ZA200100971B - Hepatitis C inhibitor tri-peptides - Google Patents
Hepatitis C inhibitor tri-peptides Download PDFInfo
- Publication number
- ZA200100971B ZA200100971B ZA200100971A ZA200100971A ZA200100971B ZA 200100971 B ZA200100971 B ZA 200100971B ZA 200100971 A ZA200100971 A ZA 200100971A ZA 200100971 A ZA200100971 A ZA 200100971A ZA 200100971 B ZA200100971 B ZA 200100971B
- Authority
- ZA
- South Africa
- Prior art keywords
- alkyl
- optionally substituted
- formula
- amido
- substituted
- Prior art date
Links
- 208000005176 Hepatitis C Diseases 0.000 title claims description 19
- 239000003112 inhibitor Substances 0.000 title claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 535
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 177
- 125000003368 amide group Chemical group 0.000 claims description 176
- 150000001875 compounds Chemical class 0.000 claims description 147
- 150000001408 amides Chemical class 0.000 claims description 136
- 125000003545 alkoxy group Chemical group 0.000 claims description 131
- -1 hydroxy, carboxyl Chemical group 0.000 claims description 131
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 126
- 125000003118 aryl group Chemical group 0.000 claims description 111
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 91
- 125000005843 halogen group Chemical group 0.000 claims description 74
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 70
- 238000000034 method Methods 0.000 claims description 65
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 57
- 125000002252 acyl group Chemical group 0.000 claims description 52
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 43
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 41
- 241000711549 Hepacivirus C Species 0.000 claims description 39
- 150000002148 esters Chemical class 0.000 claims description 39
- 230000015572 biosynthetic process Effects 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 35
- 238000003786 synthesis reaction Methods 0.000 claims description 35
- 125000006239 protecting group Chemical group 0.000 claims description 34
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 29
- 230000008569 process Effects 0.000 claims description 27
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 24
- 150000001413 amino acids Chemical class 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 21
- 238000005859 coupling reaction Methods 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 241000124008 Mammalia Species 0.000 claims description 18
- 125000001188 haloalkyl group Chemical group 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- 230000008878 coupling Effects 0.000 claims description 17
- 238000010168 coupling process Methods 0.000 claims description 17
- 125000004001 thioalkyl group Chemical group 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
- 101800001838 Serine protease/helicase NS3 Proteins 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 14
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 13
- 229920002554 vinyl polymer Chemical group 0.000 claims description 13
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 229940079322 interferon Drugs 0.000 claims description 9
- 230000009385 viral infection Effects 0.000 claims description 9
- 102000014150 Interferons Human genes 0.000 claims description 8
- 108010050904 Interferons Proteins 0.000 claims description 8
- 229940122055 Serine protease inhibitor Drugs 0.000 claims description 8
- 101710102218 Serine protease inhibitor Proteins 0.000 claims description 8
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 8
- 208000036142 Viral infection Diseases 0.000 claims description 8
- 239000003001 serine protease inhibitor Substances 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 230000003287 optical effect Effects 0.000 claims description 7
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 6
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 6
- 125000001391 thioamide group Chemical group 0.000 claims description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
- 229940124771 HCV-NS3 protease inhibitor Drugs 0.000 claims description 5
- 108060004795 Methyltransferase Proteins 0.000 claims description 5
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 230000010076 replication Effects 0.000 claims description 5
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 4
- PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical group OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000005979 2-naphthyloxy group Chemical group 0.000 claims description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 4
- 108010006035 Metalloproteases Proteins 0.000 claims description 4
- 102000005741 Metalloproteases Human genes 0.000 claims description 4
- 108091005804 Peptidases Proteins 0.000 claims description 4
- 108010033276 Peptide Fragments Proteins 0.000 claims description 4
- 102000007079 Peptide Fragments Human genes 0.000 claims description 4
- 239000004365 Protease Substances 0.000 claims description 4
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229960000329 ribavirin Drugs 0.000 claims description 4
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 4
- 125000004963 sulfonylalkyl group Chemical group 0.000 claims description 4
- 150000003573 thiols Chemical class 0.000 claims description 4
- 230000003612 virological effect Effects 0.000 claims description 4
- 125000006083 1-bromoethyl group Chemical group 0.000 claims description 3
- TXHAHOVNFDVCCC-UHFFFAOYSA-N 2-(tert-butylazaniumyl)acetate Chemical compound CC(C)(C)NCC(O)=O TXHAHOVNFDVCCC-UHFFFAOYSA-N 0.000 claims description 3
- 125000005999 2-bromoethyl group Chemical group 0.000 claims description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 3
- 125000005907 alkyl ester group Chemical group 0.000 claims description 3
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 3
- 229960003805 amantadine Drugs 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 239000012752 auxiliary agent Substances 0.000 claims description 2
- 101150093710 clec-87 gene Proteins 0.000 claims description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 2
- 150000003147 proline derivatives Chemical class 0.000 claims description 2
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 41
- 206010037742 Rabies Diseases 0.000 claims 4
- 108090000371 Esterases Proteins 0.000 claims 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 1
- 241000218642 Abies Species 0.000 claims 1
- 241000726103 Atta Species 0.000 claims 1
- 102100026816 DNA-dependent metalloprotease SPRTN Human genes 0.000 claims 1
- 101710175461 DNA-dependent metalloprotease SPRTN Proteins 0.000 claims 1
- 241000345386 Fabia Species 0.000 claims 1
- OOFLZRMKTMLSMH-UHFFFAOYSA-N H4atta Chemical compound OC(=O)CN(CC(O)=O)CC1=CC=CC(C=2N=C(C=C(C=2)C=2C3=CC=CC=C3C=C3C=CC=CC3=2)C=2N=C(CN(CC(O)=O)CC(O)=O)C=CC=2)=N1 OOFLZRMKTMLSMH-UHFFFAOYSA-N 0.000 claims 1
- 241001214257 Mene Species 0.000 claims 1
- 101100149256 Mus musculus Sema6b gene Proteins 0.000 claims 1
- 101100215778 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) ptr-1 gene Proteins 0.000 claims 1
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
- 241001208007 Procas Species 0.000 claims 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
- 241000711981 Sais Species 0.000 claims 1
- 102000005158 Subtilisins Human genes 0.000 claims 1
- 108010056079 Subtilisins Proteins 0.000 claims 1
- 241001122767 Theaceae Species 0.000 claims 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
- SNXPWYFWAZVIAU-UHFFFAOYSA-N arachidonic acid ethyl ester Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)OCC SNXPWYFWAZVIAU-UHFFFAOYSA-N 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 239000013256 coordination polymer Substances 0.000 claims 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 claims 1
- 229910052754 neon Inorganic materials 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 45
- 229940024606 amino acid Drugs 0.000 description 27
- 235000001014 amino acid Nutrition 0.000 description 24
- 150000003254 radicals Chemical class 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 239000002585 base Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 102000004196 processed proteins & peptides Human genes 0.000 description 11
- 239000011347 resin Substances 0.000 description 11
- 229920005989 resin Polymers 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 101710144111 Non-structural protein 3 Proteins 0.000 description 7
- 235000019439 ethyl acetate Nutrition 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000003443 antiviral agent Substances 0.000 description 6
- 239000007822 coupling agent Substances 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 5
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 5
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 5
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
- 102000012479 Serine Proteases Human genes 0.000 description 5
- 108010022999 Serine Proteases Proteins 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 150000002466 imines Chemical class 0.000 description 5
- 230000002519 immonomodulatory effect Effects 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 230000000840 anti-viral effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 208000019423 liver disease Diseases 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000036515 potency Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- JGABMVVOXLQCKZ-UHFFFAOYSA-N 2-phenyl-1h-quinolin-4-one Chemical class N=1C2=CC=CC=C2C(O)=CC=1C1=CC=CC=C1 JGABMVVOXLQCKZ-UHFFFAOYSA-N 0.000 description 3
- 208000006154 Chronic hepatitis C Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 239000004471 Glycine Substances 0.000 description 3
- 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 3
- 102100033174 Neutrophil elastase Human genes 0.000 description 3
- 101800001020 Non-structural protein 4A Proteins 0.000 description 3
- 102000035195 Peptidases Human genes 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 208000010710 hepatitis C virus infection Diseases 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 235000019419 proteases Nutrition 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- AITNMTXHTIIIBB-UHFFFAOYSA-N 1-bromo-4-fluorobenzene Chemical compound FC1=CC=C(Br)C=C1 AITNMTXHTIIIBB-UHFFFAOYSA-N 0.000 description 2
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate 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)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229940122604 HCV protease inhibitor Drugs 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 150000008575 L-amino acids Chemical class 0.000 description 2
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 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 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 238000006751 Mitsunobu reaction Methods 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- 108010076039 Polyproteins Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 102000004409 RNA Helicases Human genes 0.000 description 2
- 108090000944 RNA Helicases Proteins 0.000 description 2
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Substances 0.000 description 2
- 108700022715 Viral Proteases Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000003862 amino acid derivatives Chemical class 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229960005261 aspartic acid Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- LJOODBDWMQKMFB-UHFFFAOYSA-N cyclohexylacetic acid Chemical compound OC(=O)CC1CCCCC1 LJOODBDWMQKMFB-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 150000005690 diesters Chemical class 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 229960002591 hydroxyproline Drugs 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 229940072221 immunoglobulins Drugs 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940047124 interferons Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 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
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- VMPITZXILSNTON-UHFFFAOYSA-N o-anisidine Chemical compound COC1=CC=CC=C1N VMPITZXILSNTON-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- QRDZFPUVLYEQTA-UHFFFAOYSA-N quinoline-8-carboxylic acid Chemical compound C1=CN=C2C(C(=O)O)=CC=CC2=C1 QRDZFPUVLYEQTA-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 229960001153 serine Drugs 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 229960002898 threonine Drugs 0.000 description 2
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 230000029812 viral genome replication Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MJLQPFJGZTYCMH-LURJTMIESA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]-5-oxopyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1[C@H](C(O)=O)CCC1=O MJLQPFJGZTYCMH-LURJTMIESA-N 0.000 description 1
- WAMWSIDTKSNDCU-ZETCQYMHSA-N (2s)-2-azaniumyl-2-cyclohexylacetate Chemical compound OC(=O)[C@@H](N)C1CCCCC1 WAMWSIDTKSNDCU-ZETCQYMHSA-N 0.000 description 1
- BENKAPCDIOILGV-RQJHMYQMSA-N (2s,4r)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(O)=O BENKAPCDIOILGV-RQJHMYQMSA-N 0.000 description 1
- JXDNUMOTWHZSCB-XMTZKCFKSA-N (3s)-3-acetamido-4-[[(2s)-3-carboxy-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1r)-1-carboxy-2-sulfanylethyl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(O)=O JXDNUMOTWHZSCB-XMTZKCFKSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- LRANPJDWHYRCER-UHFFFAOYSA-N 1,2-diazepine Chemical compound N1C=CC=CC=N1 LRANPJDWHYRCER-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical group NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
- FVTVMQPGKVHSEY-UHFFFAOYSA-N 1-AMINOCYCLOBUTANE CARBOXYLIC ACID Chemical compound OC(=O)C1(N)CCC1 FVTVMQPGKVHSEY-UHFFFAOYSA-N 0.000 description 1
- RMSGQZDGSZOJMU-UHFFFAOYSA-N 1-butyl-2-phenylbenzene Chemical group CCCCC1=CC=CC=C1C1=CC=CC=C1 RMSGQZDGSZOJMU-UHFFFAOYSA-N 0.000 description 1
- HLDFCCHSOZWKAA-UHFFFAOYSA-N 1-fluoro-2-nitro-4-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1F HLDFCCHSOZWKAA-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- MZMNEDXVUJLQAF-YUMQZZPRSA-N 1-o-tert-butyl 2-o-methyl (2s,4s)-4-hydroxypyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@H](O)CN1C(=O)OC(C)(C)C MZMNEDXVUJLQAF-YUMQZZPRSA-N 0.000 description 1
- SXGZJKUKBWWHRA-UHFFFAOYSA-N 2-(N-morpholiniumyl)ethanesulfonate Chemical compound [O-]S(=O)(=O)CC[NH+]1CCOCC1 SXGZJKUKBWWHRA-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
- RTLKJCSGNBYCKJ-UHFFFAOYSA-N 3-oxo-3-phenylpropanamide Chemical compound NC(=O)CC(=O)C1=CC=CC=C1 RTLKJCSGNBYCKJ-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- YYVYAPXYZVYDHN-UHFFFAOYSA-N 9,10-phenanthroquinone Chemical compound C1=CC=C2C(=O)C(=O)C3=CC=CC=C3C2=C1 YYVYAPXYZVYDHN-UHFFFAOYSA-N 0.000 description 1
- 241000023308 Acca Species 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 244000186140 Asperula odorata Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 235000014698 Brassica juncea var multisecta Nutrition 0.000 description 1
- 101100440696 Caenorhabditis elegans cor-1 gene Proteins 0.000 description 1
- 241001286462 Caio Species 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 108090000317 Chymotrypsin Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 101710118188 DNA-binding protein HU-alpha Proteins 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- GKKZMYDNDDMXSE-UHFFFAOYSA-N Ethyl 3-oxo-3-phenylpropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC=C1 GKKZMYDNDDMXSE-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 241000710781 Flaviviridae Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical group [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 235000008526 Galium odoratum Nutrition 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 206010019786 Hepatitis non-A non-B Diseases 0.000 description 1
- 206010019799 Hepatitis viral 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
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-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
- 239000004472 Lysine Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 101710144128 Non-structural protein 2 Proteins 0.000 description 1
- 101800001019 Non-structural protein 4B Proteins 0.000 description 1
- 101800001014 Non-structural protein 5A Proteins 0.000 description 1
- 101710199667 Nuclear export protein Proteins 0.000 description 1
- 102000008021 Nucleoside-Triphosphatase Human genes 0.000 description 1
- 108010075285 Nucleoside-Triphosphatase Proteins 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 206010033647 Pancreatitis acute Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 240000004713 Pisum sativum Species 0.000 description 1
- 235000010582 Pisum sativum Nutrition 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000003229 acute pancreatitis Diseases 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000005076 adamantyloxycarbonyl group Chemical group C12(CC3CC(CC(C1)C3)C2)OC(=O)* 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000005256 alkoxyacyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 150000004808 allyl alcohols Chemical group 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 125000005620 boronic acid group Chemical group 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 244000275904 brauner Senf Species 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- GCSVCUMDOQKEMT-UHFFFAOYSA-N butan-1-amine;hydrofluoride Chemical compound [H+].[F-].CCCCN GCSVCUMDOQKEMT-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical compound BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 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
- 230000001684 chronic effect Effects 0.000 description 1
- 229960002376 chymotrypsin Drugs 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 150000001930 cyclobutanes Chemical class 0.000 description 1
- KTHXBEHDVMTNOH-UHFFFAOYSA-N cyclobutanol Chemical compound OC1CCC1 KTHXBEHDVMTNOH-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 108700012707 hepatitis C virus NS3 Proteins 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000028996 humoral immune response Effects 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000033116 oxidation-reduction process Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 229960005190 phenylalanine Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002064 post-exposure prophylaxis Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical group CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011945 regioselective hydrolysis Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003826 tablet Substances 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
- NYBWUHOMYZZKOR-UHFFFAOYSA-N tes-adt Chemical class C1=C2C(C#C[Si](CC)(CC)CC)=C(C=C3C(SC=C3)=C3)C3=C(C#C[Si](CC)(CC)CC)C2=CC2=C1SC=C2 NYBWUHOMYZZKOR-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000007979 thiazole derivatives Chemical class 0.000 description 1
- 150000003548 thiazolidines Chemical class 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 230000008957 viral persistence Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/02—Amides, e.g. chloramphenicol or polyamides; Imides or polyimides; Urethanes, i.e. compounds comprising N-C=O structural element or polyurethanes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/081—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
- C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
- C12P41/005—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of carboxylic acid groups in the enantiomers or the inverse reaction
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biophysics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Analytical Chemistry (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9593198P | 1998-08-10 | 1998-08-10 | |
US13238699P | 1999-05-04 | 1999-05-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200100971B true ZA200100971B (en) | 2002-06-26 |
Family
ID=26790767
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200100971A ZA200100971B (en) | 1998-08-10 | 2001-02-05 | Hepatitis C inhibitor tri-peptides |
Country Status (43)
Families Citing this family (423)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2314598A1 (en) | 1996-10-18 | 2011-04-27 | Vertex Pharmaceuticals Incorporated | Inhibitors of Hepatitis C virus NS3 serine protease |
US6767991B1 (en) | 1997-08-11 | 2004-07-27 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C inhibitor peptides |
US6323180B1 (en) * | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
US6608027B1 (en) | 1999-04-06 | 2003-08-19 | Boehringer Ingelheim (Canada) Ltd | Macrocyclic peptides active against the hepatitis C virus |
UA74546C2 (en) * | 1999-04-06 | 2006-01-16 | Boehringer Ingelheim Ca Ltd | Macrocyclic peptides having activity relative to hepatitis c virus, a pharmaceutical composition and use of the pharmaceutical composition |
JP2004534501A (ja) * | 1999-06-25 | 2004-11-18 | ビーエーエスエフ アクチェンゲゼルシャフト | 代謝経路タンパク質をコードするコリネバクテリウム−グルタミカム遺伝子 |
CN1441806A (zh) | 2000-04-05 | 2003-09-10 | 先灵公司 | 包含n-环p2部分的丙型肝炎病毒的大环ns3-丝氨酸蛋白酶抑制剂 |
CA2406532A1 (en) | 2000-04-19 | 2001-11-01 | Schering Corporation | Macrocyclic ns-3 serine protease inhibitors of hepatitis c virus compri sing alkyl and aryl alanine p2 moieties |
US6713502B2 (en) | 2000-05-05 | 2004-03-30 | Smithkline Beecham Corporation | Anti-infectives |
PE20011350A1 (es) | 2000-05-19 | 2002-01-15 | Vertex Pharma | PROFARMACO DE UN INHIBIDOR DE ENZIMA CONVERTIDORA DE INTERLEUCINA-1ß (ICE) |
AR029851A1 (es) | 2000-07-21 | 2003-07-16 | Dendreon Corp | Nuevos peptidos como inhibidores de ns3-serina proteasa del virus de hepatitis c |
US7012066B2 (en) | 2000-07-21 | 2006-03-14 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
CN1446201A (zh) | 2000-07-21 | 2003-10-01 | 先灵公司 | 用作丙型肝炎病毒ns3-丝氨酸蛋白酶抑制剂的新型肽 |
AR034127A1 (es) * | 2000-07-21 | 2004-02-04 | Schering Corp | Imidazolidinonas como inhibidores de ns3-serina proteasa del virus de hepatitis c, composicion farmaceutica, un metodo para su preparacion, y el uso de las mismas para la manufactura de un medicamento |
SV2003000617A (es) | 2000-08-31 | 2003-01-13 | Lilly Co Eli | Inhibidores de la proteasa peptidomimetica ref. x-14912m |
US6846806B2 (en) | 2000-10-23 | 2005-01-25 | Bristol-Myers Squibb Company | Peptide inhibitors of Hepatitis C virus NS3 protein |
CA2429359A1 (en) * | 2000-11-20 | 2002-08-08 | Bristol-Myers Squibb Company | Hepatitis c tripeptide inhibitors |
ATE430166T1 (de) | 2000-12-12 | 2009-05-15 | Schering Corp | Diarylrest entfassende peptide als inhibitoren des ns-3 serinproteases von hepatitis c virus |
CA2434386C (en) | 2001-01-22 | 2006-12-05 | Merck & Co., Inc. | Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase |
ES2279879T3 (es) | 2001-07-11 | 2007-09-01 | Vertex Pharmaceuticals Incorporated | Inhibidores biciclicos puente de la serina proteasa. |
DE10297210B4 (de) | 2001-09-14 | 2009-01-02 | Honda Giken Kogyo K.K. | Aufprall absorbierende Frontgrillanordnung für ein Kraftfahrzeug |
CA2462163A1 (en) | 2001-10-24 | 2003-05-01 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine protease, particularly hepatitis c virus ns3-ns4a protease, incorporating a fused ring system |
US20050009873A1 (en) * | 2001-11-02 | 2005-01-13 | Gianpaolo Bravi | Acyl dihydro pyrrole derivatives as hcv inhibitors |
US6867185B2 (en) * | 2001-12-20 | 2005-03-15 | Bristol-Myers Squibb Company | Inhibitors of hepatitis C virus |
EP1467989B1 (en) | 2002-01-23 | 2009-09-23 | Schering Corporation | Proline compounds as ns3-serine protease inhibitors for use in treatment of hepatitis c virus infection |
US7119072B2 (en) * | 2002-01-30 | 2006-10-10 | Boehringer Ingelheim (Canada) Ltd. | Macrocyclic peptides active against the hepatitis C virus |
US7091184B2 (en) * | 2002-02-01 | 2006-08-15 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
CA2370396A1 (en) * | 2002-02-01 | 2003-08-01 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c inhibitor tri-peptides |
CA2369970A1 (en) * | 2002-02-01 | 2003-08-01 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c inhibitor tri-peptides |
US6642204B2 (en) * | 2002-02-01 | 2003-11-04 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
NZ561851A (en) | 2002-04-11 | 2009-05-31 | Vertex Pharma | Inhibitors of serine proteases, particularly hepatitis C virus NS3 - NS4 protease |
JP4312718B2 (ja) * | 2002-05-20 | 2009-08-12 | ブリストル−マイヤーズ スクイブ カンパニー | C型肝炎ウイルス阻害剤 |
MY140680A (en) | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
US6869964B2 (en) | 2002-05-20 | 2005-03-22 | Bristol-Myers Squibb Company | Heterocyclicsulfonamide hepatitis C virus inhibitors |
WO2004043339A2 (en) * | 2002-05-20 | 2004-05-27 | Bristol-Myers Squibb Company | Substituted cycloalkyl p1' hepatitis c virus inhibitors |
KR100457857B1 (ko) * | 2002-05-23 | 2004-11-18 | (주) 비엔씨바이오팜 | 2-[2-(3-인돌릴)에틸아미노]피리딘 유도체, 그 제조방법및 이를 포함하는 항바이러스용 약학적 조성물 |
PT1523489E (pt) | 2002-06-28 | 2014-06-24 | Centre Nat Rech Scient | Profármacos de nucleósido modificado em 2' e 3' para tratamento de infecções por flaviridae |
US20040033959A1 (en) * | 2002-07-19 | 2004-02-19 | Boehringer Ingelheim Pharmaceuticals, Inc. | Pharmaceutical compositions for hepatitis C viral protease inhibitors |
WO2004014852A2 (en) * | 2002-08-12 | 2004-02-19 | Bristol-Myers Squibb Company | Iminothiazolidinones as inhibitors of hcv replication |
EP1408031A1 (en) * | 2002-10-09 | 2004-04-14 | 3 D Gene Pharma | Pyrolidine derivatives useful in treatment of hepatitis C virus infection |
BR0315417A (pt) | 2002-10-24 | 2005-08-16 | Glaxo Group Ltd | Derivados 1-acil-pirrolidina para o tratamento de infecções virais |
US20050075279A1 (en) * | 2002-10-25 | 2005-04-07 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis C virus |
US7601709B2 (en) | 2003-02-07 | 2009-10-13 | Enanta Pharmaceuticals, Inc. | Macrocyclic hepatitis C serine protease inhibitors |
JP4550824B2 (ja) * | 2003-03-05 | 2010-09-22 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | C型肝炎抑制化合物 |
CA2516018C (en) * | 2003-03-05 | 2011-08-23 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibitor peptide analogs |
KR100960802B1 (ko) * | 2003-03-08 | 2010-06-01 | 주식회사유한양행 | 씨형 간염바이러스 감염 치료용 엔에스3 프로테아제 억제제 |
JP4231524B2 (ja) * | 2003-04-10 | 2009-03-04 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 大環状化合物の製造方法 |
WO2004094452A2 (en) * | 2003-04-16 | 2004-11-04 | Bristol-Myers Squibb Company | Macrocyclic isoquinoline peptide inhibitors of hepatitis c virus |
US7176208B2 (en) | 2003-04-18 | 2007-02-13 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl macrocyclic hepatitis C serine protease inhibitors |
CN1788006A (zh) * | 2003-04-18 | 2006-06-14 | 安南塔制药公司 | 喹喔啉基大环丙型肝炎丝氨酸蛋白酶抑制剂 |
US6846836B2 (en) | 2003-04-18 | 2005-01-25 | Bristol-Myers Squibb Company | N-substituted phenylurea inhibitors of mitochondrial F1F0 ATP hydrolase |
ATE378334T1 (de) * | 2003-05-21 | 2007-11-15 | Boehringer Ingelheim Int | Verbindungen als hepatitis c inhibitoren |
PL3521297T3 (pl) | 2003-05-30 | 2022-04-04 | Gilead Pharmasset Llc | Zmodyfikowane fluorowane analogi nukleozydów |
US7273851B2 (en) | 2003-06-05 | 2007-09-25 | Enanta Pharmaceuticals, Inc. | Tri-peptide hepatitis C serine protease inhibitors |
WO2004113365A2 (en) * | 2003-06-05 | 2004-12-29 | Enanta Pharmaceuticals, Inc. | Hepatitis c serine protease tri-peptide inhibitors |
US7125845B2 (en) * | 2003-07-03 | 2006-10-24 | Enanta Pharmaceuticals, Inc. | Aza-peptide macrocyclic hepatitis C serine protease inhibitors |
WO2005009418A2 (en) * | 2003-07-25 | 2005-02-03 | Idenix (Cayman) Limited | Purine nucleoside analogues for treating diseases caused by flaviviridae including hepatitis c |
US7449447B2 (en) | 2003-08-26 | 2008-11-11 | Schering Corporation | Peptidomimetic NS3-serine protease inhibitors of hepatitis C virus |
US8025899B2 (en) | 2003-08-28 | 2011-09-27 | Abbott Laboratories | Solid pharmaceutical dosage form |
US8377952B2 (en) | 2003-08-28 | 2013-02-19 | Abbott Laboratories | Solid pharmaceutical dosage formulation |
PE20050374A1 (es) | 2003-09-05 | 2005-05-30 | Vertex Pharma | Inhibidores de proteasas de serina, en particular proteasa ns3-ns4a del vhc |
JP4704342B2 (ja) * | 2003-09-22 | 2011-06-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | C型肝炎ウイルスに対し活性な大環状ペプチド |
DE602004031298D1 (de) * | 2003-09-26 | 2011-03-17 | Schering Corp | Makrocyclische inhibitoren der ns3-serinprotease des hepatitis-c-virus |
NZ546663A (en) | 2003-10-10 | 2010-01-29 | Vertex Pharma | Inhibitors of serine proteases, particularly HCV NS3-NS4A protease |
US7491794B2 (en) * | 2003-10-14 | 2009-02-17 | Intermune, Inc. | Macrocyclic compounds as inhibitors of viral replication |
RS20110578A3 (en) | 2003-10-14 | 2016-02-29 | F. Hoffmann-La Roche Ltd | MACROCYCLIC CARBOXYLIC ACIDS AND ACYLSULPHONAMIDES AS HCV REPLICATION INHIBITORS |
EP1944042A1 (en) | 2003-10-27 | 2008-07-16 | Vertex Pharmceuticals Incorporated | Combinations for HCV treatment |
US8187874B2 (en) | 2003-10-27 | 2012-05-29 | Vertex Pharmaceuticals Incorporated | Drug discovery method |
AU2004285019B9 (en) | 2003-10-27 | 2011-11-24 | Vertex Pharmaceuticals Incorporated | HCV NS3-NS4A protease resistance mutants |
US20050119318A1 (en) * | 2003-10-31 | 2005-06-02 | Hudyma Thomas W. | Inhibitors of HCV replication |
US7132504B2 (en) | 2003-11-12 | 2006-11-07 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7135462B2 (en) | 2003-11-20 | 2006-11-14 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
CN1902216A (zh) * | 2003-11-20 | 2007-01-24 | 先灵公司 | 丙肝病毒ns3蛋白酶的去肽化抑制剂 |
US7309708B2 (en) * | 2003-11-20 | 2007-12-18 | Birstol-Myers Squibb Company | Hepatitis C virus inhibitors |
JP2007513200A (ja) * | 2003-12-08 | 2007-05-24 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 超臨界流体処理によるルテニウム副生物の除去 |
WO2005058884A2 (en) | 2003-12-15 | 2005-06-30 | Japan Tobacco Inc. | Cyclopropane compounds and pharmaceutical use thereof |
GB0500020D0 (en) | 2005-01-04 | 2005-02-09 | Novartis Ag | Organic compounds |
ATE495185T1 (de) * | 2004-01-21 | 2011-01-15 | Boehringer Ingelheim Int | Makrocyclische peptide mit wirkung gegen das hepatitis-c-virus |
SE0400199D0 (sv) * | 2004-01-30 | 2004-01-30 | Medivir Ab | HCV Protease inhbitors |
AR047793A1 (es) * | 2004-01-30 | 2006-02-22 | Medivir Ab | Inhibidores de la serina proteasa ns-3 del vhc |
JP2008505849A (ja) | 2004-02-04 | 2008-02-28 | バーテックス ファーマシューティカルズ インコーポレイテッド | セリンプロテアーゼ、特に、hcv、ns3−ns4aプロテアーゼの阻害剤 |
US20050182252A1 (en) | 2004-02-13 | 2005-08-18 | Reddy K. R. | Novel 2'-C-methyl nucleoside derivatives |
DK1718608T3 (da) | 2004-02-20 | 2013-10-14 | Boehringer Ingelheim Int | Virale polymeraseinhibitorer |
US20070049593A1 (en) | 2004-02-24 | 2007-03-01 | Japan Tobacco Inc. | Tetracyclic fused heterocyclic compound and use thereof as HCV polymerase inhibitor |
ATE428714T1 (de) | 2004-02-24 | 2009-05-15 | Japan Tobacco Inc | Kondensierte heterotetracyclische verbindungen und deren verwendung als hcv-polymerase-inhibitor |
WO2005085197A1 (en) * | 2004-02-27 | 2005-09-15 | Schering Corporation | Cyclobutenedione groups-containing compounds as inhibitors of hepatitis c virus ns3 serine protease |
TW200536528A (en) | 2004-02-27 | 2005-11-16 | Schering Corp | Novel inhibitors of hepatitis C virus NS3 protease |
US7816326B2 (en) | 2004-02-27 | 2010-10-19 | Schering Corporation | Sulfur compounds as inhibitors of hepatitis C virus NS3 serine protease |
JP2007525511A (ja) | 2004-02-27 | 2007-09-06 | シェーリング コーポレイション | C型肝炎ウイルスns3セリンプロテアーゼの新規のインヒビターとしての化合物 |
AU2005222060A1 (en) | 2004-02-27 | 2005-09-22 | Schering Corporation | Sulfur compounds as inhibitors of hepatitis C virus NS3 serine protease |
DE602005015834D1 (de) | 2004-02-27 | 2009-09-17 | Schering Corp | 3,4-(cyclopentyl)kondensierte prolinverbindungen als inhibitoren der ns3-serinprotease des hepatitis-c-virus |
CA2557247A1 (en) | 2004-02-27 | 2005-09-22 | Schering Corporation | Compounds as inhibitors of hepatitis c virus ns3 serine protease |
US7635694B2 (en) | 2004-02-27 | 2009-12-22 | Schering Corporation | Cyclobutenedione-containing compounds as inhibitors of hepatitis C virus NS3 serine protease |
CN103467459A (zh) * | 2004-03-12 | 2013-12-25 | 弗特克斯药品有限公司 | 制备化合物的方法 |
US20050209135A1 (en) * | 2004-03-15 | 2005-09-22 | Boehringer Ingelheim International Gmbh | Process for preparing macrocyclic compounds |
AP2006003763A0 (en) * | 2004-03-30 | 2006-10-31 | Intermune Inc | Macrocyclic compounds as inhibitors of viral replication |
WO2005107742A1 (en) | 2004-05-05 | 2005-11-17 | Yale University | Novel antiviral helioxanthin analogs |
ES2328596T3 (es) | 2004-05-20 | 2009-11-16 | Schering Corporation | Prolinas sustituidas como inhibidores de la serina proteasa del virus ns3 de la hepatitis c. |
WO2005116054A1 (en) * | 2004-05-25 | 2005-12-08 | Boehringer Ingelheim International, Gmbh | Process for preparing acyclic hcv protease inhibitors |
US7534767B2 (en) | 2004-06-15 | 2009-05-19 | Merck & Co., Inc. | C-purine nucleoside analogs as inhibitors of RNA-dependent RNA viral polymerase |
US20070265222A1 (en) | 2004-06-24 | 2007-11-15 | Maccoss Malcolm | Nucleoside Aryl Phosphoramidates for the Treatment of Rna-Dependent Rna Viral Infection |
WO2006000085A1 (en) * | 2004-06-28 | 2006-01-05 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibitor peptide analogs |
KR20070034119A (ko) * | 2004-07-16 | 2007-03-27 | 길리애드 사이언시즈, 인코포레이티드 | 항바이러스 화합물 |
ATE512971T1 (de) * | 2004-07-20 | 2011-07-15 | Boehringer Ingelheim Int | Peptidanaloga als hepatitis c-hemmer |
UY29016A1 (es) * | 2004-07-20 | 2006-02-24 | Boehringer Ingelheim Int | Analogos de dipeptidos inhibidores de la hepatitis c |
CN101023094B (zh) * | 2004-07-21 | 2011-05-18 | 法莫赛特股份有限公司 | 烷基取代的2-脱氧-2-氟代-d-呋喃核糖基嘧啶和嘌呤及其衍生物的制备 |
US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
CA2576030A1 (en) * | 2004-08-09 | 2006-02-23 | Alios Biopharma Inc. | Synthetic hyperglycosylated, protease-resistant polypeptide variants, oral formulations and methods of using the same |
JP2008511633A (ja) | 2004-08-27 | 2008-04-17 | シェーリング コーポレイション | C型肝炎ウィルスns3セリンプロテアーゼの阻害因子としてのアシルスルホンアミド化合物 |
WO2006031725A2 (en) | 2004-09-14 | 2006-03-23 | Pharmasset, Inc. | Preparation of 2'fluoro-2'- alkyl- substituted or other optionally substituted ribofuranosyl pyrimidines and purines and their derivatives |
WO2006030892A1 (ja) * | 2004-09-17 | 2006-03-23 | Nippon Shinyaku Co., Ltd. | 複素環化合物の製造方法 |
AU2005291918A1 (en) | 2004-10-01 | 2006-04-13 | Vertex Pharmaceuticals Incorporated | HCV NS3-NS4A protease inhibition |
US7659263B2 (en) | 2004-11-12 | 2010-02-09 | Japan Tobacco Inc. | Thienopyrrole compound and use thereof as HCV polymerase inhibitor |
US7323447B2 (en) * | 2005-02-08 | 2008-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
EP2332963A3 (en) | 2005-03-08 | 2011-11-16 | Boehringer Ingelheim International Gmbh | Process for preparing macrocyclic compounds |
CA2606195C (en) | 2005-05-02 | 2015-03-31 | Merck And Co., Inc. | Hcv ns3 protease inhibitors |
US7592336B2 (en) | 2005-05-10 | 2009-09-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
EA016071B1 (ru) | 2005-05-13 | 2012-01-30 | Вирокем Фарма Инк. | Соединения и способы лечения или предотвращения флавивирусных инфекций |
US20070237818A1 (en) * | 2005-06-02 | 2007-10-11 | Malcolm Bruce A | Controlled-release formulation of HCV protease inhibitor and methods using the same |
CA2611155A1 (en) * | 2005-06-02 | 2006-12-07 | Schering Corporation | Pharmaceutical formulations and methods of treatment using the same |
US20060276404A1 (en) * | 2005-06-02 | 2006-12-07 | Anima Ghosal | Medicaments and methods combining a HCV protease inhibitor and an AKR competitor |
NZ563361A (en) | 2005-06-02 | 2011-02-25 | Schering Corp | HCV protease inhibitors in combination with food |
RU2427372C2 (ru) | 2005-06-17 | 2011-08-27 | Новартис Аг | Применение санглиферина для лечения вируса гепатита с |
CN101242816B (zh) * | 2005-06-30 | 2012-10-31 | 维罗贝股份有限公司 | Hcv抑制剂 |
US7608592B2 (en) * | 2005-06-30 | 2009-10-27 | Virobay, Inc. | HCV inhibitors |
US7601686B2 (en) | 2005-07-11 | 2009-10-13 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7470664B2 (en) * | 2005-07-20 | 2008-12-30 | Merck & Co., Inc. | HCV NS3 protease inhibitors |
EP1910378B1 (en) * | 2005-07-20 | 2012-06-20 | Boehringer Ingelheim International GmbH | Hepatitis c inhibitor peptide analogs |
CN102816170A (zh) | 2005-07-25 | 2012-12-12 | 因特蒙公司 | C型肝炎病毒复制的新颖大环抑制剂 |
CN101273027B (zh) | 2005-07-29 | 2015-12-02 | 爱尔兰詹森科学公司 | 丙型肝炎病毒的大环抑制剂 |
RU2436787C2 (ru) | 2005-07-29 | 2011-12-20 | Тиботек Фармасьютикалз Лтд. | Макроциклические ингибиторы вируса гепатита с |
AR054882A1 (es) | 2005-07-29 | 2007-07-25 | Tibotec Pharm Ltd | Inhibidores macrociclicos del virus de la hepatitis c |
DK1912996T3 (da) | 2005-07-29 | 2012-09-17 | Janssen R & D Ireland | Makrocykliske inhibitorer af hepatitis C-virus |
PE20070211A1 (es) | 2005-07-29 | 2007-05-12 | Medivir Ab | Compuestos macrociclicos como inhibidores del virus de hepatitis c |
PE20070343A1 (es) | 2005-07-29 | 2007-05-12 | Medivir Ab | Inhibidores macrociclicos del virus de la hepatitis c |
PE20070210A1 (es) | 2005-07-29 | 2007-04-16 | Tibotec Pharm Ltd | Compuestos macrociclicos como inhibidores del virus de hepatitis c |
SI1912997T1 (sl) | 2005-07-29 | 2012-02-29 | Tibotec Pharm Ltd | Makrociklični inhibitorji virusa hepatitis C |
ES2359939T3 (es) | 2005-07-29 | 2011-05-30 | Tibotec Pharmaceuticals | Inhibidores macrocíclicos del virus de la hepatitis c. |
AU2006275605B2 (en) * | 2005-08-01 | 2011-01-06 | Merck Sharp & Dohme Corp. | Macrocyclic peptides as HCV NS3 protease inhibitors |
WO2007016589A2 (en) | 2005-08-02 | 2007-02-08 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases |
WO2007021610A2 (en) | 2005-08-09 | 2007-02-22 | Merck & Co., Inc. | Ribonucleoside cyclic acetal derivatives for the treatment of rna-dependent rna viral infection |
US8076365B2 (en) | 2005-08-12 | 2011-12-13 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
WO2007022459A2 (en) * | 2005-08-19 | 2007-02-22 | Vertex Pharmaceuticals Incorporated | Processes and intermediates |
US8399615B2 (en) | 2005-08-19 | 2013-03-19 | Vertex Pharmaceuticals Incorporated | Processes and intermediates |
US7964624B1 (en) | 2005-08-26 | 2011-06-21 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases |
AR055395A1 (es) | 2005-08-26 | 2007-08-22 | Vertex Pharma | Compuestos inhibidores de la actividad de la serina proteasa ns3-ns4a del virus de la hepatitis c |
PL1934243T3 (pl) | 2005-09-09 | 2011-10-31 | Boehringer Ingelheim Int | Proces metatezy z zamknięciem pierścienia w zastosowaniu do wytwarzania peptydów makrocyklicznych |
AU2006301966A1 (en) | 2005-10-11 | 2007-04-19 | Array Biopharma, Inc. | Compounds and methods for inhibiting hepatitis C viral replication |
US7772183B2 (en) | 2005-10-12 | 2010-08-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7741281B2 (en) | 2005-11-03 | 2010-06-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
CA2629343A1 (en) | 2005-11-11 | 2007-05-24 | Vertex Pharmaceuticals, Inc. | Hepatitis c virus variants |
US7705138B2 (en) | 2005-11-11 | 2010-04-27 | Vertex Pharmaceuticals Incorporated | Hepatitis C virus variants |
DE602006015861D1 (de) | 2005-12-21 | 2010-09-09 | Abbott Lab | Antivirale verbindungen |
AU2006330924B2 (en) * | 2005-12-21 | 2012-03-15 | Abbvie Inc. | Anti-viral compounds |
EP2345652A1 (en) | 2005-12-21 | 2011-07-20 | Abbott Laboratories | Antiviral compounds |
ES2395386T3 (es) | 2005-12-21 | 2013-02-12 | Abbott Laboratories | Compuestos antivirales |
US7816348B2 (en) | 2006-02-03 | 2010-10-19 | Boehringer Ingelheim International Gmbh | Viral polymerase inhibitors |
EP2340836A1 (en) | 2006-02-27 | 2011-07-06 | Vertex Pharmceuticals Incorporated | Co-crystals comprising VX-950 and their pharmaceutical compositions |
WO2007103550A2 (en) | 2006-03-08 | 2007-09-13 | Achillion Pharmaceuticals, Inc. | Substituted aminothiazole derivatives with anti-hcv activity |
BRPI0709567A2 (pt) | 2006-03-16 | 2011-07-12 | Vertex Pharma | inibidores deuterados de protease de hepatite c |
MX2008013119A (es) | 2006-04-11 | 2008-10-21 | Novartis Ag | Inhibidores de hcv/vih y sus usos. |
GB0609492D0 (en) * | 2006-05-15 | 2006-06-21 | Angeletti P Ist Richerche Bio | Therapeutic agents |
CA2651762A1 (en) | 2006-05-23 | 2007-11-29 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
US8268776B2 (en) | 2006-06-06 | 2012-09-18 | Enanta Pharmaceuticals, Inc. | Macrocylic oximyl hepatitis C protease inhibitors |
US7728148B2 (en) * | 2006-06-06 | 2010-06-01 | Enanta Pharmaceuticals, Inc. | Acyclic oximyl hepatitis C protease inhibitors |
US9526769B2 (en) | 2006-06-06 | 2016-12-27 | Enanta Pharmaceuticals, Inc. | Macrocylic oximyl hepatitis C protease inhibitors |
US20080187516A1 (en) * | 2006-06-06 | 2008-08-07 | Ying Sun | Acyclic oximyl hepatitis c protease inhibitors |
