ES2556946T3 - Pirimidinaminas como moduladores de la angiogénesis - Google Patents
Pirimidinaminas como moduladores de la angiogénesis Download PDFInfo
- Publication number
- ES2556946T3 ES2556946T3 ES09159138.8T ES09159138T ES2556946T3 ES 2556946 T3 ES2556946 T3 ES 2556946T3 ES 09159138 T ES09159138 T ES 09159138T ES 2556946 T3 ES2556946 T3 ES 2556946T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- amino
- indazol
- hydrogen
- 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.)
- Expired - Lifetime
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- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical class NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 title description 2
- 239000000587 angiogenesis modulating agent Substances 0.000 title 1
- 229940076002 angiogenesis modulator Drugs 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 150
- 150000001875 compounds Chemical class 0.000 claims abstract description 147
- 239000001257 hydrogen Substances 0.000 claims abstract description 146
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 122
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 94
- 150000003839 salts Chemical class 0.000 claims abstract description 59
- 229910052736 halogen Chemical group 0.000 claims abstract description 51
- 150000002367 halogens Chemical group 0.000 claims abstract description 51
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 47
- 239000012453 solvate Substances 0.000 claims abstract description 45
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 22
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
- 125000004966 cyanoalkyl group Chemical group 0.000 claims abstract description 13
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 11
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 8
- -1 cyanomethyl Chemical group 0.000 claims description 164
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 101
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 53
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 40
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims description 37
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 37
- 230000000694 effects Effects 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
- 239000000460 chlorine Substances 0.000 claims description 30
- 229910052801 chlorine Inorganic materials 0.000 claims description 30
- 238000002360 preparation method Methods 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 28
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 24
- 230000033115 angiogenesis Effects 0.000 claims description 21
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 15
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 10
- 230000001404 mediated effect Effects 0.000 claims description 9
- AJJWFOBQWWYSKG-UHFFFAOYSA-N 4-n-methyl-4-n-(3-methyl-2h-indazol-6-yl)-2-n-[3-(methylsulfonylmethyl)phenyl]pyrimidine-2,4-diamine Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(CS(C)(=O)=O)=C1 AJJWFOBQWWYSKG-UHFFFAOYSA-N 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- BPGZHRULBGZUFP-UHFFFAOYSA-N 1-[4-methoxy-3-[[4-[(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]propan-1-one Chemical compound CCC(=O)C1=CC=C(OC)C(NC=2N=C(NC=3C=C4NN=C(C)C4=CC=3)C=CN=2)=C1 BPGZHRULBGZUFP-UHFFFAOYSA-N 0.000 claims description 3
