TW477788B - Substituted heteroaromatic compounds and their methods for their preparation and use - Google Patents
Substituted heteroaromatic compounds and their methods for their preparation and use Download PDFInfo
- Publication number
- TW477788B TW477788B TW088100388A TW88100388A TW477788B TW 477788 B TW477788 B TW 477788B TW 088100388 A TW088100388 A TW 088100388A TW 88100388 A TW88100388 A TW 88100388A TW 477788 B TW477788 B TW 477788B
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- Taiwan
- Prior art keywords
- methyl
- ethyl
- amino
- phenyl
- amine
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 132
- 238000002360 preparation method Methods 0.000 title claims description 29
- 150000002390 heteroarenes Chemical class 0.000 title description 2
- -1 phenoxy, benzyloxy Chemical group 0.000 claims abstract description 344
- 150000001875 compounds Chemical class 0.000 claims abstract description 179
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 65
- 150000003839 salts Chemical class 0.000 claims abstract description 43
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims abstract description 5
- 150000001412 amines Chemical class 0.000 claims description 102
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 70
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 69
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 57
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 42
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 34
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 27
- 201000010099 disease Diseases 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 24
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 21
- 239000003153 chemical reaction reagent Substances 0.000 claims description 21
- SDNXQWUJWNTDCC-UHFFFAOYSA-N 2-methylsulfonylethanamine Chemical compound CS(=O)(=O)CCN SDNXQWUJWNTDCC-UHFFFAOYSA-N 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 16
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 16
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 16
- 239000011737 fluorine Substances 0.000 claims description 16
- 229910052731 fluorine Inorganic materials 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 13
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims description 11
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims description 11
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 11
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 150000002367 halogens Chemical group 0.000 claims description 9
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 108091005682 Receptor kinases Proteins 0.000 claims description 6
- 235000010290 biphenyl Nutrition 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical compound C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 4
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 4
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 4
- HWIIAAVGRHKSOJ-UHFFFAOYSA-N 2-chloro-6,7-dimethoxyquinazolin-4-amine Chemical compound ClC1=NC(N)=C2C=C(OC)C(OC)=CC2=N1 HWIIAAVGRHKSOJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000006279 3-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Br)=C1[H])C([H])([H])* 0.000 claims description 3
- 108091000080 Phosphotransferase Proteins 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 125000004175 fluorobenzyl group Chemical group 0.000 claims description 3
- 150000007857 hydrazones Chemical class 0.000 claims description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
- 102000020233 phosphotransferase Human genes 0.000 claims description 3
- 241000894006 Bacteria Species 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims 1
- NLWCWEGVNJVLAX-UHFFFAOYSA-N 1-methoxy-2-phenylbenzene Chemical compound COC1=CC=CC=C1C1=CC=CC=C1 NLWCWEGVNJVLAX-UHFFFAOYSA-N 0.000 claims 1
- UPUWMQZUXFAUCJ-UHFFFAOYSA-N 2,5-dihydro-1,2-thiazole Chemical compound C1SNC=C1 UPUWMQZUXFAUCJ-UHFFFAOYSA-N 0.000 claims 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
- 101100118548 Drosophila melanogaster Egfr gene Proteins 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- UXXAYIVASCFMEV-UHFFFAOYSA-N n-[4-(benzenesulfonyl)phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(S(=O)(=O)C=2C=CC=CC=2)C=C1 UXXAYIVASCFMEV-UHFFFAOYSA-N 0.000 claims 1
- CHBKUKJXVPEKQQ-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[4-[(2-methylsulfonylethylamino)methyl]furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound CS(=O)(=O)CCNCC1=COC(C=2N=CC3=NC=NC(NC=4C=CC(OCC=5C=C(F)C=CC=5)=CC=4)=C3C=2)=C1 CHBKUKJXVPEKQQ-UHFFFAOYSA-N 0.000 claims 1
- RZEMPBRXCDBLDH-UHFFFAOYSA-N n-[4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=CC(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 RZEMPBRXCDBLDH-UHFFFAOYSA-N 0.000 claims 1
- GVQOYYNXZCOMAL-UHFFFAOYSA-N n-[4-[(4-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC(C=C1)=CC=C1OCC1=CC=C(F)C=C1 GVQOYYNXZCOMAL-UHFFFAOYSA-N 0.000 claims 1
- 229960004448 pentamidine Drugs 0.000 claims 1
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 abstract description 32
- 150000002240 furans Chemical class 0.000 abstract description 6
- 150000002431 hydrogen Chemical class 0.000 abstract description 6
- 150000003840 hydrochlorides Chemical class 0.000 abstract description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
- 125000005955 1H-indazolyl group Chemical group 0.000 abstract 1
- 238000011049 filling Methods 0.000 description 94
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 80
- 239000007787 solid Substances 0.000 description 76
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- 239000000203 mixture Substances 0.000 description 72
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 71
- 230000002079 cooperative effect Effects 0.000 description 63
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 41
- 238000006243 chemical reaction Methods 0.000 description 39
- 238000005481 NMR spectroscopy Methods 0.000 description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
- 239000002585 base Substances 0.000 description 32
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 29
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- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000002253 acid Substances 0.000 description 22
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 22
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- 125000004122 cyclic group Chemical group 0.000 description 17
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 16
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- BDAIUOPDSRAOKI-UHFFFAOYSA-N 4-chloro-6-iodoquinazoline Chemical compound C1=C(I)C=C2C(Cl)=NC=NC2=C1 BDAIUOPDSRAOKI-UHFFFAOYSA-N 0.000 description 4
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- 239000007864 aqueous solution Substances 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
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- PDCDFXWVWXWSCY-UHFFFAOYSA-N tributyl-[3-(1,3-dioxolan-2-yl)phenyl]stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC(C2OCCO2)=C1 PDCDFXWVWXWSCY-UHFFFAOYSA-N 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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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- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- C—CHEMISTRY; METALLURGY
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- 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D405/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D411/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D411/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D411/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D417/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
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- Communicable Diseases (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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GBGB9800569.7A GB9800569D0 (en) | 1998-01-12 | 1998-01-12 | Heterocyclic compounds |
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TW477788B true TW477788B (en) | 2002-03-01 |
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TW088100388A TW477788B (en) | 1998-01-12 | 1999-01-12 | Substituted heteroaromatic compounds and their methods for their preparation and use |
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Families Citing this family (432)
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DE69838172T2 (de) | 1997-08-22 | 2008-04-10 | Astrazeneca Ab | Oxindolylchinazolinderivate als angiogenesehemmer |
RS49779B (sr) * | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
KR100860295B1 (ko) | 1998-10-08 | 2008-09-25 | 아스트라제네카 아베 | 퀴나졸린 유도체 |
GB2345486A (en) * | 1999-01-11 | 2000-07-12 | Glaxo Group Ltd | Heteroaromatic protein tyrosine kinase inhibitors |
HU228964B1 (en) | 1999-02-10 | 2013-07-29 | Astrazeneca Ab | Quinazoline derivatives as angiogenesis inhibitors, process for their preparation and medicaments containing them |
GB9910580D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
GB9910579D0 (en) | 1999-05-08 | 1999-07-07 | Zeneca Ltd | Chemical compounds |
DK1731511T3 (en) | 1999-06-21 | 2015-10-26 | Boehringer Ingelheim Pharma | Bicyclic heterocyclic structures, pharmaceutical compositions containing these compounds, their use and process for their preparation |
EP1192151B1 (en) * | 1999-07-09 | 2007-11-07 | Glaxo Group Limited | Anilinoquinazolines as protein tyrosine kinase inhibitors |
US6933299B1 (en) | 1999-07-09 | 2005-08-23 | Smithkline Beecham Corporation | Anilinoquinazolines as protein tyrosine kinase inhibitors |
RU2002110461A (ru) | 1999-09-21 | 2004-03-10 | Астразенека Аб (Se) | Производные хиназолина и их применение в качестве фармацевтических веществ |
UA74803C2 (uk) | 1999-11-11 | 2006-02-15 | Осі Фармасьютікалз, Інк. | Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування |
EP1294709A2 (en) | 2000-01-28 | 2003-03-26 | AstraZeneca AB | Quinoline derivatives and their use as aurora 2 kinase inhibitors |
GB0002952D0 (en) * | 2000-02-09 | 2000-03-29 | Pharma Mar Sa | Process for producing kahalalide F compounds |
AR035851A1 (es) * | 2000-03-28 | 2004-07-21 | Wyeth Corp | 3-cianoquinolinas, 3-ciano-1,6-naftiridinas y 3-ciano-1,7-naftiridinas como inhibidoras de proteina quinasas |
US6521618B2 (en) | 2000-03-28 | 2003-02-18 | Wyeth | 3-cyanoquinolines, 3-cyano-1,6-naphthyridines, and 3-cyano-1,7-naphthyridines as protein kinase inhibitors |
AU2001257353A1 (en) | 2000-05-02 | 2001-11-12 | Array Biopharma, Inc. | Process for the reduction of cyano-substituted sulfones to aminoalkylene-substituted sulfones |
UA73990C2 (en) | 2000-06-22 | 2005-10-17 | Pfizer Prod Inc | Substituted bicyclic derivatives for the treatment of abnormal cells growth |
IL153246A0 (en) | 2000-06-28 | 2003-07-06 | Astrazeneca Ab | Substituted quinazoline derivatives and their use as inhibitors |
DE60126611T2 (de) * | 2000-06-30 | 2007-11-22 | Glaxo Group Ltd., Greenford | Ditosylatsalze von chinazolinverbindungen |
EP1792902A1 (en) * | 2000-06-30 | 2007-06-06 | Glaxo Group Limited | Processes for preparation of 5-(6-quinazolinyl)-furan-2-carbaldehydes |
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1998
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