AU743024B2 - Formulations for hydrophobic pharmaceutical agents - Google Patents
Formulations for hydrophobic pharmaceutical agents Download PDFInfo
- Publication number
- AU743024B2 AU743024B2 AU66806/98A AU6680698A AU743024B2 AU 743024 B2 AU743024 B2 AU 743024B2 AU 66806/98 A AU66806/98 A AU 66806/98A AU 6680698 A AU6680698 A AU 6680698A AU 743024 B2 AU743024 B2 AU 743024B2
- Authority
- AU
- Australia
- Prior art keywords
- group
- formulation
- indolinone
- formula
- alkyl
- 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.)
- Ceased
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- 239000000203 mixture Substances 0.000 title claims abstract description 303
- 238000009472 formulation Methods 0.000 title claims abstract description 269
- 230000002209 hydrophobic effect Effects 0.000 title claims abstract description 121
- 239000008177 pharmaceutical agent Substances 0.000 title claims abstract description 115
- 150000001875 compounds Chemical class 0.000 claims abstract description 275
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims abstract description 137
- 238000000034 method Methods 0.000 claims abstract description 91
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims abstract description 46
- ALNUOSXDMYFQNQ-UHFFFAOYSA-N 2-nitro-1,3-thiazole Chemical compound [O-][N+](=O)C1=NC=CS1 ALNUOSXDMYFQNQ-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 142
- 125000000217 alkyl group Chemical group 0.000 claims description 123
- -1 amino, bromo, fluoro, chloro, iodo, mercapto, thio Chemical group 0.000 claims description 109
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 99
- 125000000623 heterocyclic group Chemical group 0.000 claims description 86
- 150000002148 esters Chemical group 0.000 claims description 78
- 125000004953 trihalomethyl group Chemical group 0.000 claims description 78
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 73
- 239000001257 hydrogen Substances 0.000 claims description 71
- 229910052739 hydrogen Inorganic materials 0.000 claims description 71
- 229910052736 halogen Inorganic materials 0.000 claims description 61
- 150000002367 halogens Chemical group 0.000 claims description 61
- 235000019441 ethanol Nutrition 0.000 claims description 60
- 150000002431 hydrogen Chemical class 0.000 claims description 57
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 52
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 49
- 125000001424 substituent group Chemical group 0.000 claims description 48
- 229920006395 saturated elastomer Polymers 0.000 claims description 46
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 45
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 40
- 208000035475 disorder Diseases 0.000 claims description 40
- 150000007942 carboxylates Chemical group 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 37
- 238000011282 treatment Methods 0.000 claims description 37
- 239000004094 surface-active agent Substances 0.000 claims description 36
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 claims description 33
- 206010028980 Neoplasm Diseases 0.000 claims description 31
- 125000003342 alkenyl group Chemical group 0.000 claims description 31
- 125000004414 alkyl thio group Chemical group 0.000 claims description 31
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 230000002062 proliferating effect Effects 0.000 claims description 30
- 229920001223 polyethylene glycol Polymers 0.000 claims description 29
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 28
- 125000003368 amide group Chemical group 0.000 claims description 28
- 239000004359 castor oil Substances 0.000 claims description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 28
- 125000004043 oxo group Chemical group O=* 0.000 claims description 28
- 125000003107 substituted aryl group Chemical group 0.000 claims description 28
- 150000003568 thioethers Chemical group 0.000 claims description 28
- 150000001412 amines Chemical class 0.000 claims description 26
- 230000002159 abnormal effect Effects 0.000 claims description 25
