CA2534811A1 - Quinazoline derivatives as angiogenesis inhibitors - Google Patents
Quinazoline derivatives as angiogenesis inhibitors Download PDFInfo
- Publication number
- CA2534811A1 CA2534811A1 CA002534811A CA2534811A CA2534811A1 CA 2534811 A1 CA2534811 A1 CA 2534811A1 CA 002534811 A CA002534811 A CA 002534811A CA 2534811 A CA2534811 A CA 2534811A CA 2534811 A1 CA2534811 A1 CA 2534811A1
- Authority
- CA
- Canada
- Prior art keywords
- 4alkyl
- 3alkyl
- 4alkoxy
- group
- heterocyclic group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title description 10
- 239000004037 angiogenesis inhibitor Substances 0.000 title description 3
- 229940121369 angiogenesis inhibitor Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 238
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 120
- 150000003839 salts Chemical class 0.000 claims abstract description 95
- 238000000034 method Methods 0.000 claims abstract description 86
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 81
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 79
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 46
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 35
- 230000008569 process Effects 0.000 claims abstract description 35
- 238000004519 manufacturing process Methods 0.000 claims abstract description 22
- 238000011282 treatment Methods 0.000 claims abstract description 21
- 230000008728 vascular permeability Effects 0.000 claims abstract description 21
- 241001465754 Metazoa Species 0.000 claims abstract description 19
- 230000001772 anti-angiogenic effect Effects 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 14
- 230000001603 reducing effect Effects 0.000 claims abstract description 14
- 125000003118 aryl group Chemical group 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- -1 C1-4cyanoalkyl Chemical group 0.000 claims description 379
- 125000001424 substituent group Chemical group 0.000 claims description 208
- 229910052739 hydrogen Inorganic materials 0.000 claims description 158
- 239000001257 hydrogen Substances 0.000 claims description 158
- 125000000623 heterocyclic group Chemical group 0.000 claims description 136
- 150000002431 hydrogen Chemical group 0.000 claims description 122
- 125000005843 halogen group Chemical group 0.000 claims description 104
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 103
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 96
- 125000004043 oxo group Chemical group O=* 0.000 claims description 74
- 229910052717 sulfur Inorganic materials 0.000 claims description 74
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 60
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 55
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 52
- 125000004122 cyclic group Chemical group 0.000 claims description 48
- 238000006243 chemical reaction Methods 0.000 claims description 37
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 35
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 125000003386 piperidinyl group Chemical group 0.000 claims description 23
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 125000004193 piperazinyl group Chemical group 0.000 claims description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 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 17
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 17
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 14
- 241000282414 Homo sapiens Species 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 12
- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 150000001721 carbon Chemical group 0.000 claims description 8
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 6
- 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 6
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 6
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 4
- KIDITLRMHHRNNQ-UHFFFAOYSA-N 1-[4-[2-[6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxyethyl]piperazin-1-yl]propan-2-one Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCCN1CCN(CC(C)=O)CC1 KIDITLRMHHRNNQ-UHFFFAOYSA-N 0.000 claims description 3
- ATGHIPRSDSWTAH-UHFFFAOYSA-N 1-[4-[[6-methoxy-4-[(3-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound COC1=CC2=C(OC=3C=C4C(C)=CNC4=CC=3)N=CN=C2C=C1OCC(CC1)CCN1C(=O)CN1CCCC1 ATGHIPRSDSWTAH-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- UAQNJPXMOZCSEZ-UHFFFAOYSA-N 1-[4-[2-[6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxyethyl]piperazin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCCN(CC1)CCN1C(=O)CN1CCCC1 UAQNJPXMOZCSEZ-UHFFFAOYSA-N 0.000 claims description 2
- IKXIOUNJXDGJHC-UHFFFAOYSA-N 1-[4-[[6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCC(CC1)CCN1C(=O)CN1CCCC1 IKXIOUNJXDGJHC-UHFFFAOYSA-N 0.000 claims description 2
- SDCNZLCBPPVHFM-UHFFFAOYSA-N 1-[4-[[6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxymethyl]piperidin-1-yl]propan-2-one Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OCC1CCN(CC(C)=O)CC1 SDCNZLCBPPVHFM-UHFFFAOYSA-N 0.000 claims description 2
- IOHSSFHJTGVTOZ-UHFFFAOYSA-N 5-[2-[6-methoxy-4-[(3-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxyethyl]-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole Chemical compound C1=C2NC=C(C)C2=CC(OC2=C3C=C(C(=CC3=NC=N2)OCCN2CC3OCOC3C2)OC)=C1 IOHSSFHJTGVTOZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 36
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 23
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 2
- QEMQZTUAJCGRIH-UHFFFAOYSA-N 1-[4-[2-[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxyethyl]piperazin-1-yl]propan-2-one Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCN1CCN(CC(C)=O)CC1 QEMQZTUAJCGRIH-UHFFFAOYSA-N 0.000 claims 2
- HRVVCEOIDNXSIV-UHFFFAOYSA-N 5-[2-[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxyethyl]-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole Chemical compound C1=C2NC(C)=CC2=C(F)C(OC2=C3C=C(C(=CC3=NC=N2)OCCN2CC3OCOC3C2)OC)=C1 HRVVCEOIDNXSIV-UHFFFAOYSA-N 0.000 claims 2
- PLQFHSGCVXIPKH-UHFFFAOYSA-N 1-[4-[2-[4-[(2,3-dimethyl-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxyethyl]piperazin-1-yl]propan-2-one Chemical compound COC1=CC2=C(OC=3C=C4C(C)=C(C)NC4=CC=3)N=CN=C2C=C1OCCN1CCN(CC(C)=O)CC1 PLQFHSGCVXIPKH-UHFFFAOYSA-N 0.000 claims 1
- IELFRTCUXMQWBP-UHFFFAOYSA-N 1-[4-[2-[6-methoxy-4-[(3-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxyethyl]piperazin-1-yl]propan-2-one Chemical compound COC1=CC2=C(OC=3C=C4C(C)=CNC4=CC=3)N=CN=C2C=C1OCCN1CCN(CC(C)=O)CC1 IELFRTCUXMQWBP-UHFFFAOYSA-N 0.000 claims 1
- UDNVOJWOIXRDLF-UHFFFAOYSA-N 1-[4-[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxypiperidin-1-yl]propan-2-one Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OC1CCN(CC(C)=O)CC1 UDNVOJWOIXRDLF-UHFFFAOYSA-N 0.000 claims 1
- JIDBTFNSOGJOPT-UHFFFAOYSA-N 1-[4-[6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxypiperidin-1-yl]propan-2-one Chemical compound COC1=CC2=C(OC=3C=C4C=C(C)NC4=CC=3)N=CN=C2C=C1OC1CCN(CC(C)=O)CC1 JIDBTFNSOGJOPT-UHFFFAOYSA-N 0.000 claims 1
- HWFNODHJXDEFNM-UHFFFAOYSA-N 1-[4-[6-methoxy-4-[(2-methyl-1h-indol-6-yl)oxy]quinazolin-7-yl]oxypiperidin-1-yl]propan-2-one Chemical compound COC1=CC2=C(OC=3C=C4NC(C)=CC4=CC=3)N=CN=C2C=C1OC1CCN(CC(C)=O)CC1 HWFNODHJXDEFNM-UHFFFAOYSA-N 0.000 claims 1
- GKAMEQKEZGOKEK-UHFFFAOYSA-N 1-[4-[[6-methoxy-4-[(2-methyl-1h-indol-6-yl)oxy]quinazolin-7-yl]oxymethyl]piperidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound COC1=CC2=C(OC=3C=C4NC(C)=CC4=CC=3)N=CN=C2C=C1OCC(CC1)CCN1C(=O)CN1CCCC1 GKAMEQKEZGOKEK-UHFFFAOYSA-N 0.000 claims 1
