CA2819894A1 - Composes antiviraux - Google Patents

Composes antiviraux Download PDF

Info

Publication number: CA2819894A1
Authority: CA; Canada
Prior art keywords: optionally substituted; independently; occurrence; heterocycle; membered
Prior art date: 2010-12-16
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

Application number

CA2819894A

Other languages

English (en)

Inventor

Allan C. Krueger

Warren M. Kati

William A. Carroll

John K. Pratt

Douglas K. Hutchinson

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

AbbVie Inc

Original Assignee

AbbVie Inc

Priority date (The priority date 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 date listed.)

2010-12-16

Filing date

2011-12-16

Publication date

2012-06-21

2011-12-16 Application filed by AbbVie Inc filed Critical AbbVie Inc

2012-06-21 Publication of CA2819894A1 publication Critical patent/CA2819894A1/fr

Status Abandoned legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 311
230000000840 anti-viral effect Effects 0.000 title description 2
238000000034 method Methods 0.000 claims abstract description 52
208000015181 infectious disease Diseases 0.000 claims abstract description 8
230000008569 process Effects 0.000 claims abstract description 3
-1 phosphono, thioxo Chemical group 0.000 claims description 908
125000000623 heterocyclic group Chemical group 0.000 claims description 483
229910052736 halogen Inorganic materials 0.000 claims description 336
150000002367 halogens Chemical class 0.000 claims description 332
125000001424 substituent group Chemical group 0.000 claims description 259
125000004093 cyano group Chemical group *C#N 0.000 claims description 236
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 232
125000004043 oxo group Chemical group O=* 0.000 claims description 229
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 226
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 196
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 188
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 182
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 130
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 120
125000004429 atom Chemical group 0.000 claims description 120
125000006643 (C2-C6) haloalkenyl group Chemical group 0.000 claims description 114
229910052739 hydrogen Inorganic materials 0.000 claims description 96
239000001257 hydrogen Substances 0.000 claims description 90
125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 84
150000003839 salts Chemical class 0.000 claims description 64
229910052757 nitrogen Inorganic materials 0.000 claims description 47
229910052717 sulfur Inorganic materials 0.000 claims description 33
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 27
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
150000002431 hydrogen Chemical class 0.000 claims description 21
125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 16
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 16
WSFSSNUMVMOOMR-UHFFFAOYSA-N formaldehyde Natural products O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 14
229910052760 oxygen Inorganic materials 0.000 claims description 11
125000005842 heteroatom Chemical group 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 2
125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 1
125000005865 C2-C10alkynyl group Chemical group 0.000 claims 1
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical group [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims 1
PMCJIXMWHBWYIO-UHFFFAOYSA-N [2-(carboxyamino)-3-methylbutanoyl]carbamic acid Chemical compound OC(=O)NC(C(C)C)C(=O)NC(O)=O PMCJIXMWHBWYIO-UHFFFAOYSA-N 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 78
230000010076 replication Effects 0.000 abstract description 5
230000002401 inhibitory effect Effects 0.000 abstract description 3
241000711549 Hepacivirus C Species 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 125
QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 110
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 85
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
239000000243 solution Substances 0.000 description 62
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 61
125000001153 fluoro group Chemical group F* 0.000 description 60
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 58
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 53
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
238000006243 chemical reaction Methods 0.000 description 47
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 46
239000000543 intermediate Substances 0.000 description 44
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 43
125000001309 chloro group Chemical group Cl* 0.000 description 41
125000004076 pyridyl group Chemical group 0.000 description 39
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 37
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
125000004435 hydrogen atom Chemical group [H]* 0.000 description 32
239000000047 product Substances 0.000 description 32
239000007787 solid Substances 0.000 description 31
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 30
