CA2845321A1 - Combination treatments for hepatitis c - Google Patents
Combination treatments for hepatitis c Download PDFInfo
- Publication number
- CA2845321A1 CA2845321A1 CA2845321A CA2845321A CA2845321A1 CA 2845321 A1 CA2845321 A1 CA 2845321A1 CA 2845321 A CA2845321 A CA 2845321A CA 2845321 A CA2845321 A CA 2845321A CA 2845321 A1 CA2845321 A1 CA 2845321A1
- Authority
- CA
- Canada
- Prior art keywords
- inhibitor
- methyl
- hcv
- imidazol
- carbonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 208000006454 hepatitis Diseases 0.000 title description 3
- 231100000283 hepatitis Toxicity 0.000 title description 3
- 238000011284 combination treatment Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 361
- 150000003839 salts Chemical class 0.000 claims abstract description 95
- 238000000034 method Methods 0.000 claims abstract description 76
- 239000003814 drug Substances 0.000 claims abstract description 73
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 70
- 238000011282 treatment Methods 0.000 claims abstract description 57
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 47
- 208000005176 Hepatitis C Diseases 0.000 claims abstract description 42
- 241000711549 Hepacivirus C Species 0.000 claims description 222
- 239000003112 inhibitor Substances 0.000 claims description 180
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 83
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 77
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 75
- 229940079322 interferon Drugs 0.000 claims description 63
- 102000014150 Interferons Human genes 0.000 claims description 62
- 108010050904 Interferons Proteins 0.000 claims description 62
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical group 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 57
- 239000000203 mixture Substances 0.000 claims description 56
- 239000000134 cyclophilin inhibitor Substances 0.000 claims description 54
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 54
- 229940122806 Cyclophilin inhibitor Drugs 0.000 claims description 53
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 50
- 229940127073 nucleoside analogue Drugs 0.000 claims description 48
- 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 47
- 229960000329 ribavirin Drugs 0.000 claims description 47
- 230000037353 metabolic pathway Effects 0.000 claims description 42
- 101800001019 Non-structural protein 4B Proteins 0.000 claims description 40
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims description 38
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 38
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 claims description 38
- 230000010076 replication Effects 0.000 claims description 38
- 229940124772 HCV-NS5B polymerase inhibitor Drugs 0.000 claims description 37
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 37
- 229940122750 HCV entry inhibitor Drugs 0.000 claims description 36
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 claims description 36
- 239000002955 immunomodulating agent Substances 0.000 claims description 36
- 229940121354 immunomodulator Drugs 0.000 claims description 36
- 229940123169 Caspase inhibitor Drugs 0.000 claims description 35
- 229940121759 Helicase inhibitor Drugs 0.000 claims description 35
- 230000002584 immunomodulator Effects 0.000 claims description 35
- JTZZSQYMACOLNN-VDWJNHBNSA-N simeprevir Chemical compound O=C([C@@]12C[C@H]1\C=C/CCCCN(C)C(=O)[C@H]1[C@H](C(N2)=O)C[C@H](C1)OC=1C2=CC=C(C(=C2N=C(C=1)C=1SC=C(N=1)C(C)C)C)OC)NS(=O)(=O)C1CC1 JTZZSQYMACOLNN-VDWJNHBNSA-N 0.000 claims description 35