- RZQRGWIRKGAYAD-UHFFFAOYSA-N 1-[4-[[6-methoxy-4-[(2-methyl-1h-indol-6-yl)oxy]quinazolin-7-yl]oxymethyl]piperidin-1-yl]propan-2-one Chemical compound COC1=CC2=C(OC=3C=C4NC(C)=CC4=CC=3)N=CN=C2C=C1OCC1CCN(CC(C)=O)CC1 RZQRGWIRKGAYAD-UHFFFAOYSA-N 0.000 claims 1
- RHKWHQSLWYKYCM-UHFFFAOYSA-N 1-[4-[[6-methoxy-4-[(3-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxymethyl]piperidin-1-yl]propan-2-one Chemical compound COC1=CC2=C(OC=3C=C4C(C)=CNC4=CC=3)N=CN=C2C=C1OCC1CCN(CC(C)=O)CC1 RHKWHQSLWYKYCM-UHFFFAOYSA-N 0.000 claims 1
- CVILSJNFFNFRHL-UHFFFAOYSA-N 5-[2-[4-[(2,3-dimethyl-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxyethyl]-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole Chemical compound C1=C2NC(C)=C(C)C2=CC(OC2=C3C=C(C(=CC3=NC=N2)OCCN2CC3OCOC3C2)OC)=C1 CVILSJNFFNFRHL-UHFFFAOYSA-N 0.000 claims 1
- SMUZSLBRTYLRAN-UHFFFAOYSA-N 5-[2-[6-methoxy-4-[(2-methyl-1h-indol-5-yl)oxy]quinazolin-7-yl]oxyethyl]-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole Chemical compound C1=C2NC(C)=CC2=CC(OC2=C3C=C(C(=CC3=NC=N2)OCCN2CC3OCOC3C2)OC)=C1 SMUZSLBRTYLRAN-UHFFFAOYSA-N 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 28
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract description 22
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 abstract description 22
- 206010028980 Neoplasm Diseases 0.000 abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 11
- 230000033115 angiogenesis Effects 0.000 abstract description 10
- 201000011510 cancer Diseases 0.000 abstract description 10
- 201000010099 disease Diseases 0.000 abstract description 10
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 75
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 239000000203 mixture Substances 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- 239000007787 solid Substances 0.000 description 48
- 239000002904 solvent Substances 0.000 description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
- 229910001868 water Inorganic materials 0.000 description 40
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 37
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 239000000243 solution Substances 0.000 description 32
- 238000001819 mass spectrum Methods 0.000 description 30
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- 238000001704 evaporation Methods 0.000 description 24
- 230000008020 evaporation Effects 0.000 description 24
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 23
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- 239000007858 starting material Substances 0.000 description 21
- 238000012360 testing method Methods 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 20
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 20
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
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- 238000003556 assay Methods 0.000 description 15
- 238000000921 elemental analysis Methods 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
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- 125000003545 alkoxy group Chemical group 0.000 description 12
- 150000001408 amides Chemical class 0.000 description 12
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 12
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
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- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 7
- NPHFOFOYWYLBTF-UHFFFAOYSA-N 3-methyl-1h-indol-5-ol Chemical compound C1=C(O)C=C2C(C)=CNC2=C1 NPHFOFOYWYLBTF-UHFFFAOYSA-N 0.000 description 6
- XZTBBMXMKIXQLY-UHFFFAOYSA-N 4-chloro-7-(2-chloroethoxy)-6-methoxyquinazoline Chemical compound N1=CN=C2C=C(OCCCl)C(OC)=CC2=C1Cl XZTBBMXMKIXQLY-UHFFFAOYSA-N 0.000 description 6
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- 230000006426 vascular sprouting Effects 0.000 description 1
- 230000004862 vasculogenesis Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
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- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
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- 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
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
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- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
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- 210000003905 vulva Anatomy 0.000 description 1
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Classifications
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- 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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
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- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0318422.3 | 2003-08-06 | ||
| GBGB0318422.3A GB0318422D0 (en) | 2003-08-06 | 2003-08-06 | Chemical compounds |
| PCT/GB2004/003376 WO2005014582A1 (en) | 2003-08-06 | 2004-08-05 | Quinazoline derivatives as angiogenesis inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2534811A1 true CA2534811A1 (en) | 2005-02-17 |
Family
ID=27839732
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002534811A Abandoned CA2534811A1 (en) | 2003-08-06 | 2004-08-05 | Quinazoline derivatives as angiogenesis inhibitors |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US7989460B2 (enExample) |
| EP (1) | EP1658280A1 (enExample) |
| JP (1) | JP4890249B2 (enExample) |
| KR (1) | KR20060058705A (enExample) |
| CN (1) | CN1863794B (enExample) |
| AU (1) | AU2004263360A1 (enExample) |
| BR (1) | BRPI0413284A (enExample) |
| CA (1) | CA2534811A1 (enExample) |
| GB (1) | GB0318422D0 (enExample) |
| IL (1) | IL173484A0 (enExample) |
| MX (1) | MXPA06001395A (enExample) |
| NO (1) | NO20060650L (enExample) |
| WO (1) | WO2005014582A1 (enExample) |
| ZA (1) | ZA200601025B (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EE05345B1 (et) | 1999-02-10 | 2010-10-15 | Astrazeneca Ab | Kinasoliini derivaadid angiogeneesi inhibiitoritena |
| HN2002000067A (es) * | 2001-03-23 | 2003-10-24 | Bayer Healthcare Llc | Inhibidores de la rho - quinasa. |
| EP2292615A1 (en) * | 2002-02-01 | 2011-03-09 | AstraZeneca AB | Quinazoline compounds |
| MX2007004403A (es) | 2004-10-12 | 2007-04-27 | Astrazeneca Ab | Derivados de quinazolina. |
| UY30183A1 (es) | 2006-03-02 | 2007-10-31 | Astrazeneca Ab | Derivados de quinolina |
| CL2007003158A1 (es) * | 2006-11-02 | 2008-05-16 | Astrazeneca Ab | Procedimiento de preparacion de compuestos derivados de quinazolina o sus sales farmaceuticamente aceptables; compuestos intermediarios; procedimiento de preparacion. |
| KR20100072266A (ko) * | 2007-10-24 | 2010-06-30 | 머크 샤프 앤드 돔 코포레이션 | 헤테로사이클 페닐 아미드 ｔ-형 칼슘 채널 길항제 |
| US8211911B2 (en) * | 2008-08-19 | 2012-07-03 | Guoqing Paul Chen | Compounds as kinase inhibitors |
| US8759362B2 (en) * | 2008-10-24 | 2014-06-24 | Purdue Pharma L.P. | Bicycloheteroaryl compounds and their use as TRPV1 ligands |
| US9353123B2 (en) * | 2013-02-20 | 2016-05-31 | Kala Pharmaceuticals, Inc. | Therapeutic compounds and uses thereof |
| USD746538S1 (en) * | 2014-02-03 | 2015-12-29 | Nautilus Hyosung Inc. | Automated teller machine |
| USD765340S1 (en) * | 2014-03-24 | 2016-08-30 | Nautilus Hyosung Inc. | Automated teller machine |
| USD746539S1 (en) * | 2014-03-24 | 2015-12-29 | Nautilus Hyosung Inc. | Automated teller machine |
