AU2011224319A1 - Compounds for the treatment of hepatitis C - Google Patents
Compounds for the treatment of hepatitis C Download PDFInfo
- Publication number
- AU2011224319A1 AU2011224319A1 AU2011224319A AU2011224319A AU2011224319A1 AU 2011224319 A1 AU2011224319 A1 AU 2011224319A1 AU 2011224319 A AU2011224319 A AU 2011224319A AU 2011224319 A AU2011224319 A AU 2011224319A AU 2011224319 A1 AU2011224319 A1 AU 2011224319A1
- Authority
- AU
- Australia
- Prior art keywords
- fluoro
- phenyl
- carboxamide
- fluorophenyl
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 100
- 208000005176 Hepatitis C Diseases 0.000 title claims description 3
- 239000000203 mixture Substances 0.000 claims abstract description 52
- 238000000034 method Methods 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 95
- 125000000217 alkyl group Chemical group 0.000 claims description 92
- 239000001257 hydrogen Substances 0.000 claims description 78
- -1 oxazolopyridinyl Chemical group 0.000 claims description 77
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 73
- 125000005843 halogen group Chemical group 0.000 claims description 42
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 33
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 29
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 28
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- 125000001188 haloalkyl group Chemical group 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 14
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 14
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000005602 azabenzimidazolyl group Chemical group 0.000 claims description 13
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 13
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 13
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 13
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000002393 azetidinyl group Chemical group 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000004193 piperazinyl group Chemical group 0.000 claims description 12
- 125000003386 piperidinyl group Chemical group 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000000719 pyrrolidinyl group Chemical group 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
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 11
- LIQVEXOTZPWBDF-UHFFFAOYSA-N 1-benzofuran-3-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=COC2=C1 LIQVEXOTZPWBDF-UHFFFAOYSA-N 0.000 claims description 10
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000005596 alkyl carboxamido group Chemical group 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000005059 halophenyl group Chemical group 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 5
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 5
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 5
- 150000003857 carboxamides Chemical class 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
- ODIOLICISOTSNS-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[[1-([1,3]oxazolo[4,5-c]pyridin-2-yl)cyclopropyl]carbamoyl]phenyl]-1-benzofuran-3-carboxamide Chemical compound C1=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=C1C(C(=CC=1)C)=CC=1C(=O)NC1(C=2OC3=CC=NC=C3N=2)CC1 ODIOLICISOTSNS-UHFFFAOYSA-N 0.000 claims description 3
- 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 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
- 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 3
- 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 3
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 3
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 125000005124 aminocycloalkyl group Chemical group 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 235000010290 biphenyl Nutrition 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- 125000005019 carboxyalkenyl group Chemical group 0.000 claims description 3
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 3
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 3
- 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 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 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 compound 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 compound 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
- 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 compound 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 2
- 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 compound 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 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
- 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
- NFWJVZCHHBVHHO-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[[1-(1,6-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=C3C=CN=CC3=CC=2)CC1 NFWJVZCHHBVHHO-UHFFFAOYSA-N 0.000 claims description 2
- WPNSUWPSDTWZLK-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[[1-(1,7-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=C3C=NC=CC3=CC=2)CC1 WPNSUWPSDTWZLK-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
- 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
- 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
- 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
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 11
- 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 claims 1
- FPZYEQKSIITTGZ-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=CC(F)=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 FPZYEQKSIITTGZ-UHFFFAOYSA-N 0.000 claims 1
- VWHLCCYGCSPGGT-UHFFFAOYSA-N 4-fluoro-2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[(1-pyrido[4,3-d]pyrimidin-2-ylcyclopropyl)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=CN=CC3=CN=2)CC1 VWHLCCYGCSPGGT-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- FZGBWOQBZBAPNC-UHFFFAOYSA-N 5-fluoro-2-(4-fluorophenyl)-n-methyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=C(F)C=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 FZGBWOQBZBAPNC-UHFFFAOYSA-N 0.000 claims 1
