NO321003B1 - Kinolinderivater som inhiberer effekten av vekstfaktorer som VEGF, anvendelse og fremstilling derav, samt farmasoytisk sammensetning. - Google Patents
Kinolinderivater som inhiberer effekten av vekstfaktorer som VEGF, anvendelse og fremstilling derav, samt farmasoytisk sammensetning. Download PDFInfo
- Publication number
- NO321003B1 NO321003B1 NO19991423A NO991423A NO321003B1 NO 321003 B1 NO321003 B1 NO 321003B1 NO 19991423 A NO19991423 A NO 19991423A NO 991423 A NO991423 A NO 991423A NO 321003 B1 NO321003 B1 NO 321003B1
- Authority
- NO
- Norway
- Prior art keywords
- chloro
- fluoro
- quinoline
- hydroxy
- methoxy
- Prior art date
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- 230000000694 effects Effects 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 6
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 title abstract description 22
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 title abstract description 22
- 239000003102 growth factor Substances 0.000 title description 10
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title description 3
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 173
- -1 C1-3alkanoyloxy Chemical group 0.000 claims abstract description 84
- 150000003839 salts Chemical class 0.000 claims abstract description 72
- 238000000034 method Methods 0.000 claims abstract description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 37
- 239000001257 hydrogen Substances 0.000 claims abstract description 36
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 15
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 10
- 241001465754 Metazoa Species 0.000 claims abstract description 9
- 230000001772 anti-angiogenic effect Effects 0.000 claims abstract description 9
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- 230000008569 process Effects 0.000 claims abstract description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 238000010511 deprotection reaction Methods 0.000 claims description 7
- 230000009467 reduction Effects 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 6
- 230000002137 anti-vascular effect Effects 0.000 claims description 6
- 229940100198 alkylating agent Drugs 0.000 claims description 5
- 239000002168 alkylating agent Substances 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- MITMPQKWHTYULQ-UHFFFAOYSA-N 2-[4-(4-chloro-2-fluoroanilino)-6-methoxyquinolin-7-yl]oxyethanol Chemical compound C1=CN=C2C=C(OCCO)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F MITMPQKWHTYULQ-UHFFFAOYSA-N 0.000 claims description 3
- IZXMRRKFBIVJPB-UHFFFAOYSA-N 2-chloro-5-[(7-chloroquinolin-4-yl)amino]-4-fluorophenol Chemical compound C1=C(Cl)C(O)=CC(NC=2C3=CC=C(Cl)C=C3N=CC=2)=C1F IZXMRRKFBIVJPB-UHFFFAOYSA-N 0.000 claims description 3
- CJAFWUVJVULROH-UHFFFAOYSA-N 3-[4-(4-chloro-2-fluoroanilino)-6-methoxyquinolin-7-yl]oxypropan-1-ol Chemical compound C1=CN=C2C=C(OCCCO)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F CJAFWUVJVULROH-UHFFFAOYSA-N 0.000 claims description 3
- OTUKQMIQBIOXME-UHFFFAOYSA-N 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-(3-morpholin-4-ylpropoxy)quinoline-6-carbonitrile Chemical compound C1=C(O)C(C)=CC(F)=C1NC1=CC=NC2=CC(OCCCN3CCOCC3)=C(C#N)C=C12 OTUKQMIQBIOXME-UHFFFAOYSA-N 0.000 claims description 3
- QBTOWJJXAUAUJV-UHFFFAOYSA-N 4-(2-fluoro-5-hydroxy-4-methylphenoxy)-7-(2-methoxyethoxy)quinoline-6-carbonitrile Chemical compound C=12C=C(C#N)C(OCCOC)=CC2=NC=CC=1OC1=CC(O)=C(C)C=C1F QBTOWJJXAUAUJV-UHFFFAOYSA-N 0.000 claims description 3
- XXEVYBLMBNVMAG-UHFFFAOYSA-N 4-(4-chloro-2-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinoline-6-carbonitrile Chemical compound FC1=CC(Cl)=CC=C1NC1=CC=NC2=CC(OCCCN3CCOCC3)=C(C#N)C=C12 XXEVYBLMBNVMAG-UHFFFAOYSA-N 0.000 claims description 3
- NZVUGQYAUFJZRY-UHFFFAOYSA-N 4-fluoro-5-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxy-2-methylphenol Chemical compound C1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1OC1=CC(O)=C(C)C=C1F NZVUGQYAUFJZRY-UHFFFAOYSA-N 0.000 claims description 3
- PJTBLXWDSGQSED-UHFFFAOYSA-N 5-(6,7-dimethoxyquinolin-4-yl)oxy-4-fluoro-2-methylphenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC1=CC(O)=C(C)C=C1F PJTBLXWDSGQSED-UHFFFAOYSA-N 0.000 claims description 3
- LKOZFQGIAQZPOE-UHFFFAOYSA-N 5-[(6,7-dimethoxyquinolin-4-yl)amino]-2-methylphenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1NC1=CC=C(C)C(O)=C1 LKOZFQGIAQZPOE-UHFFFAOYSA-N 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- FPIAFMPKZNGGJB-UHFFFAOYSA-N methyl 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-methoxyquinoline-6-carboxylate Chemical compound C1=CN=C2C=C(OC)C(C(=O)OC)=CC2=C1NC1=CC(O)=C(C)C=C1F FPIAFMPKZNGGJB-UHFFFAOYSA-N 0.000 claims description 3
- MSNFXXMAXYMTHJ-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)quinolin-4-amine Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=CC=1NC1=CC=C(Cl)C=C1F MSNFXXMAXYMTHJ-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 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
- LAZBPMGKMBVKBP-UHFFFAOYSA-N 2-bromo-4-fluoro-5-[(6-methoxy-7-phenylmethoxyquinolin-4-yl)amino]phenol Chemical compound C1=CN=C2C=C(OCC=3C=CC=CC=3)C(OC)=CC2=C1NC1=CC(O)=C(Br)C=C1F LAZBPMGKMBVKBP-UHFFFAOYSA-N 0.000 claims description 2
- QGRWLEOULVUBBC-UHFFFAOYSA-N 2-chloro-4-fluoro-5-[[6-methoxy-7-(2-methoxyethoxy)quinolin-4-yl]amino]phenol Chemical compound C=12C=C(OC)C(OCCOC)=CC2=NC=CC=1NC1=CC(O)=C(Cl)C=C1F QGRWLEOULVUBBC-UHFFFAOYSA-N 0.000 claims description 2
- ZYLRVVFIYFMVKZ-UHFFFAOYSA-N 2-chloro-4-fluoro-5-[[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]amino]phenol Chemical compound C1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1NC1=CC(O)=C(Cl)C=C1F ZYLRVVFIYFMVKZ-UHFFFAOYSA-N 0.000 claims description 2
- PWPUEGZAGHIOQT-UHFFFAOYSA-N 2-chloro-4-fluoro-5-[[6-methoxy-7-(3-pyridin-3-ylpropoxy)quinolin-4-yl]amino]phenol Chemical compound C1=CN=C2C=C(OCCCC=3C=NC=CC=3)C(OC)=CC2=C1NC1=CC(O)=C(Cl)C=C1F PWPUEGZAGHIOQT-UHFFFAOYSA-N 0.000 claims description 2
