MX2007001216A - Inhibidores de la senalizacion del receptor del factor de crecimiento endotelial vascular y del receptor del factor de crecimiento del hepatocito. - Google Patents
Inhibidores de la senalizacion del receptor del factor de crecimiento endotelial vascular y del receptor del factor de crecimiento del hepatocito.Info
- Publication number
- MX2007001216A MX2007001216A MX2007001216A MX2007001216A MX2007001216A MX 2007001216 A MX2007001216 A MX 2007001216A MX 2007001216 A MX2007001216 A MX 2007001216A MX 2007001216 A MX2007001216 A MX 2007001216A MX 2007001216 A MX2007001216 A MX 2007001216A
- Authority
- MX
- Mexico
- Prior art keywords
- alkyl
- group
- compound according
- aryl
- further characterized
- Prior art date
Links
- 230000011664 signaling Effects 0.000 title claims abstract description 57
- 108091008605 VEGF receptors Proteins 0.000 title claims abstract description 19
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 title claims abstract description 19
- 108091008603 HGF receptors Proteins 0.000 title claims description 25
- 239000003112 inhibitor Substances 0.000 title claims description 14
- 102000027430 HGF receptors Human genes 0.000 title claims 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 573
- 238000000034 method Methods 0.000 claims abstract description 105
- 239000000203 mixture Substances 0.000 claims abstract description 62
- 102000005962 receptors Human genes 0.000 claims abstract description 30
- 108020003175 receptors Proteins 0.000 claims abstract description 30
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 14
- 230000002062 proliferating effect Effects 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 201000010099 disease Diseases 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 522
- 125000000623 heterocyclic group Chemical group 0.000 claims description 363
- 229910052739 hydrogen Inorganic materials 0.000 claims description 273
- 125000003118 aryl group Chemical group 0.000 claims description 272
- -1 cyano, nitro, tetrazolyl Chemical group 0.000 claims description 262
- 125000001072 heteroaryl group Chemical group 0.000 claims description 260
- 229910052736 halogen Inorganic materials 0.000 claims description 144
- 150000002367 halogens Chemical class 0.000 claims description 144
- 125000005843 halogen group Chemical group 0.000 claims description 128
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 115
- 229910052757 nitrogen Inorganic materials 0.000 claims description 108
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 98
- 125000001424 substituent group Chemical group 0.000 claims description 95
- 125000003545 alkoxy group Chemical group 0.000 claims description 94
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 87
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 76
- 239000001257 hydrogen Substances 0.000 claims description 60
- 229910052760 oxygen Inorganic materials 0.000 claims description 58
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 56
- 101000599004 Homo sapiens Olfactory receptor 3A1 Proteins 0.000 claims description 55
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 55
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 51
- 125000004432 carbon atom Chemical group C* 0.000 claims description 51
- 229910052717 sulfur Inorganic materials 0.000 claims description 51
- 125000003342 alkenyl group Chemical group 0.000 claims description 47
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 46
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 45
- 125000000304 alkynyl group Chemical group 0.000 claims description 42
- 125000001188 haloalkyl group Chemical group 0.000 claims description 42
- 229910052731 fluorine Inorganic materials 0.000 claims description 39
- 125000004429 atom Chemical group 0.000 claims description 34
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 33
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 29
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- 125000004404 heteroalkyl group Chemical group 0.000 claims description 24
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 24
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- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 18
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- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 12
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- 125000003386 piperidinyl group Chemical group 0.000 claims description 11
