KR20130016263A - C형 간염의 치료를 위한 화합물 - Google Patents
C형 간염의 치료를 위한 화합물 Download PDFInfo
- Publication number
- KR20130016263A KR20130016263A KR1020127026466A KR20127026466A KR20130016263A KR 20130016263 A KR20130016263 A KR 20130016263A KR 1020127026466 A KR1020127026466 A KR 1020127026466A KR 20127026466 A KR20127026466 A KR 20127026466A KR 20130016263 A KR20130016263 A KR 20130016263A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- fluoro
- phenyl
- hydrogen
- fluorophenyl
- 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.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 95
- 238000011282 treatment Methods 0.000 title description 9
- 208000006454 hepatitis Diseases 0.000 title description 5
- 231100000283 hepatitis Toxicity 0.000 title description 5
- 239000000203 mixture Substances 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- -1 hydroxyalkyloxy Chemical group 0.000 claims description 146
- 125000000217 alkyl group Chemical group 0.000 claims description 115
- 229910052739 hydrogen Inorganic materials 0.000 claims description 106
- 239000001257 hydrogen Substances 0.000 claims description 90
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 71
- 125000005843 halogen group Chemical group 0.000 claims description 53
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 45
- 150000002431 hydrogen Chemical class 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 39
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 38
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 37
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 27
- 125000001188 haloalkyl group Chemical group 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 125000004076 pyridyl group Chemical group 0.000 claims description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
- 125000002757 morpholinyl group Chemical group 0.000 claims description 16
- 125000004193 piperazinyl group Chemical group 0.000 claims description 16
- 125000003386 piperidinyl group Chemical group 0.000 claims description 16
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 16
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 14
- 125000005602 azabenzimidazolyl group Chemical group 0.000 claims description 14
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 14
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 14
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 14
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 13
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 13
- 125000005596 alkyl carboxamido group Chemical group 0.000 claims description 12
- 125000002393 azetidinyl group Chemical group 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 11
- 239000005977 Ethylene Substances 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 8
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 8
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000005059 halophenyl group Chemical group 0.000 claims description 8
- 125000001041 indolyl group Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
- LIQVEXOTZPWBDF-UHFFFAOYSA-N 1-benzofuran-3-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=COC2=C1 LIQVEXOTZPWBDF-UHFFFAOYSA-N 0.000 claims description 5
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000005124 aminocycloalkyl group Chemical group 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 125000005019 carboxyalkenyl group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 4
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- MKCPKOUTBSNQHU-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[[1-(1,7-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-1-benzofuran-3-carboxamide Chemical class C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1)C)=CC=1C(=O)NC1(C=2N=C3C=NC=CC3=CC=2)CC1 MKCPKOUTBSNQHU-UHFFFAOYSA-N 0.000 claims description 3
- XFURMGJPAIPHLW-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[[1-(1,8-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-1-benzofuran-3-carboxamide Chemical class C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1)C)=CC=1C(=O)NC1(C=2N=C3N=CC=CC3=CC=2)CC1 XFURMGJPAIPHLW-UHFFFAOYSA-N 0.000 claims description 3
- LBUFUCLDHUACQQ-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-5-[5-[[1-(3h-imidazo[4,5-c]pyridin-2-yl)cyclopropyl]carbamoyl]-4-methoxy-2-methylphenyl]-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1OC)C)=CC=1C(=O)NC1(C=2NC3=CC=NC=C3N=2)CC1 LBUFUCLDHUACQQ-UHFFFAOYSA-N 0.000 claims description 3
