NO328731B1 - Kinazolinforbindelser samt anvendelse og fremgangsmate for fremstilling derav, og farmasoytisk preparat. - Google Patents

Kinazolinforbindelser samt anvendelse og fremgangsmate for fremstilling derav, og farmasoytisk preparat. Download PDF

Info

Publication number: NO328731B1
Authority: NO; Norway
Prior art keywords: fluoro; methoxyquinazoline; mmol; oxy; methoxy
Prior art date: 2002-02-01

Application number

NO20043162A

Other languages

English (en)

Norwegian (no)

Other versions

NO20043162L (no

Inventor

Laurent Francois Andre Hennequin

Original Assignee

Astrazeneca Ab

Priority date (The priority date 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 date listed.)

2002-02-01

Filing date

2004-07-22

Publication date

2010-05-03

2004-07-22 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

2004-07-22 Publication of NO20043162L publication Critical patent/NO20043162L/no

2010-05-03 Publication of NO328731B1 publication Critical patent/NO328731B1/no

Links

238000000034 method Methods 0.000 title claims description 72
238000002360 preparation method Methods 0.000 title claims description 39
230000008569 process Effects 0.000 title claims description 16
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title description 2
239000008194 pharmaceutical composition Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 201
150000003839 salts Chemical class 0.000 claims description 84
-1 amino C1-4alkanoyl Chemical group 0.000 claims description 54
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 21
125000000217 alkyl group Chemical group 0.000 claims description 19
BNDMWBMVOITFQA-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazolin-7-ol Chemical group C1=C2NC(C)=CC2=C(F)C(OC2=C3C=C(C(=CC3=NC=N2)O)OC)=C1 BNDMWBMVOITFQA-UHFFFAOYSA-N 0.000 claims description 18
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 16
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 14
125000004432 carbon atom Chemical group C* 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 8
QDKJEQIJPRKDSD-UHFFFAOYSA-N 1-[4-[3-[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxypropyl]piperazin-1-yl]ethanone Chemical group COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCN(C(C)=O)CC1 QDKJEQIJPRKDSD-UHFFFAOYSA-N 0.000 claims description 6
FAUIFGUQBUATLA-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-phenylmethoxyquinazoline Chemical group COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCC1=CC=CC=C1 FAUIFGUQBUATLA-UHFFFAOYSA-N 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
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 6
FYQBNQHMZBZRTF-UHFFFAOYSA-N 1-[4-[2-[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxyethyl]piperazin-1-yl]ethanone Chemical group COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCN1CCN(C(C)=O)CC1 FYQBNQHMZBZRTF-UHFFFAOYSA-N 0.000 claims description 5
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 5
241001465754 Metazoa Species 0.000 claims description 5
239000000825 pharmaceutical preparation Substances 0.000 claims description 5
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 5
BHNHHSOHWZKFOX-UHFFFAOYSA-N 2-methyl-1H-indole Chemical compound C1=CC=C2NC(C)=CC2=C1 BHNHHSOHWZKFOX-UHFFFAOYSA-N 0.000 claims description 4
239000000654 additive Substances 0.000 claims description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
HFQXPABVXVLWQX-UHFFFAOYSA-N 1-[4-[2-[6-methoxy-4-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)quinazolin-7-yl]oxyethyl]piperazin-1-yl]ethanone Chemical compound COC1=CC2=C(OC=3C=C4C=CNC4=NC=3)N=CN=C2C=C1OCCN1CCN(C(C)=O)CC1 HFQXPABVXVLWQX-UHFFFAOYSA-N 0.000 claims description 3
LSOGIDYQTNUBIF-UHFFFAOYSA-N 1-[4-[3-[4-[(4-fluoro-1h-indol-5-yl)oxy]-7-methoxyquinazolin-6-yl]oxypropyl]piperazin-1-yl]ethanone Chemical compound COC1=CC2=NC=NC(OC=3C(=C4C=CNC4=CC=3)F)=C2C=C1OCCCN1CCN(C(C)=O)CC1 LSOGIDYQTNUBIF-UHFFFAOYSA-N 0.000 claims description 3
