MXPA05011332A - Derivados de 4-anilino-quinazolina como agentes antiproliferativos. - Google Patents
Derivados de 4-anilino-quinazolina como agentes antiproliferativos.Info
- Publication number
- MXPA05011332A MXPA05011332A MXPA05011332A MXPA05011332A MXPA05011332A MX PA05011332 A MXPA05011332 A MX PA05011332A MX PA05011332 A MXPA05011332 A MX PA05011332A MX PA05011332 A MXPA05011332 A MX PA05011332A MX PA05011332 A MXPA05011332 A MX PA05011332A
- Authority
- MX
- Mexico
- Prior art keywords
- carbon atoms
- methyl
- alkyl
- amino
- formula
- Prior art date
Links
- 230000001028 anti-proliverative effect Effects 0.000 title claims abstract description 12
- MTSNDBYBIZSILH-UHFFFAOYSA-N n-phenylquinazolin-4-amine Chemical class N=1C=NC2=CC=CC=C2C=1NC1=CC=CC=C1 MTSNDBYBIZSILH-UHFFFAOYSA-N 0.000 title description 4
- 230000000694 effects Effects 0.000 claims abstract description 37
- 241001465754 Metazoa Species 0.000 claims abstract description 28
- 238000004519 manufacturing process Methods 0.000 claims abstract description 20
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims abstract description 16
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims abstract description 16
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 886
- -1 cyano, formyl Chemical group 0.000 claims description 413
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 306
- 239000001257 hydrogen Substances 0.000 claims description 299
- 229910052739 hydrogen Inorganic materials 0.000 claims description 299
- 125000000217 alkyl group Chemical group 0.000 claims description 294
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 213
- 125000001424 substituent group Chemical group 0.000 claims description 155
- 125000003545 alkoxy group Chemical group 0.000 claims description 133
- 150000001875 compounds Chemical class 0.000 claims description 128
- 229910052757 nitrogen Inorganic materials 0.000 claims description 105
- 238000006243 chemical reaction Methods 0.000 claims description 100
- 238000000034 method Methods 0.000 claims description 97
- 239000000460 chlorine Chemical group 0.000 claims description 87
- 229910052801 chlorine Inorganic materials 0.000 claims description 85
- 150000003839 salts Chemical class 0.000 claims description 76
- 229910052736 halogen Inorganic materials 0.000 claims description 75
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 74
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 73
- 150000002367 halogens Chemical group 0.000 claims description 72
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 68
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 64
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 60
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 59
- 239000011737 fluorine Chemical group 0.000 claims description 58
- 229910052731 fluorine Inorganic materials 0.000 claims description 58
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
- 229910052799 carbon Inorganic materials 0.000 claims description 57
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 56
- 230000008569 process Effects 0.000 claims description 54
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 45
- 125000003342 alkenyl group Chemical group 0.000 claims description 44
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 40
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 35
- 238000002360 preparation method Methods 0.000 claims description 34
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 33
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 33
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 32
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 32
- 125000000304 alkynyl group Chemical group 0.000 claims description 31
- 229910052760 oxygen Inorganic materials 0.000 claims description 31
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 31
- 229910052740 iodine Inorganic materials 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
- 230000005764 inhibitory process Effects 0.000 claims description 25
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 24
- 125000004429 atom Chemical group 0.000 claims description 24
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 24
- 229910052717 sulfur Inorganic materials 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
- 108091008598 receptor tyrosine kinases Proteins 0.000 claims description 22
- 125000000524 functional group Chemical group 0.000 claims description 21
- 102000027426 receptor tyrosine kinases Human genes 0.000 claims description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 19
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 17
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 17
- 125000001188 haloalkyl group Chemical group 0.000 claims description 16
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 16
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 15
- 125000004423 acyloxy group Chemical group 0.000 claims description 15
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 15
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 14
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 12
- 102000005962 receptors Human genes 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 11
- 108020003175 receptors Proteins 0.000 claims description 11
- 239000003638 chemical reducing agent Substances 0.000 claims description 10
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 9
- 229910052779 Neodymium Inorganic materials 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 9
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 9
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 8
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 8
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 8
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 8
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 7
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 229910052727 yttrium Inorganic materials 0.000 claims description 5
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 4
- 150000008049 diazo compounds Chemical class 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 241000156724 Antirhea Species 0.000 claims description 3
- PPXDYYLFQVGDMK-UHFFFAOYSA-N Cc1cc(COc2ccc(cc2C)-c2nc(N)c3ccccc3n2)no1 Chemical compound Cc1cc(COc2ccc(cc2C)-c2nc(N)c3ccccc3n2)no1 PPXDYYLFQVGDMK-UHFFFAOYSA-N 0.000 claims description 3
- OWNWTSLMCXMZQK-UHFFFAOYSA-N n-[3-chloro-4-[(5-methyl-1,2-oxazol-3-yl)methoxy]phenyl]-5-[2-(dimethylamino)ethoxy]quinazolin-4-amine Chemical compound C=12C(OCCN(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC=1C=C(C)ON=1 OWNWTSLMCXMZQK-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- RPZBHYXTHNVSOO-GOSISDBHSA-N 5-[(2r)-1-(dimethylamino)propan-2-yl]oxy-n-[3-methyl-4-(pyrazin-2-ylmethoxy)phenyl]quinazolin-4-amine Chemical compound C=12C(O[C@@H](CN(C)C)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CN=CC=N1 RPZBHYXTHNVSOO-GOSISDBHSA-N 0.000 claims description 2
- UZRURECKNYFBFA-UHFFFAOYSA-N 5-[1-(dimethylamino)propan-2-yloxy]-n-(3-methoxy-4-phenoxyphenyl)quinazolin-4-amine Chemical compound COC1=CC(NC=2C3=C(OC(C)CN(C)C)C=CC=C3N=CN=2)=CC=C1OC1=CC=CC=C1 UZRURECKNYFBFA-UHFFFAOYSA-N 0.000 claims description 2
- BWXRXGHSIQUIHR-UHFFFAOYSA-N 5-[2-(dimethylamino)-2-methylpropoxy]-n-[3-methyl-4-(1,3-thiazol-4-ylmethoxy)phenyl]quinazolin-4-amine Chemical compound C=12C(OCC(C)(C)N(C)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CSC=N1 BWXRXGHSIQUIHR-UHFFFAOYSA-N 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- POEJAIRLJJKQIP-UHFFFAOYSA-N n-[3-chloro-4-(1-methylimidazol-2-yl)sulfanylphenyl]-5-[2-(dimethylamino)ethoxy]quinazolin-4-amine Chemical compound C=12C(OCCN(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1SC1=NC=CN1C POEJAIRLJJKQIP-UHFFFAOYSA-N 0.000 claims description 2
- VBNCKTVKZOLLBE-UHFFFAOYSA-N n-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-[1-(dimethylamino)propan-2-yloxy]quinazolin-4-amine Chemical compound C=12C(OC(CN(C)C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 VBNCKTVKZOLLBE-UHFFFAOYSA-N 0.000 claims description 2
- 150000003246 quinazolines Chemical class 0.000 claims 39
- 150000002431 hydrogen Chemical class 0.000 claims 16
- 125000001589 carboacyl group Chemical group 0.000 claims 6
- XZBQSRDWZBFMFN-UHFFFAOYSA-N 2-[2-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-5-yl]oxyethyl-methylamino]ethanol Chemical compound C=12C(OCCN(CCO)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC(F)=C1 XZBQSRDWZBFMFN-UHFFFAOYSA-N 0.000 claims 1
- 125000003635 2-dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims 1
- ACDVGEQBERLOFY-LJQANCHMSA-N 5-[(2r)-1-(dimethylamino)propan-2-yl]oxy-n-[3-methyl-4-(pyridin-2-ylmethoxy)phenyl]quinazolin-4-amine Chemical compound C=12C(O[C@@H](CN(C)C)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CC=CC=N1 ACDVGEQBERLOFY-LJQANCHMSA-N 0.000 claims 1
- VBGQNCSBWRAFPZ-UHFFFAOYSA-N 5-[2-(dimethylamino)ethoxy]-n-[3-methoxy-4-(pyrazin-2-ylmethoxy)phenyl]quinazolin-4-amine Chemical compound COC1=CC(NC=2C3=C(OCCN(C)C)C=CC=C3N=CN=2)=CC=C1OCC1=CN=CC=N1 VBGQNCSBWRAFPZ-UHFFFAOYSA-N 0.000 claims 1
- HIRLFPPHNKFNND-UHFFFAOYSA-N 5-[2-(dimethylamino)ethoxy]-n-[3-methyl-4-(pyridin-2-ylmethoxy)phenyl]quinazolin-4-amine Chemical compound C=12C(OCCN(C)C)=CC=CC2=NC=NC=1NC(C=C1C)=CC=C1OCC1=CC=CC=N1 HIRLFPPHNKFNND-UHFFFAOYSA-N 0.000 claims 1
- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 claims 1
- 239000008896 Opium Substances 0.000 claims 1
- 235000001484 Trigonella foenum graecum Nutrition 0.000 claims 1
- 244000250129 Trigonella foenum graecum Species 0.000 claims 1
- HCEHQXRQLZKXLJ-OAHLLOKOSA-N n-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)phenyl]-5-[(2r)-1-(dimethylamino)propan-2-yl]oxyquinazolin-4-amine Chemical compound C=12C(O[C@@H](CN(C)C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CSC=N1 HCEHQXRQLZKXLJ-OAHLLOKOSA-N 0.000 claims 1
- QSPRUIUYBSEHKS-UHFFFAOYSA-N n-[3-chloro-4-(1,3-thiazol-4-ylmethoxy)phenyl]-5-[2-(dimethylamino)ethoxy]quinazolin-4-amine Chemical compound C=12C(OCCN(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CSC=N1 QSPRUIUYBSEHKS-UHFFFAOYSA-N 0.000 claims 1
- KSEHVVCEIFMPAP-MRXNPFEDSA-N n-[3-chloro-4-(pyrazin-2-ylmethoxy)phenyl]-5-[(2r)-1-(dimethylamino)propan-2-yl]oxyquinazolin-4-amine Chemical compound C=12C(O[C@@H](CN(C)C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CN=CC=N1 KSEHVVCEIFMPAP-MRXNPFEDSA-N 0.000 claims 1
- KSEHVVCEIFMPAP-INIZCTEOSA-N n-[3-chloro-4-(pyrazin-2-ylmethoxy)phenyl]-5-[(2s)-1-(dimethylamino)propan-2-yl]oxyquinazolin-4-amine Chemical compound C=12C(O[C@H](CN(C)C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CN=CC=N1 KSEHVVCEIFMPAP-INIZCTEOSA-N 0.000 claims 1
- KSEHVVCEIFMPAP-UHFFFAOYSA-N n-[3-chloro-4-(pyrazin-2-ylmethoxy)phenyl]-5-[1-(dimethylamino)propan-2-yloxy]quinazolin-4-amine Chemical compound C=12C(OC(CN(C)C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CN=CC=N1 KSEHVVCEIFMPAP-UHFFFAOYSA-N 0.000 claims 1
- VBNCKTVKZOLLBE-KRWDZBQOSA-N n-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-[(2s)-1-(dimethylamino)propan-2-yl]oxyquinazolin-4-amine Chemical compound C=12C(O[C@H](CN(C)C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 VBNCKTVKZOLLBE-KRWDZBQOSA-N 0.000 claims 1
- OHGYVCUFAYWBBF-UHFFFAOYSA-N n-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-[2-(dimethylamino)-2-methylpropoxy]quinazolin-4-amine Chemical compound C=12C(OCC(C)(C)N(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 OHGYVCUFAYWBBF-UHFFFAOYSA-N 0.000 claims 1
- ASWOHKYJMBVUMQ-UHFFFAOYSA-N n-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-5-[2-(dimethylamino)propoxy]quinazolin-4-amine Chemical compound C=12C(OCC(C)N(C)C)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ASWOHKYJMBVUMQ-UHFFFAOYSA-N 0.000 claims 1
- ZWYAFMLDNPRQAU-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-5-[2-[ethyl(methyl)amino]ethoxy]quinazolin-4-amine Chemical compound C=12C(OCCN(C)CC)=CC=CC2=NC=NC=1NC(C=C1Cl)=CC=C1OCC1=CC=CC(F)=C1 ZWYAFMLDNPRQAU-UHFFFAOYSA-N 0.000 claims 1
- 229960001027 opium Drugs 0.000 claims 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 80
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 76
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 69
- 125000002252 acyl group Chemical group 0.000 description 63
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 239000000203 mixture Substances 0.000 description 59
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- 239000007858 starting material Substances 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 201000011510 cancer Diseases 0.000 description 29
- 125000005843 halogen group Chemical group 0.000 description 28
- 238000012360 testing method Methods 0.000 description 23
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
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- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
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- 239000003701 inert diluent Substances 0.000 description 9
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0309009.9A GB0309009D0 (en) | 2003-04-22 | 2003-04-22 | Quinazoline derivatives |
| PCT/GB2004/001713 WO2004093880A1 (en) | 2003-04-22 | 2004-04-20 | 4-anilino-quinazoline derivatives as antiproliferative agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA05011332A true MXPA05011332A (es) | 2005-11-28 |
Family
ID=9957022
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA05011332A MXPA05011332A (es) | 2003-04-22 | 2004-04-20 | Derivados de 4-anilino-quinazolina como agentes antiproliferativos. |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US20070149546A1 (enExample) |
| EP (1) | EP1631292B1 (enExample) |
| JP (1) | JP2006524218A (enExample) |
| KR (1) | KR20060006821A (enExample) |
| CN (1) | CN100406453C (enExample) |
| AT (1) | ATE438402T1 (enExample) |
| AU (1) | AU2004231349A1 (enExample) |
| BR (1) | BRPI0409633A (enExample) |
| CA (1) | CA2526897A1 (enExample) |
| DE (1) | DE602004022404D1 (enExample) |
| ES (1) | ES2329576T3 (enExample) |
| GB (1) | GB0309009D0 (enExample) |
| MX (1) | MXPA05011332A (enExample) |
| NO (1) | NO20054856L (enExample) |
| NZ (1) | NZ543015A (enExample) |
| WO (1) | WO2004093880A1 (enExample) |
| ZA (1) | ZA200508525B (enExample) |
Families Citing this family (36)
| 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 |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| US20070021429A1 (en) * | 2003-04-09 | 2007-01-25 | Yves St-Denis | Condensed n-heterocyclic compounds and their use as crf receptor antagonists |
| GB0309850D0 (en) * | 2003-04-30 | 2003-06-04 | Astrazeneca Ab | Quinazoline derivatives |
| WO2004106308A1 (en) * | 2003-05-27 | 2004-12-09 | Pfizer Products Inc. | Quinazolines and pyrido [3,4-d] pyrimidines as receptor tyrosine kinase inhibitors |
| 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 |
| EP1664030A1 (en) * | 2003-09-16 | 2006-06-07 | 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 |
| GB0427917D0 (en) * | 2004-12-21 | 2005-01-26 | Astrazeneca Ab | Chemical compounds |
| GB0504474D0 (en) * | 2005-03-04 | 2005-04-13 | Astrazeneca Ab | Chemical compounds |
| GB0508717D0 (en) * | 2005-04-29 | 2005-06-08 | Astrazeneca Ab | Chemical compounds |
| GB0508715D0 (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 |
| WO2007063291A1 (en) * | 2005-12-02 | 2007-06-07 | Astrazeneca Ab | 4-anilino-substituted quinazoline derivatives as tyrosine kinase inhibitors |
| ATE443053T1 (de) * | 2005-12-02 | 2009-10-15 | Astrazeneca Ab | Als inhibitoren von erbb-tyrosinkinase verwendete chinazoleinderivate |
| US7547781B2 (en) | 2006-09-11 | 2009-06-16 | Curis, Inc. | Quinazoline based EGFR inhibitors containing a zinc binding moiety |
| BRPI0715016A2 (pt) | 2006-09-11 | 2013-05-28 | Curis Inc | composiÇço, composiÇço farmacÊutica, mÉtodo para tratar uma doenÇa ou distérbio relacionada com tirosina quinase de egfr em um individuo necessitando o mesmo, mÉtodo para tratar uma doenÇa mediada por hdac e mÉtodo para tratar doenÇas medidas tanto por tirosina quinase de egfr quanto hdac |
| WO2008041118A2 (en) * | 2006-10-04 | 2008-04-10 | Pfizer Products Inc. | Pyrido[4,3-d]pyrimidin-4(3h)-one derivatives as calcium receptor antagonists |
| EP1921070A1 (de) | 2006-11-10 | 2008-05-14 | Boehringer Ingelheim Pharma GmbH & Co. KG | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung |
| EA200901041A1 (ru) | 2007-02-06 | 2010-02-26 | Бёрингер Ингельхайм Интернациональ Гмбх | Бициклические гетероциклы, содержащие эти соединения лекарственные средства, их применение и способ их получения |
| TWI377944B (en) * | 2007-06-05 | 2012-12-01 | Hanmi Holdings Co Ltd | Novel amide derivative for inhibiting the growth of cancer cells |
| NZ585357A (en) | 2007-10-29 | 2012-02-24 | Natco Pharma Ltd | Novel 4-(tetrazol-5-yl)-quinazoline derivatives as anti cancer agents |
| RS52573B (sr) | 2008-02-07 | 2013-04-30 | Boehringer Ingelheim International Gmbh | Spirociklični heterocikli, lekovi koji sadrže navedeno jedinjenje, njihova primena i postupak za njihovu proizvodnju |
| 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 |
| CA2733153C (en) | 2008-08-08 | 2016-11-08 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them |
| CA2746650A1 (en) * | 2008-12-11 | 2010-06-17 | Proteus Biomedical, Inc. | Evaluation of gastrointestinal function using portable electroviscerography systems and methods of using the same |
| CN115260164B (zh) * | 2021-05-01 | 2024-03-26 | 杭州星鳌生物科技有限公司 | 新型4(3h)-喹唑啉酮类似物的制备方法、结构组成及其在抗肿瘤药物中的应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5538325A (en) * | 1978-09-11 | 1980-03-17 | Sankyo Co Ltd | 4-anilinoquinazoline derivative and its preparation |
| US4335127A (en) * | 1979-01-08 | 1982-06-15 | Janssen Pharmaceutica, N.V. | Piperidinylalkyl quinazoline compounds, composition and method of use |
| GB2160201B (en) * | 1984-06-14 | 1988-05-11 | Wyeth John & Brother Ltd | Quinazoline and cinnoline derivatives |
| 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 |
| US5721237A (en) * | 1991-05-10 | 1998-02-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylation properties |
| TW321649B (enExample) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
| US5747498A (en) * | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
| US6046206A (en) * | 1995-06-07 | 2000-04-04 | Cell Pathways, Inc. | Method of treating a patient having a precancerous lesions with amide quinazoline derivatives |
| GB9514265D0 (en) * | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| GB9624482D0 (en) * | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| CA2216169C (en) * | 1996-01-31 | 2007-01-23 | Gist-Brocades B.V. | Use of compositions comprising stabilized biologically effective compounds |
| GB9603095D0 (en) * | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
| US6004967A (en) * | 1996-09-13 | 1999-12-21 | Sugen, Inc. | Psoriasis treatment with quinazoline compounds |
| DE19651439A1 (de) * | 1996-12-11 | 1998-06-18 | Hoechst Ag | Polymerisierbare Biaryle, Verfahren zur Herstellung und deren Verwendung |
| US5929080A (en) * | 1997-05-06 | 1999-07-27 | American Cyanamid Company | Method of treating polycystic kidney disease |
| US6384223B1 (en) * | 1998-07-30 | 2002-05-07 | American Home Products Corporation | Substituted quinazoline derivatives |
| US6297258B1 (en) * | 1998-09-29 | 2001-10-02 | American Cyanamid Company | Substituted 3-cyanoquinolines |
| UA71945C2 (en) * | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| 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 |
| US6080747A (en) * | 1999-03-05 | 2000-06-27 | Hughes Institute | JAK-3 inhibitors for treating allergic disorders |
| US20020082270A1 (en) * | 2000-08-26 | 2002-06-27 | Frank Himmelsbach | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
| 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 |
| US6924285B2 (en) * | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
| GB0309850D0 (en) * | 2003-04-30 | 2003-06-04 | 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 |
| 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 |
| AU2004272350A1 (en) * | 2003-09-16 | 2005-03-24 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
| 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 |
| 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
- 2003-04-22 GB GBGB0309009.9A patent/GB0309009D0/en not_active Ceased
-
2004
- 2004-04-20 EP EP04728367A patent/EP1631292B1/en not_active Expired - Lifetime
- 2004-04-20 NZ NZ543015A patent/NZ543015A/en unknown
- 2004-04-20 ES ES04728367T patent/ES2329576T3/es not_active Expired - Lifetime
- 2004-04-20 AT AT04728367T patent/ATE438402T1/de not_active IP Right Cessation
- 2004-04-20 DE DE602004022404T patent/DE602004022404D1/de not_active Expired - Fee Related
- 2004-04-20 CA CA002526897A patent/CA2526897A1/en not_active Abandoned
- 2004-04-20 WO PCT/GB2004/001713 patent/WO2004093880A1/en not_active Ceased
- 2004-04-20 US US10/554,202 patent/US20070149546A1/en not_active Abandoned
- 2004-04-20 CN CNB2004800170469A patent/CN100406453C/zh not_active Expired - Fee Related
- 2004-04-20 AU AU2004231349A patent/AU2004231349A1/en not_active Abandoned
- 2004-04-20 KR KR1020057020096A patent/KR20060006821A/ko not_active Withdrawn
- 2004-04-20 BR BRPI0409633-9A patent/BRPI0409633A/pt not_active Application Discontinuation
- 2004-04-20 MX MXPA05011332A patent/MXPA05011332A/es unknown
- 2004-04-20 JP JP2006506155A patent/JP2006524218A/ja active Pending
-
2005
- 2005-10-20 ZA ZA200508525A patent/ZA200508525B/en unknown
- 2005-10-20 NO NO20054856A patent/NO20054856L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CN100406453C (zh) | 2008-07-30 |
| ES2329576T3 (es) | 2009-11-27 |
| KR20060006821A (ko) | 2006-01-19 |
| ATE438402T1 (de) | 2009-08-15 |
| HK1087632A1 (en) | 2006-10-20 |
| AU2004231349A1 (en) | 2004-11-04 |
| GB0309009D0 (en) | 2003-05-28 |
| CA2526897A1 (en) | 2004-11-04 |
| EP1631292B1 (en) | 2009-08-05 |
| JP2006524218A (ja) | 2006-10-26 |
| NO20054856D0 (no) | 2005-10-20 |
| ZA200508525B (en) | 2007-04-25 |
| DE602004022404D1 (de) | 2009-09-17 |
| NO20054856L (no) | 2005-11-21 |
| BRPI0409633A (pt) | 2006-04-25 |
| NZ543015A (en) | 2008-01-31 |
| US20070149546A1 (en) | 2007-06-28 |
| EP1631292A1 (en) | 2006-03-08 |
| WO2004093880A1 (en) | 2004-11-04 |
| CN1809360A (zh) | 2006-07-26 |
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