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 11
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- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 9
- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 125000006413 ring segment Chemical group 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 8
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 8
- 229910006074 SO2NH2 Inorganic materials 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
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
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- 239000011593 sulfur Substances 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- 101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 230000012010 growth Effects 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000000262 haloalkenyl group Chemical group 0.000 claims description 3
- 125000000232 haloalkynyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 16
- 238000000338 in vitro Methods 0.000 claims 8
- 241001465754 Metazoa Species 0.000 claims 4
- 229940079593 drug Drugs 0.000 claims 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000006643 (C2-C6) haloalkenyl group Chemical group 0.000 claims 1
- 125000006644 (C2-C6) haloalkynyl group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000004971 nitroalkyl group Chemical group 0.000 claims 1
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 abstract description 18
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 abstract description 18
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 abstract description 17
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 16
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 16
- 230000005764 inhibitory process Effects 0.000 abstract description 10
- 210000004027 cell Anatomy 0.000 abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 216
- 238000006243 chemical reaction Methods 0.000 description 163
- 239000007787 solid Substances 0.000 description 130
- 239000000243 solution Substances 0.000 description 126
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 122
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 120
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 108
- 235000019439 ethyl acetate Nutrition 0.000 description 105
- 239000011541 reaction mixture Substances 0.000 description 89
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
- 230000002829 reductive effect Effects 0.000 description 74
- 238000005481 NMR spectroscopy Methods 0.000 description 66
- 239000003480 eluent Substances 0.000 description 60
- 230000015572 biosynthetic process Effects 0.000 description 56
- 238000003786 synthesis reaction Methods 0.000 description 56
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- 238000004440 column chromatography Methods 0.000 description 51
- 238000012512 characterization method Methods 0.000 description 50
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 46
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
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- 150000001412 amines Chemical class 0.000 description 44
- 239000002904 solvent Substances 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- 238000000746 purification Methods 0.000 description 27
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 25
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 25
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
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- ZUAFSRDYQVCEPE-UHFFFAOYSA-N n-carbamothioyl-2-phenylacetamide Chemical compound NC(=S)NC(=O)CC1=CC=CC=C1 ZUAFSRDYQVCEPE-UHFFFAOYSA-N 0.000 description 23
- 150000002828 nitro derivatives Chemical class 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 20
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 19
- ZFJOLNZPELDZNC-UHFFFAOYSA-N 2-phenylacetyl isothiocyanate Chemical class S=C=NC(=O)CC1=CC=CC=C1 ZFJOLNZPELDZNC-UHFFFAOYSA-N 0.000 description 18
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- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 18
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- 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- 238000011282 treatment Methods 0.000 description 16
- ORPHLVJBJOCHBR-UHFFFAOYSA-N 403-19-0 Chemical compound OC1=CC=C([N+]([O-])=O)C=C1F ORPHLVJBJOCHBR-UHFFFAOYSA-N 0.000 description 15
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
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- 125000004448 alkyl carbonyl group Chemical group 0.000 description 6
