NO317093B1 - Substituerte kinazolinderivater og anvendelse derav som tyrosin-kinase-inhibitorer - Google Patents
Substituerte kinazolinderivater og anvendelse derav som tyrosin-kinase-inhibitorer Download PDFInfo
- Publication number
- NO317093B1 NO317093B1 NO20000487A NO20000487A NO317093B1 NO 317093 B1 NO317093 B1 NO 317093B1 NO 20000487 A NO20000487 A NO 20000487A NO 20000487 A NO20000487 A NO 20000487A NO 317093 B1 NO317093 B1 NO 317093B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- carbon atoms
- hydrogen
- bromo
- phenylamino
- Prior art date
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- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title description 10
- 239000005483 tyrosine kinase inhibitor Substances 0.000 title description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 169
- 229910052739 hydrogen Inorganic materials 0.000 claims description 80
- 125000004432 carbon atom Chemical group C* 0.000 claims description 74
- 239000001257 hydrogen Substances 0.000 claims description 70
- 238000006243 chemical reaction Methods 0.000 claims description 51
- 125000000217 alkyl group Chemical group 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 41
- 206010028980 Neoplasm Diseases 0.000 claims description 38
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 238000011282 treatment Methods 0.000 claims description 34
- 150000002431 hydrogen Chemical class 0.000 claims description 32
- 125000006239 protecting group Chemical group 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 30
- 239000012442 inert solvent Substances 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 150000002367 halogens Chemical group 0.000 claims description 26
- -1 4-diethylamino-but-2-enoic acid-[4-(3 -bromo-phenylamino)-quinazolin-6-yl]-amide Chemical compound 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 13
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 13
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 13
- 230000005764 inhibitory process Effects 0.000 claims description 13
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 13
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 11
- 239000000460 chlorine Substances 0.000 claims description 11
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 7
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 7
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 7
- 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 7
- 150000007530 organic bases Chemical class 0.000 claims description 7
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 7
- 210000000481 breast Anatomy 0.000 claims description 6
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 6
- 230000002074 deregulated effect Effects 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- OHGUZARBKZHFIT-UHFFFAOYSA-N 3-[[4-(3-bromoanilino)quinazolin-6-yl]amino]-4-ethoxycyclobut-3-ene-1,2-dione Chemical group O=C1C(=O)C(OCC)=C1NC1=CC=C(N=CN=C2NC=3C=C(Br)C=CC=3)C2=C1 OHGUZARBKZHFIT-UHFFFAOYSA-N 0.000 claims description 5
- 238000011161 development Methods 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 230000017066 negative regulation of growth Effects 0.000 claims description 5
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 claims description 4
- 101150029707 ERBB2 gene Proteins 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 210000003238 esophagus Anatomy 0.000 claims description 4
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- 210000000867 larynx Anatomy 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 210000000214 mouth Anatomy 0.000 claims description 4
- 210000001672 ovary Anatomy 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 210000002784 stomach Anatomy 0.000 claims description 4
- 210000003932 urinary bladder Anatomy 0.000 claims description 4
- DOTGZROJTAUYFQ-OWOJBTEDSA-N (e)-4-bromobut-2-enoic acid Chemical compound OC(=O)\C=C\CBr DOTGZROJTAUYFQ-OWOJBTEDSA-N 0.000 claims description 3
- 230000004071 biological effect Effects 0.000 claims description 3
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- DSKZTXVYAKNQCA-VOTSOKGWSA-N (e)-n-[4-(3-bromoanilino)quinazolin-6-yl]-3-chloroprop-2-enamide Chemical compound C12=CC(NC(=O)/C=C/Cl)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 DSKZTXVYAKNQCA-VOTSOKGWSA-N 0.000 claims description 2
- TUANVHQIDKPWKP-UHFFFAOYSA-N 3-[[4-(3-bromoanilino)quinazolin-6-yl]amino]-4-(dimethylamino)cyclobut-3-ene-1,2-dione Chemical compound O=C1C(=O)C(N(C)C)=C1NC1=CC=C(N=CN=C2NC=3C=C(Br)C=CC=3)C2=C1 TUANVHQIDKPWKP-UHFFFAOYSA-N 0.000 claims description 2
- QJLBYHLDTORADE-UHFFFAOYSA-N 3-[[4-(3-bromoanilino)quinazolin-6-yl]amino]-4-(methylamino)cyclobut-3-ene-1,2-dione Chemical compound O=C1C(=O)C(NC)=C1NC1=CC=C(N=CN=C2NC=3C=C(Br)C=CC=3)C2=C1 QJLBYHLDTORADE-UHFFFAOYSA-N 0.000 claims description 2
- ZVHAJSGXYIEEPK-UHFFFAOYSA-N 3-amino-4-[[4-(3-bromoanilino)quinazolin-6-yl]amino]cyclobut-3-ene-1,2-dione Chemical compound O=C1C(=O)C(N)=C1NC1=CC=C(N=CN=C2NC=3C=C(Br)C=CC=3)C2=C1 ZVHAJSGXYIEEPK-UHFFFAOYSA-N 0.000 claims description 2
- QPSMJGVGKOLLSP-UHFFFAOYSA-N 4-[bis(2-methoxyethyl)amino]-n-[4-(3-bromoanilino)quinazolin-6-yl]but-2-ynamide Chemical compound C12=CC(NC(=O)C#CCN(CCOC)CCOC)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 QPSMJGVGKOLLSP-UHFFFAOYSA-N 0.000 claims description 2
- QDMMMDHNXSJKBV-UHFFFAOYSA-N 4-amino-n-[4-(3-bromoanilino)quinazolin-6-yl]-4,5-dimethylhex-2-ynamide Chemical compound C12=CC(NC(=O)C#CC(C)(N)C(C)C)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 QDMMMDHNXSJKBV-UHFFFAOYSA-N 0.000 claims description 2
- WFQDJDAUFAIJTL-UHFFFAOYSA-N 4-amino-n-[4-(3-bromoanilino)quinazolin-6-yl]-6-methoxy-4-methylhex-2-ynamide Chemical compound C12=CC(NC(=O)C#CC(C)(N)CCOC)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 WFQDJDAUFAIJTL-UHFFFAOYSA-N 0.000 claims description 2
- JEZCURNCWCILAV-UHFFFAOYSA-N n-[4-(3-bromoanilino)quinazolin-6-yl]-4-(4-ethylpiperazin-1-yl)but-2-ynamide Chemical compound C1CN(CC)CCN1CC#CC(=O)NC1=CC=C(N=CN=C2NC=3C=C(Br)C=CC=3)C2=C1 JEZCURNCWCILAV-UHFFFAOYSA-N 0.000 claims description 2
- PFLWVIGXNYBNKD-UHFFFAOYSA-N n-[4-(3-bromoanilino)quinazolin-6-yl]-4-(4-methylpiperazin-1-yl)but-2-ynamide Chemical compound C1CN(C)CCN1CC#CC(=O)NC1=CC=C(N=CN=C2NC=3C=C(Br)C=CC=3)C2=C1 PFLWVIGXNYBNKD-UHFFFAOYSA-N 0.000 claims description 2
- OTMPOVZNMVTURI-UHFFFAOYSA-N n-[4-(3-bromoanilino)quinazolin-6-yl]-4-(dimethylamino)but-2-ynamide Chemical compound C12=CC(NC(=O)C#CCN(C)C)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 OTMPOVZNMVTURI-UHFFFAOYSA-N 0.000 claims description 2
- UCKKZOCKASQMFK-UHFFFAOYSA-N n-[4-(3-bromoanilino)quinazolin-6-yl]-4-(methoxymethoxy)but-2-ynamide Chemical compound C12=CC(NC(=O)C#CCOCOC)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 UCKKZOCKASQMFK-UHFFFAOYSA-N 0.000 claims description 2
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- VKFHLVGNIPONMR-UHFFFAOYSA-N n-[4-(3-bromoanilino)quinazolin-6-yl]-4-methoxybut-2-ynamide Chemical group C12=CC(NC(=O)C#CCOC)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 VKFHLVGNIPONMR-UHFFFAOYSA-N 0.000 claims description 2
- GGHZBUPPNLNXED-UHFFFAOYSA-N n-[4-(3-bromoanilino)quinazolin-6-yl]-4-morpholin-4-ylbut-2-ynamide Chemical group BrC1=CC=CC(NC=2C3=CC(NC(=O)C#CCN4CCOCC4)=CC=C3N=CN=2)=C1 GGHZBUPPNLNXED-UHFFFAOYSA-N 0.000 claims description 2
- XDSBIBMMFWAPMJ-UHFFFAOYSA-N n-[4-(3-bromoanilino)quinazolin-6-yl]ethenesulfonamide Chemical compound BrC1=CC=CC(NC=2C3=CC(NS(=O)(=O)C=C)=CC=C3N=CN=2)=C1 XDSBIBMMFWAPMJ-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- RHDYQUZYHZWTCI-UHFFFAOYSA-N 1-methoxy-4-phenylbenzene Chemical compound C1=CC(OC)=CC=C1C1=CC=CC=C1 RHDYQUZYHZWTCI-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—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
-
- 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
- C07D239/88—Oxygen atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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
- A61P35/04—Antineoplastic agents specific for metastasis
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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
- C07D239/93—Sulfur atoms
-
- 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
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/112—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D295/116—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/32—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US90494297A | 1997-08-01 | 1997-08-01 | |
PCT/US1998/015789 WO1999009016A1 (en) | 1997-08-01 | 1998-07-29 | Substituted quinazoline derivatives and their use as tyrosine kinase inhibitors |
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NO20000487D0 NO20000487D0 (no) | 2000-01-31 |
NO20000487L NO20000487L (no) | 2000-03-31 |
NO317093B1 true NO317093B1 (no) | 2004-08-09 |
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NO20000487A NO317093B1 (no) | 1997-08-01 | 2000-01-31 | Substituerte kinazolinderivater og anvendelse derav som tyrosin-kinase-inhibitorer |
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EP (1) | EP1000039B1 (ja) |
JP (3) | JP4988984B2 (ja) |
KR (1) | KR100511700B1 (ja) |
CN (2) | CN101857573A (ja) |
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BE (1) | BE2014C023I2 (ja) |
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ES (1) | ES2222599T3 (ja) |
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NZ (1) | NZ519387A (ja) |
PT (1) | PT1000039E (ja) |
RU (1) | RU2227798C2 (ja) |
SI (1) | SI1000039T1 (ja) |
TW (1) | TW436485B (ja) |
WO (1) | WO1999009016A1 (ja) |
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JP2994165B2 (ja) * | 1992-06-26 | 1999-12-27 | ゼネカ・リミテッド | キナゾリン誘導体、その製造法および該キナゾリン誘導体を含有する抗癌作用を得るための医薬調剤 |
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GB9314893D0 (en) * | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
GB9510757D0 (en) * | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
TW321649B (ja) * | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
GB9508565D0 (en) * | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
US5760041A (en) * | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
SI0892789T2 (sl) * | 1996-04-12 | 2010-03-31 | Warner Lambert Co | Ireverzibilni inhibitorji tirozin kinaz |
TW436485B (en) * | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
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