| US20190112317A1 (en) | 2015-10-05 | 2019-04-18 | The Trustees Of Columbia University In The City Of New York | Activators of autophagic flux and phospholipase d and clearance of protein aggregates including tau and treatment of proteinopathies |
| CN112996784B (zh) * | 2018-09-18 | 2023-05-30 | 北京越之康泰生物医药科技有限公司 | 吲哚衍生物及其在医药上的应用 |
| TW202300152A (zh) | 2021-03-10 | 2023-01-01 | 美商纜圖藥品公司 | Ｅｇｆｒ抑制劑 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
| AU661533B2 (en) | 1992-01-20 | 1995-07-27 | Astrazeneca Ab | Quinazoline derivatives |
| GB9323290D0 (en) | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
| GB9314893D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
| GB9514265D0 (en) * | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| GB9714249D0 (en) | 1997-07-08 | 1997-09-10 | Angiogene Pharm Ltd | Vascular damaging agents |
| EE05345B1 (et) | 1999-02-10 | 2010-10-15 | Astrazeneca Ab | Kinasoliini derivaadid angiogeneesi inhibiitoritena |
| GB0008269D0 (en) | 2000-04-05 | 2000-05-24 | Astrazeneca Ab | Combination chemotherapy |
| IL153805A0 (en) * | 2000-08-09 | 2003-07-31 | Astrazeneca Ab | Cinnoline compounds |
| WO2002030926A1 (en) * | 2000-10-13 | 2002-04-18 | Astrazeneca Ab | Quinazoline derivatives |
| US20040063733A1 (en) * | 2000-10-25 | 2004-04-01 | Lambert Christine Marie Paul | Quinazoline derivatives |
| ES2272737T3 (es) * | 2001-07-16 | 2007-05-01 | Astrazeneca Ab | Derivados de quinolina y su uso como inhibidores de tirosina quinasas. |
| AU2002347336A1 (en) * | 2001-12-05 | 2003-06-17 | Astrazeneca Ab | Quinoline derivatives |
| EP2292615A1 (en) | 2002-02-01 | 2011-03-09 | AstraZeneca AB | Quinazoline compounds |
| GB0424339D0 (en) * | 2004-11-03 | 2004-12-08 | Astrazeneca Ab | Combination therapy |
| CA2631764A1 (en) * | 2005-12-22 | 2007-06-28 | Astrazeneca Ab | Combination of zd6474 and pemetrexed |
-
2003
- 2003-08-06 GB GBGB0318422.3A patent/GB0318422D0/en not_active Ceased
-
2004
- 2004-08-05 EP EP04743664A patent/EP1658280A1/en not_active Withdrawn
- 2004-08-05 JP JP2006522400A patent/JP4890249B2/ja not_active Expired - Fee Related
- 2004-08-05 MX MXPA06001395A patent/MXPA06001395A/es unknown
- 2004-08-05 CA CA002534811A patent/CA2534811A1/en not_active Abandoned
- 2004-08-05 AU AU2004263360A patent/AU2004263360A1/en not_active Abandoned
- 2004-08-05 WO PCT/GB2004/003376 patent/WO2005014582A1/en not_active Ceased
- 2004-08-05 CN CN2004800290795A patent/CN1863794B/zh not_active Expired - Fee Related
- 2004-08-05 BR BRPI0413284-0A patent/BRPI0413284A/pt not_active IP Right Cessation
- 2004-08-05 US US10/566,842 patent/US7989460B2/en not_active Expired - Fee Related
- 2004-08-05 KR KR1020067002540A patent/KR20060058705A/ko not_active Withdrawn
-
2006
- 2006-01-31 IL IL173484A patent/IL173484A0/en unknown
- 2006-02-03 ZA ZA200601025A patent/ZA200601025B/en unknown
- 2006-02-09 NO NO20060650A patent/NO20060650L/no not_active Application Discontinuation
-
2011
- 2011-06-20 US US13/164,310 patent/US20120046300A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007501210A (ja) | 2007-01-25 |
| IL173484A0 (en) | 2006-06-11 |
| MXPA06001395A (es) | 2006-05-19 |
| US20080058342A1 (en) | 2008-03-06 |
| CN1863794B (zh) | 2012-04-25 |
| AU2004263360A1 (en) | 2005-02-17 |
| WO2005014582A1 (en) | 2005-02-17 |
| EP1658280A1 (en) | 2006-05-24 |
| JP4890249B2 (ja) | 2012-03-07 |
| US20120046300A1 (en) | 2012-02-23 |
| CN1863794A (zh) | 2006-11-15 |
| GB0318422D0 (en) | 2003-09-10 |
| US7989460B2 (en) | 2011-08-02 |
| KR20060058705A (ko) | 2006-05-30 |
| BRPI0413284A (pt) | 2006-10-10 |
| NO20060650L (no) | 2006-04-24 |
| ZA200601025B (en) | 2007-05-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |