DE602004011924T2 - Chinazoline derivate und ihre anwendung in der krebsbehandlung - Google Patents
Chinazoline derivate und ihre anwendung in der krebsbehandlung Download PDFInfo
- Publication number
- DE602004011924T2 DE602004011924T2 DE602004011924T DE602004011924T DE602004011924T2 DE 602004011924 T2 DE602004011924 T2 DE 602004011924T2 DE 602004011924 T DE602004011924 T DE 602004011924T DE 602004011924 T DE602004011924 T DE 602004011924T DE 602004011924 T2 DE602004011924 T2 DE 602004011924T2
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- Germany
- Prior art keywords
- alkyl
- group
- formula
- alkoxy
- amino
- 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.)
- Expired - Lifetime
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- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 51
- 238000011282 treatment Methods 0.000 title claims abstract description 43
- 201000011510 cancer Diseases 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 109
- 230000008569 process Effects 0.000 claims abstract description 41
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 29
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 29
- 238000002360 preparation method Methods 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 claims abstract description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- -1 hydroxy, cyano, amino, carboxy, carbamoyl Chemical group 0.000 claims description 836
- 125000000217 alkyl group Chemical group 0.000 claims description 467
- 229910052757 nitrogen Inorganic materials 0.000 claims description 205
- 125000000623 heterocyclic group Chemical group 0.000 claims description 174
- 125000001424 substituent group Chemical group 0.000 claims description 157
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 146
- 125000003545 alkoxy group Chemical group 0.000 claims description 133
- 150000001875 compounds Chemical class 0.000 claims description 128
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 94
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 88
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 85
- 150000003246 quinazolines Chemical class 0.000 claims description 84
- 150000003839 salts Chemical class 0.000 claims description 79
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 67
- 229910052736 halogen Inorganic materials 0.000 claims description 64
- 229910052760 oxygen Inorganic materials 0.000 claims description 62
- 150000002367 halogens Chemical class 0.000 claims description 59
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 57
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
- 239000000460 chlorine Substances 0.000 claims description 54
- 229910052801 chlorine Inorganic materials 0.000 claims description 54
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 51
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 51
- 229910052731 fluorine Inorganic materials 0.000 claims description 51
- 239000011737 fluorine Substances 0.000 claims description 51
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 50
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 48
- 125000001153 fluoro group Chemical group F* 0.000 claims description 45
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 42
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 41
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 41
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 39
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 39
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 37
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 35
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 34
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 33
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 33
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 33
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 32
- 125000006239 protecting group Chemical group 0.000 claims description 32
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 31
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 29
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 28
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 27
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 26
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 26
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 26
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 25
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 25
- 102000001301 EGF receptor Human genes 0.000 claims description 24
- 108060006698 EGF receptor Proteins 0.000 claims description 24
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 24
- 230000035755 proliferation Effects 0.000 claims description 24
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 23
- 229910052794 bromium Inorganic materials 0.000 claims description 23
- 230000005764 inhibitory process Effects 0.000 claims description 23
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 22
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 22
- 125000000524 functional group Chemical group 0.000 claims description 22
- 230000002401 inhibitory effect Effects 0.000 claims description 21
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 20
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 19
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- 125000003282 alkyl amino group Chemical group 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000004423 acyloxy group Chemical group 0.000 claims description 18
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 17
- 125000001246 bromo group Chemical group Br* 0.000 claims description 16
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 16
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- 210000004881 tumor cell Anatomy 0.000 claims description 14
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 238000003780 insertion Methods 0.000 claims description 12
- 230000037431 insertion Effects 0.000 claims description 12
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 239000011593 sulfur Chemical group 0.000 claims description 11
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 238000005859 coupling reaction Methods 0.000 claims description 10
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 9
- 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 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 230000019491 signal transduction Effects 0.000 claims description 5
- NTABFMLTRPTDHH-MRXNPFEDSA-N 1-[(2r)-2-[[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OC)=CC=1OC[C@H]1CCCN1C(=O)CN(C)C NTABFMLTRPTDHH-MRXNPFEDSA-N 0.000 claims description 4
- CELREYOLUBVIRX-SFHVURJKSA-N 1-[(2s)-2-[[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-pyrrolidin-1-ylethanone Chemical compound C([C@H]1COC=2C=C(C=C3N=CN=C(NC=4C=C(Cl)C(F)=CC=4)C3=2)OC)CCN1C(=O)CN1CCCC1 CELREYOLUBVIRX-SFHVURJKSA-N 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- UCQKNONQJLXCJZ-QGZVFWFLSA-N 1-[(2r)-2-[[4-(3-chloro-4-fluoroanilino)-7-(2-ethoxyethoxy)quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OCCOCC)=CC=1OC[C@H]1CCCN1C(=O)CO UCQKNONQJLXCJZ-QGZVFWFLSA-N 0.000 claims description 3
- UHNQJZOECUKVME-OAHLLOKOSA-N 1-[(2r)-2-[[4-(3-chloro-4-fluoroanilino)-7-(2-hydroxyethoxy)quinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OCCO)=CC=1OC[C@H]1CCCN1C(=O)CO UHNQJZOECUKVME-OAHLLOKOSA-N 0.000 claims description 3
- AKBQOXHXZCHAPE-OAHLLOKOSA-N 1-[(2r)-2-[[4-(3-chloro-4-fluoroanilino)-7-ethoxyquinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OCC)=CC=1OC[C@H]1CCCN1C(=O)CO AKBQOXHXZCHAPE-OAHLLOKOSA-N 0.000 claims description 3
- OGHGSTSLGKIJSN-CQSZACIVSA-N 1-[(2r)-2-[[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OC)=CC=1OC[C@H]1CCCN1C(=O)CO OGHGSTSLGKIJSN-CQSZACIVSA-N 0.000 claims description 3
- CJBFTSCWGFCSSK-OAHLLOKOSA-N 1-[(2r)-2-[[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-5-yl]oxymethyl]pyrrolidin-1-yl]-2-methoxyethanone Chemical compound COCC(=O)N1CCC[C@@H]1COC1=CC(OC)=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C12 CJBFTSCWGFCSSK-OAHLLOKOSA-N 0.000 claims description 3
- 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 3
- PMCYYFHUNBMWPQ-HZPDHXFCSA-N 1-[(2r,4r)-2-[[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-5-yl]oxymethyl]-4-hydroxypyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OC)=CC=1OC[C@H]1C[C@@H](O)CN1C(=O)CN(C)C PMCYYFHUNBMWPQ-HZPDHXFCSA-N 0.000 claims description 2
- ZTOORYPSOVNYFG-ZIAGYGMSSA-N 1-[(2r,4r)-2-[[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-5-yl]oxymethyl]-4-hydroxypyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OC)=CC=1OC[C@H]1C[C@@H](O)CN1C(=O)CO ZTOORYPSOVNYFG-ZIAGYGMSSA-N 0.000 claims description 2
- PIVVDSXLUSYOIB-CABCVRRESA-N 1-[(2r,4s)-2-[[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-5-yl]oxymethyl]-4-hydroxypyrrolidin-1-yl]ethanone Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OC)=CC=1OC[C@H]1C[C@H](O)CN1C(C)=O PIVVDSXLUSYOIB-CABCVRRESA-N 0.000 claims description 2
- PMCYYFHUNBMWPQ-HOTGVXAUSA-N 1-[(2s,4s)-2-[[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-5-yl]oxymethyl]-4-hydroxypyrrolidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OC)=CC=1OC[C@@H]1C[C@H](O)CN1C(=O)CN(C)C PMCYYFHUNBMWPQ-HOTGVXAUSA-N 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 8
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 3
- ZTOORYPSOVNYFG-KGLIPLIRSA-N 1-[(2r,4s)-2-[[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-5-yl]oxymethyl]-4-hydroxypyrrolidin-1-yl]-2-hydroxyethanone Chemical compound C=12C(NC=3C=C(Cl)C(F)=CC=3)=NC=NC2=CC(OC)=CC=1OC[C@H]1C[C@H](O)CN1C(=O)CO ZTOORYPSOVNYFG-KGLIPLIRSA-N 0.000 claims 1
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
- 125000005530 alkylenedioxy group Chemical group 0.000 claims 1
- 125000003790 chinazolinyl group Chemical group 0.000 claims 1
- 229940121647 egfr inhibitor Drugs 0.000 abstract description 4
- 239000005483 tyrosine kinase inhibitor Substances 0.000 abstract description 3
- 230000001404 mediated effect Effects 0.000 abstract description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 abstract description 2
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- 238000006243 chemical reaction Methods 0.000 description 73
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 63
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 61
- 210000004027 cell Anatomy 0.000 description 56
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 description 44
- 239000000243 solution Substances 0.000 description 43
- 239000007787 solid Substances 0.000 description 42
- 238000001819 mass spectrum Methods 0.000 description 38
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 34
- 239000000203 mixture Substances 0.000 description 33
- 239000011541 reaction mixture Substances 0.000 description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 28
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 28
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
- 238000012360 testing method Methods 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 23
- 230000000694 effects Effects 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- 125000002252 acyl group Chemical group 0.000 description 22
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 22
- 239000007858 starting material Substances 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 239000002585 base Substances 0.000 description 20
- 229960005419 nitrogen Drugs 0.000 description 20
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 19
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 18
- 238000003556 assay Methods 0.000 description 18
- 239000003480 eluent Substances 0.000 description 18
- 239000003112 inhibitor Substances 0.000 description 18
- 239000002953 phosphate buffered saline Substances 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 16
- 241000282414 Homo sapiens Species 0.000 description 16
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 16
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 15
- 238000004440 column chromatography Methods 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- 235000019198 oils Nutrition 0.000 description 15
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 150000001721 carbon Chemical group 0.000 description 14
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
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Classifications
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- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (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)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
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|---|---|---|---|
| GB0309850 | 2003-04-30 | ||
| GBGB0309850.6A GB0309850D0 (en) | 2003-04-30 | 2003-04-30 | Quinazoline derivatives |
| PCT/GB2004/001799 WO2004096226A1 (en) | 2003-04-30 | 2004-04-27 | Quinazoline derivatives and their use in the treatment of cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE602004011924D1 DE602004011924D1 (de) | 2008-04-03 |
| DE602004011924T2 true DE602004011924T2 (de) | 2009-01-08 |
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| DE602004011924T Expired - Lifetime DE602004011924T2 (de) | 2003-04-30 | 2004-04-27 | Chinazoline derivate und ihre anwendung in der krebsbehandlung |
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| EP (1) | EP1622620B1 (enExample) |
| JP (1) | JP4673839B2 (enExample) |
| AT (1) | ATE386530T1 (enExample) |
| DE (1) | DE602004011924T2 (enExample) |
| ES (1) | ES2300767T3 (enExample) |
| GB (1) | GB0309850D0 (enExample) |
| WO (1) | WO2004096226A1 (enExample) |
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| EP1664028A1 (en) * | 2003-09-16 | 2006-06-07 | AstraZeneca AB | Quinazoline derivatives as tyrosine kinase inhibitors |
| US7569577B2 (en) * | 2003-09-16 | 2009-08-04 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
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| GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
| GB0322409D0 (en) * | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
| GB0326459D0 (en) * | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| EP1713781B1 (en) * | 2004-02-03 | 2008-11-05 | AstraZeneca AB | Quinazoline derivatives |
| WO2005118572A1 (en) * | 2004-06-04 | 2005-12-15 | Astrazeneca Ab | Quinazoline derivatives as erbb receptor tyrosine kinases |
| US7947676B2 (en) * | 2004-12-14 | 2011-05-24 | Astrazeneca Ab | Pyrazolo[3,4-d]pyrimidine compounds as antitumor agents |
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| GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| US20090239861A1 (en) * | 2005-09-20 | 2009-09-24 | Robert Hugh Bradbury | Quinazoline derivatives as anticancer agents |
| JP2009508918A (ja) * | 2005-09-20 | 2009-03-05 | アストラゼネカ アクチボラグ | 癌治療のためのｅｒｂＢ受容体チロシンキナーゼ阻害剤としての４−（１Ｈ−インダゾール−５−イル］アミノ）キナゾリン化合物 |
| EP1957499A1 (en) * | 2005-12-02 | 2008-08-20 | AstraZeneca AB | 4-anilino-substituted quinazoline derivatives as tyrosine kinase inhibitors |
| WO2007063293A1 (en) * | 2005-12-02 | 2007-06-07 | Astrazeneca Ab | Quinazoleine derivatives used as inhibitors of erbb tyrosine kinase |
| WO2009138781A1 (en) | 2008-05-13 | 2009-11-19 | Astrazeneca Ab | Fumarate salt of 4- (3-chloro-2-fluoroanilino) -7-methoxy-6- { [1- (n-methylcarbamoylmethyl) piperidin- 4-yl] oxy}quinazoline |
| CA3081553C (en) | 2017-11-17 | 2022-11-15 | Cellix Bio Private Limited | Compositions and methods for the treatment of eye disorders |
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| JPS5538325A (en) * | 1978-09-11 | 1980-03-17 | Sankyo Co Ltd | 4-anilinoquinazoline derivative and its preparation |
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| GB2160201B (en) * | 1984-06-14 | 1988-05-11 | Wyeth John & Brother Ltd | Quinazoline and cinnoline derivatives |
| KR910006138B1 (ko) | 1986-09-30 | 1991-08-16 | 에자이 가부시끼가이샤 | 환상아민 유도체 |
| IL89029A (en) | 1988-01-29 | 1993-01-31 | Lilly Co Eli | Fungicidal quinoline and cinnoline derivatives, compositions containing them, and fungicidal methods of using them |
| US4921863A (en) * | 1988-02-17 | 1990-05-01 | Eisai Co., Ltd. | Cyclic amine derivatives |
| CA1340821C (en) * | 1988-10-06 | 1999-11-16 | Nobuyuki Fukazawa | Heterocyclic compounds and anticancer-drug reinforcing agents containing them as effective components |
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| PT100905A (pt) | 1991-09-30 | 1994-02-28 | Eisai Co Ltd | Compostos heterociclicos azotados biciclicos contendo aneis de benzeno, ciclo-hexano ou piridina e de pirimidina, piridina ou imidazol substituidos e composicoes farmaceuticas que os contem |
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| GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
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| GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
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| GB0322409D0 (en) * | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
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-
2003
- 2003-04-30 GB GBGB0309850.6A patent/GB0309850D0/en not_active Ceased
-
2004
- 2004-04-27 US US10/555,085 patent/US7659279B2/en not_active Expired - Fee Related
- 2004-04-27 DE DE602004011924T patent/DE602004011924T2/de not_active Expired - Lifetime
- 2004-04-27 AT AT04729678T patent/ATE386530T1/de not_active IP Right Cessation
- 2004-04-27 ES ES04729678T patent/ES2300767T3/es not_active Expired - Lifetime
- 2004-04-27 WO PCT/GB2004/001799 patent/WO2004096226A1/en not_active Ceased
- 2004-04-27 EP EP04729678A patent/EP1622620B1/en not_active Expired - Lifetime
- 2004-04-27 JP JP2006506187A patent/JP4673839B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20060211714A1 (en) | 2006-09-21 |
| US7659279B2 (en) | 2010-02-09 |
| JP4673839B2 (ja) | 2011-04-20 |
| EP1622620A1 (en) | 2006-02-08 |
| DE602004011924D1 (de) | 2008-04-03 |
| WO2004096226A1 (en) | 2004-11-11 |
| HK1087613A1 (en) | 2006-10-20 |
| ATE386530T1 (de) | 2008-03-15 |
| EP1622620B1 (en) | 2008-02-20 |
| JP2006525296A (ja) | 2006-11-09 |
| ES2300767T3 (es) | 2008-06-16 |
| GB0309850D0 (en) | 2003-06-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8381 | Inventor (new situation) |
Inventor name: PLOWRIGHT, ALLEYN, CHESHIRE SK10 4TG, GB Inventor name: HENNEQUIN, L. F. A., CHESHIRE SK10 4TG, GB |
|
| 8364 | No opposition during term of opposition |