125000005843 halogen group Chemical group 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
125000000335 thiazolyl group Chemical group 0.000 description 23
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 23
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
229910052799 carbon Inorganic materials 0.000 description 22
239000002253 acid Substances 0.000 description 21
125000002887 hydroxy group Chemical group [H]O* 0.000 description 21
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 21
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 20
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 19
239000002904 solvent Substances 0.000 description 19
239000000126 substance Substances 0.000 description 19
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
239000012267 brine Substances 0.000 description 18
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 18
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 17
239000002585 base Substances 0.000 description 17
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 16
239000000741 silica gel Substances 0.000 description 16
229910002027 silica gel Inorganic materials 0.000 description 16
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 15
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 15
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 15
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
238000005160 1H NMR spectroscopy Methods 0.000 description 14
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 14
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 14
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 14
230000000670 limiting effect Effects 0.000 description 14
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 13
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 13
125000003118 aryl group Chemical group 0.000 description 13
125000005873 benzo[d]thiazolyl group Chemical group 0.000 description 13
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 13
125000000714 pyrimidinyl group Chemical group 0.000 description 13
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
125000000217 alkyl group Chemical group 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
150000002148 esters Chemical class 0.000 description 12
125000003386 piperidinyl group Chemical group 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
125000003003 spiro group Chemical group 0.000 description 12
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
239000007832 Na2SO4 Substances 0.000 description 11
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
125000000753 cycloalkyl group Chemical group 0.000 description 11
239000003921 oil Substances 0.000 description 11
235000019198 oils Nutrition 0.000 description 11
229910052938 sodium sulfate Inorganic materials 0.000 description 11
235000011152 sodium sulphate Nutrition 0.000 description 11
125000001054 5 membered carbocyclic group Chemical group 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
238000006069 Suzuki reaction reaction Methods 0.000 description 10
125000002393 azetidinyl group Chemical group 0.000 description 10
239000000651 prodrug Substances 0.000 description 10
229940002612 prodrug Drugs 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 9
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 9
239000000284 extract Substances 0.000 description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 9
125000006413 ring segment Chemical group 0.000 description 9
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 description 8
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
241000065675 Cyclops Species 0.000 description 8
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 8
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 8
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 8
125000005605 benzo group Chemical group 0.000 description 8
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 8
125000001246 bromo group Chemical group Br* 0.000 description 8
125000004452 carbocyclyl group Chemical group 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 8
125000001183 hydrocarbyl group Chemical group 0.000 description 8
125000006239 protecting group Chemical group 0.000 description 8
125000000719 pyrrolidinyl group Chemical group 0.000 description 8
238000003756 stirring Methods 0.000 description 8
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
150000001336 alkenes Chemical class 0.000 description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
150000004985 diamines Chemical class 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 7
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 7
125000002950 monocyclic group Chemical group 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 6
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
101150041968 CDC13 gene Proteins 0.000 description 6
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
239000007821 HATU Substances 0.000 description 6
239000005909 Kieselgur Substances 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
229910052796 boron Inorganic materials 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
239000012043 crude product Substances 0.000 description 6
238000000605 extraction Methods 0.000 description 6
238000001914 filtration Methods 0.000 description 6
LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 6
PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
125000004433 nitrogen atom Chemical group N* 0.000 description 6
235000011181 potassium carbonates Nutrition 0.000 description 6
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
239000012453 solvate Substances 0.000 description 6
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 5
NVZWMJWMTWOVNJ-UHFFFAOYSA-N 6-azaspiro[3.4]octane Chemical compound C1CCC21CNCC2 NVZWMJWMTWOVNJ-UHFFFAOYSA-N 0.000 description 5
101100459319 Arabidopsis thaliana VIII-2 gene Proteins 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
125000001072 heteroaryl group Chemical group 0.000 description 5
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 5
238000000746 purification Methods 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
239000007858 starting material Substances 0.000 description 5
HCMJWOGOISXSDL-UHFFFAOYSA-N (2-isothiocyanato-1-phenylethyl)benzene Chemical compound C=1C=CC=CC=1C(CN=C=S)C1=CC=CC=C1 HCMJWOGOISXSDL-UHFFFAOYSA-N 0.000 description 4
CEFVHPDFGLDQKU-YFKPBYRVSA-N (2s)-2-(methoxycarbonylamino)-3-methylbutanoic acid Chemical compound COC(=O)N[C@@H](C(C)C)C(O)=O CEFVHPDFGLDQKU-YFKPBYRVSA-N 0.000 description 4
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
OJVAMHKKJGICOG-UHFFFAOYSA-N 2,5-hexanedione Chemical compound CC(=O)CCC(C)=O OJVAMHKKJGICOG-UHFFFAOYSA-N 0.000 description 4
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 4
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
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ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
230000004962 physiological condition Effects 0.000 description 1
229940075930 picrate Drugs 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
XOKSLPVRUOBDEW-UHFFFAOYSA-N pinane of uncertain configuration Natural products CC1CCC2C(C)(C)C1C2 XOKSLPVRUOBDEW-UHFFFAOYSA-N 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-M prolinate Chemical compound [O-]C(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-M 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
238000010926 purge Methods 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical compound C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 description 1
150000003235 pyrrolidines Chemical class 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
230000006340 racemization Effects 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
229960000329 ribavirin Drugs 0.000 description 1
HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 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
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 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
APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
239000008279 sol Substances 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
229910000080 stannane Inorganic materials 0.000 description 1
239000000758 substrate Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
229960001367 tartaric acid Drugs 0.000 description 1
NYUMMUQRDICKIV-ZDUSSCGKSA-N tert-butyl (2s)-2-(5-bromo-6-fluoro-1h-benzimidazol-2-yl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C1=NC2=CC(F)=C(Br)C=C2N1 NYUMMUQRDICKIV-ZDUSSCGKSA-N 0.000 description 1
BFFLLBPMZCIGRM-QMMMGPOBSA-N tert-butyl (2s)-2-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1CO BFFLLBPMZCIGRM-QMMMGPOBSA-N 0.000 description 1
YOVYMYOTJZVQEZ-SFHVURJKSA-N tert-butyl (2s)-2-[5-bromo-6-(trifluoromethyl)-1-(2-trimethylsilylethoxymethyl)benzimidazol-2-yl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C1=NC2=CC(Br)=C(C(F)(F)F)C=C2N1COCC[Si](C)(C)C YOVYMYOTJZVQEZ-SFHVURJKSA-N 0.000 description 1
AUCLUZKMVUEAAC-SFHVURJKSA-N tert-butyl (2s)-2-[5-bromo-7-(trifluoromethyl)-1-(2-trimethylsilylethoxymethyl)benzimidazol-2-yl]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C1=NC2=CC(Br)=CC(C(F)(F)F)=C2N1COCC[Si](C)(C)C AUCLUZKMVUEAAC-SFHVURJKSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000002769 thiazolinyl group Chemical group 0.000 description 1
125000003777 thiepinyl group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
125000001806 thionaphthenyl group Chemical group 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
229940062627 tribasic potassium phosphate Drugs 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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 1
229960000281 trometamol Drugs 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
210000002845 virion Anatomy 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- 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
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
- 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
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
- 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
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Epidemiology (AREA)
Virology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Gastroenterology & Hepatology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)