GB0612423D0 (en) * | 2006-06-23 | 2006-08-02 | Angeletti P Ist Richerche Bio | Therapeutic agents |
AR061629A1 (es) * | 2006-06-26 | 2008-09-10 | Enanta Pharm Inc | Quinoxalinil macrociclicos inhibidores de serina proteasa del virus de la hepatitis c. proceso de obtencion y composiciones farmaceuticas |
KR20090024834A (ko) | 2006-07-05 | 2009-03-09 | 인터뮨, 인크. | C형 간염 바이러스 복제의 신규 억제제 |
EP2049474B1 (en) | 2006-07-11 | 2015-11-04 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
US7718612B2 (en) * | 2007-08-02 | 2010-05-18 | Enanta Pharmaceuticals, Inc. | Pyridazinonyl macrocyclic hepatitis C serine protease inhibitors |
US20090035267A1 (en) * | 2007-07-31 | 2009-02-05 | Moore Joel D | Acyclic, pyridazinone-derived hepatitis c serine protease inhibitors |
US7635683B2 (en) * | 2006-08-04 | 2009-12-22 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl tripeptide hepatitis C virus inhibitors |
WO2008022006A2 (en) * | 2006-08-11 | 2008-02-21 | Enanta Pharmaceuticals, Inc. | Arylalkoxyl hepatitis c virus protease inhibitors |
US7605126B2 (en) * | 2006-08-11 | 2009-10-20 | Enanta Pharmaceuticals, Inc. | Acylaminoheteroaryl hepatitis C virus protease inhibitors |
US20090098085A1 (en) * | 2006-08-11 | 2009-04-16 | Ying Sun | Tetrazolyl acyclic hepatitis c serine protease inhibitors |
US20080038225A1 (en) * | 2006-08-11 | 2008-02-14 | Ying Sun | Triazolyl acyclic hepatitis c serine protease inhibitors |
EP1886685A1 (en) | 2006-08-11 | 2008-02-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods, uses and compositions for modulating replication of hcv through the farnesoid x receptor (fxr) activation or inhibition |
US7582605B2 (en) * | 2006-08-11 | 2009-09-01 | Enanta Pharmaceuticals, Inc. | Phosphorus-containing hepatitis C serine protease inhibitors |
US7687459B2 (en) * | 2006-08-11 | 2010-03-30 | Enanta Pharmaceuticals, Inc. | Arylalkoxyl hepatitis C virus protease inhibitors |
CN101506167A (zh) | 2006-08-17 | 2009-08-12 | 贝林格尔.英格海姆国际有限公司 | 病毒聚合酶抑制剂 |
KR20090057035A (ko) * | 2006-08-21 | 2009-06-03 | 유나이티드 세러퓨틱스 코오포레이션 | 바이러스 감염의 치료를 위한 병용 요법 |
US8138164B2 (en) * | 2006-10-24 | 2012-03-20 | Merck Sharp & Dohme Corp. | HCV NS3 protease inhibitors |
JP5345941B2 (ja) * | 2006-10-24 | 2013-11-20 | メルク・シャープ・アンド・ドーム・コーポレーション | Hcvns3プロテアーゼ阻害剤 |
AU2007309546A1 (en) * | 2006-10-24 | 2008-05-02 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | HCV NS3 protease inhibitors |
CA2667031C (en) * | 2006-10-27 | 2013-01-22 | Merck & Co., Inc. | Hcv ns3 protease inhibitors |
EP2083844B1 (en) * | 2006-10-27 | 2013-11-27 | Merck Sharp & Dohme Corp. | Hcv ns3 protease inhibitors |
US8343477B2 (en) | 2006-11-01 | 2013-01-01 | Bristol-Myers Squibb Company | Inhibitors of hepatitis C virus |
WO2008057995A2 (en) * | 2006-11-02 | 2008-05-15 | Taigen Biotechnology Co., Ltd. | Hcv protease inhibitors |
US7772180B2 (en) * | 2006-11-09 | 2010-08-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
AU2007321677B2 (en) | 2006-11-15 | 2013-04-11 | Vertex Pharmaceuticals (Canada) Incorporated | Thiophene analogues for the treatment or prevention of flavivirus infections |
US7763584B2 (en) | 2006-11-16 | 2010-07-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US7888464B2 (en) | 2006-11-16 | 2011-02-15 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US8003604B2 (en) | 2006-11-16 | 2011-08-23 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
WO2008059046A1 (en) | 2006-11-17 | 2008-05-22 | Tibotec Pharmaceuticals Ltd. | Macrocyclic inhibitors of hepatitis c virus |
WO2008073282A2 (en) | 2006-12-07 | 2008-06-19 | Schering Corporation | Ph sensitive matrix formulation |
TWI399380B (zh) * | 2006-12-20 | 2013-06-21 | Abbott Lab | 抗病毒化合物 |
GB0625345D0 (en) * | 2006-12-20 | 2007-01-31 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
GB0625349D0 (en) * | 2006-12-20 | 2007-01-31 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
AU2007335962B2 (en) * | 2006-12-20 | 2012-09-06 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa | Antiviral indoles |
WO2008074035A1 (en) * | 2006-12-27 | 2008-06-19 | Abbott Laboratories | Hcv protease inhibitors and uses thereof |
WO2008095058A1 (en) * | 2007-02-01 | 2008-08-07 | Taigen Biotechnology Co. Ltd. | Hcv protease inhibitors |
GEP20125645B (en) | 2007-02-27 | 2012-09-25 | Vertex Pharma | Co-crystals and pharmaceutical compositions comprising the same |
AU2008219704A1 (en) | 2007-02-27 | 2008-09-04 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases |
CA2696053A1 (en) | 2007-02-28 | 2008-09-04 | Conatus Pharmaceuticals, Inc. | Methods for the treatment of liver diseases |
WO2008106167A1 (en) * | 2007-02-28 | 2008-09-04 | Conatus Pharmaceuticals, Inc. | Combination therapy comprising matrix metalloproteinase inhibitors and caspase inhibitors for the treatment of liver diseases |
US20100074867A1 (en) * | 2007-03-23 | 2010-03-25 | Schering Corporation Patent Department, K-6-1; 1990 | P1-nonepimerizable ketoamide inhibitors of hcv ns3 protease |
US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
WO2008134398A1 (en) * | 2007-04-26 | 2008-11-06 | Enanta Pharmaceuticals, Inc. | Oximyl dipeptide hepatitis c protease inhibitors |
US20080267917A1 (en) * | 2007-04-26 | 2008-10-30 | Deqiang Niu | N-functionalized amides as hepatitis c serine protease inhibitors |
US20080317712A1 (en) * | 2007-04-26 | 2008-12-25 | Deqiang Niu | Arylpiperidinyl and arylpyrrolidinyl tripeptide hepatitis c serine protease inhibitors |
US7910587B2 (en) * | 2007-04-26 | 2011-03-22 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl dipeptide hepatitis C virus inhibitors |
US8377872B2 (en) | 2007-04-26 | 2013-02-19 | Enanta Pharmaceuticals, Inc. | Cyclic P3 tripeptide hepatitis C serine protease inhibitors |
KR20100024920A (ko) * | 2007-05-03 | 2010-03-08 | 인터뮨, 인크. | C형 간염 바이러스 복제의 신규 마크로사이클릭 저해제 |
WO2008137126A2 (en) | 2007-05-04 | 2008-11-13 | Vertex Pharmaceuticals Incorporated | Combination therapy for the treatment of hcv infection |
CN101679357A (zh) * | 2007-05-09 | 2010-03-24 | 辉瑞大药厂 | 取代的杂环衍生物及其组合物和作为抗菌剂的药物用途 |
EP2185524A1 (en) | 2007-05-10 | 2010-05-19 | Intermune, Inc. | Novel peptide inhibitors of hepatitis c virus replication |
GB0709791D0 (en) * | 2007-05-22 | 2007-06-27 | Angeletti P Ist Richerche Bio | Antiviral agents |
EA019749B1 (ru) * | 2007-06-29 | 2014-06-30 | Джилид Сайэнс, Инк. | Противовирусные соединения |
WO2009005677A2 (en) | 2007-06-29 | 2009-01-08 | Gilead Sciences, Inc. | Antiviral compounds |
CN101801982A (zh) * | 2007-07-17 | 2010-08-11 | P.安杰莱蒂分子生物学研究所 | 用于治疗丙型肝炎感染的大环吲哚衍生物 |
WO2009010804A1 (en) * | 2007-07-19 | 2009-01-22 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Macrocyclic compounds as antiviral agents |
EP2188274A4 (en) | 2007-08-03 | 2011-05-25 | Boehringer Ingelheim Int | VIRAL POLYMERASE HEMMER |
CN101835774B (zh) | 2007-08-30 | 2014-09-17 | 弗特克斯药品有限公司 | 共晶体和包含该共晶体的药物组合物 |
GB0718575D0 (en) | 2007-09-24 | 2007-10-31 | Angeletti P Ist Richerche Bio | Nucleoside derivatives as inhibitors of viral polymerases |
US8419332B2 (en) * | 2007-10-19 | 2013-04-16 | Atlas Bolt & Screw Company Llc | Non-dimpling fastener |
WO2009055335A2 (en) * | 2007-10-25 | 2009-04-30 | Taigen Biotechnology Co., Ltd. | Hcv protease inhibitors |
US8383583B2 (en) | 2007-10-26 | 2013-02-26 | Enanta Pharmaceuticals, Inc. | Macrocyclic, pyridazinone-containing hepatitis C serine protease inhibitors |
JP2011503201A (ja) | 2007-11-14 | 2011-01-27 | エナンタ ファーマシューティカルズ インコーポレイテッド | 大環状テトラゾリルc型肝炎セリンプロテアーゼ阻害剤 |
WO2009070689A1 (en) * | 2007-11-29 | 2009-06-04 | Enanta Pharmaceuticals, Inc. | Bicyclic, c5-substituted proline derivatives as inhibitors of the hepatitis c virus ns3 protease |
US8263549B2 (en) * | 2007-11-29 | 2012-09-11 | Enanta Pharmaceuticals, Inc. | C5-substituted, proline-derived, macrocyclic hepatitis C serine protease inhibitors |
WO2009076166A2 (en) * | 2007-12-05 | 2009-06-18 | Enanta Pharmaceuticals, Inc. | Oximyl hcv serine protease inhibitors |
MX2010006210A (es) * | 2007-12-05 | 2010-08-10 | Enanta Pharm Inc | Inhibidores de serina proteasa de hcv de tripeptido fluorado. |
US8193346B2 (en) | 2007-12-06 | 2012-06-05 | Enanta Pharmaceuticals, Inc. | Process for making macrocyclic oximyl hepatitis C protease inhibitors |
WO2009079353A1 (en) | 2007-12-14 | 2009-06-25 | Enanta Pharmaceuticals, Inc. | Triazole-containing macrocyclic hcv serine protease inhibitors |
MX2010006313A (es) | 2007-12-19 | 2010-06-25 | Boehringer Ingelheim Int | Inhibidores de la polimerasa virica. |
US8202996B2 (en) | 2007-12-21 | 2012-06-19 | Bristol-Myers Squibb Company | Crystalline forms of N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-4-((7-chloro-4-methoxy-1-isoquinolinyl)oxy)-N- ((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-L-prolinamide |
CA2713005A1 (en) * | 2008-01-24 | 2009-07-30 | Enanta Pharmaceuticals, Inc. | Difluorinated tripeptides as hcv serine protease inhibitors |
JP2011510926A (ja) * | 2008-01-24 | 2011-04-07 | エナンタ ファーマシューティカルズ インコーポレイテッド | ヘテロアリール含有トリペプチドhcvセリンプロテアーゼ阻害剤 |
RU2490272C2 (ru) | 2008-02-04 | 2013-08-20 | Айденикс Фармасьютикалз, Инк. | Макроциклические ингибиторы серинпротеазы |
CA2713108A1 (en) * | 2008-02-07 | 2009-08-13 | Virobay, Inc. | Inhibitors of cathepsin b |
WO2009108507A1 (en) | 2008-02-25 | 2009-09-03 | Merck & Co., Inc. | Therapeutic compounds |
CA2719008A1 (en) * | 2008-03-20 | 2009-09-24 | Enanta Pharmaceuticals, Inc. | Fluorinated macrocyclic compounds as hepatitis c virus inhibitors |
TW200946541A (en) * | 2008-03-27 | 2009-11-16 | Idenix Pharmaceuticals Inc | Solid forms of an anti-HIV phosphoindole compound |
AU2009249443A1 (en) | 2008-04-15 | 2009-11-26 | Intermune, Inc. | Novel macrocyclic inhibitors of hepatitis C virus replication |
US8163921B2 (en) * | 2008-04-16 | 2012-04-24 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
EP2271345B1 (en) * | 2008-04-28 | 2015-05-20 | Merck Sharp & Dohme Corp. | Hcv ns3 protease inhibitors |
WO2009134987A1 (en) * | 2008-04-30 | 2009-11-05 | Enanta Pharmaceuticals, Inc. | Difluoromethyl-containing macrocyclic compounds as hepatitis c virus inhibitors |
US20090285774A1 (en) * | 2008-05-15 | 2009-11-19 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
CN101580535B (zh) * | 2008-05-16 | 2012-10-03 | 太景生物科技股份有限公司 | 丙型肝炎病毒蛋白酶抑制剂 |
US7964560B2 (en) | 2008-05-29 | 2011-06-21 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
JP5529120B2 (ja) | 2008-05-29 | 2014-06-25 | ブリストル−マイヤーズ スクイブ カンパニー | C型肝炎ウイルス阻害剤 |
US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
WO2010014134A1 (en) | 2008-07-02 | 2010-02-04 | Idenix Pharamaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
NZ590638A (en) * | 2008-07-22 | 2012-06-29 | Merck Sharp & Dohme | MACROCYCLIC QUINOXALINE COMPOUNDS AS Hepatitis C Virus NS3 PROTEASE INHIBITORS |
KR20110033291A (ko) | 2008-07-23 | 2011-03-30 | 에프. 호프만-라 로슈 아게 | 헤테로사이클릭 항바이러스 화합물 |
US8207341B2 (en) | 2008-09-04 | 2012-06-26 | Bristol-Myers Squibb Company | Process or synthesizing substituted isoquinolines |
UY32099A (es) | 2008-09-11 | 2010-04-30 | Enanta Pharm Inc | Inhibidores macrocíclicos de serina proteasas de hepatitis c |
ES2474992T3 (es) * | 2008-09-16 | 2014-07-10 | Boehringer Ingelheim International Gmbh | Formas cristalinas de un derivado de 2-tiazolil-4-quinolinil-oxi, un potente inhibidor de HCV |
MX2011002602A (es) * | 2008-09-17 | 2011-04-07 | Boehringer Ingelheim Int | Combinacion de inhibidor de la proteasa ns3 de hcv con interferon y ribavirina. |
KR20110061640A (ko) | 2008-09-26 | 2011-06-09 | 에프. 호프만-라 로슈 아게 | Hcv 치료용 피린 또는 피라진 유도체 |
US8563505B2 (en) | 2008-09-29 | 2013-10-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US8044087B2 (en) | 2008-09-29 | 2011-10-25 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
EP3025727A1 (en) | 2008-10-02 | 2016-06-01 | The J. David Gladstone Institutes | Methods of treating liver disease |
WO2010045266A1 (en) * | 2008-10-15 | 2010-04-22 | Intermune, Inc. | Therapeutic antiviral peptides |
MX2011004133A (es) | 2008-10-30 | 2011-05-24 | Hoffmann La Roche | Derivados de arilpiridona antiviral heterociclica. |
EA022272B1 (ru) * | 2008-11-21 | 2015-12-30 | Бёрингер Ингельхайм Интернациональ Гмбх | Фармацевтическая композиция эффективного ингибитора всг для перорального введения |
EA024853B1 (ru) | 2008-12-03 | 2016-10-31 | Пресидио Фармасьютикалс, Инк. | Ингибиторы ns5a вгс |
EP2373167A4 (en) | 2008-12-03 | 2012-07-25 | Presidio Pharmaceuticals Inc | INHIBITORS OF HEPATITIS C VIRUS TYPE NS5A |
US20100272674A1 (en) * | 2008-12-04 | 2010-10-28 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
US8283310B2 (en) | 2008-12-15 | 2012-10-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
CN102300871A (zh) * | 2008-12-19 | 2011-12-28 | 吉里德科学公司 | Hcv ns3蛋白酶抑制剂 |
TW201036612A (en) | 2008-12-22 | 2010-10-16 | Gilead Sciences Inc | Antiviral compounds |
WO2010072598A1 (en) | 2008-12-22 | 2010-07-01 | F. Hoffmann-La Roche Ag | Heterocyclic antiviral compounds |
NZ593648A (en) | 2008-12-23 | 2013-09-27 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
EP2376514A2 (en) | 2008-12-23 | 2011-10-19 | Pharmasset, Inc. | Nucleoside analogs |
CL2009002206A1 (es) | 2008-12-23 | 2011-08-26 | Gilead Pharmasset Llc | Compuestos derivados de pirrolo -(2-3-d]-pirimidin-7(6h)-tetrahidrofuran-2-il fosfonamidato, composicion farmaceutica; y su uso en el tratamiento de enfermedades virales. |
RU2011127080A (ru) | 2009-01-07 | 2013-02-20 | Сайнексис, Инк. | Производное циклоспорина для применения в лечении заражения вирусом гепатита с и вич |
WO2010082050A1 (en) | 2009-01-16 | 2010-07-22 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Macrocyclic and 7-aminoalkyl-substituted benzoxazocines for treatment of hepatitis c infections |
GB0900914D0 (en) | 2009-01-20 | 2009-03-04 | Angeletti P Ist Richerche Bio | Antiviral agents |
US8102720B2 (en) * | 2009-02-02 | 2012-01-24 | Qualcomm Incorporated | System and method of pulse generation |
AR075584A1 (es) | 2009-02-27 | 2011-04-20 | Intermune Inc | COMPOSICIONES TERAPEUTICAS QUE COMPRENDEN beta-D-2'-DESOXI-2'-FLUORO-2'-C-METILCITIDINA Y UN DERIVADO DE ACIDO ISOINDOL CARBOXILICO Y SUS USOS. COMPUESTO. |
JP5690286B2 (ja) | 2009-03-04 | 2015-03-25 | イデニク プハルマセウティカルス,インコーポレイテッド | ホスホチオフェン及びホスホチアゾールhcvポリメラーゼ阻害剤 |
BRPI1016266A2 (pt) | 2009-03-06 | 2019-09-24 | Hoffmann La Roche | compostos antivirais heterocíclicos |
JP2012520884A (ja) | 2009-03-18 | 2012-09-10 | ザ ボード オブ トラスティーズ オブ ザ リランド スタンフォード ジュニア ユニバーシティー | フラビウイルス科ウイルス感染症を治療する方法および組成物 |
KR20110131312A (ko) | 2009-03-27 | 2011-12-06 | 프레시디오 파마슈티칼스, 인코포레이티드 | 융합된 고리 c형 간염 억제제 |
WO2010118009A1 (en) * | 2009-04-06 | 2010-10-14 | Ptc Therapeutics, Inc. | Hcv inhibitor and therapeutic agent combinations |
WO2010118078A1 (en) | 2009-04-08 | 2010-10-14 | Idenix Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors |
US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
US20110182850A1 (en) | 2009-04-10 | 2011-07-28 | Trixi Brandl | Organic compounds and their uses |
EP2421831A1 (en) | 2009-04-25 | 2012-02-29 | F. Hoffmann-La Roche AG | Heterocyclic antiviral compounds |
MX2011012155A (es) | 2009-05-13 | 2012-02-28 | Enanta Pharm Inc | Compuestos macrociclicos como inhibidores del virus de hepatitis c. |
US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
TWI583692B (zh) | 2009-05-20 | 2017-05-21 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
TWI428332B (zh) * | 2009-06-09 | 2014-03-01 | Hoffmann La Roche | 雜環抗病毒化合物 |
CA2762675A1 (en) | 2009-06-24 | 2010-12-29 | F. Hoffmann-La Roche Ag | Heterocyclic antiviral compound |
US8232246B2 (en) * | 2009-06-30 | 2012-07-31 | Abbott Laboratories | Anti-viral compounds |
EP2448912A4 (en) * | 2009-07-02 | 2014-05-28 | Reddys Lab Ltd Dr | ENZYMES AND METHODS FOR DEDOLDING AMINOVINYL-CYCLOPROPANECARBOXYLIC ACID DERIVATIVES |
KR101685941B1 (ko) | 2009-07-07 | 2016-12-13 | 베링거 인겔하임 인터내셔날 게엠베하 | C형 간염 바이러스 프로테아제 억제제를 위한 약제학적 조성물 |
US8828930B2 (en) | 2009-07-30 | 2014-09-09 | Merck Sharp & Dohme Corp. | Hepatitis C virus NS3 protease inhibitors |
JP2013501068A (ja) | 2009-08-05 | 2013-01-10 | アイディニックス ファーマシューティカルズ インコーポレイテッド | 大環状セリンプロテアーゼ阻害剤 |
EP2465845A4 (en) | 2009-08-10 | 2013-01-09 | Sumitomo Chemical Co | PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE 1-AMINO-2-VINYLCYCLOPROPANECARBOXYLIC ACID ESTER |
US8324417B2 (en) | 2009-08-19 | 2012-12-04 | Virobay, Inc. | Process for the preparation of (S)-2-amino-5-cyclopropyl-4,4-difluoropentanoic acid and alkyl esters and acid salts thereof |
ES2588204T3 (es) * | 2009-09-15 | 2016-10-31 | Taigen Biotechnology Co., Ltd. | Inhibidores de la proteasa de HCV |
EP2483290A4 (en) * | 2009-09-28 | 2013-05-01 | Intermune Inc | CYCLIC PEPTIC INHIBITORS FOR REPLICATION OF HEPATITIS C VIRUS |
US9193740B2 (en) * | 2009-10-19 | 2015-11-24 | Enanta Pharmaceuticals, Inc. | Bismacrocyclic compounds as hepatitis C virus inhibitors |
AU2010313497B2 (en) | 2009-10-30 | 2013-08-01 | Boehringer Ingelheim International Gmbh | Dosage regimens for HCV combination therapy comprising BI201335, interferon alpha and ribavirin |
US20110117055A1 (en) | 2009-11-19 | 2011-05-19 | Macdonald James E | Methods of Treating Hepatitis C Virus with Oxoacetamide Compounds |
AU2010326225A1 (en) | 2009-11-25 | 2012-06-07 | Vertex Pharmaceuticals Incorporated | 5-alkynyl-thiophene-2-carboxylic acid derivatives and their use for the treatment or prevention of flavivirus infections |
AR079528A1 (es) | 2009-12-18 | 2012-02-01 | Idenix Pharmaceuticals Inc | Inhibidores de arileno o heteroarileno 5,5-fusionado del virus de la hepatitis c |
AU2010336355A1 (en) | 2009-12-24 | 2012-07-05 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
US20110178107A1 (en) * | 2010-01-20 | 2011-07-21 | Taigen Biotechnology Co., Ltd. | Hcv protease inhibitors |
KR101781789B1 (ko) | 2010-01-27 | 2017-09-26 | 에이비 파르마 리미티드. | C형 간염 바이러스 억제제로 사용되는 다환 헤테로사이클릭 화합물 |
US8530497B2 (en) | 2010-03-11 | 2013-09-10 | Boehringer Ingelheim International Gmbh | Crystalline salts of a potent HCV inhibitor |
WO2011119858A1 (en) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
AU2011232348A1 (en) | 2010-03-24 | 2012-10-11 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of Flavivirus infections |
WO2011119853A1 (en) | 2010-03-24 | 2011-09-29 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
EP2550268A1 (en) | 2010-03-24 | 2013-01-30 | Vertex Pharmaceuticals Incorporated | Analogues for the treatment or prevention of flavivirus infections |
KR101715981B1 (ko) | 2010-03-31 | 2017-03-13 | 길리애드 파마셋 엘엘씨 | 뉴클레오사이드 포스포르아미데이트 |
PL3290428T3 (pl) | 2010-03-31 | 2022-02-07 | Gilead Pharmasset Llc | Tabletka zawierająca krystaliczny (S)-2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian izopropylu |
MX2012011222A (es) | 2010-04-01 | 2013-01-18 | Centre Nat Rech Scient | Compuestos y composiciones farmaceuticas para el tratamiento de infecciones virales. |
EP2575866A4 (en) | 2010-05-24 | 2013-10-16 | Presidio Pharmaceuticals Inc | HCV NS5A INHIBITORS |
WO2011156545A1 (en) | 2010-06-09 | 2011-12-15 | Vertex Pharmaceuticals Incorporated | Viral dynamic model for hcv combination therapy |
WO2011159826A2 (en) | 2010-06-15 | 2011-12-22 | Vertex Pharmaceuticals Incorporated | Hcv ns5b protease mutants |
JP2013529684A (ja) | 2010-06-28 | 2013-07-22 | バーテックス ファーマシューティカルズ インコーポレイテッド | フラビウイルス感染の処置または予防のための化合物および方法 |
WO2012006070A1 (en) | 2010-06-28 | 2012-01-12 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
JP2013531011A (ja) | 2010-06-28 | 2013-08-01 | バーテックス ファーマシューティカルズ インコーポレイテッド | フラビウイルス感染の処置または予防のための化合物および方法 |
AU2011292040A1 (en) | 2010-08-17 | 2013-03-07 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of Flaviviridae viral infections |
EP3020723A1 (en) | 2010-09-21 | 2016-05-18 | Enanta Pharmaceuticals, Inc. | Macrocyclic proline derived hcv serine protease inhibitors |
CA2813093A1 (en) * | 2010-09-30 | 2012-04-05 | Boehringer Ingelheim International Gmbh | Combination therapy for treating hcv infection |
BR112013008510A2 (pt) | 2010-10-08 | 2016-07-05 | Novartis Ag | vitamina e formulações de inibidores de sulfamida ns3 |
US8841275B2 (en) | 2010-11-30 | 2014-09-23 | Gilead Pharmasset Llc | 2′-spiro-nucleosides and derivatives thereof useful for treating hepatitis C virus and dengue virus infections |
JP5906253B2 (ja) * | 2010-12-16 | 2016-04-20 | アッヴィ・インコーポレイテッド | 抗ウイルス性化合物 |
AU2011352145A1 (en) | 2010-12-30 | 2013-07-18 | Abbvie Inc. | Phenanthridine macrocyclic hepatitis C serine protease inhibitors |
US8937041B2 (en) | 2010-12-30 | 2015-01-20 | Abbvie, Inc. | Macrocyclic hepatitis C serine protease inhibitors |
AR085352A1 (es) | 2011-02-10 | 2013-09-25 | Idenix Pharmaceuticals Inc | Inhibidores macrociclicos de serina proteasa, sus composiciones farmaceuticas y su uso para tratar infecciones por hcv |
WO2012107589A1 (en) | 2011-02-11 | 2012-08-16 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment and prevention of hcv infections |
WO2012123298A1 (en) | 2011-03-11 | 2012-09-20 | F. Hoffmann-La Roche Ag | Antiviral compounds |
JP2014514295A (ja) | 2011-03-31 | 2014-06-19 | アイディニックス ファーマシューティカルズ インコーポレイテッド | ウイルス感染の治療のための化合物および薬学的組成物 |
US20120252721A1 (en) | 2011-03-31 | 2012-10-04 | Idenix Pharmaceuticals, Inc. | Methods for treating drug-resistant hepatitis c virus infection with a 5,5-fused arylene or heteroarylene hepatitis c virus inhibitor |
US8957203B2 (en) | 2011-05-05 | 2015-02-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
US8691757B2 (en) | 2011-06-15 | 2014-04-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
CA2857705A1 (en) | 2011-06-16 | 2012-12-20 | AB Pharma Ltd. | Macrocyclic heterocyclic compounds for inhibiting hepatitis c virus and preparation and use thereof |
EP2725012A1 (en) | 2011-06-21 | 2014-04-30 | Mitsubishi Gas Chemical Company, Inc. | 1-amino-2-vinyl cyclopropane carboxylic acid amide, salt of same, and method for producing same |
US20120328565A1 (en) | 2011-06-24 | 2012-12-27 | Brinkman John A | Antiviral compounds |
CN102807607B (zh) * | 2011-07-22 | 2013-10-23 | 爱博新药研发(上海)有限公司 | 抑制丙肝病毒的稠环杂环类化合物、其中间体及其应用 |
WO2013016499A1 (en) | 2011-07-26 | 2013-01-31 | Vertex Pharmaceuticals Incorporated | Methods for preparation of thiophene compounds |
WO2013016501A1 (en) | 2011-07-26 | 2013-01-31 | Vertex Pharmaceuticals Incorporated | Formulations of thiophene compounds |
DE102012016127A1 (de) | 2011-08-31 | 2013-02-28 | Daniel Elias | Bioaktive, regenerative Mischung zur Herstellung eines Ergänzungsnahrungsmittels |
EP2755983B1 (en) | 2011-09-12 | 2017-03-15 | Idenix Pharmaceuticals LLC. | Substituted carbonyloxymethylphosphoramidate compounds and pharmaceutical compositions for the treatment of viral infections |
CN103906759A (zh) | 2011-09-12 | 2014-07-02 | 埃迪尼克斯医药公司 | 用于治疗病毒感染的化合物和药物组合物 |
EP2766365A1 (en) | 2011-10-10 | 2014-08-20 | F.Hoffmann-La Roche Ag | Antiviral compounds |
TW201331221A (zh) | 2011-10-14 | 2013-08-01 | Idenix Pharmaceuticals Inc | 嘌呤核苷酸化合物類之經取代的3’,5’-環磷酸酯及用於治療病毒感染之醫藥組成物 |
US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
GB2506085A (en) | 2011-10-21 | 2014-03-19 | Abbvie Inc | Combination treatment (eg with ABT-072 or ABT-333) of DAAS for use in treating HCV |
US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
DE112012003510T5 (de) | 2011-10-21 | 2015-03-19 | Abbvie Inc. | Verfahren zur Behandlung von HCV umfassend mindestens zwei direkt wirkende antivirale Wirkstoffe, Ribavirin aber nicht Interferon |
EP2780026B1 (en) | 2011-11-15 | 2019-10-23 | Merck Sharp & Dohme Corp. | Hcv ns3 protease inhibitors |
US8889159B2 (en) | 2011-11-29 | 2014-11-18 | Gilead Pharmasset Llc | Compositions and methods for treating hepatitis C virus |
AU2012345732B2 (en) | 2011-11-30 | 2016-07-14 | Emory University | Antiviral JAK inhibitors useful in treating or preventing retroviral and other viral infections |
AU2012347785B2 (en) | 2011-12-06 | 2017-03-16 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for treating viral diseases |
US9133170B2 (en) | 2011-12-16 | 2015-09-15 | Hoffmann-La Roche Inc. | Inhibitors of HCV NS5A |
CN104011061B (zh) | 2011-12-20 | 2017-06-13 | 里博科学有限责任公司 | 作为hcv rna复制抑制剂的2‘,4’‑二氟‑2‘‑甲基取代的核苷衍生物 |
EA024847B1 (ru) | 2011-12-20 | 2016-10-31 | Рибосайенс Ллк | 4'-азидо,3'-фторзамещенные производные нуклеозидов в качестве ингибиторов репликации рнк вируса гепатита с |
WO2013106344A1 (en) | 2012-01-12 | 2013-07-18 | Ligand Pharmaceuticals, Inc. | 2 '-c-methyl nucleosides containing a cyclic phosphate diester of 1, 3-propanediol (2-oxo-[1, 3, 2]-dioxaphosphorinane) at position 5' |
JP2015503616A (ja) | 2012-01-12 | 2015-02-02 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 強力なhcv阻害薬の安定化医薬製剤 |
US20130217644A1 (en) | 2012-02-13 | 2013-08-22 | Idenix Pharmaceuticals, Inc. | Pharmaceutical Compositions of 2'-C-Methyl-Guanosine, 5'-[2[(3-Hydroxy-2,2-Dimethyl-1-Oxopropyl)Thio]Ethyl N-(Phenylmethyl)Phosphoramidate] |
EP2817291A1 (en) | 2012-02-24 | 2014-12-31 | F. Hoffmann-La Roche AG | Antiviral compounds |
WO2013137869A1 (en) | 2012-03-14 | 2013-09-19 | Boehringer Ingelheim International Gmbh | Combination therapy for treating hcv infection in an hcv-hiv coinfected patient population |
NZ630805A (en) | 2012-03-22 | 2016-01-29 | Alios Biopharma Inc | Pharmaceutical combinations comprising a thionucleotide analog |
WO2013147750A1 (en) | 2012-03-27 | 2013-10-03 | Boehringer Ingelheim International Gmbh | Oral combination therapy for treating hcv infection in specific patient sub-population |
WO2013147749A1 (en) | 2012-03-27 | 2013-10-03 | Boehringer Ingelheim International Gmbh | Oral combination therapy for treating hcv infection in specific patient subgenotype populations |
JP2015512900A (ja) | 2012-03-28 | 2015-04-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 特別な患者の遺伝子亜型分集団のhcv感染症を治療するための併用療法 |
US9296778B2 (en) | 2012-05-22 | 2016-03-29 | Idenix Pharmaceuticals, Inc. | 3′,5′-cyclic phosphate prodrugs for HCV infection |
EA031301B1 (ru) | 2012-05-22 | 2018-12-28 | Иденикс Фармасьютикалз Ллс | D-аминокислотные химические соединения для лечения заболеваний печени |
US9109001B2 (en) | 2012-05-22 | 2015-08-18 | Idenix Pharmaceuticals, Inc. | 3′,5′-cyclic phosphoramidate prodrugs for HCV infection |
US20140010783A1 (en) | 2012-07-06 | 2014-01-09 | Hoffmann-La Roche Inc. | Antiviral compounds |
MX353422B (es) | 2012-10-08 | 2018-01-12 | Idenix Pharmaceuticals Llc | Análogos de 2'-cloronucleósido para infección por vhc. |
WO2014063019A1 (en) | 2012-10-19 | 2014-04-24 | Idenix Pharmaceuticals, Inc. | Dinucleotide compounds for hcv infection |
EA025560B1 (ru) | 2012-10-19 | 2017-01-30 | Бристол-Майерс Сквибб Компани | Ингибиторы вируса гепатита с |
EP2909222B1 (en) | 2012-10-22 | 2021-05-26 | Idenix Pharmaceuticals LLC | 2',4'-bridged nucleosides for hcv infection |
US9643999B2 (en) | 2012-11-02 | 2017-05-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
WO2014070964A1 (en) | 2012-11-02 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
EP2914598B1 (en) | 2012-11-02 | 2017-10-18 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
EP2914614B1 (en) | 2012-11-05 | 2017-08-16 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
CN103804208B (zh) * | 2012-11-14 | 2016-06-08 | 重庆博腾制药科技股份有限公司 | 一种丙肝药物中间体的制备方法 |
WO2014078436A1 (en) | 2012-11-14 | 2014-05-22 | Idenix Pharmaceuticals, Inc. | D-alanine ester of sp-nucleoside analog |
US20140140951A1 (en) | 2012-11-14 | 2014-05-22 | Idenix Pharmaceuticals, Inc. | D-Alanine Ester of Rp-Nucleoside Analog |
EP2935304A1 (en) | 2012-12-19 | 2015-10-28 | IDENIX Pharmaceuticals, Inc. | 4'-fluoro nucleosides for the treatment of hcv |
CN105073726B (zh) | 2013-01-23 | 2017-05-31 | 弗·哈夫曼-拉罗切有限公司 | 抗病毒三唑衍生物 |
WO2014121418A1 (en) | 2013-02-07 | 2014-08-14 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c |
WO2014121417A1 (en) | 2013-02-07 | 2014-08-14 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c |
US20150065439A1 (en) | 2013-02-28 | 2015-03-05 | Vertex Pharmaceuticals Incorporated | Pharmaceutical compositions |
US9339541B2 (en) | 2013-03-04 | 2016-05-17 | Merck Sharp & Dohme Corp. | Thiophosphate nucleosides for the treatment of HCV |
US9309275B2 (en) | 2013-03-04 | 2016-04-12 | Idenix Pharmaceuticals Llc | 3′-deoxy nucleosides for the treatment of HCV |
KR20150114566A (ko) | 2013-03-05 | 2015-10-12 | 에프. 호프만-라 로슈 아게 | 항바이러스 화합물 |
CN105164148A (zh) | 2013-03-07 | 2015-12-16 | 百时美施贵宝公司 | 丙型肝炎病毒抑制剂 |
WO2014138374A1 (en) | 2013-03-08 | 2014-09-12 | Boehringer Ingelheim International Gmbh | Oral combination therapy for treating hcv infection in specific patient sub-population |
SG11201507469RA (en) | 2013-03-14 | 2015-10-29 | Achillion Pharmaceuticals Inc | Processes for producing sovaprevir |
US9187515B2 (en) | 2013-04-01 | 2015-11-17 | Idenix Pharmaceuticals Llc | 2′,4′-fluoro nucleosides for the treatment of HCV |
UA123533C2 (uk) | 2013-05-16 | 2021-04-21 | Рібосаєнс Ллс | 4'-фтор-2'-метилзаміщені нуклеозидні похідні |
US20180200280A1 (en) | 2013-05-16 | 2018-07-19 | Riboscience Llc | 4'-Fluoro-2'-Methyl Substituted Nucleoside Derivatives as Inhibitors of HCV RNA Replication |
CN105307661A (zh) | 2013-05-16 | 2016-02-03 | 里博科学有限责任公司 | 4’-叠氮基,3’-脱氧基-3’-氟取代的核苷衍生物 |
WO2014197578A1 (en) | 2013-06-05 | 2014-12-11 | Idenix Pharmaceuticals, Inc. | 1',4'-thio nucleosides for the treatment of hcv |
WO2015017713A1 (en) | 2013-08-01 | 2015-02-05 | Idenix Pharmaceuticals, Inc. | D-amino acid phosphoramidate pronucleotides of halogeno pyrimidine compounds for liver disease |
ES2900570T3 (es) | 2013-08-27 | 2022-03-17 | Gilead Pharmasset Llc | Formulación de combinación de dos compuestos antivirales |
WO2015042375A1 (en) | 2013-09-20 | 2015-03-26 | Idenix Pharmaceuticals, Inc. | Hepatitis c virus inhibitors |
WO2015061683A1 (en) | 2013-10-25 | 2015-04-30 | Idenix Pharmaceuticals, Inc. | D-amino acid phosphoramidate and d-alanine thiophosphoramidate pronucleotides of nucleoside compounds useful for the treatment of hcv |
US20160271162A1 (en) | 2013-11-01 | 2016-09-22 | Idenix Pharmacueticals, Llc | D-alanine phosphoramide pronucleotides of 2'-methyl 2'-fluro guanosine nucleoside compounds for the treatment of hcv |
US20170198005A1 (en) | 2013-11-27 | 2017-07-13 | Idenix Pharmaceuticals Llc | 2'-dichloro and 2'-fluoro-2'-chloro nucleoside analogues for hcv infection |
US9717797B2 (en) | 2013-12-05 | 2017-08-01 | International Business Machines Corporation | Polycarbonates bearing aromatic N-heterocycles for drug delivery |
WO2015095419A1 (en) | 2013-12-18 | 2015-06-25 | Idenix Pharmaceuticals, Inc. | 4'-or nucleosides for the treatment of hcv |
WO2015103490A1 (en) | 2014-01-03 | 2015-07-09 | Abbvie, Inc. | Solid antiviral dosage forms |
EP2899207A1 (en) | 2014-01-28 | 2015-07-29 | Amikana.Biologics | New method for testing HCV protease inhibition |
US20170135990A1 (en) | 2014-03-05 | 2017-05-18 | Idenix Pharmaceuticals Llc | Pharmaceutical compositions comprising a 5,5-fused heteroarylene flaviviridae inhibitor and their use for treating or preventing flaviviridae infection |
US20170066779A1 (en) | 2014-03-05 | 2017-03-09 | Idenix Pharmaceuticals Llc | Solid forms of a flaviviridae virus inhibitor compound and salts thereof |
WO2015134780A1 (en) | 2014-03-05 | 2015-09-11 | Idenix Pharmaceuticals, Inc. | Solid prodrug forms of 2'-chloro-2'-methyl uridine for hcv |
US10202411B2 (en) | 2014-04-16 | 2019-02-12 | Idenix Pharmaceuticals Llc | 3′-substituted methyl or alkynyl nucleosides nucleotides for the treatment of HCV |
JP7129703B2 (ja) | 2016-04-28 | 2022-09-02 | エモリー ユニバーシティー | アルキン含有ヌクレオチド及びヌクレオシド治療組成物並びにそれらに関連した使用 |
AR112702A1 (es) | 2017-09-21 | 2019-11-27 | Riboscience Llc | Derivados de nucleósidos sustituidos con 4-fluoro-2-metilo como inhibidores de la replicación de hcv arn |
CN113167802A (zh) | 2018-12-04 | 2021-07-23 | 百时美施贵宝公司 | 通过多同位素体反应监测使用样品内校准曲线的分析方法 |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0475255A3 (en) * | 1990-09-12 | 1993-04-14 | F. Hoffmann-La Roche Ag | Process for the preparation of optically pure (s)-alpha-((tert-butylsulfonyl)methyl)hydro cinnamic acid |
JPH05155827A (ja) * | 1991-12-09 | 1993-06-22 | Banyu Pharmaceut Co Ltd | cis−2−アミノシクロプロパンカルボン酸誘導体の製造法 |
IT1272179B (it) | 1994-02-23 | 1997-06-16 | Angeletti P Ist Richerche Bio | Metodologia per riprodurre in vitro l'attivita' proteolitica della proteasi ns3 del virus hcv. |
CN1141591A (zh) * | 1994-02-23 | 1997-01-29 | 布·安格莱荻公司分子生物学研究所 | 体外再生丙型肝炎病毒(hcv)ns3蛋白酶的解蛋白活性的方法 |
GB9517022D0 (en) | 1995-08-19 | 1995-10-25 | Glaxo Group Ltd | Medicaments |
IT1277914B1 (it) * | 1995-08-22 | 1997-11-12 | Angeletti P Ist Richerche Bio | Procedimento per produrre - in forma pura e in quantita' elevate - polipeptidi con l'attivita' proteolitica della proteasi ns3 di hcv, e |
CA2165996C (en) * | 1995-12-22 | 2002-01-29 | Murray Douglas Bailey | Stereoselective preparation of 2-substituted succinic derivatives |
DE19600034C2 (de) | 1996-01-02 | 2003-12-24 | Degussa | 1,1,2-Trisubstituierte Cyclopropanverbindungen, Verfahren zu deren Herstellung und Dihydroxyethyl-substituierte 1-Amino-cyclopropan-1-carbonsäure |
US5633388A (en) | 1996-03-29 | 1997-05-27 | Viropharma Incorporated | Compounds, compositions and methods for treatment of hepatitis C |
EP2314598A1 (en) | 1996-10-18 | 2011-04-27 | Vertex Pharmaceuticals Incorporated | Inhibitors of Hepatitis C virus NS3 serine protease |
CA2291778A1 (en) | 1997-05-29 | 1998-12-03 | Merck & Co., Inc. | Heterocyclic amide compounds as cell adhesion inhibitors |
IL134232A0 (en) | 1997-08-11 | 2001-04-30 | Boehringer Ingelheim Ca Ltd | Hepatitis c inhibitor peptides |
US6767991B1 (en) | 1997-08-11 | 2004-07-27 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C inhibitor peptides |
SE9704543D0 (sv) * | 1997-12-05 | 1997-12-05 | Astra Ab | New compounds |
US6455571B1 (en) * | 1998-04-23 | 2002-09-24 | Abbott Laboratories | Inhibitors of neuraminidases |
DE19835120C1 (de) * | 1998-08-04 | 1999-10-21 | Westfalia Separator Ag | Verfahren und Vorrichtung zum Einstellen des Flüssigkeitsgehalts des aus einer selbstentleerenden Schleudertrommel eines Separators ausgetragenen Feststoffes |
US6323180B1 (en) * | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
US6277830B1 (en) * | 1998-10-16 | 2001-08-21 | Schering Corporation | 5′-amino acid esters of ribavirin and the use of same to treat hepatitis C with interferon |
US6608027B1 (en) | 1999-04-06 | 2003-08-19 | Boehringer Ingelheim (Canada) Ltd | Macrocyclic peptides active against the hepatitis C virus |
US7091184B2 (en) * | 2002-02-01 | 2006-08-15 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
US6642204B2 (en) * | 2002-02-01 | 2003-11-04 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
CA2516018C (en) * | 2003-03-05 | 2011-08-23 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibitor peptide analogs |
JP4550824B2 (ja) * | 2003-03-05 | 2010-09-22 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | C型肝炎抑制化合物 |
-
1999
- 1999-08-05 US US09/368,866 patent/US6323180B1/en not_active Expired - Lifetime
- 1999-08-09 PL PL346626A patent/PL204850B1/pl unknown
- 1999-08-09 SK SK50026-2009A patent/SK288068B6/sk not_active IP Right Cessation
- 1999-08-09 BR BRPI9913646A patent/BRPI9913646B8/pt not_active IP Right Cessation
- 1999-08-09 SI SI9931033T patent/SI1105413T1/sl unknown
- 1999-08-09 KR KR1020017001786A patent/KR100631439B1/ko not_active IP Right Cessation
- 1999-08-09 TW TW088113586A patent/TWI250165B/zh not_active IP Right Cessation
- 1999-08-09 ME MEP-2008-585A patent/ME00381B/me unknown
- 1999-08-09 CZ CZ20090004A patent/CZ302766B6/cs not_active IP Right Cessation
- 1999-08-09 EP EP99938084A patent/EP1105413B1/en not_active Expired - Lifetime
- 1999-08-09 RS YUP-94/01A patent/RS50798B/sr unknown
- 1999-08-09 EA EA200100228A patent/EA003906B1/ru not_active IP Right Cessation
- 1999-08-09 PT PT99938084T patent/PT1105413E/pt unknown
- 1999-08-09 CZ CZ20010516A patent/CZ301268B6/cs not_active IP Right Cessation
- 1999-08-09 IL IL14101299A patent/IL141012A0/xx unknown
- 1999-08-09 AU AU52731/99A patent/AU769738B2/en not_active Expired
- 1999-08-09 WO PCT/CA1999/000736 patent/WO2000009543A2/en active Application Filing
- 1999-08-09 ES ES99938084T patent/ES2326707T3/es not_active Expired - Lifetime
- 1999-08-09 NZ NZ510396A patent/NZ510396A/xx not_active IP Right Cessation
- 1999-08-09 KR KR1020067010736A patent/KR100672229B1/ko not_active IP Right Cessation
- 1999-08-09 IN IN127MUN2001 patent/IN211493B/en unknown
- 1999-08-09 TR TR2002/00129T patent/TR200200129T2/xx unknown
- 1999-08-09 RS YU20090459A patent/RS53562B1/sr unknown
- 1999-08-09 EP EP08169026A patent/EP2028186B1/en not_active Expired - Lifetime
- 1999-08-09 TR TR2001/00432T patent/TR200100432T2/xx unknown
- 1999-08-09 ES ES08169026T patent/ES2405930T3/es not_active Expired - Lifetime
- 1999-08-09 DK DK99938084T patent/DK1105413T3/da active
- 1999-08-09 CA CA2338946A patent/CA2338946C/en not_active Expired - Lifetime
- 1999-08-09 CA CA2445938A patent/CA2445938C/en not_active Expired - Lifetime
- 1999-08-09 CN CN2007101407405A patent/CN101143892B/zh not_active Expired - Lifetime
- 1999-08-09 HU HU0105144A patent/HU229262B1/hu unknown
- 1999-08-09 JP JP2000564993A patent/JP4485685B2/ja not_active Expired - Lifetime
- 1999-08-09 DK DK08169026.5T patent/DK2028186T3/da active
- 1999-08-09 BR BRPI9917805-2B1A patent/BR9917805B1/pt active IP Right Grant
- 1999-08-09 ID IDW20010316A patent/ID27839A/id unknown
- 1999-08-09 EE EEP200100081A patent/EE05517B1/xx unknown
- 1999-08-09 AT AT99938084T patent/ATE430158T1/de active
- 1999-08-09 PE PE1999000800A patent/PE20000949A1/es not_active IP Right Cessation
- 1999-08-09 SI SI9931071T patent/SI2028186T1/sl unknown
- 1999-08-09 PH PH11999002002A patent/PH11999002002B1/en unknown
- 1999-08-09 DE DE69940817T patent/DE69940817D1/de not_active Expired - Lifetime
- 1999-08-09 PT PT81690265T patent/PT2028186E/pt unknown
- 1999-08-09 CN CNB998105503A patent/CN100339389C/zh not_active Expired - Lifetime
- 1999-08-09 SK SK206-2001A patent/SK286994B6/sk not_active IP Right Cessation
- 1999-08-09 RS RSP-2009/0459A patent/RS20090459A/sr unknown
- 1999-08-09 HU HU1300080A patent/HU230701B1/hu unknown
- 1999-08-09 MY MYPI99003397A patent/MY127538A/en unknown
- 1999-08-10 CO CO99050714A patent/CO5261542A1/es active IP Right Grant
- 1999-08-10 AR ARP990103977A patent/AR020880A1/es active IP Right Grant
- 1999-09-08 UA UA2001031603A patent/UA75026C2/uk unknown
- 1999-09-28 SA SA99200617A patent/SA99200617B1/ar unknown
-
2000
- 2000-09-12 US US09/660,030 patent/US6268207B1/en not_active Expired - Lifetime
- 2000-09-29 US US09/675,398 patent/US6329379B1/en not_active Ceased
- 2000-11-01 US US09/703,751 patent/US6329417B1/en not_active Ceased
-
2001
- 2001-01-22 IL IL141012A patent/IL141012A/en not_active IP Right Cessation
- 2001-02-05 ZA ZA200100971A patent/ZA200100971B/en unknown
- 2001-02-07 MX MXPA06004222 patent/MX257413B/es unknown
- 2001-02-07 IN IN127MU2001 patent/IN2001MU00127A/en unknown
- 2001-02-07 MX MXPA01001423 patent/MX261584B/es active IP Right Grant
- 2001-02-08 HR HR20010102A patent/HRP20010102B1/xx not_active IP Right Cessation
- 2001-02-08 BG BG105232A patent/BG65738B1/bg unknown
- 2001-02-09 NO NO20010683A patent/NO328952B1/no not_active IP Right Cessation
- 2001-04-06 US US09/827,976 patent/US6420380B2/en not_active Expired - Lifetime
- 2001-05-04 US US09/849,057 patent/US6410531B1/en not_active Expired - Lifetime
-
2002
- 2002-02-25 HK HK02101407.3A patent/HK1040085B/zh not_active IP Right Cessation
- 2002-03-05 US US10/091,293 patent/US6534523B1/en not_active Ceased
-
2005
- 2005-09-30 US US11/241,899 patent/USRE40525E1/en not_active Expired - Lifetime
-
2007
- 2007-05-11 IN IN706MU2007 patent/IN2007MU00706A/en unknown
-
2008
- 2008-03-05 US US12/042,627 patent/USRE41894E1/en not_active Expired - Lifetime
- 2008-05-12 US US12/118,926 patent/USRE41356E1/en not_active Expired - Lifetime
- 2008-05-13 US US12/119,609 patent/USRE42164E1/en not_active Expired - Lifetime
- 2008-08-12 HK HK08108883.5A patent/HK1113164A1/xx not_active IP Right Cessation
- 2008-12-05 AR ARP080105301A patent/AR069583A2/es active IP Right Grant
-
2009
- 2009-01-15 IL IL196545A patent/IL196545A/en not_active IP Right Cessation
- 2009-07-23 CY CY20091100795T patent/CY1109291T1/el unknown
- 2009-11-18 JP JP2009262835A patent/JP5021711B2/ja not_active Expired - Lifetime
- 2009-11-27 AR ARP090104583A patent/AR073428A2/es not_active Application Discontinuation
-
2010
- 2010-01-05 NO NO20100004A patent/NO336663B1/no not_active IP Right Cessation
-
2013
- 2013-04-18 CY CY20131100317T patent/CY1113935T1/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ZA200100971B (en) | Hepatitis C inhibitor tri-peptides | |
AU764655B2 (en) | Hepatitis C inhibitor peptides | |
US6143715A (en) | Hepatitis C inhibitor peptide analogues | |
CA2294049A1 (en) | Hepatitis c inhibitor peptides | |
CA2370396A1 (en) | Hepatitis c inhibitor tri-peptides | |
MXPA01001422A (en) | Hepatitis c inhibitor peptides |