SK288138B6 - Quinazoline derivatives as angiogenesis inhibitors - Google Patents
Quinazoline derivatives as angiogenesis inhibitors Download PDFInfo
- Publication number
- SK288138B6 SK288138B6 SK1140-2001A SK11402001A SK288138B6 SK 288138 B6 SK288138 B6 SK 288138B6 SK 11402001 A SK11402001 A SK 11402001A SK 288138 B6 SK288138 B6 SK 288138B6
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- alkyl
- carbon atoms
- moiety
- yloxy
- Prior art date
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- 239000004037 angiogenesis inhibitor Substances 0.000 title abstract 2
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title description 12
- 229940121369 angiogenesis inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 191
- 150000003839 salts Chemical class 0.000 claims abstract description 104
- 238000000034 method Methods 0.000 claims abstract description 41
- 230000000694 effects Effects 0.000 claims abstract description 14
- 230000008728 vascular permeability Effects 0.000 claims abstract description 14
- 241001465754 Metazoa Species 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract 5
- 125000000217 alkyl group Chemical group 0.000 claims description 1155
- 125000004432 carbon atom Chemical group C* 0.000 claims description 1134
- -1 4-Fluoroindol-5-yloxy Chemical group 0.000 claims description 1052
- 125000003545 alkoxy group Chemical group 0.000 claims description 242
- 125000001424 substituent group Chemical group 0.000 claims description 173
- 229910052757 nitrogen Inorganic materials 0.000 claims description 166
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 124
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 120
- 229910052799 carbon Inorganic materials 0.000 claims description 110
- 125000002393 azetidinyl group Chemical group 0.000 claims description 107
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 104
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 103
- 229910052736 halogen Inorganic materials 0.000 claims description 101
- 125000000623 heterocyclic group Chemical group 0.000 claims description 101
- 150000002367 halogens Chemical class 0.000 claims description 100
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 91
- 125000004043 oxo group Chemical group O=* 0.000 claims description 87
- 229910052739 hydrogen Inorganic materials 0.000 claims description 84
- 239000001257 hydrogen Substances 0.000 claims description 83
- 125000003342 alkenyl group Chemical group 0.000 claims description 82
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 76
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 75
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 72
- 125000003386 piperidinyl group Chemical group 0.000 claims description 72
- 125000005842 heteroatom Chemical group 0.000 claims description 69
- 229910052760 oxygen Inorganic materials 0.000 claims description 69
- 229910052717 sulfur Inorganic materials 0.000 claims description 69
- 125000003282 alkyl amino group Chemical group 0.000 claims description 61
- 125000000304 alkynyl group Chemical group 0.000 claims description 60
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 58
- 125000004122 cyclic group Chemical group 0.000 claims description 55
- 125000004193 piperazinyl group Chemical group 0.000 claims description 52
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 50
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims description 48
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 44
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 44
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 42
- 150000002431 hydrogen Chemical class 0.000 claims description 41
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 40
- 125000003277 amino group Chemical group 0.000 claims description 39
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 39
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 38
- 125000005843 halogen group Chemical group 0.000 claims description 37
- 125000003418 alkyl amino alkoxy group Chemical group 0.000 claims description 35
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 29
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 29
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 29
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 29
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 29
- 150000001721 carbon Chemical group 0.000 claims description 25
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 25
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 24
- 230000008569 process Effects 0.000 claims description 24
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 24
- 125000004848 alkoxyethyl group Chemical group 0.000 claims description 23
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 23
- 125000004429 atom Chemical group 0.000 claims description 23
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 23
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 22
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 21
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 18
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 18
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 13
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 13
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 11
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 10
- 241000282414 Homo sapiens Species 0.000 claims description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- 239000000460 chlorine Substances 0.000 claims description 10
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 8
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 239000008096 xylene Substances 0.000 claims description 7
- RMRFFCXPLWYOOY-UHFFFAOYSA-N allyl radical Chemical group [CH2]C=C RMRFFCXPLWYOOY-UHFFFAOYSA-N 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 6
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- BHNHHSOHWZKFOX-UHFFFAOYSA-N 2-methyl-1H-indole Chemical compound C1=CC=C2NC(C)=CC2=C1 BHNHHSOHWZKFOX-UHFFFAOYSA-N 0.000 claims description 4
- VWIOUOMKJGDTHR-UHFFFAOYSA-N 6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]-7-(3-pyrrolidin-1-ylpropoxy)quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCCCN1CCCC1 VWIOUOMKJGDTHR-UHFFFAOYSA-N 0.000 claims description 4
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- YUHFKJWRLSLBBH-UHFFFAOYSA-N 4-(1h-indol-5-yloxy)-6-methoxy-7-(3-methylsulfonylpropoxy)quinazoline Chemical compound C1=C2NC=CC2=CC(OC2=C3C=C(C(=CC3=NC=N2)OCCCS(C)(=O)=O)OC)=C1 YUHFKJWRLSLBBH-UHFFFAOYSA-N 0.000 claims description 3
- QXMBFDNIAYVLFK-UHFFFAOYSA-N 4-[(2,3-dimethyl-1h-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C(C)=C(C)NC4=CC=3)N=CN=C2C=C1OCCCN1CCCC1 QXMBFDNIAYVLFK-UHFFFAOYSA-N 0.000 claims description 3
- BYXRJZJEIZSEEJ-UHFFFAOYSA-N 4-[(2,3-dimethyl-1h-indol-5-yl)oxy]-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C(C)=C(C)NC4=CC=3)N=CN=C2C=C1OCC1CCN(C)CC1 BYXRJZJEIZSEEJ-UHFFFAOYSA-N 0.000 claims description 3
- YAIZIOMJNQKWHW-UHFFFAOYSA-N 4-[(4-fluoro-1h-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=CNC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 YAIZIOMJNQKWHW-UHFFFAOYSA-N 0.000 claims description 3
- QLKYLLNKQLYUCK-UHFFFAOYSA-N 4-[(4-fluoro-1h-indol-5-yl)oxy]-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=CNC4=CC=3)F)N=CN=C2C=C1OCC1CCN(C)CC1 QLKYLLNKQLYUCK-UHFFFAOYSA-N 0.000 claims description 3
- XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 claims description 3
- NZMWZMBJACHTSF-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCCC1 NZMWZMBJACHTSF-UHFFFAOYSA-N 0.000 claims description 3
- XWOGDYNDOQKNBW-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCC1CCN(C)CC1 XWOGDYNDOQKNBW-UHFFFAOYSA-N 0.000 claims description 3
- WKHMXMYWJGLMDQ-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-[2-(1-methylpiperidin-4-yl)ethoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCC1CCN(C)CC1 WKHMXMYWJGLMDQ-UHFFFAOYSA-N 0.000 claims description 3
- UBQBLLUOQUWFBD-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCN(C)CC1 UBQBLLUOQUWFBD-UHFFFAOYSA-N 0.000 claims description 3
- CUXRYZZQLQTALS-UHFFFAOYSA-N 4-[(6-fluoro-1h-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline Chemical compound COC1=CC2=C(OC=3C(=CC=4NC=CC=4C=3)F)N=CN=C2C=C1OCCCN1CCCC1 CUXRYZZQLQTALS-UHFFFAOYSA-N 0.000 claims description 3
- QFKOPMYWROWEFC-UHFFFAOYSA-N 4-[2-[2-[6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxyethoxy]ethyl]morpholine Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCCOCCN1CCOCC1 QFKOPMYWROWEFC-UHFFFAOYSA-N 0.000 claims description 3
- AUEYCHJTTCJDQE-UHFFFAOYSA-N 4-[2-[6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxyethyl]morpholine Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCCN1CCOCC1 AUEYCHJTTCJDQE-UHFFFAOYSA-N 0.000 claims description 3
- MTIRLVIGOZBETB-UHFFFAOYSA-N 4-[3-(6-methoxy-4-quinolin-7-yloxyquinazolin-7-yl)oxypropyl]morpholine Chemical compound COC1=CC2=C(OC=3C=C4N=CC=CC4=CC=3)N=CN=C2C=C1OCCCN1CCOCC1 MTIRLVIGOZBETB-UHFFFAOYSA-N 0.000 claims description 3
- OGGVFXMSCQVORR-UHFFFAOYSA-N 4-[3-[4-(4-chloroquinolin-7-yl)oxy-6-methoxyquinazolin-7-yl]oxypropyl]morpholine Chemical compound COC1=CC2=C(OC=3C=C4N=CC=C(Cl)C4=CC=3)N=CN=C2C=C1OCCCN1CCOCC1 OGGVFXMSCQVORR-UHFFFAOYSA-N 0.000 claims description 3
- XACHHHFBHKJFTG-UHFFFAOYSA-N 4-[3-[6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxypropyl]morpholine Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCCCN1CCOCC1 XACHHHFBHKJFTG-UHFFFAOYSA-N 0.000 claims description 3
- IDJNQPAEAFFNTF-UHFFFAOYSA-N 6-methoxy-4-(4-methylquinolin-7-yl)oxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline Chemical compound COC1=CC2=C(OC=3C=C4N=CC=C(C)C4=CC=3)N=CN=C2C=C1OCCCN1CCCC1 IDJNQPAEAFFNTF-UHFFFAOYSA-N 0.000 claims description 3
- XWZDOLXRLQATMB-UHFFFAOYSA-N 6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]-7-(2-pyrrolidin-1-ylethoxy)quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCCN1CCCC1 XWZDOLXRLQATMB-UHFFFAOYSA-N 0.000 claims description 3
- HMKXLULQTFQOTJ-UHFFFAOYSA-N 6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]-7-(3-methylsulfonylpropoxy)quinazoline Chemical compound C1=C2NC(C)=CC2=CC(OC2=C3C=C(C(=CC3=NC=N2)OCCCS(C)(=O)=O)OC)=C1 HMKXLULQTFQOTJ-UHFFFAOYSA-N 0.000 claims description 3
- OTOUXILYJXJWKG-UHFFFAOYSA-N 6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]-7-(piperidin-4-ylmethoxy)quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCC1CCNCC1 OTOUXILYJXJWKG-UHFFFAOYSA-N 0.000 claims description 3
- GBGXDEQXIOILJR-UHFFFAOYSA-N 6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]-7-[2-(1,2,4-triazol-1-yl)ethoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCCN1C=NC=N1 GBGXDEQXIOILJR-UHFFFAOYSA-N 0.000 claims description 3
- IWFIXMMBXWYLPM-UHFFFAOYSA-N 6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]-7-[2-[2-(4-methylpiperazin-1-yl)ethoxy]ethoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCCOCCN1CCN(C)CC1 IWFIXMMBXWYLPM-UHFFFAOYSA-N 0.000 claims description 3
- XVERRHVZSLWUFT-UHFFFAOYSA-N 6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)-4-[[2-(trifluoromethyl)-1h-indol-5-yl]oxy]quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=C(NC4=CC=3)C(F)(F)F)N=CN=C2C=C1OCCCN1CCCC1 XVERRHVZSLWUFT-UHFFFAOYSA-N 0.000 claims description 3
- LLEKBLGYIYIZGY-UHFFFAOYSA-N 6-methoxy-7-[(1-methylpiperidin-3-yl)methoxy]-4-quinolin-7-yloxyquinazoline Chemical compound COC1=CC2=C(OC=3C=C4N=CC=CC4=CC=3)N=CN=C2C=C1OCC1CCCN(C)C1 LLEKBLGYIYIZGY-UHFFFAOYSA-N 0.000 claims description 3
- GJNCFYVBXCUDNX-UHFFFAOYSA-N 6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-4-(4-methylquinolin-7-yl)oxyquinazoline Chemical compound COC1=CC2=C(OC=3C=C4N=CC=C(C)C4=CC=3)N=CN=C2C=C1OCC1CCN(C)CC1 GJNCFYVBXCUDNX-UHFFFAOYSA-N 0.000 claims description 3
- PEKIYYDHDJIMAB-UHFFFAOYSA-N 6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-4-[[2-(trifluoromethyl)-1h-indol-5-yl]oxy]quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=C(NC4=CC=3)C(F)(F)F)N=CN=C2C=C1OCC1CCN(C)CC1 PEKIYYDHDJIMAB-UHFFFAOYSA-N 0.000 claims description 3
- GIRSQICOEKYBIB-UHFFFAOYSA-N 6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-4-naphthalen-2-yloxyquinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=CC=CC4=CC=3)N=CN=C2C=C1OCC1CCN(C)CC1 GIRSQICOEKYBIB-UHFFFAOYSA-N 0.000 claims description 3
- ZCFBUMNTQJWXDH-UHFFFAOYSA-N 6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-4-quinolin-7-yloxyquinazoline Chemical compound COC1=CC2=C(OC=3C=C4N=CC=CC4=CC=3)N=CN=C2C=C1OCC1CCN(C)CC1 ZCFBUMNTQJWXDH-UHFFFAOYSA-N 0.000 claims description 3
- CXYGHMXUYKGXHL-UHFFFAOYSA-N 6-methoxy-7-[2-(2-methoxyethoxy)ethoxy]-4-[(2-methyl-1h-indol-5-yl)oxy]quinazoline Chemical compound C1=C2NC(C)=CC2=CC(OC=2N=CN=C3C=C(C(=CC3=2)OC)OCCOCCOC)=C1 CXYGHMXUYKGXHL-UHFFFAOYSA-N 0.000 claims description 3
- BMIUIVQIHYOKBO-UHFFFAOYSA-N 6-methoxy-7-[2-(2-methoxyethoxy)ethoxy]-4-quinolin-7-yloxyquinazoline Chemical compound C1=CC=NC2=CC(OC=3N=CN=C4C=C(C(=CC4=3)OC)OCCOCCOC)=CC=C21 BMIUIVQIHYOKBO-UHFFFAOYSA-N 0.000 claims description 3
- YNIYIXLTDOQPBV-UHFFFAOYSA-N 6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]-4-quinolin-7-yloxyquinazoline Chemical compound COC1=CC2=C(OC=3C=C4N=CC=CC4=CC=3)N=CN=C2C=C1OCCCN1CCN(C)CC1 YNIYIXLTDOQPBV-UHFFFAOYSA-N 0.000 claims description 3
- HVFDRYRGNKCISB-UHFFFAOYSA-N 6-methoxy-7-[[1-(2-methoxyethyl)piperidin-4-yl]methoxy]-4-[(2-methyl-1h-indol-5-yl)oxy]quinazoline Chemical compound C1CN(CCOC)CCC1COC1=CC2=NC=NC(OC=3C=C4C=C(C)NC4=CC=3)=C2C=C1OC HVFDRYRGNKCISB-UHFFFAOYSA-N 0.000 claims description 3
- WRVLCINSRDCLKV-UHFFFAOYSA-N 6-methoxy-7-[[1-(2-methylsulfonylethyl)piperidin-4-yl]methoxy]-4-quinolin-7-yloxyquinazoline Chemical compound COC1=CC2=C(OC=3C=C4N=CC=CC4=CC=3)N=CN=C2C=C1OCC1CCN(CCS(C)(=O)=O)CC1 WRVLCINSRDCLKV-UHFFFAOYSA-N 0.000 claims description 3
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- 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
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- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99400305 | 1999-02-10 | ||
| PCT/GB2000/000373 WO2000047212A1 (en) | 1999-02-10 | 2000-02-08 | Quinazoline derivatives as angiogenesis inhibitors |
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| SK288138B6 true SK288138B6 (sk) | 2013-11-04 |
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| Application Number | Title | Priority Date | Filing Date |
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| SK1140-2001A SK288138B6 (sk) | 1999-02-10 | 2000-02-08 | Quinazoline derivatives as angiogenesis inhibitors |
| SK5029-2011A SK288365B6 (sk) | 1999-02-10 | 2000-02-08 | Medziprodukty pre chinazolínové deriváty ako inhibítory angiogenézy |
| SK50002-2013A SK288378B6 (sk) | 1999-02-10 | 2000-02-08 | Použitie chinazolínových derivátov ako inhibítorov angiogenézy |
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| SK5029-2011A SK288365B6 (sk) | 1999-02-10 | 2000-02-08 | Medziprodukty pre chinazolínové deriváty ako inhibítory angiogenézy |
| SK50002-2013A SK288378B6 (sk) | 1999-02-10 | 2000-02-08 | Použitie chinazolínových derivátov ako inhibítorov angiogenézy |
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| BR0113056A (pt) | 2000-08-09 | 2003-07-08 | Astrazeneca Ab | Composto, processo papa a preparação do mesmo, composição farmacêutica, e, método para produzir um efeito antiangiogênico e/ou redutor da permeabilidade vascular em um animal de sangue quente, e, uso de um composto |
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2000
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4A | Patent expired |
Expiry date: 20200208 |