- USBRCLRFNGONSW-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[1-([1,3]oxazolo[4,5-c]pyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-n-methyl-1-benzofuran-3-carboxamide Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1OC)C)=CC=1C(=O)NC1(C=2OC3=CC=NC=C3N=2)CC1 USBRCLRFNGONSW-UHFFFAOYSA-N 0.000 claims description 2
- BTMVLRBLGJOLCL-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[[1-(1,5-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-1-benzofuran-3-carboxamide Chemical class C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1)C)=CC=1C(=O)NC1(C=2N=C3C=CC=NC3=CC=2)CC1 BTMVLRBLGJOLCL-UHFFFAOYSA-N 0.000 claims description 2
- FEGDRSNDNOWJMG-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[[1-(1,6-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-1-benzofuran-3-carboxamide Chemical class C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1)C)=CC=1C(=O)NC1(C=2N=C3C=CN=CC3=CC=2)CC1 FEGDRSNDNOWJMG-UHFFFAOYSA-N 0.000 claims description 2
- KDLPZIZHSFYXNZ-QGZVFWFLSA-N 4-fluoro-2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[(1r)-1-([1,3]oxazolo[4,5-c]pyridin-2-yl)ethyl]carbamoyl]phenyl]-n-methyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=C(C=3C(=CC(OC)=C(C(=O)N[C@H](C)C=4OC5=CC=NC=C5N=4)C=3)C)C(F)=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 KDLPZIZHSFYXNZ-QGZVFWFLSA-N 0.000 claims description 2
- KDLPZIZHSFYXNZ-KRWDZBQOSA-N 4-fluoro-2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[(1s)-1-([1,3]oxazolo[4,5-c]pyridin-2-yl)ethyl]carbamoyl]phenyl]-n-methyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=C(C=3C(=CC(OC)=C(C(=O)N[C@@H](C)C=4OC5=CC=NC=C5N=4)C=3)C)C(F)=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 KDLPZIZHSFYXNZ-KRWDZBQOSA-N 0.000 claims description 2
- POUBHPCIAURQSZ-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[1-(1,6-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1OC)C)=CC=1C(=O)NC1(C=2N=C3C=CN=CC3=CC=2)CC1 POUBHPCIAURQSZ-UHFFFAOYSA-N 0.000 claims description 2
- VWXLINAECRUPGS-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[1-(1,7-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1OC)C)=CC=1C(=O)NC1(C=2N=C3C=NC=CC3=CC=2)CC1 VWXLINAECRUPGS-UHFFFAOYSA-N 0.000 claims description 2
- NWDHPMSTICZPRW-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[1-([1,3]oxazolo[4,5-c]pyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1OC)C)=CC=1C(=O)NC1(C=2OC3=CC=NC=C3N=2)CC1 NWDHPMSTICZPRW-UHFFFAOYSA-N 0.000 claims description 2
- OWOAMPYIKJWQPD-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[1-([1,3]oxazolo[5,4-c]pyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1OC)C)=CC=1C(=O)NC1(C=2OC3=CN=CC=C3N=2)CC1 OWOAMPYIKJWQPD-UHFFFAOYSA-N 0.000 claims description 2
- OERSXZVIJIUUCT-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-5-[5-[[1-(3h-imidazo[4,5-c]pyridin-2-yl)cyclopropyl]carbamoyl]-2-methylphenyl]-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1)C)=CC=1C(=O)NC1(C=2NC3=CC=NC=C3N=2)CC1 OERSXZVIJIUUCT-UHFFFAOYSA-N 0.000 claims description 2
- RXYMNVJZUGDQRS-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[[1-(1,8-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1)C)=CC=1C(=O)NC1(C=2N=C3N=CC=CC3=CC=2)CC1 RXYMNVJZUGDQRS-UHFFFAOYSA-N 0.000 claims description 2
- YMMNOYIJDISYRV-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[[1-(1h-pyrrolo[3,2-b]pyridin-5-yl)cyclopropyl]carbamoyl]phenyl]-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1)C)=CC=1C(=O)NC1(C=2N=C3C=CNC3=CC=2)CC1 YMMNOYIJDISYRV-UHFFFAOYSA-N 0.000 claims description 2
- LEGGFTCFMDFJSS-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[[1-(1h-pyrrolo[3,2-c]pyridin-4-yl)cyclopropyl]carbamoyl]phenyl]-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1)C)=CC=1C(=O)NC1(C=2C=3C=CNC=3C=CN=2)CC1 LEGGFTCFMDFJSS-UHFFFAOYSA-N 0.000 claims description 2
- ITDFFNLBFGSOLB-MRXNPFEDSA-N 4-fluoro-5-[3-fluoro-2-methyl-5-[[(1r)-1-([1,3]oxazolo[4,5-c]pyridin-2-yl)ethyl]carbamoyl]phenyl]-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=C(C=3C(=C(F)C=C(C=3)C(=O)N[C@H](C)C=3OC4=CC=NC=C4N=3)C)C(F)=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 ITDFFNLBFGSOLB-MRXNPFEDSA-N 0.000 claims description 2
- ITDFFNLBFGSOLB-INIZCTEOSA-N 4-fluoro-5-[3-fluoro-2-methyl-5-[[(1s)-1-([1,3]oxazolo[4,5-c]pyridin-2-yl)ethyl]carbamoyl]phenyl]-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=C(C=3C(=C(F)C=C(C=3)C(=O)N[C@@H](C)C=3OC4=CC=NC=C4N=3)C)C(F)=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 ITDFFNLBFGSOLB-INIZCTEOSA-N 0.000 claims description 2