- MGSXZPZPZIPVHO-UHFFFAOYSA-N 2-[(3-methyl-2h-indazol-6-yl)-[2-[3-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]acetonitrile Chemical compound C=1C=C2C(C)=NNC2=CC=1N(CC#N)C(N=1)=CC=NC=1NC1=CC=CC(CS(C)(=O)=O)=C1 MGSXZPZPZIPVHO-UHFFFAOYSA-N 0.000 claims description 3
- MQYXDHFLBFNMAM-UHFFFAOYSA-N 2-[(3-methyl-2h-indazol-6-yl)-[2-[4-(methylsulfonylmethyl)anilino]pyrimidin-4-yl]amino]acetonitrile Chemical compound C=1C=C2C(C)=NNC2=CC=1N(CC#N)C(N=1)=CC=NC=1NC1=CC=C(CS(C)(=O)=O)C=C1 MQYXDHFLBFNMAM-UHFFFAOYSA-N 0.000 claims description 3
- OMGYUNINHJCHHA-UHFFFAOYSA-N 2-n-(2-methoxy-5-methylsulfonylphenyl)-4-n-methyl-4-n-(3-methyl-2h-indazol-6-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC=C(S(C)(=O)=O)C=C1NC1=NC=CC(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 OMGYUNINHJCHHA-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims description 3
- YBDLZENVOVHCTJ-UHFFFAOYSA-N 2-n-(4-ethylsulfonylphenyl)-4-n-methyl-4-n-(3-methyl-2h-indazol-6-yl)pyrimidine-2,4-diamine Chemical compound C1=CC(S(=O)(=O)CC)=CC=C1NC1=NC=CC(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 YBDLZENVOVHCTJ-UHFFFAOYSA-N 0.000 claims description 2
- CMYGIORLGUFXRP-UHFFFAOYSA-N 4-n-(2,3-dimethylindazol-6-yl)-2-n-(5-ethylsulfonyl-2-methoxyphenyl)-4-n-methylpyrimidine-2,4-diamine Chemical compound CCS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(C=CN=2)N(C)C2=CC3=NN(C)C(C)=C3C=C2)=C1 CMYGIORLGUFXRP-UHFFFAOYSA-N 0.000 claims description 2
- ZDDUYAXPVKACHH-UHFFFAOYSA-N 4-n-ethynyl-4-n-(3-methyl-2h-indazol-6-yl)-2-n-[3-(methylsulfonylmethyl)phenyl]pyrimidine-2,4-diamine Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C#C)C(N=1)=CC=NC=1NC1=CC=CC(CS(C)(=O)=O)=C1 ZDDUYAXPVKACHH-UHFFFAOYSA-N 0.000 claims description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 2
- YDHRSWAPJJCSGX-UHFFFAOYSA-N n-[3-[[4-[ethyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]acetamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(CC)C(N=1)=CC=NC=1NC1=CC=CC(NC(C)=O)=C1 YDHRSWAPJJCSGX-UHFFFAOYSA-N 0.000 claims description 2
- AXBKRLMNVZOBIH-UHFFFAOYSA-N n-[3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]acetamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(NC(C)=O)=C1 AXBKRLMNVZOBIH-UHFFFAOYSA-N 0.000 claims description 2
- UYVJGZKGQJTVOP-UHFFFAOYSA-N 2-n-(2-methoxy-5-propan-2-ylsulfonylphenyl)-4-n-methyl-4-n-(3-methyl-2h-indazol-6-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC=C(S(=O)(=O)C(C)C)C=C1NC1=NC=CC(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 UYVJGZKGQJTVOP-UHFFFAOYSA-N 0.000 claims 1
- IJBAQSSFPMVEEW-UHFFFAOYSA-N 2-n-(5-ethylsulfonyl-2-methoxyphenyl)-4-n-(3-methyl-2h-indazol-6-yl)-4-n-propan-2-ylpyrimidine-2,4-diamine Chemical compound CCS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(C=CN=2)N(C(C)C)C=2C=C3NN=C(C)C3=CC=2)=C1 IJBAQSSFPMVEEW-UHFFFAOYSA-N 0.000 claims 1
- ALQFBYVDVDYXAA-UHFFFAOYSA-N 2-n-(5-ethylsulfonyl-2-methoxyphenyl)-4-n-(3-methyl-2h-indazol-6-yl)pyrimidine-2,4-diamine Chemical compound CCS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(NC=3C=C4NN=C(C)C4=CC=3)C=CN=2)=C1 ALQFBYVDVDYXAA-UHFFFAOYSA-N 0.000 claims 1
