BRPI0918174A2 - composto que apresenta atividade contra o vírus da hepatite c (hcv), sua composição e seu uso - Google Patents
composto que apresenta atividade contra o vírus da hepatite c (hcv), sua composição e seu uso Download PDFInfo
- Publication number
- BRPI0918174A2 BRPI0918174A2 BRPI0918174A BRPI0918174A BRPI0918174A2 BR PI0918174 A2 BRPI0918174 A2 BR PI0918174A2 BR PI0918174 A BRPI0918174 A BR PI0918174A BR PI0918174 A BRPI0918174 A BR PI0918174A BR PI0918174 A2 BRPI0918174 A2 BR PI0918174A2
- Authority
- BR
- Brazil
- Prior art keywords
- alkyl
- phenyl
- amino
- substituted
- hydroxyalkyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 178
- 239000000203 mixture Substances 0.000 title claims abstract description 111
- 241000711549 Hepacivirus C Species 0.000 title abstract description 77
- 230000000694 effects Effects 0.000 title abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 238000011282 treatment Methods 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 771
- 125000000217 alkyl group Chemical group 0.000 claims description 283
- -1 hydroxyalkyloxy Chemical group 0.000 claims description 188
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 164
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 101
- 239000001257 hydrogen Substances 0.000 claims description 92
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 91
- 125000003545 alkoxy group Chemical group 0.000 claims description 67
- 125000001424 substituent group Chemical group 0.000 claims description 66
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 62
- 150000002431 hydrogen Chemical class 0.000 claims description 60
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 56
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 54
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 49
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 46
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 46
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 44
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 43
- 125000004076 pyridyl group Chemical group 0.000 claims description 42
- 125000003342 alkenyl group Chemical group 0.000 claims description 38
- 125000001188 haloalkyl group Chemical group 0.000 claims description 38
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 28
- 125000002757 morpholinyl group Chemical group 0.000 claims description 27
- 125000004193 piperazinyl group Chemical group 0.000 claims description 26
- 125000003386 piperidinyl group Chemical group 0.000 claims description 26
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 26
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 25
- 125000002393 azetidinyl group Chemical group 0.000 claims description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 24
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 22
- 125000002883 imidazolyl group Chemical group 0.000 claims description 21
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 20
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 20
- 125000000335 thiazolyl group Chemical group 0.000 claims description 20
- 125000005596 alkyl carboxamido group Chemical group 0.000 claims description 19
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 17
- 125000003282 alkyl amino group Chemical group 0.000 claims description 16
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
- 125000001425 triazolyl group Chemical group 0.000 claims description 16
- 125000002541 furyl group Chemical group 0.000 claims description 14
- 125000001041 indolyl group Chemical group 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 12
- 125000001544 thienyl group Chemical group 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 125000005059 halophenyl group Chemical group 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 9
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 9
- 125000005019 carboxyalkenyl group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 8
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 8
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 8
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000002971 oxazolyl group Chemical group 0.000 claims description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 235000010290 biphenyl Nutrition 0.000 claims description 6
- 239000004305 biphenyl Substances 0.000 claims description 6
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 6
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000005188 oxoalkyl group Chemical group 0.000 claims description 6
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 5
- 239000005977 Ethylene Substances 0.000 claims description 5
- 125000005518 carboxamido group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 5
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 5
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 4
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 4
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 4
- 125000005095 alkynylaminocarbonyl group Chemical group 0.000 claims description 4
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 4
- 125000004990 dihydroxyalkyl group Chemical group 0.000 claims description 4
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 4
- 125000006542 morpholinylalkyl group Chemical group 0.000 claims description 4
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000005124 aminocycloalkyl group Chemical group 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 3
- ACOYATSVVMMLAU-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-[3-[[1-(4-fluorophenyl)cyclopropyl]carbamoyl]phenyl]-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)=C1C(C=1)=CC=CC=1C(=O)NC1(C=2C=CC(F)=CC=2)CC1 ACOYATSVVMMLAU-UHFFFAOYSA-N 0.000 claims description 2
- PAUHELJSJSVRPR-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-[2-hydroxyethyl(methylsulfonyl)amino]-n-methyl-5-[3-(2-phenylpropan-2-ylcarbamoyl)phenyl]-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)=C1C(C=1)=CC=CC=1C(=O)NC(C)(C)C1=CC=CC=C1 PAUHELJSJSVRPR-UHFFFAOYSA-N 0.000 claims description 2
- TVJAATHIDLAWME-UHFFFAOYSA-N 2-(4-fluorophenyl)-6-[2-hydroxyethyl(methylsulfonyl)amino]-n-methyl-5-[3-[(1-phenylcyclopropyl)carbamoyl]phenyl]-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)=C1C(C=1)=CC=CC=1C(=O)NC1(C=2C=CC=CC=2)CC1 TVJAATHIDLAWME-UHFFFAOYSA-N 0.000 claims description 2
- 208000005176 Hepatitis C Diseases 0.000 claims description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- JFSPBVWPKOEZCB-UHFFFAOYSA-N fenfuram Chemical group O1C=CC(C(=O)NC=2C=CC=CC=2)=C1C JFSPBVWPKOEZCB-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 34
- ALTJZVSOJAJNKQ-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[(1-pyrimidin-2-ylcyclopropyl)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=2N=CC=CN=2)CC1 ALTJZVSOJAJNKQ-UHFFFAOYSA-N 0.000 claims 1
- YTVCSPYLAXQBIC-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[1-(3-methyl-1,2,4-oxadiazol-5-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=2ON=C(C)N=2)CC1 YTVCSPYLAXQBIC-UHFFFAOYSA-N 0.000 claims 1
- ISVFDRSHXWVAKJ-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[1-(5-methyl-1,2,4-oxadiazol-3-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=2N=C(C)ON=2)CC1 ISVFDRSHXWVAKJ-UHFFFAOYSA-N 0.000 claims 1
- IHTWITBFSTYMHG-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[1-(5-methyl-1,3-oxazol-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=2OC(C)=CN=2)CC1 IHTWITBFSTYMHG-UHFFFAOYSA-N 0.000 claims 1
- JXYCXMPXYPIJBO-UHFFFAOYSA-N 2-(4-fluorophenyl)-5-[4-methoxy-2-methyl-5-[[1-(5-methyl-1,3-thiazol-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=2SC(C)=CN=2)CC1 JXYCXMPXYPIJBO-UHFFFAOYSA-N 0.000 claims 1
- LUIDEMBRIXHMJX-UHFFFAOYSA-N 2-(4-fluorophenyl)-n-methyl-5-[2-methyl-5-[(1-pyrimidin-2-ylcyclopropyl)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=CC=CN=2)CC1 LUIDEMBRIXHMJX-UHFFFAOYSA-N 0.000 claims 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- C07D307/84—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- 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
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- A—HUMAN NECESSITIES
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- 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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- 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
- C07D405/10—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 linked by a carbon chain containing aromatic rings
-
- 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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—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
- C07D413/10—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 carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—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
- 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
-
- 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
- C07D417/02—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
- C07D417/10—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 carbon chain containing aromatic rings
-
- 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
- C07D417/02—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
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- Life Sciences & Earth Sciences (AREA)
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- Oncology (AREA)
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| WO2010043721A1 (en) | 2008-10-17 | 2010-04-22 | Oryzon Genomics, S.A. | Oxidase inhibitors and their use |
| US8399494B2 (en) * | 2008-10-30 | 2013-03-19 | Merck Sharp & Dohme Corp. | 2,5-disubstituted phenyl carboxamide orexin receptor antagonists |
| US8993808B2 (en) | 2009-01-21 | 2015-03-31 | Oryzon Genomics, S.A. | Phenylcyclopropylamine derivatives and their medical use |
| CN102574778B (zh) * | 2009-06-22 | 2015-01-07 | 弗·哈夫曼-拉罗切有限公司 | 新的联苯基和苯基-吡啶酰胺类化合物 |
| BR112012006572A2 (pt) | 2009-09-25 | 2016-04-26 | Oryzon Genomics Sa | inibidores de demetilase-1 de lisina específicos e seu uso |
| WO2011042217A1 (en) | 2009-10-09 | 2011-04-14 | Oryzon Genomics S.A. | Substituted heteroaryl- and aryl- cyclopropylamine acetamides and their use |
| WO2011106573A2 (en) | 2010-02-24 | 2011-09-01 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for diseases and disorders associated with hepadnaviridae |
| US9616058B2 (en) | 2010-02-24 | 2017-04-11 | Oryzon Genomics, S.A. | Potent selective LSD1 inhibitors and dual LSD1/MAO-B inhibitors for antiviral use |
| 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. |
| US8354410B2 (en) * | 2010-03-11 | 2013-01-15 | Bristol-Meyers Squibb Company | Compounds for the treatment of hepatitis C |
| JP2013522192A (ja) * | 2010-03-11 | 2013-06-13 | 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 |
| AU2011244325B2 (en) | 2010-04-19 | 2015-12-17 | Oryzon Genomics S.A. | Lysine specific demethylase-1 inhibitors and their use |
| US8324239B2 (en) | 2010-04-21 | 2012-12-04 | Novartis Ag | Furopyridine compounds and uses thereof |
| US8877795B2 (en) | 2010-05-07 | 2014-11-04 | The Board Of Trustees Of The Leland Stanford Junior University | Identification of stabilizers of multimeric proteins |
| US8445497B2 (en) * | 2010-06-30 | 2013-05-21 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| CA2806008C (en) | 2010-07-29 | 2019-07-09 | Oryzon Genomics S.A. | Arylcyclopropylamine based demethylase inhibitors of lsd1 and their medical use |
| WO2012013727A1 (en) | 2010-07-29 | 2012-02-02 | Oryzon Genomics S.A. | Cyclopropylamine derivatives useful as lsd1 inhibitors |
| EP2963034A1 (en) | 2010-08-26 | 2016-01-06 | RFS Pharma, LLC. | Potent and selective inhibitors of hepatitis c virus |
| WO2012045883A1 (en) | 2010-10-08 | 2012-04-12 | Oryzon Genomics S.A. | Cyclopropylamine inhibitors of oxidases |
| 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 |
| WO2012072713A2 (en) * | 2010-11-30 | 2012-06-07 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for diseases and disorders associated with flaviviridae |
| US8507683B2 (en) * | 2010-12-09 | 2013-08-13 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| JP5918264B2 (ja) * | 2010-12-22 | 2016-05-18 | アッヴィ・インコーポレイテッド | C型肝炎阻害剤およびその使用 |
| EP3981395A1 (en) | 2011-02-08 | 2022-04-13 | Oryzon Genomics, S.A. | Lysine demethylase inhibitors for myeloproliferative disorders |
| WO2013033900A1 (en) * | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of viral diseases |
| WO2013033899A1 (en) * | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Substituted benzofuran compounds and methods of use thereof for the treatment of viral diseases |
| WO2013033901A1 (en) * | 2011-09-08 | 2013-03-14 | Merck Sharp & Dohme Corp. | Heterocyclic-substituted benzofuran derivatives and methods of use thereof for the treatment of viral diseases |
| KR102079406B1 (ko) | 2011-10-20 | 2020-02-19 | 오리존 지노믹스 에스.에이. | Lsd1 억제제로서의 (헤테로)아릴 사이클로프로필아민 화합물 |
| EP2768805B1 (en) | 2011-10-20 | 2020-03-25 | Oryzon Genomics, S.A. | (hetero)aryl cyclopropylamine compounds as lsd1 inhibitors |
| US9303020B2 (en) | 2012-02-08 | 2016-04-05 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| EP2831066B1 (en) | 2012-03-27 | 2016-10-05 | Bristol-Myers Squibb Company | Benzofuran derivatives for the treatment of hepatitis c |
| WO2013163466A1 (en) * | 2012-04-25 | 2013-10-31 | Presidio Pharmaceuticals, Inc. | Inhibitors of hepatitis c virus |
| US9169214B2 (en) * | 2012-12-21 | 2015-10-27 | The Board Of Trustees Of The Leland Stanford Junior University | Compounds and compositions that bind and stabilize transthyretin and their use for inhibiting transthyretin amyloidosis and protein-protein interactions |
| EP2943496B1 (en) * | 2013-01-10 | 2017-09-06 | Bristol-Myers Squibb Company | Macrocyclic benzofuran and azabenzofuran compounds for the treatment of hepatitis c |
| WO2014121416A1 (en) | 2013-02-07 | 2014-08-14 | Merck Sharp & Dohme Corp. | Tetracyclic heterocycle compounds and methods of use thereof for the treatment of hepatitis c |
| US8962651B2 (en) | 2013-03-13 | 2015-02-24 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| EP2970174B1 (en) | 2013-03-14 | 2017-05-03 | Bristol-Myers Squibb Company | Fused furans for the treatment of hepatitis c |
| WO2014205593A1 (en) * | 2013-06-24 | 2014-12-31 | Merck Sharp & Dohme Corp. | Substituted benzofuran compounds and methods of use thereof for treatment of viral diseases |
| WO2015088958A1 (en) * | 2013-12-13 | 2015-06-18 | Bristol-Myers Squibb Company | A novel compound for the treatment of hepatitis c |
| KR20160126085A (ko) * | 2014-03-21 | 2016-11-01 | 브리스톨-마이어스 스큅 컴퍼니 | C형 간염의 치료를 위한 시아노 함유 아자벤조푸란 화합물 |
| WO2015143256A1 (en) * | 2014-03-21 | 2015-09-24 | Bristol-Myers Squibb Company | Cyanoamino (aza)benzofuran compounds for the treatment of hepatitis c |
| WO2016025129A1 (en) | 2014-08-14 | 2016-02-18 | Alhamadsheh Mamoun M | Conjugation of pharmaceutically active agents with transthyretin ligands through adjustable linkers to increase serum half-life |
| US10125137B2 (en) | 2015-02-19 | 2018-11-13 | Bristol-Myers Squibb Company | Benzofurans substituted with bicyclic secondary benzamide as HCV inhibitors |
| US10087167B2 (en) | 2015-02-19 | 2018-10-02 | Bristol-Myers Squibb Company | Benzofurans substituted with secondary benzamide as HCV inhibitors |
| US10570108B2 (en) | 2015-02-19 | 2020-02-25 | Bristol-Myers Squibb Company | Substituted benzofuran compounds for the treatment of hepatitis C |
| US10131645B2 (en) | 2015-02-19 | 2018-11-20 | Bristol-Myers Squibb Company | Benzofurans substituted with primary benzamide as HCV inhibitors |
| WO2016137832A1 (en) * | 2015-02-23 | 2016-09-01 | Bristol-Myers Squibb Company | Novel compounds for the treatment of hepatitis c |
| WO2017165233A1 (en) * | 2016-03-21 | 2017-09-28 | Bristol-Myers Squibb Company | Benzofuran derivatives for the treatment of hepatitis c |
| CN116730921A (zh) | 2017-02-17 | 2023-09-12 | 文涵治疗有限公司 | Ag-10的制备方法、其中间体及其盐 |
| KR102512548B1 (ko) | 2017-12-22 | 2023-03-22 | 삼성디스플레이 주식회사 | 유기 전계 발광 소자 및 유기 전계 발광 소자용 함질소 화합물 |
| SG11202009073WA (en) | 2018-03-23 | 2020-10-29 | Eidos Therapeutics Inc | Methods of treating ttr amyloidosis using ag10 |
| MA53238A (fr) | 2018-08-17 | 2022-04-13 | Eidos Therapeutics Inc | Formules d'ag10 |
| AU2019387370A1 (en) | 2018-11-30 | 2021-06-10 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| CN114174283B (zh) * | 2019-07-18 | 2023-05-12 | 石药集团中奇制药技术(石家庄)有限公司 | 作为nmt抑制剂的化合物及其应用 |
| US20250214977A1 (en) * | 2024-01-03 | 2025-07-03 | Kymera Therapeutics, Inc. | Stat6 inhibitors and uses thereof |
Family Cites Families (11)
| 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 |
| 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 |
| CN1731993A (zh) * | 2002-11-01 | 2006-02-08 | 维洛药品公司 | 苯并呋喃化合物、组合物以及治疗和预防丙型肝炎病毒感染及相关疾病的方法 |
| US7868037B2 (en) * | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| TW200815384A (en) * | 2006-08-25 | 2008-04-01 | Viropharma Inc | Combination therapy method for treating hepatitis C virus infection and pharmaceutical compositions for use therein |
| CA2676906A1 (en) * | 2007-02-12 | 2008-08-21 | Intermune, Inc. | Novel inhibitors hepatitis c virus replication |
| GB0707000D0 (en) | 2007-04-12 | 2007-05-30 | Istituto Di Ricerche D Biolog | Antiviral agents |
| EP2245023B1 (en) | 2008-02-14 | 2011-12-28 | F. Hoffmann-La Roche AG | Heterocyclic antiviral compounds |
| 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 |
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| TW201124403A (en) | 2011-07-16 |
| EA201100390A1 (ru) | 2011-10-31 |
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| NZ591172A (en) | 2012-12-21 |
| EA019185B1 (ru) | 2014-01-30 |
| CA2736988A1 (en) | 2010-03-18 |
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