- IUDGYZRLNLWSFI-UHFFFAOYSA-N 4-fluoro-5-[3-fluoro-2-methyl-5-[[1-(1,5-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=C(F)C=1)C)=CC=1C(=O)NC1(C=2N=C3C=CC=NC3=CC=2)CC1 IUDGYZRLNLWSFI-UHFFFAOYSA-N 0.000 claims description 2
- KTERTTABBBQRRN-UHFFFAOYSA-N 4-fluoro-5-[3-fluoro-2-methyl-5-[[1-(1,6-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=C(F)C=1)C)=CC=1C(=O)NC1(C=2N=C3C=CN=CC3=CC=2)CC1 KTERTTABBBQRRN-UHFFFAOYSA-N 0.000 claims description 2
- XVGVBRGTAKDMON-UHFFFAOYSA-N 4-fluoro-5-[3-fluoro-2-methyl-5-[[1-(1,7-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=C(F)C=1)C)=CC=1C(=O)NC1(C=2N=C3C=NC=CC3=CC=2)CC1 XVGVBRGTAKDMON-UHFFFAOYSA-N 0.000 claims description 2
- GZKQEHDMQWVEQD-UHFFFAOYSA-N 4-fluoro-5-[3-fluoro-2-methyl-5-[[1-(1,8-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=C(F)C=1)C)=CC=1C(=O)NC1(C=2N=C3N=CC=CC3=CC=2)CC1 GZKQEHDMQWVEQD-UHFFFAOYSA-N 0.000 claims description 2
- ONWPMBHQPKIFRV-UHFFFAOYSA-N 4-fluoro-5-[3-fluoro-2-methyl-5-[[1-([1,3]oxazolo[4,5-c]pyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=C(F)C=1)C)=CC=1C(=O)NC1(C=2OC3=CC=NC=C3N=2)CC1 ONWPMBHQPKIFRV-UHFFFAOYSA-N 0.000 claims description 2
- FOFFRLQZFIMTJX-UHFFFAOYSA-N 4-fluoro-5-[3-fluoro-5-[[1-(3h-imidazo[4,5-c]pyridin-2-yl)cyclopropyl]carbamoyl]-2-methylphenyl]-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=C(F)C=1)C)=CC=1C(=O)NC1(C=2NC3=CC=NC=C3N=2)CC1 FOFFRLQZFIMTJX-UHFFFAOYSA-N 0.000 claims description 2
- DODKVWTYKYIFKH-UHFFFAOYSA-N 5-[2-(2-amino-2-oxoethoxy)-4-methoxy-5-[[1-(1,7-naphthyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1OC)OCC(N)=O)=CC=1C(=O)NC1(C=2N=C3C=NC=CC3=CC=2)CC1 DODKVWTYKYIFKH-UHFFFAOYSA-N 0.000 claims description 2
- 208000005176 Hepatitis C Diseases 0.000 claims description 2
- DRYPDNJBOFSJPB-UHFFFAOYSA-N CC(C(F)=CC(C(NC1(CC1)C1=NC(C=NC=C2)=C2O1)=O)=C1)=C1C1=CC=CC2=C1C(C(NC)=O)=C(C(C=C1)=CC=C1F)O2 Chemical compound CC(C(F)=CC(C(NC1(CC1)C1=NC(C=NC=C2)=C2O1)=O)=C1)=C1C1=CC=CC2=C1C(C(NC)=O)=C(C(C=C1)=CC=C1F)O2 DRYPDNJBOFSJPB-UHFFFAOYSA-N 0.000 claims 1
- 208000010710 hepatitis C virus infection Diseases 0.000 claims 1
- 241000711549 Hepacivirus C Species 0.000 abstract description 69
- 230000000694 effects Effects 0.000 abstract description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 582
- 238000004128 high performance liquid chromatography Methods 0.000 description 402
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 363
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 332
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 300
- 239000002904 solvent Substances 0.000 description 94
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 78
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 78
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 78
- 239000001099 ammonium carbonate Substances 0.000 description 78
- 239000007787 solid Substances 0.000 description 58
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 51
- 239000005695 Ammonium acetate Substances 0.000 description 51
- 235000019257 ammonium acetate Nutrition 0.000 description 51
- 229940043376 ammonium acetate Drugs 0.000 description 51
- 239000003643 water by type Substances 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
- 238000002953 preparative HPLC Methods 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 239000007821 HATU Substances 0.000 description 13
- 238000003556 assay Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 108700008776 hepatitis C virus NS-5 Proteins 0.000 description 11
- 208000015181 infectious disease Diseases 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 8
- 108010047761 Interferon-alpha Proteins 0.000 description 8
- 102000006992 Interferon-alpha Human genes 0.000 description 8
- 102000014150 Interferons Human genes 0.000 description 8
- 108010050904 Interferons Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 229940079322 interferon Drugs 0.000 description 8
- PGRSKSQLBLVNGZ-UHFFFAOYSA-N 1-([1,3]oxazolo[4,5-c]pyridin-2-yl)cyclopropan-1-amine Chemical compound N=1C2=CN=CC=C2OC=1C1(N)CC1 PGRSKSQLBLVNGZ-UHFFFAOYSA-N 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical group CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 6
- 229930105110 Cyclosporin A Natural products 0.000 description 6
- 108010036949 Cyclosporine Proteins 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 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