- KFHRYSKELLEUHL-UHFFFAOYSA-N 2-n-[2-methoxy-5-(2-methylpropylsulfonyl)phenyl]-4-n-(3-methyl-2h-indazol-6-yl)pyrimidine-2,4-diamine Chemical compound COC1=CC=C(S(=O)(=O)CC(C)C)C=C1NC1=NC=CC(NC=2C=C3NN=C(C)C3=CC=2)=N1 KFHRYSKELLEUHL-UHFFFAOYSA-N 0.000 claims 1
- BOKJLELAASHRDE-UHFFFAOYSA-N 4-n-ethyl-2-n-(5-ethylsulfonyl-2-methoxyphenyl)-4-n-(3-methyl-2h-indazol-6-yl)pyrimidine-2,4-diamine Chemical compound C=1C=C2C(C)=NNC2=CC=1N(CC)C(N=1)=CC=NC=1NC1=CC(S(=O)(=O)CC)=CC=C1OC BOKJLELAASHRDE-UHFFFAOYSA-N 0.000 claims 1
- VHICZWHVIFZTFD-UHFFFAOYSA-N 4-n-methyl-4-n-(3-methyl-2h-indazol-6-yl)-2-n-[3-(propan-2-ylsulfonylmethyl)phenyl]pyrimidine-2,4-diamine Chemical compound CC(C)S(=O)(=O)CC1=CC=CC(NC=2N=C(C=CN=2)N(C)C=2C=C3NN=C(C)C3=CC=2)=C1 VHICZWHVIFZTFD-UHFFFAOYSA-N 0.000 claims 1
- NTOREKWHRRSTTO-UHFFFAOYSA-N 4-n-methyl-4-n-(3-methyl-2h-indazol-6-yl)-2-n-[4-(propan-2-ylsulfonylmethyl)phenyl]pyrimidine-2,4-diamine Chemical compound C1=CC(CS(=O)(=O)C(C)C)=CC=C1NC1=NC=CC(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 NTOREKWHRRSTTO-UHFFFAOYSA-N 0.000 claims 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims 1
- RBENAORRCGKTLF-UHFFFAOYSA-N n-[3-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]methanesulfonamide Chemical compound C=1C=C2C(C)=NNC2=CC=1N(C)C(N=1)=CC=NC=1NC1=CC=CC(NS(C)(=O)=O)=C1 RBENAORRCGKTLF-UHFFFAOYSA-N 0.000 claims 1
- WSOASQNARKHWJC-UHFFFAOYSA-N n-[[4-[[4-[methyl-(3-methyl-2h-indazol-6-yl)amino]pyrimidin-2-yl]amino]phenyl]methyl]ethanesulfonamide Chemical compound C1=CC(CNS(=O)(=O)CC)=CC=C1NC1=NC=CC(N(C)C=2C=C3NN=C(C)C3=CC=2)=N1 WSOASQNARKHWJC-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 abstract 6
- 238000001819 mass spectrum Methods 0.000 description 86
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
- 239000000203 mixture Substances 0.000 description 59
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- 235000002639 sodium chloride Nutrition 0.000 description 53
- 239000000243 solution Substances 0.000 description 52
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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
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D235/08—Radicals containing only hydrogen and carbon atoms
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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| US25752600P | 2000-12-21 | 2000-12-21 | |
| US257526P | 2000-12-21 | ||
| US26240301P | 2001-01-16 | 2001-01-16 | |
| US262403P | 2001-01-16 |
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| ES2556946T3 true ES2556946T3 (es) | 2016-01-21 |
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| ES01994315T Expired - Lifetime ES2324981T3 (es) | 2000-12-21 | 2001-12-19 | Pirimidinaminas como moduladores de la angiogenesis. |
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| ES01994315T Expired - Lifetime ES2324981T3 (es) | 2000-12-21 | 2001-12-19 | Pirimidinaminas como moduladores de la angiogenesis. |
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Families Citing this family (250)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA02007957A (es) * | 2000-02-17 | 2002-11-29 | Amgen Inc | Inhibidores de cinasas. |
| ATE430742T1 (de) * | 2000-12-21 | 2009-05-15 | Smithkline Beecham Corp | Pyrimidinamine als angiogenesemodulatoren |
