MX2013006828A - Compuestos antivirales. - Google Patents
Compuestos antivirales.Info
- Publication number
- MX2013006828A MX2013006828A MX2013006828A MX2013006828A MX2013006828A MX 2013006828 A MX2013006828 A MX 2013006828A MX 2013006828 A MX2013006828 A MX 2013006828A MX 2013006828 A MX2013006828 A MX 2013006828A MX 2013006828 A MX2013006828 A MX 2013006828A
- Authority
- MX
- Mexico
- Prior art keywords
- optionally substituted
- independently
- time
- halogen
- appears
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 289
- 230000000840 anti-viral effect Effects 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 31
- 208000015181 infectious disease Diseases 0.000 claims abstract description 8
- -1 phosphono, oxo, thioxo Chemical group 0.000 claims description 985
- 125000000623 heterocyclic group Chemical group 0.000 claims description 483
- 229910052736 halogen Inorganic materials 0.000 claims description 399
- 150000002367 halogens Chemical class 0.000 claims description 394
- 125000001424 substituent group Chemical group 0.000 claims description 274
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 268
- 125000000217 alkyl group Chemical group 0.000 claims description 246
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 228
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 206
- 125000002947 alkylene group Chemical group 0.000 claims description 202
- 125000004043 oxo group Chemical group O=* 0.000 claims description 202
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 184
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 176
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 169
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 138
- 125000001188 haloalkyl group Chemical group 0.000 claims description 133
- 125000004429 atom Chemical group 0.000 claims description 124
- 229910052739 hydrogen Inorganic materials 0.000 claims description 114
- 239000001257 hydrogen Substances 0.000 claims description 110
- 125000000232 haloalkynyl group Chemical group 0.000 claims description 82
- 238000006243 chemical reaction Methods 0.000 claims description 76
- 150000003839 salts Chemical class 0.000 claims description 72
- 125000006643 (C2-C6) haloalkenyl group Chemical group 0.000 claims description 66
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 46
- 125000004450 alkenylene group Chemical group 0.000 claims description 29
- 125000004419 alkynylene group Chemical group 0.000 claims description 28
- 125000002837 carbocyclic group Chemical group 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 23
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 229940124683 HCV polymerase inhibitor Drugs 0.000 claims description 3
- 125000003627 8 membered carbocyclic group Chemical group 0.000 claims description 2
- 101150030723 RIR2 gene Proteins 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims 1
- 125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 claims 1
- 229940122604 HCV protease inhibitor Drugs 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 92
- 230000010076 replication Effects 0.000 abstract description 9
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 241000711549 Hepacivirus C Species 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 137
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
- 125000001153 fluoro group Chemical group F* 0.000 description 81
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 68
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 61
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 60
- 229910001868 water Inorganic materials 0.000 description 50
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 45
- 125000001309 chloro group Chemical group Cl* 0.000 description 37
- 125000004076 pyridyl group Chemical group 0.000 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 34
- 229910052757 nitrogen Inorganic materials 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 28
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 27
- 125000000335 thiazolyl group Chemical group 0.000 description 27
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 25
- 239000003208 petroleum Substances 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- 125000003342 alkenyl group Chemical group 0.000 description 22
- 125000000262 haloalkenyl group Chemical group 0.000 description 22
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 22
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 22
- 239000002253 acid Substances 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 239000000126 substance Substances 0.000 description 21
- 229910052799 carbon Inorganic materials 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
- 239000000460 chlorine Substances 0.000 description 19
- 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 18
- 125000000753 cycloalkyl group Chemical group 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 230000000670 limiting effect Effects 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 14
- 150000002576 ketones Chemical class 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 125000005873 benzo[d]thiazolyl group Chemical group 0.000 description 13
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 13
- 125000003386 piperidinyl group Chemical group 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- GTCAXTIRRLKXRU-UHFFFAOYSA-N carbamic acid methyl ester Natural products COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 12
- 239000000651 prodrug Substances 0.000 description 12
- 229940002612 prodrug Drugs 0.000 description 12
- 125000000714 pyrimidinyl group Chemical group 0.000 description 12
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 11
- 150000003254 radicals Chemical class 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 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 10
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 10
- 125000002393 azetidinyl group Chemical group 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 125000003003 spiro group Chemical group 0.000 description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- 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 9
- 239000012453 solvate Substances 0.000 description 9
- 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 8
- 229910014585 C2-Ce Inorganic materials 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 101000977048 Streptomyces cinnamonensis Uncharacterized protein in mutB 3'region Proteins 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 8
- 238000007429 general method Methods 0.000 description 8
- 125000001183 hydrocarbyl group Chemical group 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 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
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 7
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- 150000001336 alkenes Chemical class 0.000 description 7
- 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 7
- 239000012091 fetal bovine serum Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 238000002953 preparative HPLC Methods 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 6
- 125000005647 linker group Chemical group 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 6
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 125000002971 oxazolyl group Chemical group 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 5
- 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 5
- 229910052684 Cerium Inorganic materials 0.000 description 5
- 108060001084 Luciferase Proteins 0.000 description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 150000001805 chlorine compounds Chemical class 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- PQJFJRGZSZKPTF-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O.COC(N)=O PQJFJRGZSZKPTF-UHFFFAOYSA-N 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 239000012965 benzophenone Substances 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 4
- 125000001072 heteroaryl group Chemical group 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 235000005985 organic acids Nutrition 0.000 description 4
- 235000011056 potassium acetate Nutrition 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 4
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- SEULWJSKCVACTH-UHFFFAOYSA-N 1-phenylimidazole Chemical compound C1=NC=CN1C1=CC=CC=C1 SEULWJSKCVACTH-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 101800001014 Non-structural protein 5A Proteins 0.000 description 3
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
- 108700008625 Reporter Genes Proteins 0.000 description 3
- 239000012317 TBTU Substances 0.000 description 3
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
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- 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
- 229960004295 valine Drugs 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
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- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
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- 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
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- C07D207/18—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 one double bond between ring members or between a ring member and a non-ring member
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- C—CHEMISTRY; METALLURGY
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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| PCT/US2011/065486 WO2012083164A1 (en) | 2010-12-16 | 2011-12-16 | Anti-viral compounds |
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| RU2505539C2 (ru) | 2008-12-23 | 2014-01-27 | Эбботт Лэборетриз | Антивирусные соединения |
| US8541424B2 (en) | 2008-12-23 | 2013-09-24 | Abbott Laboratories | Anti-viral compounds |
| JP5734956B2 (ja) * | 2009-04-15 | 2015-06-17 | アッヴィ・インコーポレイテッド | 抗ウィルス化合物 |
| US8552047B2 (en) | 2011-02-07 | 2013-10-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US9546160B2 (en) | 2011-05-12 | 2017-01-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
| EP2730572B1 (en) | 2011-07-09 | 2015-09-16 | Sunshine Lake Pharma Co., Ltd. | Spiro compounds as hepatitis c virus inhibitors |
| US9326973B2 (en) | 2012-01-13 | 2016-05-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| TWI610916B (zh) | 2012-08-03 | 2018-01-11 | 廣東東陽光藥業有限公司 | 作爲丙型肝炎抑制劑的橋環化合物及其在藥物中的應用 |
| CN103848818B (zh) | 2012-11-29 | 2017-03-15 | 广东东阳光药业有限公司 | 作为丙型肝炎抑制剂的并环化合物、药物组合物及它们在药物中的应用 |
| WO2014082379A1 (en) | 2012-11-29 | 2014-06-05 | Sunshine Lake Pharma Co.,Ltd. | Spiro ring compound as hepatitis c virus (hcv) inhibitor and uses thereof field of the invention |
| 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 |
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| WO2015038596A1 (en) | 2013-09-11 | 2015-03-19 | Emory University | Nucleotide and nucleoside compositions and uses related thereto |
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| WO2015110048A1 (en) | 2014-01-23 | 2015-07-30 | Sunshine Lake Pharma Co., Ltd. | Bridged ring compounds as hepatitis c virus inhibitors, pharmaceutical compositions and uses thereof |
| 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 |
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| US6037157A (en) | 1995-06-29 | 2000-03-14 | Abbott Laboratories | Method for improving pharmacokinetics |
| US7906655B2 (en) * | 2008-08-07 | 2011-03-15 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| TWI438200B (zh) * | 2009-02-17 | 2014-05-21 | 必治妥美雅史谷比公司 | C型肝炎病毒抑制劑 |
| WO2010096777A1 (en) * | 2009-02-23 | 2010-08-26 | Presidio Pharmaceuticals, Inc. | Inhibitors of hcv ns5a |
| US8796466B2 (en) * | 2009-03-30 | 2014-08-05 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| JP5734956B2 (ja) * | 2009-04-15 | 2015-06-17 | アッヴィ・インコーポレイテッド | 抗ウィルス化合物 |
| US8138215B2 (en) * | 2009-05-29 | 2012-03-20 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| JP2012533569A (ja) * | 2009-07-16 | 2012-12-27 | ヴァーテックス ファーマシューティカルズ、 インコーポレイテッド | フラビウイルス感染症を治療又は予防するためのベンゾイミダゾール類似体 |
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- 2011-12-16 MX MX2013006828A patent/MX2013006828A/es not_active Application Discontinuation
- 2011-12-16 JP JP2013544824A patent/JP2013545820A/ja active Pending
- 2011-12-16 CA CA2821973A patent/CA2821973A1/en not_active Abandoned
- 2011-12-16 EP EP11808486.2A patent/EP2651924A1/en not_active Withdrawn
- 2011-12-16 CN CN2011800677647A patent/CN103384664A/zh active Pending
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2013
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| EP2651924A1 (en) | 2013-10-23 |
| JP2013545820A (ja) | 2013-12-26 |
| WO2012083164A1 (en) | 2012-06-21 |
| CA2821973A1 (en) | 2012-06-21 |
| US20120115918A1 (en) | 2012-05-10 |
| CN103384664A (zh) | 2013-11-06 |
| US20140155382A1 (en) | 2014-06-05 |
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