- 101710144111 Non-structural protein 3 Proteins 0.000 description 6
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 description 6
- 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 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 229960001265 ciclosporin Drugs 0.000 description 6
- 230000003013 cytotoxicity Effects 0.000 description 6
- 231100000135 cytotoxicity Toxicity 0.000 description 6
- LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 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 6
- 229960000329 ribavirin Drugs 0.000 description 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- XATJGCLNZVBJCC-UHFFFAOYSA-N 1-(1,8-naphthyridin-2-yl)cyclopropan-1-amine Chemical compound C=1C=C2C=CC=NC2=NC=1C1(N)CC1 XATJGCLNZVBJCC-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 239000003039 volatile agent Substances 0.000 description 5
- OHNJQDSFGBFTJT-UHFFFAOYSA-N 1-(3h-imidazo[4,5-c]pyridin-2-yl)cyclopropan-1-amine Chemical compound N=1C2=CN=CC=C2NC=1C1(N)CC1 OHNJQDSFGBFTJT-UHFFFAOYSA-N 0.000 description 4
- ZAYQIBAADVPTHC-UHFFFAOYSA-N 3-[4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]-4-methylbenzoic acid Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C1=CC(C(O)=O)=CC=C1C ZAYQIBAADVPTHC-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 4
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 101800001554 RNA-directed RNA polymerase Proteins 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 229930182912 cyclosporin Natural products 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 238000001952 enzyme assay Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 0 *c1c(*)[o]c2c1nccc2 Chemical compound *c1c(*)[o]c2c1nccc2 0.000 description 3
- RSHFFOXJYREUSO-UHFFFAOYSA-N 1-(1,7-naphthyridin-2-yl)cyclopropan-1-amine Chemical compound C=1C=C2C=CN=CC2=NC=1C1(N)CC1 RSHFFOXJYREUSO-UHFFFAOYSA-N 0.000 description 3
- KHINKCGJKZSHAJ-UHFFFAOYSA-N 1-(phenylmethoxycarbonylamino)cyclopropane-1-carboxylic acid Chemical compound C=1C=CC=CC=1COC(=O)NC1(C(=O)O)CC1 KHINKCGJKZSHAJ-UHFFFAOYSA-N 0.000 description 3
- UTMCCHYUGCVEPX-UHFFFAOYSA-N 1-pyrido[4,3-d]pyrimidin-2-ylcyclopropan-1-amine Chemical compound N=1C=C2C=NC=CC2=NC=1C1(N)CC1 UTMCCHYUGCVEPX-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 108010006035 Metalloproteases Proteins 0.000 description 3
- 102000005741 Metalloproteases Human genes 0.000 description 3
- 108060004795 Methyltransferase Proteins 0.000 description 3
- 101800001020 Non-structural protein 4A Proteins 0.000 description 3
- 101800001019 Non-structural protein 4B Proteins 0.000 description 3
- 101800001014 Non-structural protein 5A Proteins 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 108010022999 Serine Proteases Proteins 0.000 description 3
- 102000012479 Serine Proteases Human genes 0.000 description 3
- 101800001838 Serine protease/helicase NS3 Proteins 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
- 238000013459 approach Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- HHIFWQTTYNUXAD-UHFFFAOYSA-N benzyl n-[1-(3h-imidazo[4,5-c]pyridin-2-yl)cyclopropyl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)NC1(C=2NC3=CC=NC=C3N=2)CC1 HHIFWQTTYNUXAD-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 238000002165 resonance energy transfer Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- BAOKISIAKJBFRC-RXMQYKEDSA-N (1r)-1-([1,3]oxazolo[4,5-c]pyridin-2-yl)ethanamine Chemical compound N1=CC=C2OC([C@H](N)C)=NC2=C1 BAOKISIAKJBFRC-RXMQYKEDSA-N 0.000 description 2
- BAOKISIAKJBFRC-YFKPBYRVSA-N (1s)-1-([1,3]oxazolo[4,5-c]pyridin-2-yl)ethanamine Chemical compound N1=CC=C2OC([C@@H](N)C)=NC2=C1 BAOKISIAKJBFRC-YFKPBYRVSA-N 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- LNTPUKHIWAQWJN-UHFFFAOYSA-N 1-(1,6-naphthyridin-2-yl)cyclopropan-1-amine Chemical compound C=1C=C2C=NC=CC2=NC=1C1(N)CC1 LNTPUKHIWAQWJN-UHFFFAOYSA-N 0.000 description 2
- UBCHPRBFMUDMNC-UHFFFAOYSA-N 1-(1-adamantyl)ethanamine Chemical compound C1C(C2)CC3CC2CC1(C(N)C)C3 UBCHPRBFMUDMNC-UHFFFAOYSA-N 0.000 description 2
- PAJPWUMXBYXFCZ-UHFFFAOYSA-N 1-aminocyclopropanecarboxylic acid Chemical compound OC(=O)C1(N)CC1 PAJPWUMXBYXFCZ-UHFFFAOYSA-N 0.000 description 2
- SMPCGXWMVFUYSK-UHFFFAOYSA-N 1-pyrido[3,4-d]pyrimidin-2-ylcyclopropan-1-amine Chemical compound N=1C=C2C=CN=CC2=NC=1C1(N)CC1 SMPCGXWMVFUYSK-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- CCDUGSFHJUWUPF-UHFFFAOYSA-N 3-[2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]-4-methylbenzoic acid Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C1=CC(C(O)=O)=CC=C1C CCDUGSFHJUWUPF-UHFFFAOYSA-N 0.000 description 2