- RAGLCLQAAWTUFO-UHFFFAOYSA-N 2-chloro-4-fluoro-5-[[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-yl]amino]phenol Chemical compound C1=CN=C2C=C(OCCCN3CCCC3)C(OC)=CC2=C1NC1=CC(O)=C(Cl)C=C1F RAGLCLQAAWTUFO-UHFFFAOYSA-N 0.000 claims description 2
- RVMYPLFBWHJURN-UHFFFAOYSA-N 2-chloro-4-fluoro-5-[[6-methoxy-7-(pyridin-4-ylmethoxy)quinolin-4-yl]amino]phenol Chemical compound C1=CN=C2C=C(OCC=3C=CN=CC=3)C(OC)=CC2=C1NC1=CC(O)=C(Cl)C=C1F RVMYPLFBWHJURN-UHFFFAOYSA-N 0.000 claims description 2
- XODPOQPDOYXAAW-UHFFFAOYSA-N 2-chloro-4-fluoro-5-[[6-methoxy-7-[(2-methyl-1,3-thiazol-4-yl)methoxy]quinolin-4-yl]amino]phenol Chemical compound C1=CN=C2C=C(OCC=3N=C(C)SC=3)C(OC)=CC2=C1NC1=CC(O)=C(Cl)C=C1F XODPOQPDOYXAAW-UHFFFAOYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- ZPFNGIBSIYZMPX-UHFFFAOYSA-N 3-[(6,7-dimethoxyquinolin-4-yl)amino]phenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1NC1=CC=CC(O)=C1 ZPFNGIBSIYZMPX-UHFFFAOYSA-N 0.000 claims description 2
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
- MEFRZMUNPPMFQZ-UHFFFAOYSA-N 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-(2-methoxyethoxy)quinoline-6-carbonitrile Chemical compound C=12C=C(C#N)C(OCCOC)=CC2=NC=CC=1NC1=CC(O)=C(C)C=C1F MEFRZMUNPPMFQZ-UHFFFAOYSA-N 0.000 claims description 2
- GNFLQOZYHWBHGM-UHFFFAOYSA-N 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-methoxyquinoline-6-carbonitrile Chemical compound C=12C=C(C#N)C(OC)=CC2=NC=CC=1NC1=CC(O)=C(C)C=C1F GNFLQOZYHWBHGM-UHFFFAOYSA-N 0.000 claims description 2
- ILFLCJAURKJLJR-UHFFFAOYSA-N 4-(3-hydroxy-4-methylanilino)-7-(2-methoxyethoxy)quinoline-6-carbonitrile Chemical compound C=12C=C(C#N)C(OCCOC)=CC2=NC=CC=1NC1=CC=C(C)C(O)=C1 ILFLCJAURKJLJR-UHFFFAOYSA-N 0.000 claims description 2
- VLOUIJNKISCYCN-UHFFFAOYSA-N 4-(4-chloro-2-fluoroanilino)-7-(2-methoxyethoxy)quinoline-6-carbonitrile Chemical compound C=12C=C(C#N)C(OCCOC)=CC2=NC=CC=1NC1=CC=C(Cl)C=C1F VLOUIJNKISCYCN-UHFFFAOYSA-N 0.000 claims description 2
- ZSTAHIPLVXVPPN-UHFFFAOYSA-N 4-(4-chloro-2-fluorophenoxy)-6,7-dimethoxyquinoline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1OC1=CC=C(Cl)C=C1F ZSTAHIPLVXVPPN-UHFFFAOYSA-N 0.000 claims description 2
- AQNXHBFSMBNESC-UHFFFAOYSA-N 4-[(6,7-dimethoxyquinolin-4-yl)amino]phenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1NC1=CC=C(O)C=C1 AQNXHBFSMBNESC-UHFFFAOYSA-N 0.000 claims description 2
- LEXABZADCXRMQB-UHFFFAOYSA-N 4-fluoro-5-[[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]amino]-2-methylphenol Chemical compound C1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1NC1=CC(O)=C(C)C=C1F LEXABZADCXRMQB-UHFFFAOYSA-N 0.000 claims description 2
- IEMRYWXZRLVFSJ-UHFFFAOYSA-N 5-[(6,7-dimethoxyquinolin-4-yl)amino]-4-fluoro-2-methylphenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1NC1=CC(O)=C(C)C=C1F IEMRYWXZRLVFSJ-UHFFFAOYSA-N 0.000 claims description 2
- LMJBUKPJZRXLQJ-UHFFFAOYSA-N 5-[(6-methoxy-7-phenylmethoxyquinolin-4-yl)amino]-2-methylphenol Chemical compound C1=CN=C2C=C(OCC=3C=CC=CC=3)C(OC)=CC2=C1NC1=CC=C(C)C(O)=C1 LMJBUKPJZRXLQJ-UHFFFAOYSA-N 0.000 claims description 2