CA2819894A 2010-12-16 2011-12-16 Composes antiviraux Abandoned CA2819894A1 (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US42390610P	2010-12-16	2010-12-16
US61/423,906		2010-12-16
PCT/US2011/065501 WO2012083170A1 (fr)	2010-12-16	2011-12-16	Composés antiviraux

Publications (1)

Publication Number	Publication Date
CA2819894A1 true CA2819894A1 (fr)	2012-06-21

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ID=45464913

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2819894A Abandoned CA2819894A1 (fr)	2010-12-16	2011-12-16	Composes antiviraux

Country Status (6)

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EP (1)	EP2651885A1 (fr)
JP (1)	JP5906253B2 (fr)
CN (1)	CN103354808B (fr)
CA (1)	CA2819894A1 (fr)
MX (1)	MX2013006951A (fr)
WO (1)	WO2012083170A1 (fr)

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SI3043803T1 (sl)	2013-09-11	2022-09-30	Emory University	Nukleotidne in nukleozidne sestave in njihova uporaba
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CN104672261A (zh) *	2015-02-27	2015-06-03	成都安斯利生物医药有限公司	一种制备四氢呋喃-3-硼酸频呐醇酯的方法
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GB201506660D0 (en)	2015-04-20	2015-06-03	Cellcentric Ltd	Pharmaceutical compounds
US10617675B2 (en)	2015-08-06	2020-04-14	Bristol-Myers Squibb Company	Hepatitis C virus inhibitors
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US10898504B2 (en)	2016-03-10	2021-01-26	Janssen Pharmaceutica Nv	Substituted nucleoside analogues for use as PRMT5 inhibitors
GEP20207149B (en)	2016-03-22	2020-09-10	Merck Sharp & Dohme	Allosteric modulators of nicotinic acetylcholine receptors
EP3448392A4 (fr)	2016-04-28	2020-01-15	Emory University	Compositions thérapeutiques à base de nucléotides et nucléosides contenant un alcyne et utilisations associées
EP3519413A1 (fr)	2016-10-03	2019-08-07	Janssen Pharmaceutica NV	Nouveaux analogues de carbanucléoside substitués par un système cyclique, monocyclique et bicyclique destinés à être utilisés en tant qu'inhibiteurs de prmt5
PE20191359A1 (es)	2017-02-27	2019-10-01	Janssen Pharmaceutica Nv	Uso de biomarcadores en la identificacion de pacientes con cancer que seran sensibles al tratamiento con un inhibidor de prmt5
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TWI476190B (zh) *	2009-03-30	2015-03-11	必治妥美雅史谷比公司	Ｃ型肝炎病毒抑制劑
TW201038559A (en) *	2009-04-09	2010-11-01	Bristol Myers Squibb Co	Hepatitis C virus inhibitors
PE20110679A1 (es)	2009-06-11	2011-10-20	Abbvie Bahamas Ltd	Derivados de (4-tert-butilfenil)pirrolidin-2,5-difenil como inhibidores del hcv
WO2010148006A1 (fr) *	2009-06-16	2010-12-23	Enanta Pharmaceuticals, Inc.	Inhibiteurs du virus de l'hépatite c
BR112012022311A2 (pt) *	2010-03-04	2016-08-23	Enanta Pharm Inc	agentes farmacêuticos de combinação como inibidores da replicação de hcv.

2011
- 2011-12-16 CN CN201180066574.3A patent/CN103354808B/zh active Active
- 2011-12-16 CA CA2819894A patent/CA2819894A1/fr not_active Abandoned
- 2011-12-16 EP EP11806100.1A patent/EP2651885A1/fr not_active Ceased
- 2011-12-16 JP JP2013544826A patent/JP5906253B2/ja active Active
- 2011-12-16 WO PCT/US2011/065501 patent/WO2012083170A1/fr not_active Ceased
- 2011-12-16 MX MX2013006951A patent/MX2013006951A/es not_active Application Discontinuation

Also Published As

Publication number	Publication date
MX2013006951A (es)	2013-10-03
JP5906253B2 (ja)	2016-04-20
EP2651885A1 (fr)	2013-10-23
JP2014504296A (ja)	2014-02-20
CN103354808B (zh)	2016-08-10
WO2012083170A1 (fr)	2012-06-21
CN103354808A (zh)	2013-10-16

Publication	Publication Date	Title
CN103354808B (zh)	2016-08-10	抗病毒化合物
US9394279B2 (en)	2016-07-19	Anti-viral compounds
CA2807847C (fr)	2016-09-20	Composes antiviraux
EP2367824B1 (fr)	2016-03-23	Dérivés de pyrimidine antiviraux
US8921514B2 (en)	2014-12-30	Anti-viral compounds
US20120115918A1 (en)	2012-05-10	Anti-Viral Compounds
DK2692346T3 (en)	2016-02-29	Antiviral 1-phenyl-2,5-DIBENZIMIDAZOL-5-yl-pyrrolidine derivative
AU2016238925B2 (en)	2018-12-20	Anti-viral compounds
AU2014203655B2 (en)	2016-07-07	Anti-viral compounds
HK1159619B (en)	2016-10-14	Anti-viral derivatives of pyrimidine

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