ES2300767T3 - Derivados de quinazolina y su uso en el tratamiento del cancer. - Google Patents
Derivados de quinazolina y su uso en el tratamiento del cancer. Download PDFInfo
- Publication number
- ES2300767T3 ES2300767T3 ES04729678T ES04729678T ES2300767T3 ES 2300767 T3 ES2300767 T3 ES 2300767T3 ES 04729678 T ES04729678 T ES 04729678T ES 04729678 T ES04729678 T ES 04729678T ES 2300767 T3 ES2300767 T3 ES 2300767T3
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- Prior art keywords
- alkyl
- amino
- group
- quad
- alkoxy
- 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 53
- 238000011282 treatment Methods 0.000 title claims abstract description 46
- 201000011510 cancer Diseases 0.000 title claims abstract description 32
- 238000000034 method Methods 0.000 claims abstract description 153
- 230000008569 process Effects 0.000 claims abstract description 80
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 claims abstract description 64
- 238000002360 preparation method Methods 0.000 claims abstract description 26
- 239000003814 drug Substances 0.000 claims abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 201000010099 disease Diseases 0.000 claims abstract description 10
- 230000001404 mediated effect Effects 0.000 claims abstract description 8
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims abstract description 8
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- -1 hydroxy, cyano, amino, carboxy, carbamoyl Chemical group 0.000 claims description 552
- 125000000217 alkyl group Chemical group 0.000 claims description 403
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 194
- 125000001424 substituent group Chemical group 0.000 claims description 169
- 125000000623 heterocyclic group Chemical group 0.000 claims description 162
- 150000001875 compounds Chemical class 0.000 claims description 150
- 125000003545 alkoxy group Chemical group 0.000 claims description 133
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 121
- 229910052757 nitrogen Inorganic materials 0.000 claims description 111
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 106
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 101
- 125000001153 fluoro group Chemical group F* 0.000 claims description 95
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 92
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 82
- 150000003839 salts Chemical class 0.000 claims description 81
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 74
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 61
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 60
- 229910052736 halogen Inorganic materials 0.000 claims description 59
- 125000000304 alkynyl group Chemical group 0.000 claims description 57
- 150000002367 halogens Chemical class 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 49
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 239000001257 hydrogen Substances 0.000 claims description 43
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 41
- 229910052760 oxygen Inorganic materials 0.000 claims description 41
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 40
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 38
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 38
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 36
- 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 36
- 125000003342 alkenyl group Chemical group 0.000 claims description 33
- 229910052799 carbon Inorganic materials 0.000 claims description 32
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 30
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 29
- 230000000694 effects Effects 0.000 claims description 29
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 29
- 102000001301 EGF receptor Human genes 0.000 claims description 28
- 108060006698 EGF receptor Proteins 0.000 claims description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 28
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 23
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 23
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 23
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 22
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 22
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 21
- 230000005764 inhibitory process Effects 0.000 claims description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 125000001246 bromo group Chemical group Br* 0.000 claims description 20
- 229920006395 saturated elastomer Polymers 0.000 claims description 20
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 19
- 125000000524 functional group Chemical group 0.000 claims description 19
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 19
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 16
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 16
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 15
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims description 14
- 210000004881 tumor cell Anatomy 0.000 claims description 14
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 12
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 12
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 239000011593 sulfur Chemical group 0.000 claims description 12
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 11
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 11
- 238000003780 insertion Methods 0.000 claims description 11
- 230000037431 insertion Effects 0.000 claims description 11
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 11
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 10
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 10
- 238000005859 coupling reaction Methods 0.000 claims description 10
- 230000019491 signal transduction Effects 0.000 claims description 9
- 239000003085 diluting agent Substances 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 7
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 7
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 7
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 7
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims description 6
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
- 230000008878 coupling Effects 0.000 claims description 6
- 238000010168 coupling process Methods 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 230000004663 cell proliferation Effects 0.000 claims description 5
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 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 5
- 230000001012 protector Effects 0.000 claims description 5
- 125000006526 (C1-C2) alkyl group Chemical group 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
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 4
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 4
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 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
- 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 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000000446 sulfanediyl group Chemical group *S* 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 2
- 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 2
- 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 2
- 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 2
- 125000001589 carboacyl group Chemical group 0.000 claims 26
- 150000003246 quinazolines Chemical class 0.000 claims 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 125000005243 carbonyl alkyl group Chemical group 0.000 claims 2
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000005429 oxyalkyl group Chemical group 0.000 claims 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 18
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 18
- 229940121647 egfr inhibitor Drugs 0.000 abstract description 3
- 229940124597 therapeutic agent Drugs 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 116
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
- 238000006243 chemical reaction Methods 0.000 description 80
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 61
- 239000007787 solid Substances 0.000 description 57
- 238000001819 mass spectrum Methods 0.000 description 56
- 210000004027 cell Anatomy 0.000 description 48
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 45
- 125000002252 acyl group Chemical group 0.000 description 43
- 239000000203 mixture Substances 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 38
- 239000000243 solution Substances 0.000 description 38
- 239000007858 starting material Substances 0.000 description 37
- 125000006239 protecting group Chemical group 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 24
- 239000002253 acid Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 239000002585 base Substances 0.000 description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
- 229960005419 nitrogen Drugs 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 239000003480 eluent Substances 0.000 description 21
- 239000003112 inhibitor Substances 0.000 description 21
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 20
- 241000282414 Homo sapiens Species 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 20
- 238000004440 column chromatography Methods 0.000 description 19
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 18
- 230000035755 proliferation Effects 0.000 description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 17
- 239000002953 phosphate buffered saline Substances 0.000 description 17
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 17
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 238000003556 assay Methods 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 15
- 239000012299 nitrogen atmosphere Substances 0.000 description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 125000004429 atom Chemical group 0.000 description 14
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 14
- 229910052794 bromium Inorganic materials 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 13
- 230000002401 inhibitory effect Effects 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 description 13
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 229910021529 ammonia Inorganic materials 0.000 description 12
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- 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
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0309850.6A GB0309850D0 (en) | 2003-04-30 | 2003-04-30 | Quinazoline derivatives |
| GB0309850 | 2003-04-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2300767T3 true ES2300767T3 (es) | 2008-06-16 |
Family
ID=9957316
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES04729678T Expired - Lifetime ES2300767T3 (es) | 2003-04-30 | 2004-04-27 | Derivados de quinazolina y su uso en el tratamiento del cancer. |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US7659279B2 (enExample) |
| 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) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005515176A (ja) * | 2001-11-03 | 2005-05-26 | アストラゼネカ アクチボラグ | 抗腫瘍剤としてのキナゾリン誘導体 |
| GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| GB0309009D0 (en) * | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
| EP1664030A1 (en) * | 2003-09-16 | 2006-06-07 | AstraZeneca AB | Quinazoline derivatives |
| US7569577B2 (en) * | 2003-09-16 | 2009-08-04 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
| AU2004272350A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| 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 |
| ATE413389T1 (de) * | 2004-02-03 | 2008-11-15 | Astrazeneca Ab | Chinazolinderivate |
| CA2567832A1 (en) * | 2004-06-04 | 2005-12-15 | Astrazeneca Ab | Quinazoline derivatives as erbb receptor tyrosine kinases |
| CN101124228B (zh) * | 2004-12-14 | 2011-06-15 | 阿斯利康(瑞典)有限公司 | 用作抗肿瘤药物的吡唑并嘧啶化合物 |
| GB0427697D0 (en) | 2004-12-17 | 2005-01-19 | Astrazeneca Ab | Chemical process |
| GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| GB0504475D0 (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 |
| US7820683B2 (en) * | 2005-09-20 | 2010-10-26 | Astrazeneca Ab | 4-(1H-indazol-5-yl-amino)-quinazoline compounds as erbB receptor tyrosine kinase inhibitors for the treatment of cancer |
| US20090239861A1 (en) * | 2005-09-20 | 2009-09-24 | Robert Hugh Bradbury | Quinazoline derivatives as anticancer agents |
| ATE443053T1 (de) * | 2005-12-02 | 2009-10-15 | Astrazeneca Ab | Als inhibitoren von erbb-tyrosinkinase verwendete chinazoleinderivate |
| WO2007063291A1 (en) * | 2005-12-02 | 2007-06-07 | Astrazeneca Ab | 4-anilino-substituted quinazoline derivatives as tyrosine kinase inhibitors |
| BRPI0912170A2 (pt) | 2008-05-13 | 2015-10-13 | Astrazeneca Ab | composto, forma a, processo para a preparação da mesma, composição farmacêutica, uso de um composto, e, método para tratar um câncer em um animal de sangue quente |
| AU2018367909B2 (en) | 2017-11-17 | 2022-03-10 | Cellix Bio Private Limited | Compositions and methods for the treatment of eye disorders |
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| SK284073B6 (sk) | 1996-04-12 | 2004-09-08 | Warner-Lambert Company | Polycyklické zlúčeniny, ich použitie a farmaceutické kompozície na ich báze |
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| AR012634A1 (es) | 1997-05-02 | 2000-11-08 | Sugen Inc | Compuesto basado en quinazolina, composicion famaceutica que lo comprende, metodo para sintetizarlo, su uso, metodos de modulacion de la funcion deserina/treonina proteinaquinasa con dicho compuesto y metodo in vitro para identificar compuestos que modulan dicha funcion |
| US5929080A (en) | 1997-05-06 | 1999-07-27 | American Cyanamid Company | Method of treating polycystic kidney disease |
| DK0980244T3 (da) | 1997-05-06 | 2003-09-29 | Wyeth Corp | Anvendelse af quinazoline forbindelser til behandling af polycystisk nyresygdom |
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| JP4245682B2 (ja) | 1997-12-25 | 2009-03-25 | 協和発酵キリン株式会社 | キノリン誘導体、イソキノリン誘導体、およびシンノリン誘導体、並びに抗炎症剤および抗アレルギー剤 |
| GB9800575D0 (en) | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| HUP0102793A3 (en) | 1998-05-28 | 2002-07-29 | Parker Hughes Inst St Paul | Quinazolines for treating brain tumor and medicaments containing them |
| AU4851599A (en) | 1998-06-30 | 2000-01-17 | Parker Hughes Institute | Method for inhibiting c-jun expression using jak-3 inhibitors |
| US6384223B1 (en) | 1998-07-30 | 2002-05-07 | American Home Products Corporation | Substituted quinazoline derivatives |
| AR020114A1 (es) | 1998-07-30 | 2002-04-10 | America Home Products Corp | Proceso para la preparacion de derivados de quinazolina sustituida y compuestos para su exclusivo uso en dicho proceso |
| WO2000009481A1 (en) | 1998-08-11 | 2000-02-24 | Takeda Chemical Industries, Ltd. | Cyclic amide compounds, process for producing the same, intermediates thereof and herbicides |
| KR20010089171A (ko) | 1998-08-21 | 2001-09-29 | 추후제출 | 퀴나졸린 유도체 |
| US6297258B1 (en) | 1998-09-29 | 2001-10-02 | American Cyanamid Company | Substituted 3-cyanoquinolines |
| HU230728B1 (hu) | 1998-09-29 | 2017-12-28 | Wyeth Holdings Llc | Szubsztituált 3-cianokinolinok mint protein tirozin kinázok inhibitorai |
| BR9914162A (pt) | 1998-10-01 | 2001-06-26 | Astrazeneca Ab | Derivado de amida, processo para preparar um derivado de amida, ou um sal farmaceuticamente aceitável ou éster clivável in vivo do mesmo, composição farmacêutica e uso de um derivado de amida, ou um sal farmaceuticamente aceitável ou éster clivável in vivo do mesmo |
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| BRPI0017548B8 (pt) | 1999-02-10 | 2023-05-02 | Astrazeneca Ab | Composto |
| AU3281600A (en) | 1999-02-27 | 2000-09-21 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 4-amino-quinazoline and quinoline derivatives having an inhibitory effect on signal transsduction mediated by tyrosine kinases |
| DE19908567A1 (de) | 1999-02-27 | 2000-08-31 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| US6080747A (en) | 1999-03-05 | 2000-06-27 | Hughes Institute | JAK-3 inhibitors for treating allergic disorders |
| DE19911509A1 (de) | 1999-03-15 | 2000-09-21 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| UA73993C2 (uk) * | 2000-06-06 | 2005-10-17 | Астразенека Аб | Хіназолінові похідні для лікування пухлин та фармацевтична композиція |
| DE10040527A1 (de) | 2000-08-18 | 2002-02-28 | Boehringer Ingelheim Pharma | Chinazoline und Verfahren zu ihrer Herstellung |
| US6617329B2 (en) | 2000-08-26 | 2003-09-09 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines and their use as medicaments |
| US20020082270A1 (en) | 2000-08-26 | 2002-06-27 | Frank Himmelsbach | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| NZ516873A (en) | 2001-02-12 | 2003-11-28 | Warner Lambert Co | Compositions containing retinoids and erb inhibitors and their use in inhibiting retinoid skin damage |
| TWI309647B (enExample) | 2001-02-21 | 2009-05-11 | Mitsubishi Tanabe Pharma Corp | |
| US6562319B2 (en) | 2001-03-12 | 2003-05-13 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Radiolabeled irreversible inhibitors of epidermal growth factor receptor tyrosine kinase and their use in radioimaging and radiotherapy |
| WO2002094790A1 (en) | 2001-05-23 | 2002-11-28 | Mitsubishi Pharma Corporation | Fused heterocyclic compound and medicinal use thereof |
| JP2005515176A (ja) | 2001-11-03 | 2005-05-26 | アストラゼネカ アクチボラグ | 抗腫瘍剤としてのキナゾリン誘導体 |
| GB0126433D0 (en) | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| TWI324597B (en) | 2002-03-28 | 2010-05-11 | Astrazeneca Ab | Quinazoline derivatives |
| GB0309009D0 (en) | 2003-04-22 | 2003-05-28 | Astrazeneca Ab | Quinazoline derivatives |
| GB0317665D0 (en) | 2003-07-29 | 2003-09-03 | Astrazeneca Ab | Qinazoline derivatives |
| BRPI0413066A (pt) | 2003-07-29 | 2006-10-17 | Astrazeneca Ab | derivado de quinazolina, ou um sal farmaceuticamente aceitável, ou um éster farmaceuticamente aceitável do mesmo, da fórmula i, uso e processo para a preparação do mesmo, composto, composição farmacêutica, e, métodos para a produção de um efeito antiproliferativo em um animal de sangue quente, para a prevenção ou tratamento de um tumor, para prover um efeito inibitório de tirosina quinase de egfr seletivo, e para tratar um cáncer em um animal de sangue quente |
| US7569577B2 (en) | 2003-09-16 | 2009-08-04 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| 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 |
| GB0321648D0 (en) * | 2003-09-16 | 2003-10-15 | Astrazeneca Ab | Quinazoline derivatives |
| AU2004272350A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| DE602004004811T2 (de) | 2003-09-19 | 2007-11-22 | Astrazeneca Ab | Chinazolinderivate |
| US20070043010A1 (en) | 2003-09-25 | 2007-02-22 | Astrazeneca Uk Limited | 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 |
| ATE413389T1 (de) | 2004-02-03 | 2008-11-15 | Astrazeneca Ab | Chinazolinderivate |
| CA2567832A1 (en) | 2004-06-04 | 2005-12-15 | Astrazeneca Ab | Quinazoline derivatives as erbb receptor tyrosine kinases |
-
2003
- 2003-04-30 GB GBGB0309850.6A patent/GB0309850D0/en not_active Ceased
-
2004
- 2004-04-27 AT AT04729678T patent/ATE386530T1/de not_active IP Right Cessation
- 2004-04-27 US US10/555,085 patent/US7659279B2/en not_active Expired - Fee Related
- 2004-04-27 JP JP2006506187A patent/JP4673839B2/ja not_active Expired - Fee Related
- 2004-04-27 ES ES04729678T patent/ES2300767T3/es not_active Expired - Lifetime
- 2004-04-27 DE DE602004011924T patent/DE602004011924T2/de 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
Also Published As
| Publication number | Publication date |
|---|---|
| EP1622620A1 (en) | 2006-02-08 |
| DE602004011924D1 (de) | 2008-04-03 |
| DE602004011924T2 (de) | 2009-01-08 |
| ATE386530T1 (de) | 2008-03-15 |
| US20060211714A1 (en) | 2006-09-21 |
| WO2004096226A1 (en) | 2004-11-11 |
| JP4673839B2 (ja) | 2011-04-20 |
| EP1622620B1 (en) | 2008-02-20 |
| US7659279B2 (en) | 2010-02-09 |
| HK1087613A1 (en) | 2006-10-20 |
| JP2006525296A (ja) | 2006-11-09 |
| GB0309850D0 (en) | 2003-06-04 |
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