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)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (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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| WO2003040108A1 (en) * | 2001-11-03 | 2003-05-15 | Astrazeneca Ab | Quinazoline derivatives as antitumor agents |
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| GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
| AU2004272345A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives |
| US20070032508A1 (en) * | 2003-09-16 | 2007-02-08 | Bradbury Robert H | Quinazoline derivatives as tyrosine kinase inhibitors |
| ATE395346T1 (de) * | 2003-09-16 | 2008-05-15 | Astrazeneca Ab | Chinazolinderivate als tyrosinkinaseinhibitoren |
| GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
| BRPI0414488A (pt) * | 2003-09-16 | 2006-11-14 | Astrazeneca Ab | derivado de quinazolina, composição farmacêutica, uso de um derivado de quinazolina, métodos para produzir um efeito anti - proliferativo em um animal de sangue quente, para prevenção ou tratamento de tumores em um aminal de sangue quente, para fornecer um efeito inibidor da tirosina quinase de egfr seletivo em um animal de sangue quente e para tratar um cáncer em um animal de sangue quente e, processo para a preparação de um derivado de quinazolina |
| GB0322409D0 (en) * | 2003-09-25 | 2003-10-29 | Astrazeneca Ab | Quinazoline derivatives |
| GB0326459D0 (en) * | 2003-11-13 | 2003-12-17 | Astrazeneca Ab | Quinazoline derivatives |
| ES2315834T3 (es) | 2004-02-03 | 2009-04-01 | Astrazeneca Ab | Derivados de quinazolina. |
| CA2567832A1 (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 |
| GB0427697D0 (en) * | 2004-12-17 | 2005-01-19 | Astrazeneca Ab | Chemical process |
| GB0504475D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| GB0508715D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| DE602006018331D1 (de) * | 2005-09-20 | 2010-12-30 | Astrazeneca Ab | 4-(1h-indazol-5-ylamino)chinazolinverbindungen als inhibitoren der erbb-rezeptortyrosinkinase zur behandlung von krebs |
| EP1940825A1 (en) * | 2005-09-20 | 2008-07-09 | Astra Zeneca AB | Quinazoline derivatives as anticancer agents |
| US20100222344A1 (en) * | 2005-12-02 | 2010-09-02 | Astrazeneca Ab | 4-anilino-substituted quinazoline derivatives as tyrosine kinase inhibitors |
| US20090029968A1 (en) * | 2005-12-02 | 2009-01-29 | Bernard Christophe Barlaam | Quinazoline derivatives used as inhibitors of erbb tyrosine kinase |
| ES2444128T3 (es) | 2008-05-13 | 2014-02-24 | Astrazeneca Ab | Nueva SAL-554 |
| JP7006990B2 (ja) | 2017-11-17 | 2022-02-10 | セリックス バイオ プライヴェート リミテッド | 眼障害の処置のための組成物及び方法 |
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| 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 |
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| NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
| 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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| GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
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| GB2295387A (en) | 1994-11-23 | 1996-05-29 | Glaxo Inc | Quinazoline antagonists of alpha 1c adrenergic receptors |
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-
2003
- 2003-04-30 GB GBGB0309850.6A patent/GB0309850D0/en not_active Ceased
-
2004
- 2004-04-27 ES ES04729678T patent/ES2300767T3/es not_active Expired - Lifetime
- 2004-04-27 AT AT04729678T patent/ATE386530T1/de not_active IP Right Cessation
- 2004-04-27 DE DE602004011924T patent/DE602004011924T2/de not_active Expired - Lifetime
- 2004-04-27 JP JP2006506187A patent/JP4673839B2/ja not_active Expired - Fee Related
- 2004-04-27 WO PCT/GB2004/001799 patent/WO2004096226A1/en not_active Ceased
- 2004-04-27 US US10/555,085 patent/US7659279B2/en not_active Expired - Fee Related
- 2004-04-27 EP EP04729678A patent/EP1622620B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP4673839B2 (ja) | 2011-04-20 |
| DE602004011924D1 (de) | 2008-04-03 |
| EP1622620A1 (en) | 2006-02-08 |
| GB0309850D0 (en) | 2003-06-04 |
| US7659279B2 (en) | 2010-02-09 |
| US20060211714A1 (en) | 2006-09-21 |
| JP2006525296A (ja) | 2006-11-09 |
| HK1087613A1 (en) | 2006-10-20 |
| ES2300767T3 (es) | 2008-06-16 |
| EP1622620B1 (en) | 2008-02-20 |
| WO2004096226A1 (en) | 2004-11-11 |
| ATE386530T1 (de) | 2008-03-15 |
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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 |