12r,15s,18s,21s,24s,27r,30s,33s)-27-[2-(dimethylamino)ethylsulfanyl]-30-ethyl-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-24-(2-hydroxy-2-methylpropyl)-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10, Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)(C)O)N(C)C(=O)[C@@H](SCCN(C)C)N(C)C1=O AQHMBDAHQGYLIU-XNFHFXFQSA-N 0.000 description 1
• CNPVJJQCETWNEU-CYFREDJKSA-N (4,6-dimethyl-5-pyrimidinyl)-[4-[(3S)-4-[(1R)-2-methoxy-1-[4-(trifluoromethyl)phenyl]ethyl]-3-methyl-1-piperazinyl]-4-methyl-1-piperidinyl]methanone Chemical compound N([C@@H](COC)C=1C=CC(=CC=1)C(F)(F)F)([C@H](C1)C)CCN1C(CC1)(C)CCN1C(=O)C1=C(C)N=CN=C1C CNPVJJQCETWNEU-CYFREDJKSA-N 0.000 description 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
• IRFSXVIRXMYULF-UHFFFAOYSA-N 1,2-dihydroquinoline Chemical group C1=CC=C2C=CCNC2=C1 IRFSXVIRXMYULF-UHFFFAOYSA-N 0.000 description 1
• 150000000180 1,2-diols Chemical class 0.000 description 1
• CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical group C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
• OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
• HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
• NVWVWEWVLBKPSM-UHFFFAOYSA-N 2,4-difluorophenol Chemical compound OC1=CC=C(F)C=C1F NVWVWEWVLBKPSM-UHFFFAOYSA-N 0.000 description 1
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
• PDQGEKGUTOTUNV-TZSSRYMLSA-N 4'-deoxy-4'-iododoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](I)[C@H](C)O1 PDQGEKGUTOTUNV-TZSSRYMLSA-N 0.000 description 1
• ROSNVSQTEGHUKU-UHFFFAOYSA-N 4-[4-(4-chloro-phenoxy)-benzenesulfonylmethyl]-tetrahydro-pyran-4-carboxylic acid hydroxyamide Chemical compound C=1C=C(OC=2C=CC(Cl)=CC=2)C=CC=1S(=O)(=O)CC1(C(=O)NO)CCOCC1 ROSNVSQTEGHUKU-UHFFFAOYSA-N 0.000 description 1
• GWNOTCOIYUNTQP-FQLXRVMXSA-N 4-[4-[[(3r)-1-butyl-3-[(r)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undecan-9-yl]methyl]phenoxy]benzoic acid Chemical compound N([C@@H](C(=O)N1CCCC)[C@H](O)C2CCCCC2)C(=O)C1(CC1)CCN1CC(C=C1)=CC=C1OC1=CC=C(C(O)=O)C=C1 GWNOTCOIYUNTQP-FQLXRVMXSA-N 0.000 description 1
• LKDMKWNDBAVNQZ-WJNSRDFLSA-N 4-[[(2s)-1-[[(2s)-1-[(2s)-2-[[(2s)-1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-WJNSRDFLSA-N 0.000 description 1
• PPUDLEUZKVJXSZ-VPCXQMTMSA-N 4-amino-1-[(2r,3r,4r,5r)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidin-2-one Chemical compound C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 PPUDLEUZKVJXSZ-VPCXQMTMSA-N 0.000 description 1
• NYPIRLYMDJMKGW-VPCXQMTMSA-N 4-amino-1-[(2r,3r,4r,5r)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidin-2-one Chemical compound C[C@@]1(F)[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)N=C(N)C=C1 NYPIRLYMDJMKGW-VPCXQMTMSA-N 0.000 description 1
• ODLGMSQBFONGNG-JVZYCSMKSA-N 4-amino-1-[(2r,3r,4s,5r)-5-azido-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](O)[C@](CO)(N=[N+]=[N-])O1 ODLGMSQBFONGNG-JVZYCSMKSA-N 0.000 description 1
• WPMJNLCLKAKMLA-UHFFFAOYSA-N 5-(3,3-dimethylbut-1-ynyl)-3-[(4-hydroxycyclohexyl)-[(4-methylcyclohexyl)-oxomethyl]amino]-2-thiophenecarboxylic acid Chemical compound C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C1CCC(O)CC1 WPMJNLCLKAKMLA-UHFFFAOYSA-N 0.000 description 1
• XBEQSQDCBSKCHJ-UHFFFAOYSA-N 5-[[6-[2,4-bis(trifluoromethyl)phenyl]pyridazin-3-yl]methyl]-2-(2-fluorophenyl)imidazo[4,5-c]pyridine Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC=3N=NC(=CC=3)C=3C(=CC(=CC=3)C(F)(F)F)C(F)(F)F)C=CC2=N1 XBEQSQDCBSKCHJ-UHFFFAOYSA-N 0.000 description 1
• 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• RFGUWOCFYCYEDM-ZOMNBDOOSA-N 8v42y78hru Chemical compound OP([C@@]12C[C@H]1CCCCCCC[C@@H](C(=O)N1[C@H](C(N2)=O)C[C@H](C1)OC=1C2=CC=C(C(=C2N=C(C=1)C=1N=C(NC(C)C)SC=1)Cl)OC)NC(=O)OC1CCCC1)(=O)CC1=C(F)C=CC=C1F RFGUWOCFYCYEDM-ZOMNBDOOSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 102100028161 ATP-binding cassette sub-family C member 2 Human genes 0.000 description 1