- 235000019438 castor oil Nutrition 0.000 claims description 25
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 25
- 229960005130 niridazole Drugs 0.000 claims description 23
- RDXLYGJSWZYTFJ-UHFFFAOYSA-N Niridazole Chemical group S1C([N+](=O)[O-])=CN=C1N1C(=O)NCC1 RDXLYGJSWZYTFJ-UHFFFAOYSA-N 0.000 claims description 22
- 239000008180 pharmaceutical surfactant Substances 0.000 claims description 21
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 20
- XLMXUUQMSMKFMH-UZRURVBFSA-N 2-hydroxyethyl (z,12r)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC(=O)OCCO XLMXUUQMSMKFMH-UZRURVBFSA-N 0.000 claims description 19
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 19
- WUWDLXZGHZSWQZ-UHFFFAOYSA-N 3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one Chemical compound N1C(C)=CC(C)=C1C=C1C2=CC=CC=C2NC1=O WUWDLXZGHZSWQZ-UHFFFAOYSA-N 0.000 claims description 18
- 150000001298 alcohols Chemical class 0.000 claims description 18
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 13
- 210000004204 blood vessel Anatomy 0.000 claims description 12
- 150000001299 aldehydes Chemical class 0.000 claims description 11
- 150000001408 amides Chemical class 0.000 claims description 11
- 150000002576 ketones Chemical class 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 150000003457 sulfones Chemical class 0.000 claims description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 9
- 230000003176 fibrotic effect Effects 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- XLBQNZICMYZIQT-UHFFFAOYSA-N 5-chloro-3-[(3,5-dimethyl-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound N1C(C)=CC(C)=C1C=C1C2=CC(Cl)=CC=C2NC1=O XLBQNZICMYZIQT-UHFFFAOYSA-N 0.000 claims description 6
- 208000023275 Autoimmune disease Diseases 0.000 claims description 5
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 5
- 239000000194 fatty acid Substances 0.000 claims description 5
- 229930195729 fatty acid Natural products 0.000 claims description 5
- 239000002736 nonionic surfactant Substances 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 5
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 5
- XYONNOXYJMPBMA-UHFFFAOYSA-N 5-amino-3-[(3,5-dimethyl-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound N1C(C)=CC(C)=C1C=C1C2=CC(N)=CC=C2NC1=O XYONNOXYJMPBMA-UHFFFAOYSA-N 0.000 claims description 4
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 4
- 150000001719 carbohydrate derivatives Chemical class 0.000 claims description 4
- 150000001720 carbohydrates Chemical class 0.000 claims description 4
- 235000014633 carbohydrates Nutrition 0.000 claims description 4
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 4
- 125000005702 oxyalkylene group Chemical group 0.000 claims description 4
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 4
- 229920003169 water-soluble polymer Polymers 0.000 claims description 4
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 3
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 3
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 3
- BLOVEWWCSGSEOG-UHFFFAOYSA-N 4-(3-bromophenyl)-6,7-dimethoxyquinazoline Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1C1=CC=CC(Br)=C1 BLOVEWWCSGSEOG-UHFFFAOYSA-N 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 3
- 229920001577 copolymer Polymers 0.000 claims description 3
- 238000007865 diluting Methods 0.000 claims description 3
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 3
- 150000003077 polyols Chemical class 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims 3
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229920005862 polyol Polymers 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 239000007787 solid Substances 0.000 abstract description 34
- 239000007788 liquid Substances 0.000 abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 44
- 229940079593 drug Drugs 0.000 description 31
- 210000004027 cell Anatomy 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 150000002632 lipids Chemical class 0.000 description 21
- 239000002904 solvent Substances 0.000 description 20
- 102000001253 Protein Kinase Human genes 0.000 description 19
- 108060006633 protein kinase Proteins 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- 102100025093 Zinc fingers and homeoboxes protein 2 Human genes 0.000 description 17
- 238000001914 filtration Methods 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 229960004217 benzyl alcohol Drugs 0.000 description 15
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000000306 component Substances 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
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- 239000000546 pharmaceutical excipient Substances 0.000 description 12
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- 230000006870 function Effects 0.000 description 10
- 241000282472 Canis lupus familiaris Species 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 230000004663 cell proliferation Effects 0.000 description 9
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- 201000010099 disease Diseases 0.000 description 9
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- 239000007903 gelatin capsule Substances 0.000 description 8
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- 238000010998 test method Methods 0.000 description 8
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- ZFIDHZVBIBPRBQ-UHFFFAOYSA-N 5-fluoroquinazoline-2,4-diamine Chemical compound FC1=CC=CC2=NC(N)=NC(N)=C21 ZFIDHZVBIBPRBQ-UHFFFAOYSA-N 0.000 description 6
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- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 6
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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Landscapes
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- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Epidemiology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| AU27726/02A AU770904B2 (en) | 1997-03-05 | 2002-03-28 | Formulations for hydrophobic pharmaceutical agents |
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| PCT/US1998/004134 WO1998038984A2 (en) | 1997-03-05 | 1998-03-04 | Formulations for hydrophobic pharmaceutical agents |
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| US5880141A (en) | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| AR012634A1 (es) * | 1997-05-02 | 2000-11-08 | Sugen Inc | Compuesto basado en quinazolina, composicion famaceutica que lo comprende, metodo para sintetizarlo, su uso, metodos de modulacion de la funcion deserina/treonina proteinaquinasa con dicho compuesto y metodo in vitro para identificar compuestos que modulan dicha funcion |
| US6235769B1 (en) | 1997-07-03 | 2001-05-22 | Sugen, Inc. | Methods of preventing and treating neurological disorders with compounds that modulate the function of the C-RET receptor protein tyrosine kinase |
| US6569868B2 (en) | 1998-04-16 | 2003-05-27 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| EP1082305A4 (en) | 1998-05-29 | 2001-09-26 | Sugen Inc | PYRROL SUBSTITUTED 2-INDOLINONE EFFECTIVE AS A PROTEIN KINASE INHIBITOR |
| US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| EP1162974A1 (en) * | 1999-03-19 | 2001-12-19 | Parker Hughes Institute | Quinazoline formulations and therapeutic use thereof |
| US7064114B2 (en) | 1999-03-19 | 2006-06-20 | Parker Hughes Institute | Gel-microemulsion formulations |
| CA2365945A1 (en) * | 1999-04-09 | 2000-10-19 | Max-Planck-Institute For Biochemistry | Products and methods for treating ptp lar related diseases |
| ATE375984T1 (de) * | 1999-07-07 | 2007-11-15 | Astrazeneca Uk Ltd | Chinazolin derivate |
| GB9925127D0 (en) * | 1999-10-22 | 1999-12-22 | Pharmacia & Upjohn Spa | Oral formulations for anti-tumor compounds |
| US6878733B1 (en) | 1999-11-24 | 2005-04-12 | Sugen, Inc. | Formulations for pharmaceutical agents ionizable as free acids or free bases |
| DE60030164T2 (de) * | 1999-12-30 | 2007-08-30 | Sugen, Inc., San Francisco | 3-Heteroarylidenyl-2-Indolinon Derivate für die Modulierung der Aktivität einer Proteinkinase und für die Verwendung bei der Chemotherapie von Krebs |
| MXPA02008021A (es) | 2000-02-15 | 2004-04-05 | Sugen Inc | Indolinonas sustituidas con pirroles inhibidoras de proteinquinasas. |
| WO2001066099A2 (en) | 2000-03-06 | 2001-09-13 | Astrazeneca Ab | Use of quinazoline derivatives as angiogenesis inhibitors |
| MY128449A (en) | 2000-05-24 | 2007-02-28 | Sugen Inc | Prodrugs of 3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
| AU2001268154A1 (en) | 2000-06-02 | 2001-12-17 | Sugen, Inc. | Indolinone derivatives as protein kinase/phosphatase inhibitors |
| US7001904B1 (en) | 2000-06-24 | 2006-02-21 | Astrazeneca Ab | Guanidine derivatives quinazoline and quinoline for use in the treatment of autoimmune diseases |
| AU2002216758A1 (en) * | 2000-07-03 | 2002-01-14 | Astrazeneca Ab | Quinazolines with therapeutic use |
| WO2002007712A2 (en) * | 2000-07-24 | 2002-01-31 | Pharmacia & Upjohn Company | Self-emulsifying drug delivery systems for extremely water-insoluble, lipophilic drugs |
| CA2417813A1 (en) * | 2000-08-10 | 2002-02-21 | Delsys Pharmaceutical Corporation | Improved solid pharmaceutical dosage formulation of hydrophobic drugs |
| WO2002030466A2 (en) * | 2000-10-11 | 2002-04-18 | Purdue Research Foundation | Pharmaceutical applications of hydrotropic agents, polymers thereof, and hydrogels thereof |
| US20050158271A1 (en) * | 2000-10-11 | 2005-07-21 | Lee Sang C. | Pharmaceutical applications of hydrotropic polymer micelles |
| AR042586A1 (es) | 2001-02-15 | 2005-06-29 | Sugen Inc | 3-(4-amidopirrol-2-ilmetiliden)-2-indolinona como inhibidores de la protein quinasa; sus composiciones farmaceuticas; un metodo para la modulacion de la actividad catalitica de la proteinquinasa; un metodo para tratar o prevenir una afeccion relacionada con la proteinquinasa |
| AU2002244865A1 (en) * | 2001-03-02 | 2002-09-19 | Dr. Reddy's Laboratories Ltd. | Pharmaceutical composition of ibuprofen |
| US6912582B2 (en) | 2001-03-30 | 2005-06-28 | Microsoft Corporation | Service routing and web integration in a distributed multi-site user authentication system |
| WO2002096361A2 (en) | 2001-05-30 | 2002-12-05 | Sugen, Inc. | 5-aralkylsulfonyl-3- (pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors |
| US6720002B2 (en) * | 2001-07-20 | 2004-04-13 | R.P. Scherer Technologies, Inc. | Antihistamine formulations for soft capsule dosage forms |
| GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| JP2005514368A (ja) * | 2001-11-21 | 2005-05-19 | スージェン・インコーポレーテッド | インドリノン誘導体を含む医薬製剤 |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| US6797825B2 (en) | 2001-12-13 | 2004-09-28 | Abbott Laboratories | Protein kinase inhibitors |
| US20030139386A1 (en) * | 2001-12-21 | 2003-07-24 | Sophie Cote | Pharmaceutical compositions based on azetidine derivatives |
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- 1998-03-04 AU AU66806/98A patent/AU743024B2/en not_active Ceased
- 1998-03-04 CA CA2282439A patent/CA2282439C/en not_active Expired - Fee Related
- 1998-03-04 NZ NZ510991A patent/NZ510991A/xx not_active IP Right Cessation
- 1998-03-04 ES ES98908884T patent/ES2384551T3/es not_active Expired - Lifetime
- 1998-03-04 CO CO98011791A patent/CO4940469A1/es unknown
- 1998-03-04 WO PCT/US1998/004134 patent/WO1998038984A2/en not_active Ceased
- 1998-03-04 JP JP53869898A patent/JP4713698B2/ja not_active Expired - Fee Related
- 1998-03-04 AT AT98908884T patent/ATE554750T1/de active
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Also Published As
| Publication number | Publication date |
|---|---|
| WO1998038984A2 (en) | 1998-09-11 |
| EP1014953A2 (en) | 2000-07-05 |
| JP4713698B2 (ja) | 2011-06-29 |
| NZ510991A (en) | 2002-11-26 |
| CA2282439C (en) | 2010-05-04 |
| AU6680698A (en) | 1998-09-22 |
| US6248771B1 (en) | 2001-06-19 |
| JP2001514626A (ja) | 2001-09-11 |
| EP1014953B1 (en) | 2012-04-25 |
| CO4940469A1 (es) | 2000-07-24 |
| CA2282439A1 (en) | 1998-09-11 |
| ATE554750T1 (de) | 2012-05-15 |
| WO1998038984A3 (en) | 1999-01-28 |
| ES2384551T3 (es) | 2012-07-06 |
| US6696482B2 (en) | 2004-02-24 |
| HK1028548A1 (en) | 2001-02-23 |
| US20010012844A1 (en) | 2001-08-09 |
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