| US7153871B2 (en) | 2001-01-22 | 2006-12-26 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs |
| US7205320B2 (en) | 2001-01-22 | 2007-04-17 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| MEP13408A (en) | 2001-05-29 | 2010-06-10 | Bayer Schering Pharma Ag | Cdk inhibiting pyrimidines, production thereof and their use as medicaments |
| HUP0401711A3 (en) | 2001-06-26 | 2009-07-28 | Bristol Myers Squibb Co | N-heterocyclic inhibitors of tnf-alpha and pharmaceutical compositions containing them |
| US6939874B2 (en) | 2001-08-22 | 2005-09-06 | Amgen Inc. | Substituted pyrimidinyl derivatives and methods of use |
| US7115617B2 (en) | 2001-08-22 | 2006-10-03 | Amgen Inc. | Amino-substituted pyrimidinyl derivatives and methods of use |
| EP1438053B1 (de) * | 2001-10-17 | 2008-09-10 | Boehringer Ingelheim Pharma GmbH & Co.KG | Pyrimidinderivate, arzneimittel enthaltend diese verbindungen, deren verwendung und verfahren zu ihrer herstellung |
| IL161663A0 (en) * | 2001-11-01 | 2004-09-27 | Janssen Pharmaceutica Nv | AMINOBENZAMIDE DERIVATIVES AS GLYCOGEN SYNTHASE KINASE 3beta INHIBITORS |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| JP2005524668A (ja) | 2002-03-01 | 2005-08-18 | スミスクライン ビーチャム コーポレーション | ジアミノピリミジン類及びそれらの血管新生阻害薬としての使用 |
| EP1515955A4 (en) * | 2002-06-17 | 2006-05-03 | Smithkline Beecham Corp | CHEMICAL PROCESS |
| AU2003256616B2 (en) | 2002-07-19 | 2009-08-27 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including N-substituted aniline and diphenylamine analogs |
| HRP20050082A2 (en) * | 2002-07-19 | 2005-06-30 | Memory Pharmaceuticals Corporation | 6-amino-1h-indazole and 4-aminobenzofuran compounds as phosphodiesterase 4 inhibitors |
| HRP20050089B1 (hr) | 2002-07-29 | 2015-06-19 | Rigel Pharmaceuticals | Upotreba 2,4 pirimidindiaminskog spoja za proizvodnju lijeka za lijeäśenje ili sprjeäśavanje autoimunosne bolesti |
| US7189712B2 (en) * | 2002-10-10 | 2007-03-13 | Smithkline Beecham Corporation | 1,3-Oxazole compounds for the treatment of cancer |
| RU2356893C2 (ru) | 2002-11-19 | 2009-05-27 | Мемори Фармасьютиклз Корпорейшн | Ингибиторы фосфодиэстеразы 4 |
| UA80767C2 (en) * | 2002-12-20 | 2007-10-25 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| CA2529611C (en) | 2002-12-20 | 2009-12-15 | Pfizer Products Inc. | Pyrimidine derivatives for the treatment of abnormal cell growth |
| US7109337B2 (en) | 2002-12-20 | 2006-09-19 | Pfizer Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| US20040167132A1 (en) * | 2003-01-16 | 2004-08-26 | Geetha Shankar | Methods of treating conditions associted with an Edg-2 receptor |
| US7514446B2 (en) | 2003-02-20 | 2009-04-07 | Smithkline Beecham Corporation | Pyrimidine compounds |
| MXPA06000508A (es) | 2003-07-18 | 2006-04-05 | Amgen Inc | Agentes de union especifica al factor del crecimiento de los hepatocitos. |
| JP4886511B2 (ja) | 2003-07-30 | 2012-02-29 | ライジェル ファーマシューティカルズ， インコーポレイテッド | ２，４−ピリミジンジアミン化合物による自己免疫疾患の治療または予防方法 |
| JP4741491B2 (ja) | 2003-08-07 | 2011-08-03 | ライジェル ファーマシューティカルズ， インコーポレイテッド | 抗増殖剤としての２，４−ピリミジンジアミン化合物および使用 |
| AU2004288715A1 (en) * | 2003-11-06 | 2005-05-26 | Celgene Corporation | Methods of using and compositions comprising a JNK inhibitor for the treatment and management of asbestos-related diseases and disorders |
| JP2007532658A (ja) * | 2004-04-16 | 2007-11-15 | スミスクライン ビーチャム コーポレーション | がんの治療方法 |
| MXPA06013164A (es) | 2004-05-14 | 2007-02-13 | Pfizer Prod Inc | Derivados de pirimidina para el tratamiento de crecimiento de celulas anormal. |
| BRPI0510963A (pt) | 2004-05-14 | 2007-11-20 | Pfizer Prod Inc | derivados pirimidina para o tratamento do crescimento anormal de células |
| WO2005111024A1 (en) | 2004-05-14 | 2005-11-24 | Pfizer Products Inc. | Pyrimidine derivatives for the treatment of abnormal cell growth |
| JP4812763B2 (ja) | 2004-05-18 | 2011-11-09 | ライジェル ファーマシューティカルズ， インコーポレイテッド | シクロアルキル置換ピリミジンジアミン化合物およびそれらの用途 |
| WO2006020564A1 (en) * | 2004-08-09 | 2006-02-23 | Smithkline Beecham Corporation | Pyrimidin derivatives for the treatment of multiple myeloma |
| KR20070084067A (ko) * | 2004-10-13 | 2007-08-24 | 와이어쓰 | Ｎ-벤젠설포닐 치환 아닐리노-피리미딘 동족체 |
| GB2420559B (en) | 2004-11-15 | 2008-08-06 | Rigel Pharmaceuticals Inc | Stereoisomerically enriched 3-aminocarbonyl bicycloheptene pyrimidinediamine compounds and their uses |
| CN100516049C (zh) | 2004-11-16 | 2009-07-22 | 永信药品工业股份有限公司 | 抗血管生成药n2-(取代的芳基甲基)-3-(取代的苯基)吲唑的合成 |
| ATE540035T1 (de) | 2004-11-24 | 2012-01-15 | Rigel Pharmaceuticals Inc | Spiro-2,4-pyrimidindiamin-verbindungen und ihre verwendungen |
| JP2008521900A (ja) | 2004-11-30 | 2008-06-26 | アムジエン・インコーポレーテツド | キノリン及びキナゾリン類似体並びにがん治療のための医薬としてのその使用 |
| CN101115761B (zh) | 2005-01-19 | 2012-07-18 | 里格尔药品股份有限公司 | 2,4-嘧啶二胺化合物的前药及其应用 |
| US8227455B2 (en) | 2005-04-18 | 2012-07-24 | Rigel Pharmaceuticals, Inc. | Methods of treating cell proliferative disorders |
| WO2006129100A1 (en) * | 2005-06-03 | 2006-12-07 | Glaxo Group Limited | Novel compounds |
| US20070203161A1 (en) | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| AU2006254840B2 (en) | 2005-06-08 | 2012-08-02 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
| US8926945B2 (en) | 2005-10-07 | 2015-01-06 | Guerbet | Compounds comprising a biological target recognizing part, coupled to a signal part capable of complexing gallium |
| US8986650B2 (en) | 2005-10-07 | 2015-03-24 | Guerbet | Complex folate-NOTA-Ga68 |
| EP1954281B1 (en) | 2005-11-29 | 2011-03-09 | GlaxoSmithKline LLC | Cancer treatment method |
| MX2008006379A (es) * | 2005-11-29 | 2009-03-03 | Smithkline Beecham Corp | Metodo de tratamiento. |
| US20080108664A1 (en) | 2005-12-23 | 2008-05-08 | Liu Belle B | Solid-state form of AMG 706 and pharmaceutical compositions thereof |
| TW200736232A (en) * | 2006-01-26 | 2007-10-01 | Astrazeneca Ab | Pyrimidine derivatives |
| AR059066A1 (es) * | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| ES2353482T3 (es) | 2006-02-10 | 2011-03-02 | Amgen, Inc | Formas hidrato de amg706. |
| ES2622493T3 (es) | 2006-02-24 | 2017-07-06 | Rigel Pharmaceuticals, Inc. | Composiciones y métodos para la inhibición de la ruta de JAK |
| WO2007143483A2 (en) * | 2006-06-01 | 2007-12-13 | Smithkline Beecham Corporation | Combination of pazopanib and lapatinib for treating cancer |
| PE20080403A1 (es) | 2006-07-14 | 2008-04-25 | Amgen Inc | Derivados heterociclicos fusionados y metodos de uso |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| US8193197B2 (en) | 2006-10-19 | 2012-06-05 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the JAK pathway |
| WO2008057461A2 (en) | 2006-11-02 | 2008-05-15 | Acceleron Pharma, Inc. | Alk1 receptor and ligand antagonists and uses thereof |
| EP2125781A2 (en) | 2006-12-20 | 2009-12-02 | Amgen Inc. | Substituted heterocycles and methods of use |
| ES2449482T3 (es) | 2007-01-09 | 2014-03-19 | Amgen Inc. | Derivados de bis-aril-amida útiles para el tratamiento de cáncer |
| FR2911604B1 (fr) | 2007-01-19 | 2009-04-17 | Sanofi Aventis Sa | Derives de n-(heteroaryl-1h-indole-2-carboxamides, leur preparation et leur application en therapeutique |
| CA2676173A1 (en) | 2007-02-16 | 2008-08-28 | Amgen Inc. | Nitrogen-containing heterocyclyl ketones and their use as c-met inhibitors |
| NZ580671A (en) * | 2007-04-16 | 2012-03-30 | Hutchison Medipharma Entpr Ltd | Pyrimidine derivatives |
| MX2010001918A (es) | 2007-08-21 | 2010-03-11 | Amgen Inc | Proteinas enlazadas al antigeno humano de celula de cepa mcdonough de felino. |
| EP2058307A1 (en) * | 2007-11-12 | 2009-05-13 | Cellzome Ag | Methods for the identification of JAK kinase interacting molecules and for the purification of JAK kinases |
| CA2728893C (en) | 2008-04-16 | 2017-03-14 | Portola Pharmaceuticals, Inc. | Inhibitors of syk protein kinase |
| US8138339B2 (en) | 2008-04-16 | 2012-03-20 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| MX2010011463A (es) | 2008-04-16 | 2011-06-03 | Portola Pharm Inc | 2,6-diamino-pirimidin-5-il-carboxamidas como inhibidores de syk o jak quinasas. |
| JP2011518219A (ja) | 2008-04-22 | 2011-06-23 | ポートラ ファーマシューティカルズ， インコーポレイテッド | タンパク質キナーゼの阻害剤 |
| US9273077B2 (en) | 2008-05-21 | 2016-03-01 | Ariad Pharmaceuticals, Inc. | Phosphorus derivatives as kinase inhibitors |
| MX2010012703A (es) | 2008-05-21 | 2010-12-21 | Ariad Pharma Inc | Derivados fosforosos como inhibidores de cinasa. |
| US20100029689A1 (en) * | 2008-07-02 | 2010-02-04 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
| WO2010036796A1 (en) * | 2008-09-26 | 2010-04-01 | Concert Pharmaceuticals, Inc. | Pyridineamine derivatives |
| FR2942227B1 (fr) | 2009-02-13 | 2011-04-15 | Guerbet Sa | Utilisation de tampons pour la complexation de radionucleides |
| WO2011039648A1 (en) | 2009-09-30 | 2011-04-07 | Glaxo Wellcome Manufacturing Pte Ltd. | Methods of administration and treatment |
| EP2490536A4 (en) * | 2009-10-23 | 2013-04-17 | Glaxo Wellcome Mfg Pte Ltd | COMPOSITION AND METHOD |
| WO2011058179A1 (en) | 2009-11-16 | 2011-05-19 | Ratiopharm Gmbh | 5- (4- (n- (2, 3 -dimethyl- 2h- indazol- 6 -yl) -n-methylamino) pyrimidin- 2 -ylamino) -2 -methylbenzenesulfonamide |
| WO2011069053A1 (en) | 2009-12-04 | 2011-06-09 | Teva Pharmaceutical Industries Ltd. | Process for the preparation of pazopanip hcl and crystalline forms of pazopanib hcl |
| TW201201808A (en) * | 2010-01-06 | 2012-01-16 | Glaxo Wellcome Mfg Pte Ltd | Treatment method |
| WO2013022801A1 (en) | 2011-08-05 | 2013-02-14 | Forsight Vision4, Inc. | Small molecule delivery with implantable therapeutic device |
| BR112012024380A2 (pt) | 2010-03-25 | 2015-09-15 | Glaxosmithkline Llc | compostos químicos |
| CN103003264B (zh) | 2010-05-21 | 2014-08-06 | 切米利亚股份公司 | 嘧啶衍生物 |