- WTDWVLJJJOTABN-UHFFFAOYSA-N 5-cyclopropyl-2-(4-fluorophenyl)-6-[(2-hydroxyethyl)(methylsulfonyl)amino]-n-methyl-1-benzofuran-3-carboxamide Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC(N(CCO)S(C)(=O)=O)=C1C1CC1 WTDWVLJJJOTABN-UHFFFAOYSA-N 0.000 description 2
- 108020005544 Antisense RNA Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
- 241000710781 Flaviviridae Species 0.000 description 2
- 101710200424 Inosine-5'-monophosphate dehydrogenase Proteins 0.000 description 2
- 102100040018 Interferon alpha-2 Human genes 0.000 description 2
- 108010079944 Interferon-alpha2b Proteins 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- 102000004889 Interleukin-6 Human genes 0.000 description 2
- 108090001005 Interleukin-6 Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 108010076039 Polyproteins Proteins 0.000 description 2
- 108010052090 Renilla Luciferases Proteins 0.000 description 2
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 2
- 230000005867 T cell response Effects 0.000 description 2
- 239000012317 TBTU Substances 0.000 description 2
- 108700022715 Viral Proteases Proteins 0.000 description 2
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 2
- 229960003805 amantadine Drugs 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000011210 chromatographic step Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000003184 complementary RNA Substances 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 2
- 229960002751 imiquimod Drugs 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000002348 inosinate dehydrogenase inhibitor Substances 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 108700027921 interferon tau Proteins 0.000 description 2
- 229940117681 interleukin-12 Drugs 0.000 description 2
- 229940100601 interleukin-6 Drugs 0.000 description 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
- 229960000274 lysozyme Drugs 0.000 description 2
- 235000010335 lysozyme Nutrition 0.000 description 2
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 229960000888 rimantadine Drugs 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 238000000825 ultraviolet detection Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- BSVHTRRLCAVQCZ-JDEXMCKMSA-N (2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-1-[(2s)-2-[[(2s)-1-[(2s)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-carboxypropanoyl]pyrrolidine-2-carbonyl]amino]propanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]pyrro Chemical compound C([C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(O)=O)C1=CC=C(O)C=C1 BSVHTRRLCAVQCZ-JDEXMCKMSA-N 0.000 description 1
- JXDNUMOTWHZSCB-XMTZKCFKSA-N (3s)-3-acetamido-4-[[(2s)-3-carboxy-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1r)-1-carboxy-2-sulfanylethyl]carbamoyl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(O)=O JXDNUMOTWHZSCB-XMTZKCFKSA-N 0.000 description 1
- TXMALZHJXRWAOX-UHFFFAOYSA-N 1-(1,5-naphthyridin-2-yl)cyclopropan-1-amine Chemical compound C=1C=C2N=CC=CC2=NC=1C1(N)CC1 TXMALZHJXRWAOX-UHFFFAOYSA-N 0.000 description 1
- PQQHFZUFZOLWSK-UHFFFAOYSA-N 1-([1,3]oxazolo[5,4-c]pyridin-2-yl)cyclopropan-1-amine Chemical compound N=1C2=CC=NC=C2OC=1C1(N)CC1 PQQHFZUFZOLWSK-UHFFFAOYSA-N 0.000 description 1
- DSKCOVBHIFAJRI-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopropane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NC1(C(O)=O)CC1 DSKCOVBHIFAJRI-UHFFFAOYSA-N 0.000 description 1
- VLPFHGWGUYXKRJ-UHFFFAOYSA-N 1-benzofuran;trifluoromethanesulfonic acid Chemical compound OS(=O)(=O)C(F)(F)F.C1=CC=C2OC=CC2=C1 VLPFHGWGUYXKRJ-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- WHGVTQGMNBUPBK-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=CC=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 WHGVTQGMNBUPBK-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- OIIBRAGQGFLUFI-UHFFFAOYSA-N 3-amino-1h-pyridin-4-one Chemical compound NC1=CNC=CC1=O OIIBRAGQGFLUFI-UHFFFAOYSA-N 0.000 description 1
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 1
- JDINFTIKEGYLID-UHFFFAOYSA-N 3-fluoro-5-[2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]-4-methylbenzoic acid Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C1=CC(C(O)=O)=CC(F)=C1C JDINFTIKEGYLID-UHFFFAOYSA-N 0.000 description 1
- SDVJAMIUDMRVSN-UHFFFAOYSA-N 3-fluoro-5-[4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]-4-methylbenzoic acid Chemical compound FC1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C1=CC(C(O)=O)=CC(F)=C1C SDVJAMIUDMRVSN-UHFFFAOYSA-N 0.000 description 1
- WCKQPPQRFNHPRJ-UHFFFAOYSA-N 4-[[4-(dimethylamino)phenyl]diazenyl]benzoic acid Chemical compound C1=CC(N(C)C)=CC=C1N=NC1=CC=C(C(O)=O)C=C1 WCKQPPQRFNHPRJ-UHFFFAOYSA-N 0.000 description 1
- GTPZHMGXKZIHKW-UHFFFAOYSA-N 4-aminopyridine-3-carbaldehyde Chemical compound NC1=CC=NC=C1C=O GTPZHMGXKZIHKW-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- SJISCEAZUHNOMD-UHFFFAOYSA-N 4-phenylcyclohexan-1-amine Chemical compound C1CC(N)CCC1C1=CC=CC=C1 SJISCEAZUHNOMD-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- SJQRQOKXQKVJGJ-UHFFFAOYSA-N 5-(2-aminoethylamino)naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(NCCN)=CC=CC2=C1S(O)(=O)=O SJQRQOKXQKVJGJ-UHFFFAOYSA-N 0.000 description 1
- RONRXPUCBNYDIU-UHFFFAOYSA-N 5-[2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]-2-methoxy-4-methylbenzoic acid Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C1=CC(C(O)=O)=C(OC)C=C1C RONRXPUCBNYDIU-UHFFFAOYSA-N 0.000 description 1
- PFKQJQLANCGSEV-UHFFFAOYSA-N 5-[3-fluoro-2-methyl-5-[[1-([1,3]oxazolo[4,5-c]pyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=C(F)C=1)C)=CC=1C(=O)NC1(C=2OC3=CC=NC=C3N=2)CC1 PFKQJQLANCGSEV-UHFFFAOYSA-N 0.000 description 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 1
- 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 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- DXCLCZPSQROVTG-UHFFFAOYSA-N C1(CC1)NC(OC(NC1=C(C=NC=C1)N)=O)=O Chemical compound C1(CC1)NC(OC(NC1=C(C=NC=C1)N)=O)=O DXCLCZPSQROVTG-UHFFFAOYSA-N 0.000 description 1
- ANVUCPZCQYCSTF-UHFFFAOYSA-N CN(CCCC1)S1(=O)=O Chemical compound CN(CCCC1)S1(=O)=O ANVUCPZCQYCSTF-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- HHYVVMQXNVIJPD-UHFFFAOYSA-N Cc(c(-c(c([F]N1)c23)ccc2[o]c(-c(cc2)ccc2F)c3C1=O)cc(C(NC1(CC1)c1nc2ccncc2cc1)=O)c1)c1F Chemical compound Cc(c(-c(c([F]N1)c23)ccc2[o]c(-c(cc2)ccc2F)c3C1=O)cc(C(NC1(CC1)c1nc2ccncc2cc1)=O)c1)c1F HHYVVMQXNVIJPD-UHFFFAOYSA-N 0.000 description 1
- HDQVIEFKNARPEJ-UHFFFAOYSA-N Cc(ccc(C(NC1(CC1)c1nc2cnccc2cc1)=O)c1)c1-c(ccc1c2c3c(-c(cc4)ccc4F)[o]1)c2[F]NC3=O Chemical compound Cc(ccc(C(NC1(CC1)c1nc2cnccc2cc1)=O)c1)c1-c(ccc1c2c3c(-c(cc4)ccc4F)[o]1)c2[F]NC3=O HDQVIEFKNARPEJ-UHFFFAOYSA-N 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
- 238000010485 C−C bond formation reaction Methods 0.000 description 1
- 101710118188 DNA-binding protein HU-alpha Proteins 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229940122604 HCV protease inhibitor Drugs 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 101710144128 Non-structural protein 2 Proteins 0.000 description 1
- 101710199667 Nuclear export protein Proteins 0.000 description 1
- 102000008021 Nucleoside-Triphosphatase Human genes 0.000 description 1
- 108010075285 Nucleoside-Triphosphatase Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010077495 Peptide oostatic hormone Proteins 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 108090000944 RNA Helicases Proteins 0.000 description 1
- 102000004409 RNA Helicases Human genes 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- BFPLMTPHDFFMTG-UHFFFAOYSA-N [1,3]oxazolo[5,4-b]pyridine Chemical compound C1=CN=C2OC=NC2=C1 BFPLMTPHDFFMTG-UHFFFAOYSA-N 0.000 description 1
- QKQPBGKAOCILPJ-UHFFFAOYSA-N [F].[F].[F].[F].N1(N=NC2=C1C=CC=C2)OC(=[N+](C)C)N(C)C Chemical compound [F].[F].[F].[F].N1(N=NC2=C1C=CC=C2)OC(=[N+](C)C)N(C)C QKQPBGKAOCILPJ-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- OYTKINVCDFNREN-UHFFFAOYSA-N amifampridine Chemical compound NC1=CC=NC=C1N OYTKINVCDFNREN-UHFFFAOYSA-N 0.000 description 1
- 229960004012 amifampridine Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- MJSHDCCLFGOEIK-UHFFFAOYSA-N benzyl (2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCC1=CC=CC=C1 MJSHDCCLFGOEIK-UHFFFAOYSA-N 0.000 description 1
- BFSYSRIIAXMGNB-UHFFFAOYSA-N benzyl n-[1-[(3-aminopyridin-4-yl)carbamoyl]cyclopropyl]carbamate Chemical compound NC1=CN=CC=C1NC(=O)C1(NC(=O)OCC=2C=CC=CC=2)CC1 BFSYSRIIAXMGNB-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000010170 biological method Methods 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- 229940045348 brown mixture Drugs 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- RZZFOJKGQIYSBE-UHFFFAOYSA-N cyclopropyl carbamate Chemical compound NC(=O)OC1CC1 RZZFOJKGQIYSBE-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 239000013003 healing agent Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- VHHHONWQHHHLTI-UHFFFAOYSA-N hexachloroethane Chemical compound ClC(Cl)(Cl)C(Cl)(Cl)Cl VHHHONWQHHHLTI-UHFFFAOYSA-N 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