- ZVTDLPBHTSMEJZ-JSZLBQEHSA-N danoprevir Chemical compound O=C([C@@]12C[C@H]1\C=C/CCCCC[C@@H](C(N1C[C@@H](C[C@H]1C(=O)N2)OC(=O)N1CC2=C(F)C=CC=C2C1)=O)NC(=O)OC(C)(C)C)NS(=O)(=O)C1CC1 ZVTDLPBHTSMEJZ-JSZLBQEHSA-N 0.000 claims description 34
- 229940121649 protein inhibitor Drugs 0.000 claims description 34
- 239000012268 protein inhibitor Substances 0.000 claims description 34
- 229960002091 simeprevir Drugs 0.000 claims description 34
- MLESJYFEMSJZLZ-MAAOGQSESA-N [(2r,3r,4r,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-4-fluoro-4-methyl-3-(2-methylpropanoyloxy)oxolan-2-yl]methyl 2-methylpropanoate Chemical compound C[C@@]1(F)[C@H](OC(=O)C(C)C)[C@@H](COC(=O)C(C)C)O[C@H]1N1C(=O)N=C(N)C=C1 MLESJYFEMSJZLZ-MAAOGQSESA-N 0.000 claims description 32
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 32
- VPHXUNBMNWOYNQ-XLBCSPGISA-N setrobuvir Chemical compound N1([C@H]2[C@@H]3CC[C@@H](C3)[C@H]2C(=O)/C(C1=O)=C1/NC2=CC=C(C=C2S(=O)(=O)N1)NS(=O)(=O)C)CC1=CC=C(F)C=C1 VPHXUNBMNWOYNQ-XLBCSPGISA-N 0.000 claims description 31
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 30
- 101800001838 Serine protease/helicase NS3 Proteins 0.000 claims description 24
- 125000003003 spiro group Chemical group 0.000 claims description 24
- XBEQSQDCBSKCHJ-UHFFFAOYSA-N 5-[[6-[2,4-bis(trifluoromethyl)phenyl]pyridazin-3-yl]methyl]-2-(2-fluorophenyl)imidazo[4,5-c]pyridine Chemical compound FC1=CC=CC=C1C1=NC2=CN(CC=3N=NC(=CC=3)C=3C(=CC(=CC=3)C(F)(F)F)C(F)(F)F)C=CC2=N1 XBEQSQDCBSKCHJ-UHFFFAOYSA-N 0.000 claims description 22
- 229940126656 GS-4224 Drugs 0.000 claims description 22
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 229950002891 danoprevir Drugs 0.000 claims description 17
- 229910052805 deuterium Inorganic materials 0.000 claims description 17
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 17
- DEKOYVOWOVJMPM-RLHIPHHXSA-N setrobuvir Chemical compound N1([C@H]2[C@@H]3CC[C@@H](C3)[C@H]2C(O)=C(C1=O)C=1NC2=CC=C(C=C2S(=O)(=O)N=1)NS(=O)(=O)C)CC1=CC=C(F)C=C1 DEKOYVOWOVJMPM-RLHIPHHXSA-N 0.000 claims description 17
- 229940124683 HCV polymerase inhibitor Drugs 0.000 claims description 16
- 229950010383 mericitabine Drugs 0.000 claims description 16
- 229950004113 setrobuvir Drugs 0.000 claims description 16
- UOBYJVFBFSLCTQ-UHFFFAOYSA-N tmc647055 Chemical compound C12=CC=C(C(NS(=O)(=O)N(C)CCOCCN(C)C3=O)=O)C=C2N2CC3=CC3=CC(OC)=CC=C3C2=C1C1CCCCC1 UOBYJVFBFSLCTQ-UHFFFAOYSA-N 0.000 claims description 15
- SLVAPEZTBDBAPI-GDLZYMKVSA-N filibuvir Chemical compound CCC1=NC(CC)=CC(CC[C@]2(OC(=O)C(CC3=NN4C(C)=CC(C)=NC4=N3)=C(O)C2)C2CCCC2)=C1 SLVAPEZTBDBAPI-GDLZYMKVSA-N 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- MUICUPWICXUNRS-UVXQUXCMSA-N 5-(3,3-dimethylbut-1-ynyl)-3-[[4-hydroxy-4-[[(3s)-oxolan-3-yl]oxymethyl]cyclohexyl]-[(1r)-4-methylcyclohex-3-ene-1-carbonyl]amino]thiophene-2-carboxylic acid Chemical compound C1CC(C)=CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)C1CCC(O)(CO[C@@H]2COCC2)CC1 MUICUPWICXUNRS-UVXQUXCMSA-N 0.000 claims description 12
- TTZHDVOVKQGIBA-IQWMDFIBSA-N sofosbuvir Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@]2(F)C)O)CO[P@@](=O)(N[C@@H](C)C(=O)OC(C)C)OC=2C=CC=CC=2)C=CC(=O)NC1=O TTZHDVOVKQGIBA-IQWMDFIBSA-N 0.000 claims description 12
- 229950004886 tegobuvir Drugs 0.000 claims description 12
- 108010078049 Interferon alpha-2 Proteins 0.000 claims description 11
- 108010047761 Interferon-alpha Proteins 0.000 claims description 11
