CA2784662A1 - Hepatitis c virus inhibitors - Google Patents
Hepatitis c virus inhibitors Download PDFInfo
- Publication number
- CA2784662A1 CA2784662A1 CA2784662A CA2784662A CA2784662A1 CA 2784662 A1 CA2784662 A1 CA 2784662A1 CA 2784662 A CA2784662 A CA 2784662A CA 2784662 A CA2784662 A CA 2784662A CA 2784662 A1 CA2784662 A1 CA 2784662A1
- Authority
- CA
- Canada
- Prior art keywords
- cap
- mmol
- anal
- found
- hcv
- 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
- 241000711549 Hepacivirus C Species 0.000 title abstract description 51
- 239000003112 inhibitor Substances 0.000 title description 39
- 239000000203 mixture Substances 0.000 claims abstract description 287
- 150000001875 compounds Chemical class 0.000 claims abstract description 142
- 238000000034 method Methods 0.000 claims abstract description 85
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 208000015181 infectious disease Diseases 0.000 claims abstract description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 219
- 125000000217 alkyl group Chemical group 0.000 claims description 72
- 150000003839 salts Chemical class 0.000 claims description 61
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 37
- 125000005843 halogen group Chemical group 0.000 claims description 30
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 26
- 229940079322 interferon Drugs 0.000 claims description 26
- 108010050904 Interferons Proteins 0.000 claims description 24
- 102000014150 Interferons Human genes 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 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 18
- 229960000329 ribavirin Drugs 0.000 claims description 18
- 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 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 108010047761 Interferon-alpha Proteins 0.000 claims description 12
- 102000006992 Interferon-alpha Human genes 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 6
- 101710200424 Inosine-5'-monophosphate dehydrogenase Proteins 0.000 claims description 6
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- 238000011161 development Methods 0.000 claims description 5
- UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 claims description 4
- 108020005544 Antisense RNA Proteins 0.000 claims description 4
- 229940124186 Dehydrogenase inhibitor Drugs 0.000 claims description 4
- HAEJPQIATWHALX-KQYNXXCUSA-N ITP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(N=CNC2=O)=C2N=C1 HAEJPQIATWHALX-KQYNXXCUSA-N 0.000 claims description 4
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- 230000005867 T cell response Effects 0.000 claims description 4
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 4
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- 210000002443 helper t lymphocyte Anatomy 0.000 claims description 4
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- 229940100601 interleukin-6 Drugs 0.000 claims description 4
- 229960000888 rimantadine Drugs 0.000 claims description 4
- 150000002431 hydrogen Chemical group 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 505
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 200
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 197
- 239000000243 solution Substances 0.000 description 194
- 238000005160 1H NMR spectroscopy Methods 0.000 description 185
- 235000019439 ethyl acetate Nutrition 0.000 description 162
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 108
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 105
- 239000002904 solvent Substances 0.000 description 101
- 239000007787 solid Substances 0.000 description 94
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 89
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 80
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 74
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- 238000006243 chemical reaction Methods 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 59
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- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 54
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- 239000000741 silica gel Substances 0.000 description 45
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 45
- 238000000746 purification Methods 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 40
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 40
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 40
- 235000019341 magnesium sulphate Nutrition 0.000 description 40
- 238000003756 stirring Methods 0.000 description 39
- 238000005481 NMR spectroscopy Methods 0.000 description 38
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 38
- -1 NS3 Proteins 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- 230000000840 anti-viral effect Effects 0.000 description 35
- 238000003818 flash chromatography Methods 0.000 description 34
- 239000000725 suspension Substances 0.000 description 33
- 239000000047 product Substances 0.000 description 31
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 29
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 27
- 239000012230 colorless oil Substances 0.000 description 27
- 239000000706 filtrate Substances 0.000 description 27
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
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- 239000012043 crude product Substances 0.000 description 25
- 238000002360 preparation method Methods 0.000 description 25
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- 239000011734 sodium Substances 0.000 description 25
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 239000013058 crude material Substances 0.000 description 24
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- 239000003814 drug Substances 0.000 description 23
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 19
- 239000000463 material Substances 0.000 description 19
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
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- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 5
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- 235000013874 shellac Nutrition 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
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- 239000000661 sodium alginate Substances 0.000 description 1
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- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- SSERCMQZZYTNBY-UHFFFAOYSA-M sodium;3-[(4-hydroxycyclohexyl)-(4-methylcyclohexanecarbonyl)amino]-5-phenylthiophene-2-carboxylate Chemical compound [Na+].C1CC(C)CCC1C(=O)N(C1=C(SC(=C1)C=1C=CC=CC=1)C([O-])=O)C1CCC(O)CC1 SSERCMQZZYTNBY-UHFFFAOYSA-M 0.000 description 1
- XSVKAYYNFNXTDA-BGCDDMGFSA-N solanapyrone f Chemical compound C1([C@H]2[C@@H]3CC[C@H](O)C[C@@H]3C=C[C@@H]2C)=CC(N)=C(C=O)C(=O)O1 XSVKAYYNFNXTDA-BGCDDMGFSA-N 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 239000011593 sulfur Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
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- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- NHKZSTHOYNWEEZ-AFCXAGJDSA-N taribavirin Chemical compound N1=C(C(=N)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NHKZSTHOYNWEEZ-AFCXAGJDSA-N 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- JENNMRCJADUWJR-LLVKDONJSA-N tert-butyl (2r)-2-(methoxycarbonylamino)-2-phenylacetate Chemical compound COC(=O)N[C@@H](C(=O)OC(C)(C)C)C1=CC=CC=C1 JENNMRCJADUWJR-LLVKDONJSA-N 0.000 description 1
- XASPGLPXANLVTJ-RITPCOANSA-N tert-butyl (2s,3r)-2-amino-3-hydroxybutanoate Chemical compound C[C@@H](O)[C@H](N)C(=O)OC(C)(C)C XASPGLPXANLVTJ-RITPCOANSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- LCJVIYPJPCBWKS-NXPQJCNCSA-N thymosin Chemical compound SC[C@@H](N)C(=O)N[C@H](CO)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CO)C(=O)N[C@H](CO)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@H]([C@H](C)O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@H](CCC(O)=O)C(O)=O LCJVIYPJPCBWKS-NXPQJCNCSA-N 0.000 description 1
- 229940044655 toll-like receptor 9 agonist Drugs 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
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- 230000007704 transition Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- SANWDQJIWZEKOD-UHFFFAOYSA-N tributyl(furan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CO1 SANWDQJIWZEKOD-UHFFFAOYSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- AJSTXXYNEIHPMD-UHFFFAOYSA-N triethyl borate Chemical compound CCOB(OCC)OCC AJSTXXYNEIHPMD-UHFFFAOYSA-N 0.000 description 1
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- 238000001665 trituration Methods 0.000 description 1
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- 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
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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| US12/957,512 | 2010-12-01 | ||
| PCT/US2010/060077 WO2011075439A1 (en) | 2009-12-16 | 2010-12-13 | Hepatitis c virus inhibitors |
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2010
- 2010-12-01 US US12/957,512 patent/US8377980B2/en active Active
- 2010-12-10 TW TW099143331A patent/TWI487702B/zh not_active IP Right Cessation
- 2010-12-13 CA CA2784662A patent/CA2784662A1/en not_active Abandoned
- 2010-12-13 BR BR112012014677A patent/BR112012014677A2/pt not_active IP Right Cessation
- 2010-12-13 WO PCT/US2010/060077 patent/WO2011075439A1/en not_active Ceased
- 2010-12-13 NZ NZ601220A patent/NZ601220A/en not_active IP Right Cessation
- 2010-12-13 CN CN201080062796.3A patent/CN102741242B/zh not_active Expired - Fee Related
- 2010-12-13 PH PH1/2012/500979A patent/PH12012500979A1/en unknown
- 2010-12-13 PE PE2012000831A patent/PE20121479A1/es not_active Application Discontinuation
- 2010-12-13 EA EA201270656A patent/EA020815B1/ru not_active IP Right Cessation
- 2010-12-13 JP JP2012544681A patent/JP5785189B2/ja not_active Expired - Fee Related
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- 2010-12-13 MX MX2012006635A patent/MX2012006635A/es active IP Right Grant
- 2010-12-13 KR KR1020127018317A patent/KR20120107991A/ko not_active Withdrawn
- 2010-12-13 AU AU2010332034A patent/AU2010332034B2/en not_active Ceased
- 2010-12-13 EP EP10796540.2A patent/EP2513091B1/en not_active Not-in-force
- 2010-12-16 AR ARP100104697A patent/AR079634A1/es unknown
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2012
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- 2012-06-06 MA MA34944A patent/MA33806B1/fr unknown
- 2012-06-15 CL CL2012001637A patent/CL2012001637A1/es unknown
- 2012-07-04 CO CO12111939A patent/CO6561788A2/es not_active Application Discontinuation
Also Published As
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|---|---|
| AR079634A1 (es) | 2012-02-08 |
| EP2513091B1 (en) | 2017-04-12 |
| TN2012000264A1 (en) | 2013-12-12 |
| KR20120107991A (ko) | 2012-10-04 |
| EP2513091A1 (en) | 2012-10-24 |
| MX2012006635A (es) | 2012-06-21 |
| US8377980B2 (en) | 2013-02-19 |
| JP2013514359A (ja) | 2013-04-25 |
| WO2011075439A1 (en) | 2011-06-23 |
| AU2010332034A1 (en) | 2012-08-02 |
| NZ601220A (en) | 2014-07-25 |
| AU2010332034B2 (en) | 2016-04-14 |
| PH12012500979A1 (en) | 2014-09-05 |
| BR112012014677A2 (pt) | 2015-09-15 |
| TW201130825A (en) | 2011-09-16 |
| CO6561788A2 (es) | 2012-11-15 |
| TWI487702B (zh) | 2015-06-11 |
| CL2012001637A1 (es) | 2012-10-12 |
| US20110286961A1 (en) | 2011-11-24 |
| EA020815B1 (ru) | 2015-01-30 |
| CN102741242A (zh) | 2012-10-17 |
| MA33806B1 (fr) | 2012-12-03 |
| PE20121479A1 (es) | 2012-11-07 |
| EA201270656A1 (ru) | 2012-11-30 |
| JP5785189B2 (ja) | 2015-09-24 |
| CN102741242B (zh) | 2015-07-01 |
| SG181700A1 (en) | 2012-07-30 |
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| FZDE | Discontinued |
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