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- XKANXPZRRXSCHQ-UHFFFAOYSA-N n-[[3-fluoro-4-[2-(piperidine-1-carbonyl)thieno[3,2-b]pyridin-7-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide Chemical compound C=1C=C(OC=2C=3SC(=CC=3N=CC=2)C(=O)N2CCCCC2)C(F)=CC=1NC(=S)NC(=O)CC1=CC=CC=C1 XKANXPZRRXSCHQ-UHFFFAOYSA-N 0.000 description 6
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- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 5
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
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- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
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- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
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- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
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- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
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- QYJVBVKFXDHFPQ-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)-n-methylcarbamate Chemical compound NCCN(C)C(=O)OC(C)(C)C QYJVBVKFXDHFPQ-UHFFFAOYSA-N 0.000 description 1
- LIYMTLVBAVHPBU-UHFFFAOYSA-N tert-butyl n-(4-hydroxybutyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCO LIYMTLVBAVHPBU-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
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- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 description 1
- RBNBDIMXFJYDLQ-UHFFFAOYSA-N thieno[3,2-d]pyrimidine Chemical compound C1=NC=C2SC=CC2=N1 RBNBDIMXFJYDLQ-UHFFFAOYSA-N 0.000 description 1
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- LYRCQNDYYRPFMF-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C LYRCQNDYYRPFMF-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—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
- A61K31/4355—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 oxygen as a ring hetero atom
-
- 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
- A61K31/4365—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 having sulfur as a ring hetero atom, e.g. ticlopidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
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- 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)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US59291304P | 2004-07-30 | 2004-07-30 | |
| US68303805P | 2005-05-20 | 2005-05-20 | |
| PCT/CA2005/001177 WO2006010264A1 (en) | 2004-07-30 | 2005-07-28 | Inhibitors of vegf receptor and hgf receptor signaling |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2007001216A true MX2007001216A (es) | 2007-03-23 |
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| MX2007001216A MX2007001216A (es) | 2004-07-30 | 2005-07-28 | Inhibidores de la senalizacion del receptor del factor de crecimiento endotelial vascular y del receptor del factor de crecimiento del hepatocito. |
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| Country | Link |
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| US (2) | US7772247B2 (https=) |
| EP (1) | EP1781664B1 (https=) |
| JP (1) | JP5096142B2 (https=) |
| KR (1) | KR101257343B1 (https=) |
| CN (1) | CN101031570B (https=) |
| AU (1) | AU2005266803B2 (https=) |
| BR (1) | BRPI0513982A (https=) |
| CA (1) | CA2573538C (https=) |
| ES (1) | ES2438017T3 (https=) |
| IL (1) | IL180788A0 (https=) |
| MX (1) | MX2007001216A (https=) |
| RU (1) | RU2007107167A (https=) |
| WO (1) | WO2006010264A1 (https=) |
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| CA2569016C (en) * | 2004-06-02 | 2012-11-27 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
| ES2438017T3 (es) | 2004-07-30 | 2014-01-15 | Methylgene Inc. | Inhibidores de la señalización del receptor del VEGF y del receptor del HGF |
| AU2006229343A1 (en) * | 2005-03-28 | 2006-10-05 | Kirin Pharma Kabushiki Kaisha | Thienopyridine derivative, or quinoline derivative, or quinazoline derivative, having c-Met autophosphorylation inhibiting potency |
| JP2008536932A (ja) * | 2005-04-18 | 2008-09-11 | サイード・アール・カーン | チューブリン重合阻害剤：ボンゾイルフェニル尿素（ｂｐｕ）硫黄類似体の設計及び合成 |
| KR101378716B1 (ko) * | 2005-05-20 | 2014-04-10 | 메틸진 인코포레이티드 | Ｖｅｇｆ 수용체 및 ｈｇｆ 수용체 신호전달의 억제제 |
| AU2006313456B2 (en) | 2005-05-20 | 2011-06-23 | Methylgene Inc. | Inhibitors of VEGF receptor and HGF receptor signaling |
| TW200730527A (en) * | 2005-12-02 | 2007-08-16 | Takeda Pharmaceuticals Co | Fused heterocyclic compound |