FQYMVHSRPUTQEZ-UHFFFAOYSA-N 1-[4-[3-[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-7-methoxyquinazolin-6-yl]oxypropyl]piperazin-1-yl]ethanone Chemical compound COC1=CC2=NC=NC(OC=3C(=C4C=C(C)NC4=CC=3)F)=C2C=C1OCCCN1CCN(C(C)=O)CC1 FQYMVHSRPUTQEZ-UHFFFAOYSA-N 0.000 claims description 3
ONPJRNVWLPOYFF-UHFFFAOYSA-N 1-[4-[3-[6-methoxy-4-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)quinazolin-7-yl]oxypropyl]piperazin-1-yl]ethanone Chemical compound COC1=CC2=C(OC=3C=C4C=CNC4=NC=3)N=CN=C2C=C1OCCCN1CCN(C(C)=O)CC1 ONPJRNVWLPOYFF-UHFFFAOYSA-N 0.000 claims description 3
HWKQQUBWNOFVQN-UHFFFAOYSA-N 2-[4-[3-[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxypropyl]piperazin-1-yl]acetamide Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCN(CC(N)=O)CC1 HWKQQUBWNOFVQN-UHFFFAOYSA-N 0.000 claims description 3
QFPYNQNIAAPBLC-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-[3-(4-prop-2-ynylpiperazin-1-yl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCN(CC#C)CC1 QFPYNQNIAAPBLC-UHFFFAOYSA-N 0.000 claims description 3
JIYCGXSXOQNEDX-UHFFFAOYSA-N 6-methoxy-7-[3-(4-methylsulfonylpiperazin-1-yl)propoxy]-4-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=CNC4=NC=3)N=CN=C2C=C1OCCCN1CCN(S(C)(=O)=O)CC1 JIYCGXSXOQNEDX-UHFFFAOYSA-N 0.000 claims description 3
NGAKDPBUVQIMRZ-UHFFFAOYSA-N 7-methoxy-6-[3-(4-methylsulfonylpiperazin-1-yl)propoxy]-4-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)quinazoline Chemical compound COC1=CC2=NC=NC(OC=3C=C4C=CNC4=NC=3)=C2C=C1OCCCN1CCN(S(C)(=O)=O)CC1 NGAKDPBUVQIMRZ-UHFFFAOYSA-N 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 3
230000000996 additive effect Effects 0.000 claims description 3
229940079593 drug Drugs 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 2
ANQPIXCSCFVEHS-QGZVFWFLSA-N 1-[(2r)-2-[[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxymethyl]pyrrolidin-1-yl]-2-methylpropan-1-one Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OC[C@H]1CCCN1C(=O)C(C)C ANQPIXCSCFVEHS-QGZVFWFLSA-N 0.000 claims description 2
JSRAZILILWWTBE-UHFFFAOYSA-N 1-[4-[3-[4-[(4-fluoro-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxypropyl]piperazin-1-yl]ethanone Chemical compound COC1=CC2=C(OC=3C(=C4C=CNC4=CC=3)F)N=CN=C2C=C1OCCCN1CCN(C(C)=O)CC1 JSRAZILILWWTBE-UHFFFAOYSA-N 0.000 claims description 2
YZKIYTPMUOGBDO-UHFFFAOYSA-N 1-[4-[3-[7-methoxy-4-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)quinazolin-6-yl]oxypropyl]piperazin-1-yl]ethanone Chemical compound COC1=CC2=NC=NC(OC=3C=C4C=CNC4=NC=3)=C2C=C1OCCCN1CCN(C(C)=O)CC1 YZKIYTPMUOGBDO-UHFFFAOYSA-N 0.000 claims description 2
RLOAHFBRRWMPSP-UHFFFAOYSA-N 1-[4-[[4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxyquinazolin-7-yl]oxymethyl]piperidin-1-yl]ethanone Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCC1CCN(C(C)=O)CC1 RLOAHFBRRWMPSP-UHFFFAOYSA-N 0.000 claims description 2
IYJVRLZBXUTPAA-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-[3-(4-methylsulfonylpiperazin-1-yl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCN(S(C)(=O)=O)CC1 IYJVRLZBXUTPAA-UHFFFAOYSA-N 0.000 claims description 2
AMABXCVEKLZGKZ-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-7-methoxy-6-[3-(4-methylsulfonylpiperazin-1-yl)propoxy]quinazoline Chemical compound COC1=CC2=NC=NC(OC=3C(=C4C=C(C)NC4=CC=3)F)=C2C=C1OCCCN1CCN(S(C)(=O)=O)CC1 AMABXCVEKLZGKZ-UHFFFAOYSA-N 0.000 claims description 2
LXWJPNMAWYCDGS-UHFFFAOYSA-N 6-methoxy-7-[3-(4-prop-2-enylpiperazin-1-yl)propoxy]-4-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=CNC4=NC=3)N=CN=C2C=C1OCCCN1CCN(CC=C)CC1 LXWJPNMAWYCDGS-UHFFFAOYSA-N 0.000 claims description 2
MABQRUNLUFIVRS-UHFFFAOYSA-N 6-methoxy-7-[3-(4-prop-2-ynylpiperazin-1-yl)propoxy]-4-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)quinazoline Chemical compound COC1=CC2=C(OC=3C=C4C=CNC4=NC=3)N=CN=C2C=C1OCCCN1CCN(CC#C)CC1 MABQRUNLUFIVRS-UHFFFAOYSA-N 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
230000001093 anti-cancer Effects 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
125000004193 piperazinyl group Chemical group 0.000 claims description 2
125000003386 piperidinyl group Chemical group 0.000 claims description 2
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 1
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
PDSPNGGVEIUMHV-UHFFFAOYSA-N 2-methylindole Chemical compound C1=C[CH]C2=NC(C)=CC2=C1 PDSPNGGVEIUMHV-UHFFFAOYSA-N 0.000 claims 1
OHPPLKBEKSKLOJ-UHFFFAOYSA-N 4-[(4-fluoro-1h-indol-5-yl)oxy]-7-methoxy-6-(1-methylsulfonylpiperidin-4-yl)oxyquinazoline Chemical compound COC1=CC2=NC=NC(OC=3C(=C4C=CNC4=CC=3)F)=C2C=C1OC1CCN(S(C)(=O)=O)CC1 OHPPLKBEKSKLOJ-UHFFFAOYSA-N 0.000 claims 1
SRCMTRCFCPJQKB-OAHLLOKOSA-N 4-[(4-fluoro-2-methyl-1h-indol-5-yl)oxy]-6-methoxy-7-[[(2r)-1-methylsulfonylpyrrolidin-2-yl]methoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OC[C@H]1CCCN1S(C)(=O)=O SRCMTRCFCPJQKB-OAHLLOKOSA-N 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 519
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 408
239000000203 mixture Substances 0.000 description 204
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 153
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 138
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 133
239000007858 starting material Substances 0.000 description 124
238000004440 column chromatography Methods 0.000 description 94
239000007787 solid Substances 0.000 description 90
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BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 70
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 64
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 50
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 45
239000011541 reaction mixture Substances 0.000 description 42
230000002829 reductive effect Effects 0.000 description 42
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 41
239000000047 product Substances 0.000 description 40
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
239000012267 brine Substances 0.000 description 36
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 36
229910000027 potassium carbonate Inorganic materials 0.000 description 35
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
239000002904 solvent Substances 0.000 description 32
239000000706 filtrate Substances 0.000 description 28
238000006243 chemical reaction Methods 0.000 description 26
229910052943 magnesium sulfate Inorganic materials 0.000 description 25
235000019341 magnesium sulphate Nutrition 0.000 description 25
229920006395 saturated elastomer Polymers 0.000 description 24
230000000694 effects Effects 0.000 description 23
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
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108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 21
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
210000004027 cell Anatomy 0.000 description 20
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 20
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VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 18
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- 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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Health & Medical Sciences (AREA)
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Organic Chemistry (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Heart & Thoracic Surgery (AREA)
Diabetes (AREA)
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Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

NO20043162A 2002-02-01 2004-07-22 Kinazolinforbindelser samt anvendelse og fremgangsmate for fremstilling derav, og farmasoytisk preparat. NO328731B1 (no)

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EP02290242		2002-02-01
PCT/GB2003/000343 WO2003064413A1 (en)	2002-02-01	2003-01-28	Quinazoline compounds

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US (3)	US7268230B2 (uk)
EP (2)	EP1474420B1 (uk)
JP (2)	JP4608215B2 (uk)
KR (1)	KR101093345B1 (uk)
CN (2)	CN1625555A (uk)
AR (1)	AR038476A1 (uk)
AT (1)	ATE549329T1 (uk)
AU (1)	AU2003202094B2 (uk)
BR (1)	BR0307151A (uk)
CA (1)	CA2473572C (uk)
CY (1)	CY1112835T1 (uk)
DK (1)	DK1474420T3 (uk)
ES (1)	ES2381781T3 (uk)
HU (1)	HUP0402588A3 (uk)
IL (2)	IL163022A (uk)
IS (1)	IS7362A (uk)
MX (1)	MXPA04007459A (uk)
MY (1)	MY144042A (uk)
NO (1)	NO328731B1 (uk)
NZ (1)	NZ534171A (uk)
PL (1)	PL371486A1 (uk)
PT (1)	PT1474420E (uk)
RU (3)	RU2362774C1 (uk)
SI (1)	SI1474420T1 (uk)
TW (1)	TWI337866B (uk)
UA (1)	UA81619C2 (uk)
WO (1)	WO2003064413A1 (uk)
ZA (1)	ZA200405908B (uk)

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Publication number	Publication date
CN1625555A (zh)	2005-06-08
TWI337866B (en)	2011-03-01
DK1474420T3 (da)	2012-05-21
ATE549329T1 (de)	2012-03-15
EP1474420B1 (en)	2012-03-14
US20050085465A1 (en)	2005-04-21
RU2362775C1 (ru)	2009-07-27
NZ534171A (en)	2007-06-29
IL163022A (en)	2012-10-31
BR0307151A (pt)	2004-12-07
US7268230B2 (en)	2007-09-11
AR038476A1 (es)	2005-01-19
PT1474420E (pt)	2012-05-10
RU2008100766A (ru)	2009-05-10
KR20040077922A (ko)	2004-09-07
MY144042A (en)	2011-07-29
CA2473572C (en)	2011-05-10
UA81619C2 (uk)	2008-01-25
ES2381781T3 (es)	2012-05-31
MXPA04007459A (es)	2005-09-08
HK1070367A1 (en)	2005-06-17
CA2473572A1 (en)	2003-08-07
EP2292615A1 (en)	2011-03-09
US20090156821A1 (en)	2009-06-18
CY1112835T1 (el)	2016-02-10
RU2362774C1 (ru)	2009-07-27
NO20043162L (no)	2004-07-22
RU2365588C2 (ru)	2009-08-27
AU2003202094B2 (en)	2009-10-08
HUP0402588A2 (hu)	2005-05-30
US8293902B2 (en)	2012-10-23
PL371486A1 (en)	2005-06-13
RU2004126612A (ru)	2005-07-10
JP4608215B2 (ja)	2011-01-12
SI1474420T1 (sl)	2012-06-29
KR101093345B1 (ko)	2011-12-14
JP2005522428A (ja)	2005-07-28
ZA200405908B (en)	2005-11-30
IS7362A (is)	2004-07-22
WO2003064413A1 (en)	2003-08-07
US20080027069A1 (en)	2008-01-31
TW200302727A (en)	2003-08-16
JP2010100642A (ja)	2010-05-06
IL210785A0 (en)	2011-03-31
RU2008100767A (ru)	2009-05-10
HUP0402588A3 (en)	2009-09-28
EP1474420A1 (en)	2004-11-10
CN101607958A (zh)	2009-12-23

Publication	Publication Date	Title
NO328731B1 (no)	2010-05-03	Kinazolinforbindelser samt anvendelse og fremgangsmate for fremstilling derav, og farmasoytisk preparat.
RU2262935C2 (ru)	2005-10-27	Производные хиназолина в качестве ингибиторов ангиогенеза
US20120046300A1 (en)	2012-02-23	Quinazoline Derivatives as Angiogenesis Inhibitors
AU2003202094A1 (en)	2003-09-18	Quinazoline compounds
JP2004505965A (ja)	2004-02-26	化合物
MXPA06001394A (es)	2006-05-19	Derivados de quinazolina como inhibidores de cinasas de tirosina de receptor vegf.
HK1139675A (en)	2010-09-24	Quinazoline compounds
HK1154586A (en)	2012-04-27	Quinazoline compounds
HK1070367B (en)	2012-10-19	Quinazoline compounds

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