- 150000003903 lactic acid esters Chemical class 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000003468 luciferase reporter gene assay Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000011045 prefiltration Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- MKIPOIJQGKXCFG-UHFFFAOYSA-N tert-butyl n-(1-acetylcyclopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1(C(=O)C)CC1 MKIPOIJQGKXCFG-UHFFFAOYSA-N 0.000 description 1
- QRCDHLUHNINTQN-UHFFFAOYSA-N tert-butyl n-(1-carbamimidoylcyclopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1(C(N)=N)CC1 QRCDHLUHNINTQN-UHFFFAOYSA-N 0.000 description 1
- ICGSPEGXFWRTBV-UHFFFAOYSA-N tert-butyl n-[1-(1,8-naphthyridin-2-yl)cyclopropyl]carbamate Chemical compound C=1C=C2C=CC=NC2=NC=1C1(NC(=O)OC(C)(C)C)CC1 ICGSPEGXFWRTBV-UHFFFAOYSA-N 0.000 description 1
- LCWCTOTUCCNHIW-UHFFFAOYSA-N tert-butyl n-[1-[methoxy(methyl)carbamoyl]cyclopropyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1(C(=O)N(C)OC)CC1 LCWCTOTUCCNHIW-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 239000000080 wetting agent Substances 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
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- 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
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31276810P | 2010-03-11 | 2010-03-11 | |
| US61/312,768 | 2010-03-11 | ||
| US13/043,747 US8354410B2 (en) | 2010-03-11 | 2011-03-09 | Compounds for the treatment of hepatitis C |
| US13/043,747 | 2011-03-09 | ||
| PCT/US2011/027823 WO2011112769A1 (en) | 2010-03-11 | 2011-03-10 | Compounds for the treatment of hepatitis c |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20130016263A true KR20130016263A (ko) | 2013-02-14 |
Family
ID=43903118
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020127026466A Withdrawn KR20130016263A (ko) | 2010-03-11 | 2011-03-10 | C형 간염의 치료를 위한 화합물 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US8354410B2 (enExample) |
| EP (1) | EP2545051B1 (enExample) |
| JP (1) | JP5735551B2 (enExample) |
| KR (1) | KR20130016263A (enExample) |
| CN (1) | CN102892767A (enExample) |
| AU (1) | AU2011224319A1 (enExample) |
| MX (1) | MX2012010216A (enExample) |
| WO (1) | WO2011112769A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112013009789A2 (pt) | 2010-10-26 | 2016-07-19 | Presidio Pharmaceuticals Inc | inibidores do vírus da hepatite c |
| US8507683B2 (en) | 2010-12-09 | 2013-08-13 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US9303020B2 (en) | 2012-02-08 | 2016-04-05 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| EP2943496B1 (en) * | 2013-01-10 | 2017-09-06 | Bristol-Myers Squibb Company | Macrocyclic benzofuran and azabenzofuran compounds for the treatment of hepatitis c |
| JP6423372B2 (ja) | 2013-02-28 | 2018-11-14 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 強力なｒｏｃｋ１およびｒｏｃｋ２阻害剤としてのフェニルピラゾール誘導体 |
| TW201444798A (zh) | 2013-02-28 | 2014-12-01 | 必治妥美雅史谷比公司 | 作爲強效ｒｏｃｋ１及ｒｏｃｋ２抑制劑之苯基吡唑衍生物 |
| WO2014205594A1 (en) * | 2013-06-24 | 2014-12-31 | Merck Sharp & Dohme Corp. | Substituted benzofuran compounds and methods of use thereof for treatment of viral diseases |
| WO2014205592A1 (en) * | 2013-06-24 | 2014-12-31 | Merck Sharp & Dohme Corp. | Heterocyclic compounds and methods of use thereof for treatment of hepatitis c |
| EP3119769A1 (en) * | 2014-03-21 | 2017-01-25 | Bristol-Myers Squibb Pharma Company | Cyanoamino (aza)benzofuran compounds for the treatment of hepatitis c |
| CN105732602B (zh) * | 2015-09-23 | 2017-04-19 | 常州寅盛药业有限公司 | 作为ns4b抑制剂的苯并呋喃类似物 |
| CN114957110A (zh) * | 2021-02-26 | 2022-08-30 | 清华大学 | 一种抗病毒化合物及其制备方法和应用 |
| EP4509494A1 (en) * | 2022-04-29 | 2025-02-19 | Tsinghua University | Plpro protein inhibitor, and preparation method and application thereof |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57123181A (en) | 1981-01-23 | 1982-07-31 | Mitsubishi Paper Mills Ltd | Preparation of pyrazolo (1,5-a) pyridine derivative |
| EE200100341A (et) * | 1998-12-24 | 2002-12-16 | Aventis Pharmaceuticals Products Inc. | Asendatud (aminoiminometüül- või aminometüül)bensoheteroarüülühendid, nende kasutamine ja farmatseutiline kompositsioon |
| PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| JP2004525150A (ja) | 2001-03-30 | 2004-08-19 | スミスクライン ビーチャム コーポレーション | 治療用化合物としてのピラゾロピリジン類の使用 |
| HN2003000348A (es) | 2002-11-01 | 2008-10-14 | Viropharma Inc | Compuestos de benzofurano, composiciones y metodos para tratamiento y profilaxis de infeccion virales de hepatitis c y enfermedades asociadas. |
| US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| MX2009008439A (es) * | 2007-02-12 | 2009-08-13 | Intermune Inc | Nuevos inhibidores de la replicacion del virus de hepatitis c. |
| GB0707000D0 (en) | 2007-04-12 | 2007-05-30 | Istituto Di Ricerche D Biolog | Antiviral agents |
| CN101910145A (zh) | 2008-02-14 | 2010-12-08 | 弗·哈夫曼-拉罗切有限公司 | 抗病毒的杂环化合物 |
| WO2009137500A1 (en) | 2008-05-05 | 2009-11-12 | Wyeth | 6-substituted benzofuran compounds to treat infection with hepatitis c virus |
| WO2009137493A1 (en) | 2008-05-05 | 2009-11-12 | Wyeth | 2-substituted benzofuran compounds to treat infection with hepatitis c virus |
| US8048887B2 (en) | 2008-09-11 | 2011-11-01 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US7994171B2 (en) * | 2008-09-11 | 2011-08-09 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| US8198449B2 (en) | 2008-09-11 | 2012-06-12 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| AR080185A1 (es) | 2010-02-19 | 2012-03-21 | Glaxo Group Ltd | Derivados de acido boronico y benzofurano, composiciones farmaceuticas que los contienen,y uso de los mismos en el tratamiento y/o prevencion de infecciones virales, en particular por el virus de hepatitis c(hcv). |
| CA2756746C (en) | 2010-03-01 | 2012-10-23 | Plasco Energy Group Inc. | A lateral transfer system |
| AR080433A1 (es) | 2010-03-02 | 2012-04-11 | Merck Sharp & Dohme | Derivados de benzofurancarboxamidas utiles para tratar o prevenir infecciones por vhc y composiciones farmaceuticas que los contienen. |
| WO2011106929A1 (en) | 2010-03-02 | 2011-09-09 | Merck Sharp & Dohme Corp. | Inhibitors of hepatitis c virus ns5b polymerase |
-
2011
- 2011-03-09 US US13/043,747 patent/US8354410B2/en active Active
- 2011-03-10 EP EP11708667.8A patent/EP2545051B1/en not_active Not-in-force
- 2011-03-10 AU AU2011224319A patent/AU2011224319A1/en not_active Abandoned
- 2011-03-10 MX MX2012010216A patent/MX2012010216A/es active IP Right Grant
- 2011-03-10 JP JP2012557233A patent/JP5735551B2/ja not_active Expired - Fee Related
- 2011-03-10 KR KR1020127026466A patent/KR20130016263A/ko not_active Withdrawn
- 2011-03-10 WO PCT/US2011/027823 patent/WO2011112769A1/en not_active Ceased
- 2011-03-10 CN CN2011800236466A patent/CN102892767A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20120059019A1 (en) | 2012-03-08 |
| EP2545051B1 (en) | 2017-04-19 |
| WO2011112769A1 (en) | 2011-09-15 |
| MX2012010216A (es) | 2012-10-03 |
| CN102892767A (zh) | 2013-01-23 |
| US8354410B2 (en) | 2013-01-15 |
| JP5735551B2 (ja) | 2015-06-17 |
| JP2013522224A (ja) | 2013-06-13 |
| EP2545051A1 (en) | 2013-01-16 |
| AU2011224319A1 (en) | 2012-11-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20130016263A (ko) | C형 간염의 치료를 위한 화합물 | |
| JP5406837B2 (ja) | Ｃ型肝炎を治療するための四環系化合物 | |
| JP5416710B2 (ja) | シクロプロピル縮合インドロベンズアゼピンｈｃｖｎｓ５ｂ阻害剤 | |
| KR20110056537A (ko) | Ｃ형 간염의 치료를 위한 화합물 | |
| WO2007143521A1 (en) | Cyclopropyl fused indolobenzazepine hcv inhibitors | |
| KR20090008344A (ko) | 시클로프로필 융합된 인돌로벤즈아제핀 ｈｃｖ ｎｓ5ｂ 억제제 | |
| KR20080102161A (ko) | Ｈｃｖ ｎｓ5ｂ 억제제 | |
| WO2007140254A2 (en) | Cyclopropyl fused indolobenzazepine hcv ns5b inhibitors | |
| WO2008109584A1 (en) | Hcv ns5b inhibitors | |
| JP2010521484A (ja) | Ｃ型肝炎の治療のための化合物 | |
| JP2012519173A (ja) | シクロプロピル縮合インドロベンズアゼピンｈｃｖｎｓ５ｂ阻害剤 | |
| EP2276764B1 (en) | Compounds for the treatment of hepatitis c | |
| MX2010011921A (es) | Compuestos para el tratamiento de la hepatitis c. | |
| KR20130008570A (ko) | Ｃ형 간염의 치료를 위한 피라졸로피리다진 유도체 | |
| KR20100126560A (ko) | 피롤리딘 융합된 인돌로벤자디아제핀 ｈｃｖ ｎｓ5ｂ 억제제 | |
| JP2016505011A (ja) | Ｃ型肝炎の治療用の大環状ベンゾフランおよびアザベンゾフラン化合物 | |
| KR20100124848A (ko) | 방향족 헤테로시클릭 융합된 인돌로벤자디아제핀 ｈｃｖ ｎｓ5ｂ 억제제 | |
| CN101981038B (zh) | 二氧戊环和二氧戊环酮稠合的吲哚并苯并二氮杂*hcv ns5b抑制剂 | |
| WO2016133970A1 (en) | Benzofurans substituted with primary benzamide as hcv inhibitors | |
| AU2009228214B2 (en) | Dioxolane and dioxolanone fused indolobenzadiazepine HCV NS5B inhibitors | |
| AU2009228325B2 (en) | Pyrrolidine fused indolobenzadiazepine HCV NS5B inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20121010 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |