UA79834C2 - Benzofuran compounds, compositions and methods for treatment and prophylaxis of hepatitis c viral infections and associated diseases - Google Patents
Benzofuran compounds, compositions and methods for treatment and prophylaxis of hepatitis c viral infections and associated diseases Download PDFInfo
- Publication number
- UA79834C2 UA79834C2 UAA200505142A UA2005005142A UA79834C2 UA 79834 C2 UA79834 C2 UA 79834C2 UA A200505142 A UAA200505142 A UA A200505142A UA 2005005142 A UA2005005142 A UA 2005005142A UA 79834 C2 UA79834 C2 UA 79834C2
- Authority
- UA
- Ukraine
- Prior art keywords
- fluorophenyl
- carboxylic acid
- methylamide
- benzofuran
- isopropoxy
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 132
- 238000011282 treatment Methods 0.000 title claims abstract description 40
- 201000010099 disease Diseases 0.000 title claims abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 18
- 208000036142 Viral infection Diseases 0.000 title claims abstract description 16
- 230000009385 viral infection Effects 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title claims description 54
- 150000001907 coumarones Chemical class 0.000 title abstract 2
- 238000011321 prophylaxis Methods 0.000 title abstract 2
- 208000006454 hepatitis Diseases 0.000 title description 4
- 231100000283 hepatitis Toxicity 0.000 title description 2
- -1 hydroxy, hydroxy Chemical group 0.000 claims description 803
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 757
- BENJFDPHDCGUAQ-UHFFFAOYSA-N 1-benzofuran-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=COC2=C1 BENJFDPHDCGUAQ-UHFFFAOYSA-N 0.000 claims description 270
- 150000001875 compounds Chemical class 0.000 claims description 174
- 150000003254 radicals Chemical class 0.000 claims description 128
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 103
- 239000002253 acid Substances 0.000 claims description 92
- 125000000217 alkyl group Chemical group 0.000 claims description 75
- 125000001424 substituent group Chemical group 0.000 claims description 68
- 125000003545 alkoxy group Chemical group 0.000 claims description 57
- 229910052736 halogen Inorganic materials 0.000 claims description 56
- 150000002367 halogens Chemical class 0.000 claims description 55
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 48
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical class NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 43
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 32
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 28
- 150000002431 hydrogen Chemical class 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 26
- 108010050904 Interferons Proteins 0.000 claims description 25
- 102000014150 Interferons Human genes 0.000 claims description 25
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 150000007513 acids Chemical class 0.000 claims description 24
- 150000003857 carboxamides Chemical class 0.000 claims description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
- 229940079322 interferon Drugs 0.000 claims description 20
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 125000003277 amino group Chemical group 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 17
- 125000003368 amide group Chemical group 0.000 claims description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 208000015181 infectious disease Diseases 0.000 claims description 14
- 230000002265 prevention Effects 0.000 claims description 14
- 229940124530 sulfonamide Drugs 0.000 claims description 14
- 150000003456 sulfonamides Chemical class 0.000 claims description 14
- 235000011054 acetic acid Nutrition 0.000 claims description 13
- 125000001769 aryl amino group Chemical group 0.000 claims description 12
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 11
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 10
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 10
- 125000004494 ethyl ester group Chemical group 0.000 claims description 10
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical group [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical class [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 150000004702 methyl esters Chemical class 0.000 claims description 9
- 208000005176 Hepatitis C Diseases 0.000 claims description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- VBRUONUESYTIDA-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-(methanesulfonamido)-n-methyl-5-propan-2-yloxy-1-benzofuran-3-carboxamide Chemical compound O1C2=CC(NS(C)(=O)=O)=C(OC(C)C)C=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 VBRUONUESYTIDA-UHFFFAOYSA-N 0.000 claims description 7
- CQHPNIAOVFEVJE-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-2-(4-fluorophenyl)-5-methoxy-1-benzofuran-3-carboxylic acid Chemical compound COC1=CC=2C(C(O)=O)=C(C=3C=CC(F)=CC=3)OC=2C=C1C=1C(C)=NOC=1C CQHPNIAOVFEVJE-UHFFFAOYSA-N 0.000 claims description 7
- 241000282414 Homo sapiens Species 0.000 claims description 7
- 239000013543 active substance Substances 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 239000003443 antiviral agent Substances 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 208000010710 hepatitis C virus infection Diseases 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 7
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 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 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 229960000329 ribavirin Drugs 0.000 claims 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 claims description 6
- XOSIWYSOMSELMK-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-morpholin-4-yl-5-propan-2-yloxy-1-benzofuran-3-carboxylic acid Chemical compound CC(C)OC1=CC=2C(C(O)=O)=C(C=3C=CC(F)=CC=3)OC=2C=C1N1CCOCC1 XOSIWYSOMSELMK-UHFFFAOYSA-N 0.000 claims description 5
- JWUAQCLETXKURH-UHFFFAOYSA-N 5-ethoxy-2-(4-fluorophenyl)-n-methyl-6-[methyl(methylsulfonyl)amino]-1-benzofuran-3-carboxamide Chemical compound O1C=2C=C(N(C)S(C)(=O)=O)C(OCC)=CC=2C(C(=O)NC)=C1C1=CC=C(F)C=C1 JWUAQCLETXKURH-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 5
- ALJUZFCNVDCBNZ-UHFFFAOYSA-N 2-(3,4-difluorophenyl)-5-methoxy-n-methyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=C(OC)C=C2C(C(=O)NC)=C1C1=CC=C(F)C(F)=C1 ALJUZFCNVDCBNZ-UHFFFAOYSA-N 0.000 claims description 4
- UFKWZRJTFCEGBY-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-methoxy-n-methyl-6-morpholin-4-yl-1-benzofuran-3-carboxamide Chemical compound COC=1C=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=1N1CCOCC1 UFKWZRJTFCEGBY-UHFFFAOYSA-N 0.000 claims description 4
- FPHFLXXZZSTNJG-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-(methanesulfonamido)-5-propan-2-yloxy-1-benzofuran-3-carboxylic acid Chemical compound O1C=2C=C(NS(C)(=O)=O)C(OC(C)C)=CC=2C(C(O)=O)=C1C1=CC=C(F)C=C1 FPHFLXXZZSTNJG-UHFFFAOYSA-N 0.000 claims description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 4
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 125000000565 sulfonamide group Chemical group 0.000 claims description 4
- VEOLBNFJJNOOBD-UHFFFAOYSA-N 2-(4-fluorophenyl)-n,5-dimethyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=C(C)C=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 VEOLBNFJJNOOBD-UHFFFAOYSA-N 0.000 claims description 3
- IMGXNJXLAOFSTA-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-6-morpholin-4-yl-5-phenylmethoxy-1-benzofuran-3-carboxamide Chemical compound C=1C=CC=CC=1COC=1C=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=1N1CCOCC1 IMGXNJXLAOFSTA-UHFFFAOYSA-N 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- ZRJPGUSCWPLKHI-UHFFFAOYSA-N 5-cyano-n-methyl-2-phenyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=C(C#N)C=C2C(C(=O)NC)=C1C1=CC=CC=C1 ZRJPGUSCWPLKHI-UHFFFAOYSA-N 0.000 claims description 3
- KOKLRUYYSXFBBS-UHFFFAOYSA-N 6-(3,5-dimethyl-1,2-oxazol-4-yl)-2-(4-fluorophenyl)-5-methoxy-n-methyl-1-benzofuran-3-carboxamide Chemical compound COC=1C=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=1C=1C(C)=NOC=1C KOKLRUYYSXFBBS-UHFFFAOYSA-N 0.000 claims description 3
- 108060003951 Immunoglobulin Proteins 0.000 claims description 3
- 239000003242 anti bacterial agent Substances 0.000 claims description 3
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 3
- 230000000692 anti-sense effect Effects 0.000 claims description 3
- 229940088710 antibiotic agent Drugs 0.000 claims description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 102000018358 immunoglobulin Human genes 0.000 claims description 3
- 229940072221 immunoglobulins Drugs 0.000 claims description 3
- 239000002955 immunomodulating agent Substances 0.000 claims description 3
- 229940121354 immunomodulator Drugs 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000003729 nucleotide group Chemical group 0.000 claims description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 3
- 229960004889 salicylic acid Drugs 0.000 claims description 3
- 150000003384 small molecules Chemical class 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 2
- JXDFDXUQASSKBK-UHFFFAOYSA-N 2-(3,4-difluorophenyl)-5-methoxy-1-benzofuran-3-carboxylic acid Chemical compound OC(=O)C=1C2=CC(OC)=CC=C2OC=1C1=CC=C(F)C(F)=C1 JXDFDXUQASSKBK-UHFFFAOYSA-N 0.000 claims description 2
- ZFTWRTZSFOXIGP-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-(2-methoxyethylamino)-n-methyl-5-propan-2-yloxy-1-benzofuran-3-carboxamide Chemical compound O1C2=CC(NCCOC)=C(OC(C)C)C=C2C(C(=O)NC)=C1C1=CC=C(F)C=C1 ZFTWRTZSFOXIGP-UHFFFAOYSA-N 0.000 claims description 2
- UINGXHFXRZNZDE-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-[5-(hydroxymethyl)-1,2-oxazol-3-yl]-5-methoxy-n-methyl-1-benzofuran-3-carboxamide Chemical compound COC=1C=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=1C=1C=C(CO)ON=1 UINGXHFXRZNZDE-UHFFFAOYSA-N 0.000 claims description 2
- QQLKMSVDKFETIG-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-[5-(hydroxymethyl)-1,2-oxazol-3-yl]-5-propan-2-yloxy-1-benzofuran-3-carboxylic acid Chemical class CC(C)OC1=CC=2C(C(O)=O)=C(C=3C=CC(F)=CC=3)OC=2C=C1C=1C=C(CO)ON=1 QQLKMSVDKFETIG-UHFFFAOYSA-N 0.000 claims description 2
- XAKPZSLAGNKHOQ-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-6-[methylsulfonyl(1,3-thiazol-4-ylmethyl)amino]-5-propan-2-yloxy-1-benzofuran-3-carboxamide Chemical compound CC(C)OC=1C=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=1N(S(C)(=O)=O)CC1=CSC=N1 XAKPZSLAGNKHOQ-UHFFFAOYSA-N 0.000 claims description 2
- VUZVNMMDUYNULQ-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-6-morpholin-4-yl-5-(1,3-thiazol-2-ylmethoxy)-1-benzofuran-3-carboxamide Chemical compound N=1C=CSC=1COC=1C=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=1N1CCOCC1 VUZVNMMDUYNULQ-UHFFFAOYSA-N 0.000 claims description 2
- MLLBWJNVZMWGMO-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-6-morpholin-4-yl-5-(1,3-thiazol-4-ylmethoxy)-1-benzofuran-3-carboxamide Chemical compound C=1SC=NC=1COC=1C=C2C(C(=O)NC)=C(C=3C=CC(F)=CC=3)OC2=CC=1N1CCOCC1 MLLBWJNVZMWGMO-UHFFFAOYSA-N 0.000 claims description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- YJUHZLKKVSPRSG-UHFFFAOYSA-N 2-phenyl-5-(2,2,2-trifluoroethoxy)-1-benzofuran-3-carboxylic acid Chemical compound O1C2=CC=C(OCC(F)(F)F)C=C2C(C(=O)O)=C1C1=CC=CC=C1 YJUHZLKKVSPRSG-UHFFFAOYSA-N 0.000 claims description 2
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 2
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 2
- AJIXLXCXSOYEGV-UHFFFAOYSA-N 5-methoxy-n,4-dimethyl-2-phenyl-1-benzofuran-3-carboxamide Chemical compound O1C2=CC=C(OC)C(C)=C2C(C(=O)NC)=C1C1=CC=CC=C1 AJIXLXCXSOYEGV-UHFFFAOYSA-N 0.000 claims description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 2
- GWPLPBRIXMCFAO-UHFFFAOYSA-N OC(=O)C=1C2=CC(OC(C)C)=CC=C2OC=1C1=CC=NC=C1 Chemical compound OC(=O)C=1C2=CC(OC(C)C)=CC=C2OC=1C1=CC=NC=C1 GWPLPBRIXMCFAO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000005336 allyloxy group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- QPJDMGCKMHUXFD-UHFFFAOYSA-N cyanogen chloride Chemical compound ClC#N QPJDMGCKMHUXFD-UHFFFAOYSA-N 0.000 claims description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 2
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
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- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
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- LALRXNPLTWZJIJ-UHFFFAOYSA-N triethylborane Chemical group CCB(CC)CC LALRXNPLTWZJIJ-UHFFFAOYSA-N 0.000 description 1
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- CWZAHASBSZJRDV-UHFFFAOYSA-N trimethyl(2-pyridin-4-ylethynyl)silane Chemical compound C[Si](C)(C)C#CC1=CC=NC=C1 CWZAHASBSZJRDV-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D307/83—Oxygen atoms
-
- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
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- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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Applications Claiming Priority (5)
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US51594403P | 2003-10-30 | 2003-10-30 | |
PCT/US2003/034962 WO2004041201A2 (fr) | 2002-11-01 | 2003-10-31 | Composes de benzofurane, compositions et methodes utilisees pour le traitement et la prophylaxie des infections virales induites par l'hepatite c et des maladies associees |
Publications (1)
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UA79834C2 true UA79834C2 (en) | 2007-07-25 |
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UAA200505142A UA79834C2 (en) | 2002-11-01 | 2003-10-31 | Benzofuran compounds, compositions and methods for treatment and prophylaxis of hepatitis c viral infections and associated diseases |
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US (3) | US7265152B2 (fr) |
EP (1) | EP1581207A4 (fr) |
JP (1) | JP4537315B2 (fr) |
KR (1) | KR20050065661A (fr) |
CN (1) | CN1731993A (fr) |
AU (1) | AU2003290584B2 (fr) |
BR (1) | BR0315937A (fr) |
CA (1) | CA2504344A1 (fr) |
EA (1) | EA009943B1 (fr) |
EC (1) | ECSP055801A (fr) |
HN (1) | HN2003000348A (fr) |
IL (1) | IL168282A (fr) |
MX (1) | MXPA05004608A (fr) |
NI (1) | NI200500090A (fr) |
NO (1) | NO20052071L (fr) |
NZ (1) | NZ539727A (fr) |
UA (1) | UA79834C2 (fr) |
WO (1) | WO2004041201A2 (fr) |
ZA (1) | ZA200503501B (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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RU2672257C2 (ru) * | 2014-09-26 | 2018-11-13 | Чанчжоу Иньшэн Фармасьютикал Ко., Лтд. | Аналог бензофурана в качестве ингибитора ns4b |
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Families Citing this family (115)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MY140680A (en) | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
EA009943B1 (ru) * | 2002-11-01 | 2008-04-28 | Вирофарма Инкорпорейтед | Соединения бензофурана, композиции и способы лечения и профилактики инфекций, вызванных вирусом гепатита с, и связанных с ним заболеваний |
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WO2006010008A1 (fr) * | 2004-06-22 | 2006-01-26 | Vertex Pharmaceuticals Incorporated | Dérivés hétérocycliques pour moduler les canaux calciques |
CA2606195C (fr) | 2005-05-02 | 2015-03-31 | Merck And Co., Inc. | Inhibiteurs de la protease ns3 du vhc |
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BRPI0614205A2 (pt) | 2005-08-01 | 2016-11-22 | Merck & Co Inc | composto, composição farmacêutica, e, uso de composto |
WO2007059422A2 (fr) * | 2005-11-10 | 2007-05-24 | Wyeth | Formulations pharmaceutiques contenant le 5-cyclopropyl-2(4-fluorophenyl)-6-[(2-hydroxyethyl)(methylsulfonyl)amino]-n-methyl-1-benzofuran-3-carboxamide et procede de preparation de celles-ci |
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EP1981523A2 (fr) * | 2006-02-09 | 2008-10-22 | Schering Corporation | Nouvelles combinaisons d'inhibiteurs du vhc et méthodes |
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GB0612423D0 (en) | 2006-06-23 | 2006-08-02 | Angeletti P Ist Richerche Bio | Therapeutic agents |
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US20080182895A1 (en) * | 2006-08-25 | 2008-07-31 | Howe Anita Y M | Identification and characterization of hcv replicon variants with reduced susceptibility to hcv-796, and methods related thereto |
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CA2667165A1 (fr) | 2006-10-24 | 2008-05-02 | Merck & Co., Inc. | Inhibiteurs de la protease hcv ns3 |
WO2008051514A2 (fr) | 2006-10-24 | 2008-05-02 | Merck & Co., Inc. | Inhibiteurs de la protéase ns3 du hcv |
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GB0625349D0 (en) | 2006-12-20 | 2007-01-31 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
JP2010513450A (ja) | 2006-12-20 | 2010-04-30 | イステイチユート・デイ・リチエルケ・デイ・ビオロジア・モレコラーレ・ピ・アンジエレツテイ・エツセ・ピー・アー | 抗ウイルス性インドール |
CN101687789A (zh) * | 2007-02-12 | 2010-03-31 | 因特蒙公司 | C型肝炎病毒复制的新颖抑制剂 |
US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
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MX2009011930A (es) | 2007-05-04 | 2009-11-18 | Vertex Pharma | Terapia de combinacion para el tratamiento de infeccion de virus de hepatitis c. |
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NZ586231A (en) * | 2007-12-21 | 2012-12-21 | Avila Therapeutics Inc | HCV protease inhibitors comprising a functionalised proline derivative |
US8309685B2 (en) * | 2007-12-21 | 2012-11-13 | Celgene Avilomics Research, Inc. | HCV protease inhibitors and uses thereof |
US8293705B2 (en) | 2007-12-21 | 2012-10-23 | Avila Therapeutics, Inc. | HCV protease inhibitors and uses thereof |
AU2008340261C1 (en) * | 2007-12-21 | 2015-12-10 | Celgene Avilomics Research, Inc. | HCV protease inhibitors and uses thereof |
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AU2009241445A1 (en) | 2008-04-28 | 2009-11-05 | Merck Sharp & Dohme Corp. | HCV NS3 protease inhibitors |
WO2009137493A1 (fr) * | 2008-05-05 | 2009-11-12 | Wyeth | Composés benzofurane substitués en position 2 pour traiter une infection par le virus de l'hépatite c |
WO2009137500A1 (fr) * | 2008-05-05 | 2009-11-12 | Wyeth | Composés de benzofurane substitués en 6 pour traiter l’infection par le virus de l’hépatite c |
US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
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US8188137B2 (en) | 2008-08-15 | 2012-05-29 | Avila Therapeutics, Inc. | HCV protease inhibitors and uses thereof |
US7994171B2 (en) | 2008-09-11 | 2011-08-09 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
US8293909B2 (en) * | 2008-09-11 | 2012-10-23 | 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 |
US8198449B2 (en) * | 2008-09-11 | 2012-06-12 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
WO2010075517A2 (fr) | 2008-12-23 | 2010-07-01 | Pharmasset, Inc. | Analogues de nucléoside |
CL2009002207A1 (es) | 2008-12-23 | 2011-02-18 | Gilead Pharmasset Llc | Compuestos derivados de 3-hidroxi-5-(9h-purin-9-il)tetrahidrofuran-2-il, inhibidor de la replicacion de arn viral dependiente de arn; composicion farmaceutica; uso para el tratamiento de hepatitis c. |
SG172363A1 (en) | 2008-12-23 | 2011-07-28 | Pharmasset Inc | Synthesis of purine nucleosides |
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US8143244B2 (en) | 2009-02-26 | 2012-03-27 | Bristol-Myers Squibb Company | Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors |
US8618076B2 (en) | 2009-05-20 | 2013-12-31 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
TWI583692B (zh) | 2009-05-20 | 2017-05-21 | 基利法瑪席特有限責任公司 | 核苷磷醯胺 |
WO2011014487A1 (fr) | 2009-07-30 | 2011-02-03 | Merck Sharp & Dohme Corp. | Inhibiteurs de protéase ns3 du virus de l'hépatite c |
US8324212B2 (en) | 2010-02-25 | 2012-12-04 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
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 (fr) * | 2010-03-02 | 2011-09-09 | Merck Sharp & Dohme Corp. | Inhibiteurs de polymérase du virus de l'hépatite c ns5b |
WO2011106986A1 (fr) * | 2010-03-02 | 2011-09-09 | Merck Sharp & Dohme Corp. | Inhibiteurs de polymérase du virus de l'hépatite c ns5b |
JP5572725B2 (ja) * | 2010-03-10 | 2014-08-13 | ブリストル−マイヤーズ スクイブ カンパニー | C型肝炎の処置のための化合物 |
US8354410B2 (en) * | 2010-03-11 | 2013-01-15 | Bristol-Meyers Squibb Company | Compounds for the treatment of hepatitis C |
WO2011112191A1 (fr) | 2010-03-11 | 2011-09-15 | Bristol-Myers Squibb Company | Composés utilisables pour le traitement de l'hépatite c |
UY33310A (es) | 2010-03-31 | 2011-10-31 | Pharmasset Inc | Sintesis estereoselectiva de activos que contienen fosforo |
AP3515A (en) | 2010-03-31 | 2016-01-11 | Gilead Pharmasset Llc | Nucleoside phosphoramidates |
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EP2630128A1 (fr) | 2010-10-20 | 2013-08-28 | Biota Scientific Management Pty Ltd | Inhibiteurs d'une polymérase virale |
MX2013004655A (es) * | 2010-10-26 | 2013-08-27 | Presidio Pharmaceuticals Inc | Inhibidores del virus de la hepatitis c. |
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CA2822357A1 (fr) | 2010-12-22 | 2012-06-28 | Abbvie Inc. | Inhibiteurs de l'hepatite c et leurs utilisations |
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WO2013025975A1 (fr) * | 2011-08-17 | 2013-02-21 | Glaxosmithkline Llc | Traitements combinés pour l'hépatite c |
CN103929965B (zh) * | 2011-08-17 | 2016-08-17 | 葛兰素史克有限责任公司 | 治疗方法 |
JP6367712B2 (ja) * | 2011-08-19 | 2018-08-01 | グラクソ グループ リミテッドGlaxo Group Limited | C型肝炎ウイルス感染の治療のためのベンゾフラン化合物 |
WO2013033900A1 (fr) * | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Composés hétérocycliques tétracycliques et leurs procédés d'utilisation pour le traitement de maladies virales |
WO2013033901A1 (fr) * | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Dérivés benzofuranes substitués par un hétérocycle et leurs procédés d'utilisation pour le traitement de maladies virales |
WO2013033899A1 (fr) * | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Composés benzofuranes substitués et leur procédés d'utilisation pour le traitement de maladies virales |
UA116087C2 (uk) | 2011-09-16 | 2018-02-12 | Гіліад Фармассет Елелсі | Композиція для лікування вірусу гепатиту c |
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KR20200106088A (ko) | 2012-01-16 | 2020-09-10 | 엘라자베스 맥켄나 | 간 질환들 및 장애들의 치료를 위한 조성물들 및 방법들 |
US9303020B2 (en) | 2012-02-08 | 2016-04-05 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
WO2013148620A1 (fr) | 2012-03-27 | 2013-10-03 | Bristol-Myers Squibb Company | Dérivés de benzofuranne pour le traitement de l'hépatite c |
US9120775B2 (en) | 2012-04-11 | 2015-09-01 | Biota Scientific Management Pty Ltd | Viral polymerase inhibitors |
WO2014047588A1 (fr) | 2012-09-21 | 2014-03-27 | Elizabeth Mckenna | Compositions à base d'oligonucléotides cpg naturels et leurs utilisations thérapeutiques |
EP2933254B1 (fr) | 2012-12-14 | 2021-01-20 | Korea Research Institute of Chemical Technology | Nouveau composé, sel pharmaceutiquement acceptable ou isomère optique de celui-ci, procédé de préparation de celui-ci et composition pharmaceutique pour la prévention ou le traitement de maladies virales contenant celui-ci en tant que principe actif |
JP2016505011A (ja) | 2013-01-10 | 2016-02-18 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 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 |
KR20140119012A (ko) | 2013-01-31 | 2014-10-08 | 길리어드 파마셋 엘엘씨 | 두 항바이러스 화합물의 병용 제형물 |
WO2014121416A1 (fr) * | 2013-02-07 | 2014-08-14 | Merck Sharp & Dohme Corp. | Composés hétérocycliques tétracycliques et leurs procédés d'utilisation pour le traitement de l'hépatite c |
WO2014121417A1 (fr) | 2013-02-07 | 2014-08-14 | Merck Sharp & Dohme Corp. | Composés hétérocycliques tétracycliques et leurs procédés d'utilisation pour le traitement de l'hépatite c |
WO2014121418A1 (fr) | 2013-02-07 | 2014-08-14 | Merck Sharp & Dohme Corp. | Composés hétérocycliques tétracycliques et leurs méthodes d'utilisation pour le traitement de l'hépatite c |
US8962651B2 (en) | 2013-03-13 | 2015-02-24 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
CN103288805B (zh) * | 2013-03-13 | 2016-09-14 | 天津药物研究院有限公司 | 含有苯并呋喃的嘧啶类化合物及其制备方法和用途 |
EP2970174B1 (fr) | 2013-03-14 | 2017-05-03 | Bristol-Myers Squibb Company | Furanes fusionnes pour le traitement de l'hépatite c |
WO2014205592A1 (fr) | 2013-06-24 | 2014-12-31 | Merck Sharp & Dohme Corp. | Composés hétérocycliques et leurs procédés d'utilisation pour le traitement de l'hépatite c |
WO2014205593A1 (fr) * | 2013-06-24 | 2014-12-31 | Merck Sharp & Dohme Corp. | Composés de benzofurane substitués et leurs méthodes d'utilisation pour le traitement de maladies virales |
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US9630896B2 (en) | 2013-11-22 | 2017-04-25 | Tansna Therapeutics, Inc. | 2,5-dialkyl-4-H/halo/ether-phenol compounds |
WO2015088958A1 (fr) * | 2013-12-13 | 2015-06-18 | Bristol-Myers Squibb Company | Nouveau composé destiné au traitement de l'hépatite c |
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EP3119769A1 (fr) * | 2014-03-21 | 2017-01-25 | Bristol-Myers Squibb Pharma Company | Composés cyanoamino (aza)benzofurane pour le traitement de l'hépatite c |
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EP3154963A1 (fr) | 2014-06-11 | 2017-04-19 | Bristol-Myers Squibb Company | Composés 2-phényl (aza)benzofurane substitué pour le traitement de l'hépatite c |
EP3180346A1 (fr) | 2014-08-05 | 2017-06-21 | Bristol-Myers Squibb Company | Composés furopyridine pour le traitement de l'hépatite c |
US10202403B2 (en) | 2014-10-02 | 2019-02-12 | Bristol-Myers Squibb Company | Macrocyclic benzofuran compounds for the treatment of hepatitis C |
WO2016133948A1 (fr) | 2015-02-19 | 2016-08-25 | Bristol-Myers Squibb Company | Composés de benzofurane pour le traitement de l'hépatite c |
WO2016133970A1 (fr) | 2015-02-19 | 2016-08-25 | Bristol-Myers Squibb Company | Benzofuranes substitués par un benzamide primaire utilisés comme inhibiteurs du vhc |
US10087167B2 (en) | 2015-02-19 | 2018-10-02 | Bristol-Myers Squibb Company | Benzofurans substituted with secondary benzamide as HCV inhibitors |
WO2016133961A1 (fr) | 2015-02-19 | 2016-08-25 | Bristol-Myers Squibb Company | Benzofuranes substitués par des benzamides secondaires bicycliques en tant qu'inhibiteurs du vhc |
US10570108B2 (en) | 2015-02-19 | 2020-02-25 | Bristol-Myers Squibb Company | Substituted benzofuran compounds for the treatment of hepatitis C |
TWI731854B (zh) * | 2015-03-23 | 2021-07-01 | 美商共結晶製藥公司 | C型肝炎病毒聚合酶之抑制劑 |
WO2016172498A1 (fr) * | 2015-04-22 | 2016-10-27 | The Texas A&M University System | Dérivés de benzofurane substitués utilisés comme nouveaux agents anti-mycobactériens |
CN106278831B (zh) * | 2015-06-10 | 2019-08-09 | 联化科技(台州)有限公司 | 2-苯乙基苯酚衍生物及其中间体的制备方法及中间体 |
KR102527786B1 (ko) | 2016-04-07 | 2023-04-28 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | 단백질 조정제로서 유용한 헤테로시클릭 아미드 |
CN111285844B (zh) * | 2020-02-24 | 2022-08-12 | 河南师范大学 | 具有生物活性的苯并噻吩取代酰胺类化合物及其合成方法和应用 |
AR129420A1 (es) * | 2022-05-25 | 2024-08-21 | Univ Leuven Kath | Nuevos derivados para tratar trastornos mediados por trpm3 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2608598B1 (fr) * | 1986-12-23 | 1989-04-14 | Roussel Uclaf | Nouveaux derives de l'indane, leur procede de preparation et les nouveaux intermediaires ainsi obtenus, leur application comme medicaments et les compositions les renfermant |
US4988727A (en) * | 1986-12-23 | 1991-01-29 | Roussel Uclaf | N-(aminoindanyl)amides as analgesics and antiarrhythmics |
EP0532466A3 (en) * | 1991-09-12 | 1993-06-16 | Ciba-Geigy Ag | Derivatives of 5-amino-4-hydroxy-hexanoic acid and their therapeutical use |
US5721233A (en) * | 1992-04-06 | 1998-02-24 | Merrell Pharmaceuticals Inc. | Derivatives of 2,3-dihydro benzofuranols |
JP3246741B2 (ja) * | 1992-04-06 | 2002-01-15 | メレルダウファーマス−ティカルズ インコーポレイテッド | 2,3−ジヒドロベンゾフラノールの新規な誘導体及びその製法 |
WO2001006763A1 (fr) * | 1999-07-16 | 2001-01-25 | Silicon Film Technologies, Inc. | Cartouche reglable pour film electronique |
US6414013B1 (en) * | 2000-06-19 | 2002-07-02 | Pharmacia & Upjohn S.P.A. | Thiophene compounds, process for preparing the same, and pharmaceutical compositions containing the same background of the invention |
EP1472241A4 (fr) * | 2002-02-07 | 2005-06-29 | Galileo Pharmaceuticals Inc | Derives de benzofurane cytoprotecteurs |
US6653346B1 (en) * | 2002-02-07 | 2003-11-25 | Galileo Pharmaceuticals, Inc. | Cytoprotective benzofuran derivatives |
EA009943B1 (ru) * | 2002-11-01 | 2008-04-28 | Вирофарма Инкорпорейтед | Соединения бензофурана, композиции и способы лечения и профилактики инфекций, вызванных вирусом гепатита с, и связанных с ним заболеваний |
-
2003
- 2003-10-31 EA EA200500723A patent/EA009943B1/ru not_active IP Right Cessation
- 2003-10-31 WO PCT/US2003/034962 patent/WO2004041201A2/fr active Application Filing
- 2003-10-31 EP EP03783119A patent/EP1581207A4/fr not_active Withdrawn
- 2003-10-31 CN CNA2003801078840A patent/CN1731993A/zh active Pending
- 2003-10-31 JP JP2005502256A patent/JP4537315B2/ja not_active Expired - Fee Related
- 2003-10-31 US US10/699,336 patent/US7265152B2/en not_active Expired - Fee Related
- 2003-10-31 NZ NZ539727A patent/NZ539727A/en unknown
- 2003-10-31 UA UAA200505142A patent/UA79834C2/uk unknown
- 2003-10-31 MX MXPA05004608A patent/MXPA05004608A/es active IP Right Grant
- 2003-10-31 BR BR0315937-0A patent/BR0315937A/pt not_active IP Right Cessation
- 2003-10-31 HN HN2003000348A patent/HN2003000348A/es unknown
- 2003-10-31 KR KR1020057007719A patent/KR20050065661A/ko active IP Right Grant
- 2003-10-31 CA CA002504344A patent/CA2504344A1/fr not_active Abandoned
- 2003-10-31 AU AU2003290584A patent/AU2003290584B2/en not_active Expired - Fee Related
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2005
- 2005-04-27 NO NO20052071A patent/NO20052071L/no not_active Application Discontinuation
- 2005-04-27 NI NI200500090A patent/NI200500090A/es unknown
- 2005-04-27 IL IL168282A patent/IL168282A/en not_active IP Right Cessation
- 2005-05-03 ZA ZA200503501A patent/ZA200503501B/en unknown
- 2005-05-19 EC EC2005005801A patent/ECSP055801A/es unknown
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2007
- 2007-05-24 US US11/753,145 patent/US7666863B2/en not_active Expired - Fee Related
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2009
- 2009-07-09 US US12/499,876 patent/US20090281336A1/en not_active Abandoned
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2574591C2 (ru) * | 2011-06-16 | 2016-02-10 | Корея Рисерч Инститьют Оф Кемикал Текнолоджи | Производное инданона, его фармацевтически приемлемая соль или энантиомер, способ его получения и содержащая его фармацевтическая композиция для профилактики или лечения вирусного заболевания |
RU2672257C2 (ru) * | 2014-09-26 | 2018-11-13 | Чанчжоу Иньшэн Фармасьютикал Ко., Лтд. | Аналог бензофурана в качестве ингибитора ns4b |
US12083092B2 (en) | 2020-04-20 | 2024-09-10 | Novartis Ag | Antiviral 1,3-di-oxo-indene compounds |
Also Published As
Publication number | Publication date |
---|---|
HN2003000348A (es) | 2008-10-14 |
US7666863B2 (en) | 2010-02-23 |
US7265152B2 (en) | 2007-09-04 |
EA009943B1 (ru) | 2008-04-28 |
EP1581207A2 (fr) | 2005-10-05 |
ECSP055801A (es) | 2005-11-22 |
MXPA05004608A (es) | 2005-09-20 |
JP4537315B2 (ja) | 2010-09-01 |
WO2004041201A3 (fr) | 2004-08-19 |
ZA200503501B (en) | 2006-10-25 |
KR20050065661A (ko) | 2005-06-29 |
WO2004041201A2 (fr) | 2004-05-21 |
EA200500723A1 (ru) | 2006-02-24 |
BR0315937A (pt) | 2005-09-13 |
IL168282A (en) | 2009-11-18 |
AU2003290584A1 (en) | 2004-06-07 |
NO20052071L (no) | 2005-05-23 |
JP2006510736A (ja) | 2006-03-30 |
NZ539727A (en) | 2008-01-31 |
CN1731993A (zh) | 2006-02-08 |
AU2003290584B2 (en) | 2009-07-16 |
US20070231318A1 (en) | 2007-10-04 |
NI200500090A (es) | 2006-05-25 |
EP1581207A4 (fr) | 2007-07-25 |
US20090281336A1 (en) | 2009-11-12 |
CA2504344A1 (fr) | 2004-05-21 |
US20040162318A1 (en) | 2004-08-19 |
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