- 102000006992 Interferon-alpha Human genes 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- LHHCSNFAOIFYRV-DOVBMPENSA-N boceprevir Chemical compound O=C([C@@H]1[C@@H]2[C@@H](C2(C)C)CN1C(=O)[C@@H](NC(=O)NC(C)(C)C)C(C)(C)C)NC(C(=O)C(N)=O)CC1CCC1 LHHCSNFAOIFYRV-DOVBMPENSA-N 0.000 claims description 10
- 229960000517 boceprevir Drugs 0.000 claims description 10
- MIXCUJKCXRNYFM-UHFFFAOYSA-M sodium;diiodomethanesulfonate;n-propyl-n-[2-(2,4,6-trichlorophenoxy)ethyl]imidazole-1-carboxamide Chemical compound [Na+].[O-]S(=O)(=O)C(I)I.C1=CN=CN1C(=O)N(CCC)CCOC1=C(Cl)C=C(Cl)C=C1Cl MIXCUJKCXRNYFM-UHFFFAOYSA-M 0.000 claims description 10
- BBAWEDCPNXPBQM-GDEBMMAJSA-N telaprevir Chemical compound N([C@H](C(=O)N[C@H](C(=O)N1C[C@@H]2CCC[C@@H]2[C@H]1C(=O)N[C@@H](CCC)C(=O)C(=O)NC1CC1)C(C)(C)C)C1CCCCC1)C(=O)C1=CN=CC=N1 BBAWEDCPNXPBQM-GDEBMMAJSA-N 0.000 claims description 10
- 229960002935 telaprevir Drugs 0.000 claims description 10
- 108010017101 telaprevir Proteins 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 9
- 150000002431 hydrogen Chemical group 0.000 claims description 9
- 239000001257 hydrogen Chemical group 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 229950000843 vaniprevir Drugs 0.000 claims description 8
- HPAPGONEMPZXMM-CMWVUSIZSA-N vaniprevir Chemical compound O=C([C@H]1C[C@@H]2OC(=O)N3CC=4C=CC=C(C=4C3)CCCCC(C)(C)COC(=O)N[C@@H](C(N1C2)=O)C(C)(C)C)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C HPAPGONEMPZXMM-CMWVUSIZSA-N 0.000 claims description 8
- OLROWHGDTNFZBH-XEMWPYQTSA-N Alisporivir Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(CC)C(=O)[C@@H](C)N(C)C1=O OLROWHGDTNFZBH-XEMWPYQTSA-N 0.000 claims description 7
- MHFMTUBUVQZIRE-WINRQGAFSA-N Sovaprevir Chemical compound C([C@H](C(=O)N1[C@@H](C[C@H](C1)OC=1C2=CC=C(C=C2N=C(C=1)C=1C=CC=CC=1)OC)C(=O)N[C@]1([C@@H](C1)C=C)C(=O)NS(=O)(=O)C1CC1)C(C)(C)C)C(=O)N1CCCCC1 MHFMTUBUVQZIRE-WINRQGAFSA-N 0.000 claims description 7
- 108010058359 alisporivir Proteins 0.000 claims description 7
- WPMJNLCLKAKMLA-VVPTUSLJSA-N chembl3039503 Chemical compound C1C[C@@H](C)CC[C@@H]1C(=O)N(C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O)[C@@H]1CC[C@@H](O)CC1 WPMJNLCLKAKMLA-VVPTUSLJSA-N 0.000 claims description 7
- NBRBXGKOEOGLOI-UHFFFAOYSA-N dasabuvir Chemical compound C1=C(C(C)(C)C)C(OC)=C(C=2C=C3C=CC(NS(C)(=O)=O)=CC3=CC=2)C=C1N1C=CC(=O)NC1=O NBRBXGKOEOGLOI-UHFFFAOYSA-N 0.000 claims description 7
- 229960001418 dasabuvir Drugs 0.000 claims description 7
- UDMJANYPQWEDFT-ZAWFUYGJSA-N deldeprevir Chemical compound C([C@@H]1C(=O)N2[C@H](C(N[C@@]3(C[C@H]3\C=C/CCCCC1)C(=O)NS(=O)(=O)C1CC1)=O)C[C@H](C2)OC=1C2=CC=C(C(=C2N=C(C=1)C=1SC=C(N=1)C(C)C)C)OC)C(=O)N1CCCC(F)(F)C1 UDMJANYPQWEDFT-ZAWFUYGJSA-N 0.000 claims description 7
- 229950011045 filibuvir Drugs 0.000 claims description 7
- OBMNJSNZOWALQB-NCQNOWPTSA-N grazoprevir Chemical compound O=C([C@@H]1C[C@@H]2CN1C(=O)[C@@H](NC(=O)O[C@@H]1C[C@H]1CCCCCC1=NC3=CC=C(C=C3N=C1O2)OC)C(C)(C)C)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C OBMNJSNZOWALQB-NCQNOWPTSA-N 0.000 claims description 7
- XMZSTQYSBYEENY-RMKNXTFCSA-N n-[4-[(e)-2-[3-tert-butyl-5-(2,4-dioxopyrimidin-1-yl)-2-methoxyphenyl]ethenyl]phenyl]methanesulfonamide Chemical compound C1=C(N2C(NC(=O)C=C2)=O)C=C(C(C)(C)C)C(OC)=C1\C=C\C1=CC=C(NS(C)(=O)=O)C=C1 XMZSTQYSBYEENY-RMKNXTFCSA-N 0.000 claims description 7
- UAUIUKWPKRJZJV-MDJGTQRPSA-N paritaprevir Chemical compound C1=NC(C)=CN=C1C(=O)N[C@@H]1C(=O)N2C[C@H](OC=3C4=CC=CC=C4C4=CC=CC=C4N=3)C[C@H]2C(=O)N[C@]2(C(=O)NS(=O)(=O)C3CC3)C[C@@H]2\C=C/CCCCC1 UAUIUKWPKRJZJV-MDJGTQRPSA-N 0.000 claims description 7
- 229960002754 paritaprevir Drugs 0.000 claims description 7
- AQHMBDAHQGYLIU-XNFHFXFQSA-N (3s,6s,9s,12r,15s,18s,21s,24s,27r,30s,33s)-27-[2-(dimethylamino)ethylsulfanyl]-30-ethyl-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-24-(2-hydroxy-2-methylpropyl)-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10, Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)(C)O)N(C)C(=O)[C@@H](SCCN(C)C)N(C)C1=O AQHMBDAHQGYLIU-XNFHFXFQSA-N 0.000 claims description 6
- 229940122604 HCV protease inhibitor Drugs 0.000 claims description 6
- 108010090287 SCY-635 Proteins 0.000 claims description 6
- 108010006088 interferon alfa-n1 Proteins 0.000 claims description 6
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 claims description 6
- 229960000518 ombitasvir Drugs 0.000 claims description 6
- 108010092853 peginterferon alfa-2a Proteins 0.000 claims description 6
- 108010092851 peginterferon alfa-2b Proteins 0.000 claims description 6
- FGHMGRXAHIXTBM-TWFJNEQDSA-N s-[2-[[(2r,3r,4r,5r)-5-(2-amino-6-oxo-3h-purin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-(benzylamino)phosphoryl]oxyethyl] 3-hydroxy-2,2-dimethylpropanethioate Chemical compound C([C@@H]1[C@H]([C@@](C)(O)[C@H](N2C3=C(C(NC(N)=N3)=O)N=C2)O1)O)OP(=O)(OCCSC(=O)C(C)(CO)C)NCC1=CC=CC=C1 FGHMGRXAHIXTBM-TWFJNEQDSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- FKRSSPOQAMALKA-CUPIEXAXSA-N daclatasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2N=C(NC=2)[C@H]2N(CCC2)C(=O)[C@@H](NC(=O)OC)C(C)C)=CN1 FKRSSPOQAMALKA-CUPIEXAXSA-N 0.000 claims description 5
- 229960003521 interferon alfa-2a Drugs 0.000 claims description 5
- 229960003507 interferon alfa-2b Drugs 0.000 claims description 5
- 229960004061 interferon alfa-n1 Drugs 0.000 claims description 5
- 108010010648 interferon alfacon-1 Proteins 0.000 claims description 5
- ATOLIHZIXHZSBA-BTSKBWHGSA-N methyl n-[(1r)-2-[(2s)-2-[5-[4-[6-[2-[(2s)-1-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]pyrrolidin-2-yl]-3h-benzimidazol-5-yl]thieno[3,2-b]thiophen-3-yl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-2-oxo-1-phenylethyl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC2=CC(C=3C=4SC=C(C=4SC=3)C=3C=CC(=CC=3)C=3N=C(NC=3)[C@H]3N(CCC3)C(=O)[C@H](NC(=O)OC)C=3C=CC=CC=3)=CC=C2N1 ATOLIHZIXHZSBA-BTSKBWHGSA-N 0.000 claims description 5
- JYLMWUZJMRNMDA-SPRBZRACSA-N methyl n-[(2s)-1-[(2s)-2-[5-[6-[2-[(2s)-1-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]pyrrolidin-2-yl]-3h-benzimidazol-5-yl]naphthalen-2-yl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate;dihydrochloride Chemical compound Cl.Cl.COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(C=2C=C3C=CC(=CC3=CC=2)C=2C=C3NC(=NC3=CC=2)[C@H]2N(CCC2)C(=O)[C@@H](NC(=O)OC)C(C)C)N1 JYLMWUZJMRNMDA-SPRBZRACSA-N 0.000 claims description 5
- LSYBRGMTRKJATA-IVEWBXRVSA-N odalasvir Chemical compound C1=C2NC([C@H]3N([C@H]4CCCC[C@H]4C3)C(=O)[C@H](C(C)C)NC(=O)OC)=NC2=CC=C1C(C(CC1)=CC=2)=CC=2CCC2=CC=C1C=C2C1=CC=C(N=C(N2)[C@H]3N([C@H]4CCCC[C@H]4C3)C(=O)[C@@H](NC(=O)OC)C(C)C)C2=C1 LSYBRGMTRKJATA-IVEWBXRVSA-N 0.000 claims description 5
- 229960003930 peginterferon alfa-2a Drugs 0.000 claims description 5
- 229960003931 peginterferon alfa-2b Drugs 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 229960003358 interferon alfacon-1 Drugs 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 102100040018 Interferon alpha-2 Human genes 0.000 claims description 3
- 108010079944 Interferon-alpha2b Proteins 0.000 claims description 3
- 108010045648 interferon omega 1 Proteins 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 15
- 229910052760 oxygen Inorganic materials 0.000 claims 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- LTUKXEMMWOLVRU-ZNJJWNFJSA-N methyl 2-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-3-[5-[4-[4-[2-[(2s)-1-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]pyrrolidin-2-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)C2N(CC3(C2)CCN(CC3)C(=O)OC)C(=O)[C@@H](NC(=O)OC)C(C)C)N1 LTUKXEMMWOLVRU-ZNJJWNFJSA-N 0.000 claims 1
- SNRXOPQBKGTIBO-ICUIMKRYSA-N methyl n-[(2s)-1-[(2s)-2-[5-[4-[4-[2-(1-acetyl-8,8-difluoro-1-azaspiro[4.5]decan-2-yl)-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2N=C(NC=2)C2N(C3(CCC(F)(F)CC3)CC2)C(C)=O)=CN1 SNRXOPQBKGTIBO-ICUIMKRYSA-N 0.000 claims 1
- ULALYOIGGLHHMJ-ICUIMKRYSA-N methyl n-[(2s)-1-[(2s)-2-[5-[4-[4-[2-(1-acetyl-8-oxa-1-azaspiro[4.5]decan-2-yl)-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2N=C(NC=2)C2N(C3(CCOCC3)CC2)C(C)=O)=CN1 ULALYOIGGLHHMJ-ICUIMKRYSA-N 0.000 claims 1
- UKHMNSSWMSHEOB-ZYADHFCISA-N methyl n-[(2s)-1-[(2s)-2-[5-[4-[4-[2-[(3s)-2-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-6,10-dioxa-2-azaspiro[4.5]decan-3-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)[C@H]2N(CC3(C2)OCCCO3)C(=O)[C@@H](NC(=O)OC)C(C)C)N1 UKHMNSSWMSHEOB-ZYADHFCISA-N 0.000 claims 1
- NQRVKNKBHRPJGT-KXGVLIAMSA-N methyl n-[(2s)-1-[(2s)-2-[5-[4-[4-[2-[1-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-8-oxa-1-azaspiro[4.5]decan-2-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)C2N(C3(CCOCC3)CC2)C(=O)[C@@H](NC(=O)OC)C(C)C)N1 NQRVKNKBHRPJGT-KXGVLIAMSA-N 0.000 claims 1
- HKAWUDAITRQWJJ-KXGVLIAMSA-N methyl n-[(2s)-1-[(2s)-2-[5-[4-[4-[2-[2-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-2,8-diazaspiro[4.5]decan-3-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)C2N(CC3(C2)CCNCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)N1 HKAWUDAITRQWJJ-KXGVLIAMSA-N 0.000 claims 1
- SPIDCIIBHBZMOS-KXGVLIAMSA-N methyl n-[(2s)-1-[(2s)-2-[5-[4-[4-[2-[2-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-8,8-dioxo-8$l^{6}-thia-2-azaspiro[4.5]decan-3-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)C2N(CC3(C2)CCS(=O)(=O)CC3)C(=O)[C@@H](NC(=O)OC)C(C)C)N1 SPIDCIIBHBZMOS-KXGVLIAMSA-N 0.000 claims 1
- JVBWSVPKKDDELW-KXGVLIAMSA-N methyl n-[(2s)-1-[(2s)-2-[5-[4-[4-[2-[2-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-8-oxa-2-azaspiro[4.5]decan-3-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)C2N(CC3(C2)CCOCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)N1 JVBWSVPKKDDELW-KXGVLIAMSA-N 0.000 claims 1
- YWRGEKUPOVKWHV-KXGVLIAMSA-N methyl n-[(2s)-1-[(2s)-2-[5-[4-[4-[2-[2-acetyl-6-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-2,6-diazaspiro[3.4]octan-7-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)C2N(CC3(CN(C3)C(C)=O)C2)C(=O)[C@@H](NC(=O)OC)C(C)C)N1 YWRGEKUPOVKWHV-KXGVLIAMSA-N 0.000 claims 1
- VWIPTEQWSYRWTI-PRABGMNFSA-N methyl n-[(2s)-1-[(2s)-2-[5-[4-[4-[2-[6-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-2-methylsulfonyl-2,6-diazaspiro[3.4]octan-7-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)C2N(CC3(CN(C3)S(C)(=O)=O)C2)C(=O)[C@@H](NC(=O)OC)C(C)C)N1 VWIPTEQWSYRWTI-PRABGMNFSA-N 0.000 claims 1
- CFVDPLHWBFVJRE-JMMADWMLSA-N methyl n-[(2s)-1-[(2s)-2-[5-[4-[4-[2-[8-acetyl-2-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-2,8-diazaspiro[4.5]decan-3-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C1=NC=C(C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)C2N(CC3(C2)CCN(CC3)C(C)=O)C(=O)[C@@H](NC(=O)OC)C(C)C)N1 CFVDPLHWBFVJRE-JMMADWMLSA-N 0.000 claims 1
- RVQVYWRQBBSQID-MFFRHLKCSA-N methyl n-[(2s)-1-[(3s)-3-[5-[4-[4-[2-[(2s)-1-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]pyrrolidin-2-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]-6,10-dioxa-2-azaspiro[4.5]decan-2-yl]-1-oxopropan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C)C(=O)N([C@@H](C1)C=2NC(=CN=2)C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)[C@H]2N(CCC2)C(=O)[C@@H](NC(=O)OC)C(C)C)CC21OCCCO2 RVQVYWRQBBSQID-MFFRHLKCSA-N 0.000 claims 1
- CYDCGTIECOWZAN-YKKXUYLKSA-N methyl n-[(2s)-1-[(3s)-3-[5-[4-[4-[2-[(3s)-2-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-8-oxa-2-azaspiro[4.5]decan-3-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]-8-oxa-2-azaspiro[4.5]decan-2-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N([C@@H](C1)C=2NC=C(N=2)C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2N=C(NC=2)[C@H]2N(CC3(C2)CCOCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)CC21CCOCC2 CYDCGTIECOWZAN-YKKXUYLKSA-N 0.000 claims 1
- WVDLFOBBAVELAQ-ROZOJAHRSA-N methyl n-[(2s)-1-[(3s,7s,9s)-3-[5-[4-[4-[2-[(3s,7s,9s)-2-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-7,9-dimethyl-6,10-dioxa-2-azaspiro[4.5]decan-3-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]-7,9-dimethyl-6,10-dioxa-2-azaspiro[4.5]decan-2-y Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N([C@@H](C1)C=2NC(=CN=2)C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2NC(=NC=2)[C@H]2N(CC3(C2)O[C@@H](C)C[C@H](C)O3)C(=O)[C@@H](NC(=O)OC)C(C)C)CC21O[C@@H](C)C[C@H](C)O2 WVDLFOBBAVELAQ-ROZOJAHRSA-N 0.000 claims 1
- VKCLQPYBIASBLZ-ZYADHFCISA-N methyl n-[(2s)-1-[(8s)-8-[5-[4-[4-[2-[(8s)-7-[(2s)-2-(methoxycarbonylamino)-3-methylbutanoyl]-1,4-dioxa-7-azaspiro[4.4]nonan-8-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]-1,4-dioxa-7-azaspiro[4.4]nonan-7-yl]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N([C@@H](C1)C=2NC=C(N=2)C=2C=CC(=CC=2)C=2C=CC(=CC=2)C=2N=C(NC=2)[C@H]2N(CC3(C2)OCCO3)C(=O)[C@@H](NC(=O)OC)C(C)C)CC21OCCO2 VKCLQPYBIASBLZ-ZYADHFCISA-N 0.000 claims 1
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Classifications
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
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- A—HUMAN NECESSITIES
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- 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]
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- A—HUMAN NECESSITIES
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- 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]
- A61K38/217—IFN-gamma
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Public Health (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161526798P | 2011-08-24 | 2011-08-24 | |
| US61/526,798 | 2011-08-24 | ||
| US201161529358P | 2011-08-31 | 2011-08-31 | |
| US61/529,358 | 2011-08-31 | ||
| US201261617813P | 2012-03-30 | 2012-03-30 | |
| US61/617,813 | 2012-03-30 | ||
| PCT/US2012/052216 WO2013028953A1 (en) | 2011-08-24 | 2012-08-24 | Combination treatments for hepatitis c |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2845321A1 true CA2845321A1 (en) | 2013-02-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2845321A Abandoned CA2845321A1 (en) | 2011-08-24 | 2012-08-24 | Combination treatments for hepatitis c |
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| Country | Link |
|---|---|
| US (1) | US20140234253A1 (enExample) |
| EP (1) | EP2747569A4 (enExample) |
| JP (2) | JP2014527061A (enExample) |
| KR (1) | KR20140065427A (enExample) |
| CN (1) | CN103917095A (enExample) |
| AU (1) | AU2012298750A1 (enExample) |
| BR (1) | BR112014004182A2 (enExample) |
| CA (1) | CA2845321A1 (enExample) |
| CL (1) | CL2014000428A1 (enExample) |
| CO (1) | CO6890100A2 (enExample) |
| CR (1) | CR20140086A (enExample) |
| EA (1) | EA201490254A1 (enExample) |
| HK (1) | HK1198869A1 (enExample) |
| IL (1) | IL230844A0 (enExample) |
| MX (1) | MX2014002171A (enExample) |
| PH (1) | PH12014500386A1 (enExample) |
| SG (1) | SG2014010490A (enExample) |
| WO (1) | WO2013028953A1 (enExample) |
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| PE20120993A1 (es) * | 2009-09-04 | 2012-08-22 | Janssen Pharmaceuticals Inc | Derivados bifenilicos como antivirales |
| KR101975233B1 (ko) | 2011-08-17 | 2019-05-07 | 글락소스미스클라인 엘엘씨 | 치료 방법 |
| US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
| PT107894A (pt) | 2011-10-21 | 2014-10-31 | Abbvie Inc | Métodos para o tratamento de hcv compreendendo pelo menos dois agentes antivirais de actuação directa, ribavirina, mas não interferão. |
| GB2515942A (en) | 2011-10-21 | 2015-01-07 | Abbvie Inc | Combination treatment (e.g. 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 |
| US9326973B2 (en) | 2012-01-13 | 2016-05-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN105705511A (zh) | 2013-04-12 | 2016-06-22 | 艾其林医药公司 | 用于治疗hcv的氘化核苷前药 |
| US9717712B2 (en) | 2013-07-02 | 2017-08-01 | Bristol-Myers Squibb Company | Combinations comprising tricyclohexadecahexaene derivatives for use in the treatment of hepatitis C virus |
| US20150023913A1 (en) | 2013-07-02 | 2015-01-22 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| EP3019196B1 (en) * | 2013-07-09 | 2018-06-06 | Bristol-Myers Squibb Company | Combinations of hepatitis c virus inhibitors |
| WO2015009744A1 (en) | 2013-07-17 | 2015-01-22 | Bristol-Myers Squibb Company | Combinations comprising biphenyl derivatives for use in the treatment of hcv |
| CN104725365B (zh) * | 2013-12-23 | 2019-02-26 | 南京圣和药业股份有限公司 | 丙型肝炎病毒抑制剂及其应用 |
| CA2935089C (en) * | 2013-12-31 | 2018-11-27 | Nanjing Sanhome Pharmaceutical Co., Ltd. | 9,9,10,10-tetrafluoro-9,10-dihydrophenanthrene hepatitis c virus inhibitor and application thereof |
| CN106279121B (zh) * | 2014-01-21 | 2019-05-24 | 杭州普晒医药科技有限公司 | 一种化合物的盐及晶型或无定型物、其制备方法、含有它们的药物组合物和用途 |
| SG11201703645XA (en) * | 2014-11-10 | 2017-06-29 | Glaxosmithkline Intellectual Property (No 2) Ltd | Long acting pharmaceutical compositions for hepatitis c |
| MA41812A (fr) * | 2015-03-27 | 2018-01-30 | Janssen Pharmaceuticals Inc | Procédés et intermédiaires pour la préparation d'un inhibiteur de protéase macrocyclique du vhc |
| US10617675B2 (en) | 2015-08-06 | 2020-04-14 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US11192914B2 (en) | 2016-04-28 | 2021-12-07 | Emory University | Alkyne containing nucleotide and nucleoside therapeutic compositions and uses related thereto |
| CN110693887B (zh) * | 2019-05-17 | 2022-06-17 | 歌礼药业（浙江）有限公司 | 包含索磷布韦和拉维达韦的片剂及其制备方法 |
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| US20100158862A1 (en) * | 2006-08-11 | 2010-06-24 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US8329159B2 (en) * | 2006-08-11 | 2012-12-11 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8303944B2 (en) * | 2006-08-11 | 2012-11-06 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7704992B2 (en) * | 2008-02-13 | 2010-04-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| ES2435799T3 (es) * | 2008-10-09 | 2013-12-23 | Anadys Pharmaceuticals, Inc. | Un método de inhibición del virus de la hepatitis C mediante combinación de una 5,6-dihidro-1H-piridin-2-ona y de uno o más compuestos antivirales adicionales |
| WO2010062821A1 (en) * | 2008-11-28 | 2010-06-03 | Glaxosmithkline Llc | Anti-viral compounds, compositions, and methods of use |
| MX2011007195A (es) * | 2009-01-07 | 2013-07-12 | Scynexis Inc | Derivado de ciclosporina para el uso en el tratamiento de infección de virus de hepatitis c (vhc) y virus de inmunodeficiencia humana (vih). |
| MX363732B (es) * | 2009-05-13 | 2019-04-01 | Gilead Pharmasset Llc Star | Compuestos antivirales. |
| PE20120993A1 (es) * | 2009-09-04 | 2012-08-22 | Janssen Pharmaceuticals Inc | Derivados bifenilicos como antivirales |
| US8415374B2 (en) * | 2009-10-12 | 2013-04-09 | Bristol-Myers Squibb Company | Combinations of hepatitis C virus inhibitors |
| US8377980B2 (en) * | 2009-12-16 | 2013-02-19 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CA2784748A1 (en) * | 2009-12-18 | 2011-06-23 | Idenix Pharmaceuticals, Inc. | 5,5-fused arylene or heteroarylene hepatitis c virus inhibitors |
| WO2012040126A1 (en) * | 2010-09-22 | 2012-03-29 | Alios Biopharma, Inc. | Substituted nucleotide analogs |
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2012
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- 2012-08-24 PH PH1/2014/500386A patent/PH12014500386A1/en unknown
- 2012-08-24 KR KR1020147007736A patent/KR20140065427A/ko not_active Withdrawn
- 2012-08-24 CN CN201280052257.0A patent/CN103917095A/zh active Pending
- 2012-08-24 JP JP2014527322A patent/JP2014527061A/ja active Pending
- 2012-08-24 EA EA201490254A patent/EA201490254A1/ru unknown
- 2012-08-24 WO PCT/US2012/052216 patent/WO2013028953A1/en not_active Ceased
- 2012-08-24 MX MX2014002171A patent/MX2014002171A/es unknown
- 2012-08-24 SG SG2014010490A patent/SG2014010490A/en unknown
- 2012-08-24 US US14/240,420 patent/US20140234253A1/en not_active Abandoned
- 2012-08-24 BR BR112014004182A patent/BR112014004182A2/pt not_active IP Right Cessation
- 2012-08-24 EP EP12826268.0A patent/EP2747569A4/en not_active Withdrawn
- 2012-08-24 HK HK14112612.7A patent/HK1198869A1/xx unknown
- 2012-08-24 AU AU2012298750A patent/AU2012298750A1/en not_active Abandoned
-
2014
- 2014-02-06 IL IL230844A patent/IL230844A0/en unknown
- 2014-02-21 CL CL2014000428A patent/CL2014000428A1/es unknown
- 2014-02-24 CR CR20140086A patent/CR20140086A/es unknown
- 2014-02-26 CO CO14040944A patent/CO6890100A2/es unknown
-
2017
- 2017-04-20 JP JP2017083252A patent/JP2017165746A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| BR112014004182A2 (pt) | 2017-03-14 |
| IL230844A0 (en) | 2014-03-31 |
| HK1198869A1 (en) | 2015-06-19 |
| EA201490254A1 (ru) | 2014-07-30 |
| KR20140065427A (ko) | 2014-05-29 |
| EP2747569A1 (en) | 2014-07-02 |
| CN103917095A (zh) | 2014-07-09 |
| AU2012298750A1 (en) | 2014-03-13 |
| CR20140086A (es) | 2014-05-02 |
| JP2014527061A (ja) | 2014-10-09 |
| CO6890100A2 (es) | 2014-03-10 |
| WO2013028953A1 (en) | 2013-02-28 |
| SG2014010490A (en) | 2014-04-28 |
| MX2014002171A (es) | 2014-04-25 |
| JP2017165746A (ja) | 2017-09-21 |
| CL2014000428A1 (es) | 2014-08-01 |
| US20140234253A1 (en) | 2014-08-21 |
| PH12014500386A1 (en) | 2019-10-07 |
| EP2747569A4 (en) | 2015-07-08 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20170824 |