| JP2009526761A (ja) * | 2006-01-30 | 2009-07-23 | アレイ バイオファーマ、インコーポレイテッド | ヘテロ二環式チオフェン化合物および使用の方法 |
| AR060061A1 (es) * | 2006-03-22 | 2008-05-21 | Methylgene Inc | Inhibidores de la actividad de la proteina tirosina quinasa |
| JP2009539878A (ja) * | 2006-06-08 | 2009-11-19 | アレイ バイオファーマ、インコーポレイテッド | キノリン化合物および使用方法 |
| ES2593279T3 (es) | 2007-08-29 | 2016-12-07 | Methylgene Inc. | Procesos e intermedios para preparar inhibidores de cinasa heterocíclicos condensados |
| PL2183254T3 (pl) | 2007-08-29 | 2017-10-31 | Methylgene Inc | Inhibitory aktywności białkowej kinazy tyrozynowej |
| NZ588355A (en) | 2008-03-05 | 2012-03-30 | Methylgene Inc | Inhibitors of protein tyrosine kinase activity |
| ES2599458T3 (es) * | 2008-10-14 | 2017-02-01 | Sunshine Lake Pharma Co., Ltd. | Compuestos y métodos de uso |
| EP2408300B1 (en) * | 2009-03-21 | 2016-05-11 | Sunshine Lake Pharma Co., Ltd. | Amino ester derivatives, salts thereof and methods of use |
| JP2013525286A (ja) * | 2010-04-16 | 2013-06-20 | メチルジーン・インコーポレイテッド | タンパク質チロシンキナーゼ活性の阻害剤 |
| US20130225581A1 (en) | 2010-07-16 | 2013-08-29 | Kyowa Hakko Kirin Co., Ltd | Nitrogen-containing aromatic heterocyclic derivative |
| TW201217387A (en) | 2010-09-15 | 2012-05-01 | Hoffmann La Roche | Azabenzothiazole compounds, compositions and methods of use |
| RU2568258C2 (ru) | 2011-02-28 | 2015-11-20 | Саншайн Лейк Фарма Ко., Лтд | Замещенные соединения хинолина и способы их использования |
| HUE056194T2 (hu) | 2012-02-21 | 2022-01-28 | Towa Pharmaceutical Europe S L | Dabigatrán-etexilát orális gyógyszerészeti készítményei |
| TWI520962B (zh) * | 2012-06-29 | 2016-02-11 | As the c-Met tyrosine kinase inhibitors novel fused pyridine derivatives | |
| JP6342392B2 (ja) | 2012-07-28 | 2018-06-13 | カリター・サイエンシーズ・エルエルシー | 置換型ピラゾロン化合物及び使用方法 |
| TWI574962B (zh) | 2012-11-14 | 2017-03-21 | 加拓科學公司 | 作爲ｐｉ３激酶調節劑的芳雜環化合物及其使用方法和用途 |
| MX2015010700A (es) | 2013-02-21 | 2017-01-23 | Calitor Sciences Llc | Compuestos heteroaromaticos como moduladores de la p13 cinasa. |
| RS58361B1 (sr) * | 2013-07-31 | 2019-03-29 | Merck Patent Gmbh | Piridini, pirimidini i pirazini, kao inhibitori btk i njihova upotreba |
| US10308658B2 (en) | 2015-10-19 | 2019-06-04 | Sunshine Lake Pharma Co., Ltd. | Salt of EGFR inhibitor, crystalline form and uses thereof |
| EP3646887A4 (en) | 2017-06-30 | 2021-03-24 | Korea Advanced Institute of Science and Technology | CONJUGATE OF VEGF GRAB PROTEIN AND MEDICINAL PRODUCTS AND USES THEREOF |
| US11623923B2 (en) | 2017-11-24 | 2023-04-11 | Medshine Discovery, Inc. | Uracil compound as c-MET/AXL inhibitor |
| WO2020132384A1 (en) | 2018-12-21 | 2020-06-25 | Celgene Corporation | Thienopyridine inhibitors of ripk2 |
| US20250188147A1 (en) | 2022-03-04 | 2025-06-12 | Panalos Bioscience, Inc. | Composition for combi-therapy comprising vegf-grab and pd-1 or pd-l1 antagonist |
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| US6107300A (en) * | 1996-03-27 | 2000-08-22 | Dupont Pharmaceuticals | Arylamino fused pyrimidines |
| EP1028964A1 (en) * | 1997-11-11 | 2000-08-23 | Pfizer Products Inc. | Thienopyrimidine and thienopyridine derivatives useful as anticancer agents |
| US6232320B1 (en) * | 1998-06-04 | 2001-05-15 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| AU4231299A (en) | 1998-06-04 | 1999-12-20 | Abbott Laboratories | Cell adhesion-inhibiting antinflammatory compounds |
| WO2000075145A1 (en) | 1999-06-03 | 2000-12-14 | Abbott Laboratories | Cell adhesion-inhibiting antiinflammatory compounds |
| BR0111377A (pt) | 2000-06-06 | 2003-06-03 | Pfizer Prod Inc | Derivados de tiofeno úteis como agentes anticancerìgenos |
| US20020004511A1 (en) * | 2000-06-28 | 2002-01-10 | Luzzio Michael Joseph | Thiophene derivatives useful as anticancer agents |
| AU9598601A (en) * | 2000-10-20 | 2002-04-29 | Eisai Co Ltd | Nitrogenous aromatic ring compounds |
| WO2003000194A2 (en) | 2001-06-21 | 2003-01-03 | Pfizer Inc. | Thienopyridine and thienopyrimidine anticancer agents |
| GB0115109D0 (en) * | 2001-06-21 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
| AU2002313249B2 (en) * | 2001-06-22 | 2008-08-21 | Kirin Pharma Kabushiki Kaisha | Quinoline derivative and quinazoline derivate inhibiting self-phosphorylation of hepatocytus proliferator receptor, and medicinal composition containing the same |
| GB0119249D0 (en) * | 2001-08-07 | 2001-10-03 | Novartis Ag | Organic compounds |
| AU2003206068A1 (en) | 2002-03-01 | 2003-09-16 | Pfizer Inc. | Indolyl-urea derivatives of thienopyridines useful as anti-angiogenic agents |
| US20030199525A1 (en) * | 2002-03-21 | 2003-10-23 | Hirst Gavin C. | Kinase inhibitors |
| CL2003002287A1 (es) * | 2002-11-25 | 2005-01-14 | Wyeth Corp | COMPUESTOS DERIVADOS DE TIENO[3,2-b]-PIRIDINA-6-CARBONITRILOS Y TIENEO[2,3-b]-PIRIDINA-5-CARBONITRILOS, COMPOSICION FARMACEUTICA, PROCEDIMIENTO DE PREPARACION Y COMPUESTOS INTERMEDIARIOS, Y SU USO EN EL TRATAMIENTO DEL CANCER, APOPLEJIA, OSTEOPOROSIS |
| DE10335598A1 (de) | 2003-08-04 | 2005-02-24 | Robert Bosch Gmbh | Pedal-Vorrichtung für Kraftfahrzeuge |
| ES2314444T3 (es) | 2003-08-29 | 2009-03-16 | Pfizer Inc. | Tienopiridina-fenilacetaminasy sus derivados utiles como nuevos agentes antiangiogenicos. |
| WO2005052872A1 (en) * | 2003-11-21 | 2005-06-09 | Facil, Llc | Financial transaction system and method |
| JP2007518823A (ja) * | 2004-01-23 | 2007-07-12 | アムゲン インコーポレイテッド | キノリン、キナゾリン、ピリジン、及びピリミジン化合物と炎症、血管新生、及び癌に対する治療におけるそれら化合物の用途 |
| US7459562B2 (en) | 2004-04-23 | 2008-12-02 | Bristol-Myers Squibb Company | Monocyclic heterocycles as kinase inhibitors |
| TW200538453A (en) * | 2004-04-26 | 2005-12-01 | Bristol Myers Squibb Co | Bicyclic heterocycles as kinase inhibitors |
| WO2005121125A1 (en) | 2004-06-09 | 2005-12-22 | Pfizer Inc. | Ether-linked heteroaryl compounds |
| US7439246B2 (en) * | 2004-06-28 | 2008-10-21 | Bristol-Myers Squibb Company | Fused heterocyclic kinase inhibitors |
| US7173031B2 (en) | 2004-06-28 | 2007-02-06 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
| US7977345B2 (en) | 2004-07-02 | 2011-07-12 | Exelixis, Inc. | c-MET modulators and method of use |
| MX2007000631A (es) | 2004-07-16 | 2007-03-30 | Sunesis Pharmaceuticals Inc | Tienopirimidinas utiles como inhibidores de aurora cinasa. |
| ES2438017T3 (es) | 2004-07-30 | 2014-01-15 | Methylgene Inc. | Inhibidores de la señalización del receptor del VEGF y del receptor del HGF |
| AU2006229343A1 (en) | 2005-03-28 | 2006-10-05 | Kirin Pharma Kabushiki Kaisha | Thienopyridine derivative, or quinoline derivative, or quinazoline derivative, having c-Met autophosphorylation inhibiting potency |
| JO2787B1 (en) | 2005-04-27 | 2014-03-15 | امجين إنك, | Alternative amide derivatives and methods of use |
| AU2006313456B2 (en) * | 2005-05-20 | 2011-06-23 | Methylgene Inc. | Inhibitors of VEGF receptor and HGF receptor signaling |
| KR101378716B1 (ko) | 2005-05-20 | 2014-04-10 | 메틸진 인코포레이티드 | Ｖｅｇｆ 수용체 및 ｈｇｆ 수용체 신호전달의 억제제 |
-
2005
- 2005-07-28 ES ES05770304.3T patent/ES2438017T3/es not_active Expired - Lifetime
- 2005-07-28 AU AU2005266803A patent/AU2005266803B2/en not_active Ceased
- 2005-07-28 CA CA2573538A patent/CA2573538C/en not_active Expired - Fee Related
- 2005-07-28 KR KR1020077005060A patent/KR101257343B1/ko not_active Expired - Fee Related
- 2005-07-28 EP EP05770304.3A patent/EP1781664B1/en not_active Expired - Lifetime
- 2005-07-28 WO PCT/CA2005/001177 patent/WO2006010264A1/en not_active Ceased
- 2005-07-28 CN CN2005800331963A patent/CN101031570B/zh not_active Expired - Fee Related
- 2005-07-28 US US11/191,617 patent/US7772247B2/en active Active
- 2005-07-28 BR BRPI0513982-1A patent/BRPI0513982A/pt not_active Application Discontinuation
- 2005-07-28 JP JP2007522886A patent/JP5096142B2/ja not_active Expired - Fee Related
- 2005-07-28 MX MX2007001216A patent/MX2007001216A/es active IP Right Grant
- 2005-07-28 RU RU2007107167/04A patent/RU2007107167A/ru not_active Application Discontinuation
-
2007
- 2007-01-18 IL IL180788A patent/IL180788A0/en unknown
-
2010
- 2010-05-06 US US12/775,090 patent/US8470850B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU2005266803B2 (en) | 2011-10-27 |
| US20100216766A1 (en) | 2010-08-26 |
| JP5096142B2 (ja) | 2012-12-12 |
| KR101257343B1 (ko) | 2013-04-23 |
| WO2006010264A1 (en) | 2006-02-02 |
| US20060074056A1 (en) | 2006-04-06 |
| IL180788A0 (en) | 2007-06-03 |
| BRPI0513982A (pt) | 2007-11-27 |
| EP1781664A1 (en) | 2007-05-09 |
| EP1781664B1 (en) | 2013-09-04 |
| ES2438017T3 (es) | 2014-01-15 |
| KR20070051876A (ko) | 2007-05-18 |
| US7772247B2 (en) | 2010-08-10 |
| EP1781664A4 (en) | 2010-06-02 |
| CN101031570B (zh) | 2012-09-05 |
| AU2005266803A1 (en) | 2006-02-02 |
| JP2008508192A (ja) | 2008-03-21 |
| CA2573538C (en) | 2014-11-25 |
| US8470850B2 (en) | 2013-06-25 |
| RU2007107167A (ru) | 2008-09-10 |
| CA2573538A1 (en) | 2006-02-02 |
| CN101031570A (zh) | 2007-09-05 |
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