- YROMMFXLLCEKHU-UHFFFAOYSA-N 5-[(7-chloroquinolin-4-yl)amino]-4-fluoro-2-methylphenol Chemical compound C1=C(O)C(C)=CC(F)=C1NC1=CC=NC2=CC(Cl)=CC=C12 YROMMFXLLCEKHU-UHFFFAOYSA-N 0.000 claims description 2
- LNWZGSHVJGRBNH-UHFFFAOYSA-N 6,7-dimethoxy-n-phenylquinolin-4-amine Chemical compound C=12C=C(OC)C(OC)=CC2=NC=CC=1NC1=CC=CC=C1 LNWZGSHVJGRBNH-UHFFFAOYSA-N 0.000 claims description 2
- UYCVPLDJGKKARL-UHFFFAOYSA-N N-(2-bromo-4,5-dimethoxyphenyl)-6,7-dimethoxyquinolin-4-amine Chemical compound BrC1=C(NC2=CC=NC3=CC(=C(C=C23)OC)OC)C=C(C(=C1)OC)OC UYCVPLDJGKKARL-UHFFFAOYSA-N 0.000 claims description 2
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- RJJKXXSFIZEAMB-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)-6-methoxy-7-(2-methoxyethoxy)quinolin-4-amine Chemical compound C=12C=C(OC)C(OCCOC)=CC2=NC=CC=1NC1=CC=C(Cl)C=C1F RJJKXXSFIZEAMB-UHFFFAOYSA-N 0.000 claims description 2
- XOTSAZVFXBQWPR-UHFFFAOYSA-N n-(4-chloro-2-fluorophenyl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-amine Chemical compound C1=CN=C2C=C(OCCCN3CCOCC3)C(OC)=CC2=C1NC1=CC=C(Cl)C=C1F XOTSAZVFXBQWPR-UHFFFAOYSA-N 0.000 claims description 2
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 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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- 239000013598 vector Substances 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
-
- 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
-
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom 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
- C07D417/12—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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP96402034 | 1996-09-25 | ||
PCT/GB1997/002587 WO1998013350A1 (fr) | 1996-09-25 | 1997-09-23 | Derives quinolines inhibant les effets de facteurs de croissance tels que le facteur de croissance endotheliale vasculaire |
Publications (3)
Publication Number | Publication Date |
---|---|
NO991423D0 NO991423D0 (no) | 1999-03-24 |
NO991423L NO991423L (no) | 1999-05-11 |
NO321003B1 true NO321003B1 (no) | 2006-02-27 |
Family
ID=8225290
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19991423A NO321003B1 (no) | 1996-09-25 | 1999-03-24 | Kinolinderivater som inhiberer effekten av vekstfaktorer som VEGF, anvendelse og fremstilling derav, samt farmasoytisk sammensetning. |
Country Status (13)
Country | Link |
---|---|
US (1) | US6809097B1 (fr) |
EP (1) | EP0929526B1 (fr) |
JP (1) | JP2001500890A (fr) |
KR (1) | KR100567649B1 (fr) |
CN (1) | CN1252054C (fr) |
AT (1) | ATE300521T1 (fr) |
AU (1) | AU733551B2 (fr) |
CA (1) | CA2263479A1 (fr) |
DE (1) | DE69733825T2 (fr) |
IL (1) | IL128994A (fr) |
NO (1) | NO321003B1 (fr) |
NZ (1) | NZ334125A (fr) |
WO (1) | WO1998013350A1 (fr) |
Families Citing this family (134)
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GB9707800D0 (en) | 1996-05-06 | 1997-06-04 | Zeneca Ltd | Chemical compounds |
GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
WO1999010349A1 (fr) | 1997-08-22 | 1999-03-04 | Zeneca Limited | Derives d'oxindolylquinazoline utiles comme inhibiteurs d'angiogenese |
JP2002522475A (ja) * | 1998-08-13 | 2002-07-23 | ノバルティス アクチエンゲゼルシャフト | 眼血管新生疾患の処置方法 |
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US6297258B1 (en) | 1998-09-29 | 2001-10-02 | American Cyanamid Company | Substituted 3-cyanoquinolines |
US6288082B1 (en) | 1998-09-29 | 2001-09-11 | American Cyanamid Company | Substituted 3-cyanoquinolines |
EP1950201A1 (fr) | 1998-09-29 | 2008-07-30 | Wyeth Holdings Corporation | Cyanoquinolines 3 substituées en tant qu'inhibiteurs de kinases de la protéine tyrosine |
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GB9904103D0 (en) | 1999-02-24 | 1999-04-14 | Zeneca Ltd | Quinoline derivatives |
US6355636B1 (en) | 1999-04-21 | 2002-03-12 | American Cyanamid Company | Substituted 3-cyano-[1.7],[1.5], and [1.8] naphthyridine inhibitors of tyrosine kinases |
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GB9910577D0 (en) * | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
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-
1997
- 1997-09-23 KR KR1019997002502A patent/KR100567649B1/ko not_active IP Right Cessation
- 1997-09-23 CA CA002263479A patent/CA2263479A1/fr not_active Abandoned
- 1997-09-23 AU AU43137/97A patent/AU733551B2/en not_active Ceased
- 1997-09-23 NZ NZ334125A patent/NZ334125A/xx unknown
- 1997-09-23 US US09/254,440 patent/US6809097B1/en not_active Expired - Fee Related
- 1997-09-23 WO PCT/GB1997/002587 patent/WO1998013350A1/fr active IP Right Grant
- 1997-09-23 EP EP97941115A patent/EP0929526B1/fr not_active Expired - Lifetime
- 1997-09-23 CN CNB971999295A patent/CN1252054C/zh not_active Expired - Fee Related
- 1997-09-23 JP JP10515386A patent/JP2001500890A/ja active Pending
- 1997-09-23 AT AT97941115T patent/ATE300521T1/de not_active IP Right Cessation
- 1997-09-23 DE DE69733825T patent/DE69733825T2/de not_active Expired - Fee Related
- 1997-09-23 IL IL12899497A patent/IL128994A/en not_active IP Right Cessation
-
1999
- 1999-03-24 NO NO19991423A patent/NO321003B1/no not_active IP Right Cessation
Also Published As
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---|---|
CA2263479A1 (fr) | 1998-04-02 |
CN1252054C (zh) | 2006-04-19 |
AU733551B2 (en) | 2001-05-17 |
ATE300521T1 (de) | 2005-08-15 |
IL128994A (en) | 2004-12-15 |
WO1998013350A1 (fr) | 1998-04-02 |
EP0929526B1 (fr) | 2005-07-27 |
AU4313797A (en) | 1998-04-17 |
IL128994A0 (en) | 2000-02-17 |
NZ334125A (en) | 2000-10-27 |
KR20000048575A (ko) | 2000-07-25 |
DE69733825D1 (de) | 2005-09-01 |
US6809097B1 (en) | 2004-10-26 |
DE69733825T2 (de) | 2006-06-08 |
NO991423D0 (no) | 1999-03-24 |
CN1237963A (zh) | 1999-12-08 |
NO991423L (no) | 1999-05-11 |
EP0929526A1 (fr) | 1999-07-21 |
JP2001500890A (ja) | 2001-01-23 |
KR100567649B1 (ko) | 2006-04-05 |
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