• 208000004998 Abdominal Pain Diseases 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 201000004384 Alopecia Diseases 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• 208000032467 Aplastic anaemia Diseases 0.000 description 1
• 229910015845 BBr3 Inorganic materials 0.000 description 1
• 208000027496 Behcet disease Diseases 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
• 239000004364 Benzylated hydrocarbon Substances 0.000 description 1
• 208000006304 Bethlem myopathy Diseases 0.000 description 1
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
• 206010004659 Biliary cirrhosis Diseases 0.000 description 1
• 108700031361 Brachyury Proteins 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 1
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
• 101100275473 Caenorhabditis elegans ctc-3 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 102000019034 Chemokines Human genes 0.000 description 1
• 108010012236 Chemokines Proteins 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
• 208000015943 Coeliac disease Diseases 0.000 description 1
• 208000003322 Coinfection Diseases 0.000 description 1
• 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
• 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
• 229940126657 Compound 17 Drugs 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000711573 Coronaviridae Species 0.000 description 1
• 241000699662 Cricetomys gambianus Species 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• NPEONIHYDZZZGH-UHFFFAOYSA-N Cyclosporin T Natural products CCC1NC(=O)C(C(O)C(C)CC=CC)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)NC(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(C(C)C)NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O NPEONIHYDZZZGH-UHFFFAOYSA-N 0.000 description 1
• 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
• 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
• 101710128746 Cytochrome b6-f complex iron-sulfur subunit 1 Proteins 0.000 description 1
• 241000701022 Cytomegalovirus Species 0.000 description 1
• 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
• 241000725619 Dengue virus Species 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
• 206010059866 Drug resistance Diseases 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 1
• 108010032976 Enfuvirtide Proteins 0.000 description 1
• 101000867232 Escherichia coli Heat-stable enterotoxin II Proteins 0.000 description 1
• 241001302160 Escherichia coli str. K-12 substr. DH10B Species 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 208000010201 Exanthema Diseases 0.000 description 1
• 241000725579 Feline coronavirus Species 0.000 description 1
• 241000710781 Flaviviridae Species 0.000 description 1
• OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
• 229930182566 Gentamicin Natural products 0.000 description 1
• CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
• 108010024636 Glutathione Proteins 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 102000003886 Glycoproteins Human genes 0.000 description 1
• 108090000288 Glycoproteins Proteins 0.000 description 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 229910003556 H2 SO4 Inorganic materials 0.000 description 1
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
• 241000700739 Hepadnaviridae Species 0.000 description 1
• 206010019799 Hepatitis viral Diseases 0.000 description 1
• 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
• 101000610212 Homo sapiens Adenylyl-sulfate kinase Proteins 0.000 description 1
• 101000610215 Homo sapiens Adenylyl-sulfate kinase Proteins 0.000 description 1
• 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
• 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 1
• 101001027631 Homo sapiens Kinesin-like protein KIF20B Proteins 0.000 description 1
• 101000957437 Homo sapiens Mitochondrial carnitine/acylcarnitine carrier protein Proteins 0.000 description 1
• 101000590687 Homo sapiens U3 small nucleolar ribonucleoprotein protein MPP10 Proteins 0.000 description 1
• 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
• 244000309467 Human Coronavirus Species 0.000 description 1