- 208000010710 hepatitis C virus infection Diseases 0.000 claims 1
- 241000711549 Hepacivirus C Species 0.000 abstract description 71
- 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 436
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 369
- 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 295
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 98
- 239000002904 solvent Substances 0.000 description 93
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 77
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 77
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 77
- 239000001099 ammonium carbonate Substances 0.000 description 77
- 239000007787 solid Substances 0.000 description 58
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 57
- 239000005695 Ammonium acetate Substances 0.000 description 57
- 235000019257 ammonium acetate Nutrition 0.000 description 57
- 229940043376 ammonium acetate Drugs 0.000 description 57
- 238000005481 NMR spectroscopy Methods 0.000 description 54
- 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 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-SVYQBANQSA-N oxolane-d8 Chemical compound [2H]C1([2H])OC([2H])([2H])C([2H])([2H])C1([2H])[2H] WYURNTSHIVDZCO-SVYQBANQSA-N 0.000 description 26
- 239000003112 inhibitor Substances 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
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- 238000002953 preparative HPLC Methods 0.000 description 17
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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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (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 |
|---|---|
| AU2011224319A1 true AU2011224319A1 (en) | 2012-11-01 |
Family
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Family Applications (1)
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| AU2011224319A Abandoned AU2011224319A1 (en) | 2010-03-11 | 2011-03-10 | Compounds for the treatment of hepatitis C |
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| EP (1) | EP2545051B1 (enExample) |
| JP (1) | JP5735551B2 (enExample) |
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| CN (1) | CN102892767A (enExample) |
| AU (1) | AU2011224319A1 (enExample) |
| MX (1) | MX2012010216A (enExample) |
| WO (1) | WO2011112769A1 (enExample) |
Families Citing this family (12)
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| CN103269586B (zh) | 2010-10-26 | 2015-07-15 | 普雷西迪奥制药公司 | 丙型肝炎病毒抑制剂 |
| 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 |
| US9434738B2 (en) | 2013-01-10 | 2016-09-06 | Bristol-Myers Squibb Company | Macrocyclic benzofuran and azabenzofuran compounds for the treatment of hepatitis C |
| 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 |
| US9828345B2 (en) | 2013-02-28 | 2017-11-28 | Bristol-Myers Squibb Company | Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors |
| 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 |
| US20250289826A1 (en) * | 2022-04-29 | 2025-09-18 | Tsinghua University | Plpro protein inhibitor, and preparation method and application thereof |
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| JPS57123181A (en) | 1981-01-23 | 1982-07-31 | Mitsubishi Paper Mills Ltd | Preparation of pyrazolo (1,5-a) pyridine derivative |
| CZ20012350A3 (cs) * | 1998-12-24 | 2001-09-12 | Aventis Pharmaceuticals Products Inc. | Substituované (aminoiminomethyl nebo aminomethyl) benzoheteroarylové sloučeniny |
| PE20020506A1 (es) | 2000-08-22 | 2002-07-09 | Glaxo Group Ltd | Derivados de pirazol fusionados como inhibidores de la proteina cinasa |
| EP1372642A1 (en) | 2001-03-30 | 2004-01-02 | SmithKline Beecham Corporation | Use of pyrazolopyridines as therapeutic compounds |
| AU2003290584B2 (en) | 2002-11-01 | 2009-07-16 | Viropharma Incorporated | Benzofuran compounds, compositions and methods for treatment and prophylaxis of hepatitis C viral infections and associated diseases |
| 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 |
| KR20100117073A (ko) | 2008-02-14 | 2010-11-02 | 에프. 호프만-라 로슈 아게 | 헤테로사이클릭 항바이러스 화합물 |
| WO2009137493A1 (en) | 2008-05-05 | 2009-11-12 | Wyeth | 2-substituted benzofuran compounds to treat infection with hepatitis c virus |
| WO2009137500A1 (en) | 2008-05-05 | 2009-11-12 | Wyeth | 6-substituted benzofuran compounds to treat infection with hepatitis c virus |
| US8198449B2 (en) | 2008-09-11 | 2012-06-12 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| 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 |
| 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). |
| SG183222A1 (en) | 2010-03-01 | 2012-09-27 | Plascoenergy Ip Holdings S L Bilbao Schaffhausen Branch | A lateral transfer system |
| WO2011106929A1 (en) | 2010-03-02 | 2011-09-09 | Merck Sharp & Dohme Corp. | Inhibitors of hepatitis c virus ns5b polymerase |
| TW201136919A (en) | 2010-03-02 | 2011-11-01 | Merck Sharp & Amp Dohme Corp | Inhibitors of hepatitis C virus NS5B polymerase |
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2011
- 2011-03-09 US US13/043,747 patent/US8354410B2/en active Active
- 2011-03-10 MX MX2012010216A patent/MX2012010216A/es active IP Right Grant
- 2011-03-10 KR KR1020127026466A patent/KR20130016263A/ko not_active Withdrawn
- 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 JP JP2012557233A patent/JP5735551B2/ja not_active Expired - Fee Related
- 2011-03-10 CN CN2011800236466A patent/CN102892767A/zh active Pending
- 2011-03-10 WO PCT/US2011/027823 patent/WO2011112769A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP2545051A1 (en) | 2013-01-16 |
| JP2013522224A (ja) | 2013-06-13 |
| WO2011112769A1 (en) | 2011-09-15 |
| US20120059019A1 (en) | 2012-03-08 |
| MX2012010216A (es) | 2012-10-03 |
| CN102892767A (zh) | 2013-01-23 |
| EP2545051B1 (en) | 2017-04-19 |
| US8354410B2 (en) | 2013-01-15 |
| JP5735551B2 (ja) | 2015-06-17 |
| KR20130016263A (ko) | 2013-02-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |