AU2006236423B2 - Pharmaceutical composition - Google Patents
Pharmaceutical composition Download PDFInfo
- Publication number
- AU2006236423B2 AU2006236423B2 AU2006236423A AU2006236423A AU2006236423B2 AU 2006236423 B2 AU2006236423 B2 AU 2006236423B2 AU 2006236423 A AU2006236423 A AU 2006236423A AU 2006236423 A AU2006236423 A AU 2006236423A AU 2006236423 B2 AU2006236423 B2 AU 2006236423B2
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- AU
- Australia
- Prior art keywords
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- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000008194 pharmaceutical composition Substances 0.000 title description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 56
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 40
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 40
- 239000008203 oral pharmaceutical composition Substances 0.000 claims description 39
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 37
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 37
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 37
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 37
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 37
- 229940069328 povidone Drugs 0.000 claims description 37
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 33
- 239000008109 sodium starch glycolate Substances 0.000 claims description 33
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 33
- 235000019359 magnesium stearate Nutrition 0.000 claims description 28
- 150000004682 monohydrates Chemical class 0.000 claims description 24
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 239000003826 tablet Substances 0.000 description 101
- 239000000203 mixture Substances 0.000 description 100
- 150000001875 compounds Chemical class 0.000 description 71
- 239000008187 granular material Substances 0.000 description 69
- 239000004480 active ingredient Substances 0.000 description 67
- 239000007884 disintegrant Substances 0.000 description 50
- 239000011230 binding agent Substances 0.000 description 45
- 150000003839 salts Chemical class 0.000 description 45
- 238000007906 compression Methods 0.000 description 44
- 230000006835 compression Effects 0.000 description 44
- 239000003085 diluting agent Substances 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
- 239000000243 solution Substances 0.000 description 34
- 238000000034 method Methods 0.000 description 33
- 239000000314 lubricant Substances 0.000 description 31
- -1 (2-methanesulphonyl-ethylamino)-methyl Chemical group 0.000 description 27
- 239000007917 core tablet composition Substances 0.000 description 22
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 239000012453 solvate Substances 0.000 description 19
- 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 17
- 238000004090 dissolution Methods 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 16
- 238000005469 granulation Methods 0.000 description 16
- 230000003179 granulation Effects 0.000 description 16
- 229910052757 nitrogen Inorganic materials 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 208000035475 disorder Diseases 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 102000001301 EGF receptor Human genes 0.000 description 11
- 108060006698 EGF receptor Proteins 0.000 description 11
- 230000001594 aberrant effect Effects 0.000 description 11
- 239000003112 inhibitor Substances 0.000 description 11
- 239000008213 purified water Substances 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 241000124008 Mammalia Species 0.000 description 8
- 238000011319 anticancer therapy Methods 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 8
- 235000010980 cellulose Nutrition 0.000 description 8
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- 238000009501 film coating Methods 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000007916 tablet composition Substances 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000011248 coating agent Substances 0.000 description 7
- 238000000576 coating method Methods 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- UWYXLGUQQFPJRI-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine;4-methylbenzenesulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 UWYXLGUQQFPJRI-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000008186 active pharmaceutical agent Substances 0.000 description 6
- 229940088679 drug related substance Drugs 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 238000005029 sieve analysis Methods 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 229940034982 antineoplastic agent Drugs 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 5
- 229920000053 polysorbate 80 Polymers 0.000 description 5
- DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical class C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- FWMBEYDLDLJTDP-UHFFFAOYSA-N 2-iodoquinazoline Chemical compound C1=CC=CC2=NC(I)=NC=C21 FWMBEYDLDLJTDP-UHFFFAOYSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- HAZFJZBNKXYYNZ-UHFFFAOYSA-N O.S(=O)(=O)(O)C1=CC=C(C)C=C1.S(=O)(=O)(O)C1=CC=C(C)C=C1.CS(=O)(=O)CCNCC1=CC=C(O1)C1=NC2=CC=CC=C2C(=N1)N Chemical compound O.S(=O)(=O)(O)C1=CC=C(C)C=C1.S(=O)(=O)(O)C1=CC=C(C)C=C1.CS(=O)(=O)CCNCC1=CC=C(O1)C1=NC2=CC=CC=C2C(=N1)N HAZFJZBNKXYYNZ-UHFFFAOYSA-N 0.000 description 3
- 229920003110 Primojel Polymers 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- 108091008605 VEGF receptors Proteins 0.000 description 3
- 229940124650 anti-cancer therapies Drugs 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000000973 chemotherapeutic effect Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- MTSNDBYBIZSILH-UHFFFAOYSA-N n-phenylquinazolin-4-amine Chemical class N=1C=NC2=CC=CC=C2C=1NC1=CC=CC=C1 MTSNDBYBIZSILH-UHFFFAOYSA-N 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 235000015424 sodium Nutrition 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
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- 229940032147 starch Drugs 0.000 description 3
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- 239000000126 substance Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-UHFFFAOYSA-N 2-(hydroxymethyl)-6-[4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol Chemical compound OCC1OC(OC2C(O)C(O)C(O)OC2CO)C(O)C(O)C1O GUBGYTABKSRVRQ-UHFFFAOYSA-N 0.000 description 2
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
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- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
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- 125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 description 2
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- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
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- 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
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- 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
Landscapes
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- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
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| US67280505P | 2005-04-19 | 2005-04-19 | |
| US60/672,805 | 2005-04-19 | ||
| PCT/US2006/014447 WO2006113649A1 (en) | 2005-04-19 | 2006-04-18 | Pharmaceutical composition |
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| AU2006236423A1 AU2006236423A1 (en) | 2006-10-26 |
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| WO2009137714A2 (en) * | 2008-05-07 | 2009-11-12 | Teva Pharmaceutical Industries Ltd. | Forms of lapatinib ditosylate and processes for preparation thereof |
| EP2158912A1 (en) * | 2008-08-25 | 2010-03-03 | Ratiopharm GmbH | Pharmaceutical composition comprising N-[3-chhloro-4-[3-fluorophenyl)methoxy)phenyl]6-[5[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine |
| EP2158913A1 (en) * | 2008-08-25 | 2010-03-03 | Ratiopharm GmbH | Pharmaceutical composition comprising N-[3-chhloro-4-[(3-fluorophenyl)methoxy]phenyl]6-(5[[[2-(methylsulfonyl)ethyl]amino]methyl]-2-furyl]-4-quinazolinamine |
| WO2010099150A1 (en) * | 2009-02-24 | 2010-09-02 | Smithkline Beecham (Cork) Limited | Pharmaceutical tablet and process |
| WO2011039759A1 (en) * | 2009-09-29 | 2011-04-07 | Natco Pharma Limited | A new process for the preparation of lapatinib and its pharmaceutically acceptable salts |
| ES2530755T3 (es) | 2010-05-21 | 2015-03-05 | Glaxosmithkline Llc | Terapia de combinación para el tratamiento del cáncer |
| JP2013526578A (ja) | 2010-05-21 | 2013-06-24 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 組合せ |
| BR112013002511A2 (pt) | 2010-08-03 | 2017-06-27 | Altherx Inc | combinações de agonistas de receptores adrenérgicos beta - 3 e antagonistas receptores muscarínicos para tratamento da bexica hiperativa |
| US9907767B2 (en) | 2010-08-03 | 2018-03-06 | Velicept Therapeutics, Inc. | Pharmaceutical compositions and the treatment of overactive bladder |
| ES2635620T3 (es) * | 2013-02-19 | 2017-10-04 | Hexal Ag | Composición farmacéutica que comprende n-[3-cloro-4-(3-fluorobenciloxi)fenil]-6-[5({[2-(metilsulfonil)etil]amino} metil)-2-furil]quinazolin-4-amina o una sal, solvato o sal solvatada farmacéuticamente aceptables de la misma |
| WO2014170910A1 (en) | 2013-04-04 | 2014-10-23 | Natco Pharma Limited | Process for the preparation of lapatinib |
| US9636340B2 (en) | 2013-11-12 | 2017-05-02 | Ayyappan K. Rajasekaran | Kinase inhibitors |
| CN107205964A (zh) | 2014-12-03 | 2017-09-26 | 威力塞帕特治疗股份有限公司 | 使用调节释放索拉贝隆用于下尿路症状的组合物和方法 |
| CN106389373B (zh) * | 2015-07-29 | 2019-07-02 | 四川科伦药物研究院有限公司 | 一种二甲苯磺酸拉帕替尼片剂及其制备方法 |
| CN106511289A (zh) * | 2015-09-10 | 2017-03-22 | 湖北生物医药产业技术研究院有限公司 | 甲苯磺酸拉帕替尼片剂及其制备方法 |
| CN108290824B (zh) | 2015-10-23 | 2022-03-11 | B3Ar治疗股份有限公司 | 索拉贝隆两性离子及其应用 |
| EP4725489A2 (en) | 2019-08-02 | 2026-04-15 | OneHealthCompany, Inc. | Treatment of canine cancers |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999035146A1 (en) * | 1998-01-12 | 1999-07-15 | Glaxo Group Limited | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors |
| WO2002002552A1 (en) * | 2000-06-30 | 2002-01-10 | Glaxo Group Limited | Quinazoline ditosylate salt compounds |
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| US5506248A (en) * | 1993-08-02 | 1996-04-09 | Bristol-Myers Squibb Company | Pharmaceutical compositions having good dissolution properties |
| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
| US5760041A (en) | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
| RU2205831C2 (ru) | 1997-04-25 | 2003-06-10 | Янссен Фармацевтика Н.В. | Хиназолиноны, ингибирующие фарнезилтрансферазу |
| TW436485B (en) | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
| DE60203260T2 (de) | 2001-01-16 | 2006-02-02 | Glaxo Group Ltd., Greenford | Pharmazeutische kombination, die ein 4-chinazolinamin und paclitaxel, carboplatin oder vinorelbin enthält, zur behandlung von krebs |
| AU2003221684A1 (en) | 2002-04-08 | 2003-10-27 | Smithkline Beecham Corporation | Cancer treatment method comprising administering an erb-family inhibitor and a raf and/or ras inhibitor |
| AU2003235470A1 (en) * | 2002-06-19 | 2004-01-06 | Smithkline Beecham Corporation | Predictive markers in cancer therapy |
| CA2606207C (en) * | 2005-04-19 | 2014-11-18 | Smithkline Beecham (Cork) Limited | Pharmaceutical composition |
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- 2007-10-07 IL IL186336A patent/IL186336A0/en unknown
- 2007-10-09 NO NO20075111A patent/NO20075111L/no not_active Application Discontinuation
- 2007-10-11 ZA ZA200708705A patent/ZA200708705B/xx unknown
- 2007-10-25 MA MA30318A patent/MA29404B1/fr unknown
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2014
- 2014-07-28 US US14/444,637 patent/US20140335177A1/en not_active Abandoned
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- 2016-01-29 US US15/009,927 patent/US20160143909A1/en not_active Abandoned
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| WO1999035146A1 (en) * | 1998-01-12 | 1999-07-15 | Glaxo Group Limited | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors |
| WO2002002552A1 (en) * | 2000-06-30 | 2002-01-10 | Glaxo Group Limited | Quinazoline ditosylate salt compounds |
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