• 108090000144 Human Proteins Proteins 0.000 description 1
• 102000003839 Human Proteins Human genes 0.000 description 1
• 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
• 208000023105 Huntington disease Diseases 0.000 description 1
• 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 1
• 241000712431 Influenza A virus Species 0.000 description 1
• 206010022004 Influenza like illness Diseases 0.000 description 1
• 102100034343 Integrase Human genes 0.000 description 1
• 102000013462 Interleukin-12 Human genes 0.000 description 1
• 108010065805 Interleukin-12 Proteins 0.000 description 1
• 102000004889 Interleukin-6 Human genes 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• 102000004195 Isomerases Human genes 0.000 description 1
• 108090000769 Isomerases Proteins 0.000 description 1
• 206010023126 Jaundice Diseases 0.000 description 1
• 229910004861 K2 HPO4 Inorganic materials 0.000 description 1
• 239000007836 KH2PO4 Substances 0.000 description 1
• KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• 239000012839 Krebs-Henseleit buffer Substances 0.000 description 1
• HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• 102100022745 Laminin subunit alpha-2 Human genes 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 239000005089 Luciferase Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 240000003183 Manihot esculenta Species 0.000 description 1
• 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 102100038738 Mitochondrial carnitine/acylcarnitine carrier protein Human genes 0.000 description 1
• 101000686985 Mouse mammary tumor virus (strain C3H) Protein PR73 Proteins 0.000 description 1
• 108010066419 Multidrug Resistance-Associated Protein 2 Proteins 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• NEAPKZHDYMQZCB-UHFFFAOYSA-N N-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]ethyl]-2-oxo-3H-1,3-benzoxazole-6-carboxamide Chemical group C1CN(CCN1CCNC(=O)C2=CC3=C(C=C2)NC(=O)O3)C4=CN=C(N=C4)NC5CC6=CC=CC=C6C5 NEAPKZHDYMQZCB-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 206010028851 Necrosis Diseases 0.000 description 1
• 229930193140 Neomycin Natural products 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 206010065673 Nephritic syndrome Diseases 0.000 description 1
• 241000221960 Neurospora Species 0.000 description 1
• YEPBUHWNLNKZBW-UEMKMYPFSA-N O=C([C@]12NC(=O)[C@H]3N(C(N(C)CCCC\C=C/[C@@H]1C2)=O)CC[C@@H](C3)OC=1C2=CC=C(C(=C2N=C(C=1)C=1SC=C(N=1)C(F)(F)F)C)OC)NS(=O)(=O)C1(C)CC1 Chemical compound O=C([C@]12NC(=O)[C@H]3N(C(N(C)CCCC\C=C/[C@@H]1C2)=O)CC[C@@H](C3)OC=1C2=CC=C(C(=C2N=C(C=1)C=1SC=C(N=1)C(F)(F)F)C)OC)NS(=O)(=O)C1(C)CC1 YEPBUHWNLNKZBW-UEMKMYPFSA-N 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 108010087367 P-glycoprotein 2 Proteins 0.000 description 1
• 238000012408 PCR amplification Methods 0.000 description 1
• 206010034133 Pathogen resistance Diseases 0.000 description 1
• 101000579646 Penaeus vannamei Penaeidin-1 Proteins 0.000 description 1
• 102100040283 Peptidyl-prolyl cis-trans isomerase B Human genes 0.000 description 1
• 102000009658 Peptidylprolyl Isomerase Human genes 0.000 description 1
• 108010020062 Peptidylprolyl Isomerase Proteins 0.000 description 1
• 239000001888 Peptone Substances 0.000 description 1
• 108010080698 Peptones Proteins 0.000 description 1
• 102000003992 Peroxidases Human genes 0.000 description 1
• 208000037581 Persistent Infection Diseases 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 108010059712 Pronase Proteins 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 208000009341 RNA Virus Infections Diseases 0.000 description 1
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
• 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 1
• 238000011529 RT qPCR Methods 0.000 description 1
• 101100131297 Rattus norvegicus Abcc2 gene Proteins 0.000 description 1
• PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 1
• NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• 108010090287 SCY-635 Proteins 0.000 description 1
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
• 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
• 102000015785 Serine C-Palmitoyltransferase Human genes 0.000 description 1
• 108010024814 Serine C-palmitoyltransferase Proteins 0.000 description 1
• 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 244000061456 Solanum tuberosum Species 0.000 description 1
• 235000002595 Solanum tuberosum Nutrition 0.000 description 1
• 102100027233 Solute carrier organic anion transporter family member 1B1 Human genes 0.000 description 1
• MHFMTUBUVQZIRE-WINRQGAFSA-N Sovaprevir Chemical compound C([C@H](C(=O)N1[C@@H](C[C@H](C1)OC=1C2=CC=C(C=C2N=C(C=1)C=1C=CC=CC=1)OC)C(=O)N[C@]1([C@@H](C1)C=C)C(=O)NS(=O)(=O)C1CC1)C(C)(C)C)C(=O)N1CCCCC1 MHFMTUBUVQZIRE-WINRQGAFSA-N 0.000 description 1
• 235000019764 Soybean Meal Nutrition 0.000 description 1
• 241000191940 Staphylococcus Species 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 241000187747 Streptomyces Species 0.000 description 1
• 108091027544 Subgenomic mRNA Proteins 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 208000000389 T-cell leukemia Diseases 0.000 description 1
• 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 101800001530 Thymosin alpha Proteins 0.000 description 1
• 206010066901 Treatment failure Diseases 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
• 102100032497 U3 small nucleolar ribonucleoprotein protein MPP10 Human genes 0.000 description 1
• 229910052770 Uranium Inorganic materials 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
• 108010067390 Viral Proteins Proteins 0.000 description 1
• 108020000999 Viral RNA Proteins 0.000 description 1
• 206010047700 Vomiting Diseases 0.000 description 1
• 241000710886 West Nile virus Species 0.000 description 1
• 241000710772 Yellow fever virus Species 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000016383 Zea mays subsp huehuetenangensis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• MLESJYFEMSJZLZ-MAAOGQSESA-N [(2r,3r,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-4-fluoro-4-methyl-3-(2-methylpropanoyloxy)oxolan-2-yl]methyl 2-methylpropanoate Chemical compound C[C@@]1(F)[C@H](OC(=O)C(C)C)[C@@H](COC(=O)C(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 MLESJYFEMSJZLZ-MAAOGQSESA-N 0.000 description 1
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
• VKXWOLCNTHXCLF-DXEZIKHYSA-N [(2r,3s,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-2-azido-3,4-bis(2-methylpropanoyloxy)oxolan-2-yl]methyl 2-methylpropanoate Chemical compound CC(C)C(=O)O[C@@H]1[C@H](OC(=O)C(C)C)[C@](COC(=O)C(C)C)(N=[N+]=[N-])O[C@H]1N1C(=O)N=C(N)C=C1 VKXWOLCNTHXCLF-DXEZIKHYSA-N 0.000 description 1
• XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical compound CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 description 1
• 229960002122 acebutolol Drugs 0.000 description 1
• YQNQNVDNTFHQSW-UHFFFAOYSA-N acetic acid [2-[[(5-nitro-2-thiazolyl)amino]-oxomethyl]phenyl] ester Chemical compound CC(=O)OC1=CC=CC=C1C(=O)NC1=NC=C([N+]([O-])=O)S1 YQNQNVDNTFHQSW-UHFFFAOYSA-N 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000009056 active transport Effects 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 231100000360 alopecia Toxicity 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 239000012491 analyte Substances 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000000798 anti-retroviral effect Effects 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940121357 antivirals Drugs 0.000 description 1
• 229950006356 aplaviroc Drugs 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
• PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 229960002118 asunaprevir Drugs 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• GLDOAMWVDAZGLH-UHFFFAOYSA-N azane;guanidine Chemical compound N.NC(N)=N GLDOAMWVDAZGLH-UHFFFAOYSA-N 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• ZTTKEBYSXUCBSE-QDFUAKMASA-N beclabuvir Chemical compound C1([C@@H]2C[C@@]2(CN2C3=CC(=CC=C33)C(=O)NS(=O)(=O)N(C)C)C(=O)N4[C@@H]5CC[C@H]4CN(C)C5)=CC(OC)=CC=C1C2=C3C1CCCCC1 ZTTKEBYSXUCBSE-QDFUAKMASA-N 0.000 description 1
• 229950010541 beclabuvir Drugs 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
• YJEJKUQEXFSVCJ-WRFMNRASSA-N bevirimat Chemical compound C1C[C@H](OC(=O)CC(C)(C)C(O)=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C YJEJKUQEXFSVCJ-WRFMNRASSA-N 0.000 description 1
• 229950002892 bevirimat Drugs 0.000 description 1
• BPYKTIZUTYGOLE-UHFFFAOYSA-N billirubin-IXalpha Natural products N1C(=O)C(C)=C(C=C)C1=CC1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(C=C3C(=C(C=C)C(=O)N3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-UHFFFAOYSA-N 0.000 description 1
• 239000012148 binding buffer Substances 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 108010044481 calcineurin phosphatase Proteins 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 238000011088 calibration curve Methods 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 210000004970 cd4 cell Anatomy 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 239000012578 cell culture reagent Substances 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 238000001516 cell proliferation assay Methods 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• JQXXHWHPUNPDRT-YOPQJBRCSA-N chembl1332716 Chemical compound O([C@](C1=O)(C)O\C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)/C=C\C=C(C)/C(=O)NC=2C(O)=C3C(O)=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CCN(C)CC1 JQXXHWHPUNPDRT-YOPQJBRCSA-N 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• 229960002023 chloroprocaine Drugs 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
• QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical group C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
• PJZPDFUUXKKDNB-KNINVFKUSA-N ciluprevir Chemical compound N([C@@H]1C(=O)N2[C@H](C(N[C@@]3(C[C@H]3\C=C/CCCCC1)C(O)=O)=O)C[C@H](C2)OC=1C2=CC=C(C=C2N=C(C=1)C=1N=C(NC(C)C)SC=1)OC)C(=O)OC1CCCC1 PJZPDFUUXKKDNB-KNINVFKUSA-N 0.000 description 1
• CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
• 229960001380 cimetidine Drugs 0.000 description 1
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical group N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 238000007697 cis-trans-isomerization reaction Methods 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 229940125797 compound 12 Drugs 0.000 description 1
• 229940126543 compound 14 Drugs 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940126142 compound 16 Drugs 0.000 description 1
• 229940125810 compound 20 Drugs 0.000 description 1
• 239000007891 compressed tablet Substances 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 239000000039 congener Substances 0.000 description 1
• 201000006815 congenital muscular dystrophy Diseases 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
• 239000012228 culture supernatant Substances 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• 108010048032 cyclophilin B Proteins 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 229960005449 daclatasvir Drugs 0.000 description 1
• FKRSSPOQAMALKA-CUPIEXAXSA-N daclatasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2N=C(NC=2)[C@H]2N(CCC2)C(=O)[C@@H](NC(=O)OC)C(C)C)=CN1 FKRSSPOQAMALKA-CUPIEXAXSA-N 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 229950002891 danoprevir Drugs 0.000 description 1
• 229960001418 dasabuvir Drugs 0.000 description 1
• NBRBXGKOEOGLOI-UHFFFAOYSA-N dasabuvir Chemical compound C1=C(C(C)(C)C)C(OC)=C(C=2C=C3C=CC(NS(C)(=O)=O)=CC3=CC=2)C=C1N1C=CC(=O)NC1=O NBRBXGKOEOGLOI-UHFFFAOYSA-N 0.000 description 1
• 230000009849 deactivation Effects 0.000 description 1
• 230000034994 death Effects 0.000 description 1
• 239000013530 defoamer Substances 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• BMAIGAHXAJEULY-UKTHLTGXSA-N deleobuvir Chemical compound C12=CC=C(C(=O)NC3(CCC3)C=3N(C4=CC(\C=C\C(O)=O)=CC=C4N=3)C)C=C2N(C)C(C=2N=CC(Br)=CN=2)=C1C1CCCC1 BMAIGAHXAJEULY-UKTHLTGXSA-N 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 235000021185 dessert Nutrition 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 229940043237 diethanolamine Drugs 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• 238000009792 diffusion process Methods 0.000 description 1
• LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
• 229960005156 digoxin Drugs 0.000 description 1
• LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
• 150000002009 diols Chemical class 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• WTDRDQBEARUVNC-UHFFFAOYSA-N dopa Chemical compound OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000002651 drug therapy Methods 0.000 description 1
• 241001493065 dsRNA viruses Species 0.000 description 1
• 229960003804 efavirenz Drugs 0.000 description 1
• XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 1
• 238000004520 electroporation Methods 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 206010014599 encephalitis Diseases 0.000 description 1
• 229960002062 enfuvirtide Drugs 0.000 description 1
• PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• 201000005884 exanthem Diseases 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 230000027950 fever generation Effects 0.000 description 1
• 229950011045 filibuvir Drugs 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 230000009969 flowable effect Effects 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 230000009246 food effect Effects 0.000 description 1
• 235000021471 food effect Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 229940125777 fusion inhibitor Drugs 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 229960002518 gentamicin Drugs 0.000 description 1
• 239000003365 glass fiber Substances 0.000 description 1
• 230000005182 global health Effects 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• 229940049654 glyceryl behenate Drugs 0.000 description 1
• OBMNJSNZOWALQB-NCQNOWPTSA-N grazoprevir Chemical compound O=C([C@@H]1C[C@@H]2CN1C(=O)[C@@H](NC(=O)O[C@@H]1C[C@H]1CCCCCC1=NC3=CC=C(C=C3N=C1O2)OC)C(C)(C)C)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C OBMNJSNZOWALQB-NCQNOWPTSA-N 0.000 description 1
• JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 208000014951 hematologic disease Diseases 0.000 description 1
• 230000002440 hepatic effect Effects 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000033444 hydroxylation Effects 0.000 description 1
• 238000005805 hydroxylation reaction Methods 0.000 description 1
• UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
• 229950010245 ibalizumab Drugs 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 239000002955 immunomodulating agent Substances 0.000 description 1
• 229940121354 immunomodulator Drugs 0.000 description 1
• 229940124589 immunosuppressive drug Drugs 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 239000000411 inducer Substances 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 239000002054 inoculum Substances 0.000 description 1
• 229910052816 inorganic phosphate Inorganic materials 0.000 description 1
• 238000003780 insertion Methods 0.000 description 1
• 230000037431 insertion Effects 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 229940079322 interferon Drugs 0.000 description 1
• 229940047124 interferons Drugs 0.000 description 1
• 229940117681 interleukin-12 Drugs 0.000 description 1
• 229940100601 interleukin-6 Drugs 0.000 description 1
• 239000013067 intermediate product Substances 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical group C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
• 229960004125 ketoconazole Drugs 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
• 201000002364 leukopenia Diseases 0.000 description 1
• 231100001022 leukopenia Toxicity 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 210000001853 liver microsome Anatomy 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 229960004525 lopinavir Drugs 0.000 description 1
• 231100000053 low toxicity Toxicity 0.000 description 1
• 238000000464 low-speed centrifugation Methods 0.000 description 1
• 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
• 239000008176 lyophilized powder Substances 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 238000002803 maceration Methods 0.000 description 1
• 239000003120 macrolide antibiotic agent Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 235000009973 maize Nutrition 0.000 description 1
• 229960004710 maraviroc Drugs 0.000 description 1
• GSNHKUDZZFZSJB-QYOOZWMWSA-N maraviroc Chemical compound CC(C)C1=NN=C(C)N1[C@@H]1C[C@H](N2CC[C@H](NC(=O)C3CCC(F)(F)CC3)C=3C=CC=CC=3)CC[C@H]2C1 GSNHKUDZZFZSJB-QYOOZWMWSA-N 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• JZWGXLUVGQQZRY-VIFPVBQESA-N methyl (2s)-2-amino-3-(3-aminophenyl)propanoate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC(N)=C1 JZWGXLUVGQQZRY-VIFPVBQESA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 210000003470 mitochondria Anatomy 0.000 description 1
• 230000004898 mitochondrial function Effects 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
• 235000019796 monopotassium phosphate Nutrition 0.000 description 1
• 238000000465 moulding Methods 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• XMZSTQYSBYEENY-RMKNXTFCSA-N n-[4-[(e)-2-[3-tert-butyl-5-(2,4-dioxopyrimidin-1-yl)-2-methoxyphenyl]ethenyl]phenyl]methanesulfonamide Chemical compound C1=C(N2C(NC(=O)C=C2)=O)C=C(C(C)(C)C)C(OC)=C1\C=C\C1=CC=C(NS(C)(=O)=O)C=C1 XMZSTQYSBYEENY-RMKNXTFCSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 230000017074 necrotic cell death Effects 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 229960004927 neomycin Drugs 0.000 description 1
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
• 229960002480 nitazoxanide Drugs 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
• 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• 230000036542 oxidative stress Effects 0.000 description 1
• QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• UAUIUKWPKRJZJV-MDJGTQRPSA-N paritaprevir Chemical compound C1=NC(C)=CN=C1C(=O)N[C@@H]1C(=O)N2C[C@H](OC=3C4=CC=CC=C4C4=CC=CC=C4N=3)C[C@H]2C(=O)N[C@]2(C(=O)NS(=O)(=O)C3CC3)C[C@@H]2\C=C/CCCCC1 UAUIUKWPKRJZJV-MDJGTQRPSA-N 0.000 description 1
• 229960002754 paritaprevir Drugs 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 108010044156 peptidyl-prolyl cis-trans isomerase b Proteins 0.000 description 1
• 235000019319 peptone Nutrition 0.000 description 1
• 210000005259 peripheral blood Anatomy 0.000 description 1
• 239000011886 peripheral blood Substances 0.000 description 1
• 210000004976 peripheral blood cell Anatomy 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 238000011422 pharmacological therapy Methods 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
• 239000008389 polyethoxylated castor oil Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 150000003881 polyketide derivatives Chemical class 0.000 description 1
• 125000000830 polyketide group Chemical group 0.000 description 1
• 229920001296 polysiloxane Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 238000012809 post-inoculation Methods 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
• 239000008057 potassium phosphate buffer Substances 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• RYXIBQLRUHDYEE-UHFFFAOYSA-M potassium;5-(cyclohexen-1-yl)-3-[(4-methoxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]thiophene-2-carboxylate Chemical compound [K+].C1CC(OC)CCC1N(C1=C(SC(=C1)C=1CCCCC=1)C([O-])=O)C(=O)C1CCC(C)CC1 RYXIBQLRUHDYEE-UHFFFAOYSA-M 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 230000003334 potential effect Effects 0.000 description 1
• 238000012746 preparative thin layer chromatography Methods 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 1
• 230000012846 protein folding Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical group N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 206010037844 rash Diseases 0.000 description 1
• 238000000611 regression analysis Methods 0.000 description 1
• 230000012121 regulation of immune response Effects 0.000 description 1
• 230000027221 regulation of protein secretion Effects 0.000 description 1
• 230000037425 regulation of transcription Effects 0.000 description 1
• 230000010410 reperfusion Effects 0.000 description 1
• HSSLDCABUXLXKM-UHFFFAOYSA-N resorufin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3N=C21 HSSLDCABUXLXKM-UHFFFAOYSA-N 0.000 description 1
• 238000003757 reverse transcription PCR Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 210000003705 ribosome Anatomy 0.000 description 1
• 229960001225 rifampicin Drugs 0.000 description 1
• 229960000311 ritonavir Drugs 0.000 description 1
• NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
• 238000002390 rotary evaporation Methods 0.000 description 1
• 210000003752 saphenous vein Anatomy 0.000 description 1
• 238000003345 scintillation counting Methods 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
• DEKOYVOWOVJMPM-RLHIPHHXSA-N setrobuvir Chemical compound N1([C@H]2[C@@H]3CC[C@@H](C3)[C@H]2C(O)=C(C1=O)C=1NC2=CC=C(C=C2S(=O)(=O)N=1)NS(=O)(=O)C)CC1=CC=C(F)C=C1 DEKOYVOWOVJMPM-RLHIPHHXSA-N 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• 229960002091 simeprevir Drugs 0.000 description 1
• JTZZSQYMACOLNN-VDWJNHBNSA-N simeprevir Chemical compound O=C([C@@]12C[C@H]1\C=C/CCCCN(C)C(=O)[C@H]1[C@H](C(N2)=O)C[C@H](C1)OC=1C2=CC=C(C(=C2N=C(C=1)C=1SC=C(N=1)C(C)C)C)OC)NS(=O)(=O)C1CC1 JTZZSQYMACOLNN-VDWJNHBNSA-N 0.000 description 1
• 229960002855 simvastatin Drugs 0.000 description 1
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
• 239000002356 single layer Substances 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 231100000046 skin rash Toxicity 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 229940023144 sodium glycolate Drugs 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 229960002063 sofosbuvir Drugs 0.000 description 1
• TTZHDVOVKQGIBA-IQWMDFIBSA-N sofosbuvir Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@]2(F)C)O)CO[P@@](=O)(N[C@@H](C)C(=O)OC(C)C)OC=2C=CC=CC=2)C=CC(=O)NC1=O TTZHDVOVKQGIBA-IQWMDFIBSA-N 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 238000000638 solvent extraction Methods 0.000 description 1
• 238000009331 sowing Methods 0.000 description 1
• 239000004455 soybean meal Substances 0.000 description 1
• 230000028070 sporulation Effects 0.000 description 1
• 230000005477 standard model Effects 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 238000000547 structure data Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 231100000617 superantigen Toxicity 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 description 1
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
• BBAWEDCPNXPBQM-GDEBMMAJSA-N telaprevir Chemical compound N([C@H](C(=O)N[C@H](C(=O)N1C[C@@H]2CCC[C@@H]2[C@H]1C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1)C(C)(C)C)C1CCCCC1)C(=O)C1=CN=CC=N1 BBAWEDCPNXPBQM-GDEBMMAJSA-N 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 229940104230 thymidine Drugs 0.000 description 1
• 231100000440 toxicity profile Toxicity 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 150000005671 trienes Chemical class 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
• 229910021642 ultra pure water Inorganic materials 0.000 description 1
• 239000012498 ultrapure water Substances 0.000 description 1
• 229960005486 vaccine Drugs 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 229950009860 vicriviroc Drugs 0.000 description 1
• 230000007502 viral entry Effects 0.000 description 1
• 230000029812 viral genome replication Effects 0.000 description 1
• 201000001862 viral hepatitis Diseases 0.000 description 1
• 230000017613 viral reproduction Effects 0.000 description 1
• 210000001835 viscera Anatomy 0.000 description 1
• 230000008673 vomiting Effects 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 229940100445 wheat starch Drugs 0.000 description 1
• 239000012224 working solution Substances 0.000 description 1
• 229940051021 yellow-fever virus Drugs 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1