| JP2013526613A (ja) * | 2010-05-26 | 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 |
| HUE029196T2 (en) | 2010-06-04 | 2017-02-28 | Hoffmann La Roche | Aminoprimidine derivatives as LRRK2 modulators |
| WO2011161217A2 (en) | 2010-06-23 | 2011-12-29 | Palacký University in Olomouc | Targeting of vegfr2 |
| WO2012027438A1 (en) | 2010-08-26 | 2012-03-01 | Glaxosmithkline Llc | Pharmaceutical combination of a vegfr inhibitor and a mek inhibitor useful for treating cancer |
| US20130172378A1 (en) * | 2010-09-14 | 2013-07-04 | Glaxosmithkline Llc | Combination of BRAF and VEGF Inhibitors |
| MX2013004086A (es) * | 2010-10-14 | 2013-07-05 | Ariad Pharma Inc | Metodos para inhibir proliferacion celular en cancers accionados por egfr. |
| US20130317029A1 (en) | 2010-11-01 | 2013-11-28 | Portola Pharmaceuticals, Inc. | Oxypyrimidines as syk modulators |
| AU2011323484B2 (en) | 2010-11-01 | 2016-10-06 | Portola Pharmaceuticals, Inc. | Benzamides and nicotinamides as Syk modulators |
| WO2012061428A2 (en) | 2010-11-01 | 2012-05-10 | Portola Pharmaceuticals, Inc. | Nicotinamides as jak kinase modulators |
| SG189043A1 (en) | 2010-11-10 | 2013-05-31 | Hoffmann La Roche | Pyrazole aminopyrimidine derivatives as lrrk2 modulators |
| CA2818612C (en) | 2010-11-19 | 2020-12-29 | Forsight Vision4, Inc. | Therapeutic agent formulations for implanted devices |
| WO2012073254A1 (en) | 2010-11-29 | 2012-06-07 | Hetero Research Foundation | A process for the preparation of pazopanib using novel intermediate |
| CN102093339B (zh) * | 2010-12-09 | 2013-06-12 | 天津药物研究院 | 一类嘧啶衍生物的制备及用途 |
| CN102060848B (zh) * | 2010-12-09 | 2013-09-18 | 天津药物研究院 | 芳香胺取代的嘧啶衍生物的制备及用途 |
| CN102093340B (zh) * | 2010-12-09 | 2013-07-17 | 天津药物研究院 | 2-甲基吲唑衍生物的制备及用途 |
| WO2012082337A2 (en) | 2010-12-17 | 2012-06-21 | Glaxo Wellcome Manufacturing Pte Ltd | Combination |
| FR2968999B1 (fr) | 2010-12-20 | 2013-01-04 | Guerbet Sa | Nanoemulsion de chelate pour irm |
| US20130303560A1 (en) | 2011-02-01 | 2013-11-14 | Sunnybrook Research Institute | Combination |
| PT2688887E (pt) | 2011-03-23 | 2015-07-06 | Amgen Inc | Inibidores duais tricíclicos fusionados de cdk 4/6 e flt3 |
| CA2830129C (en) | 2011-03-24 | 2016-07-19 | Chemilia Ab | Novel pyrimidine derivatives |
| CA2833288A1 (en) * | 2011-04-19 | 2012-10-26 | Bayer Intellectual Property Gmbh | Substituted 4-aryl-n-phenyl-1,3,5-triazin-2-amines |
| BR112013027734A2 (pt) | 2011-05-04 | 2017-08-08 | Ariad Pharma Inc | compostos para a inibição de proliferação celular em cânceres impulsionados pelo egfr, método e composição farmacêutica |
| TWI555737B (zh) * | 2011-05-24 | 2016-11-01 | 拜耳知識產權公司 | 含有硫醯亞胺基團之４－芳基－ｎ－苯基－１，３，５－三氮雜苯－２－胺 |
| WO2013025939A2 (en) | 2011-08-16 | 2013-02-21 | Indiana University Research And Technology Corporation | Compounds and methods for treating cancer by inhibiting the urokinase receptor |
| JP5976814B2 (ja) * | 2011-09-16 | 2016-08-24 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ | スルホキシイミン基を含有する二置換５−フルオロピリミジン誘導体 |
| FR2980364B1 (fr) | 2011-09-26 | 2018-08-31 | Guerbet | Nanoemulsions et leur utilisation comme agents de contraste |
| IN2014CN02850A (enExample) | 2011-10-31 | 2015-07-03 | Glaxosmithkline Intellectual Property Ltd | |
| SG11201402570QA (en) | 2011-11-23 | 2014-06-27 | Portola Pharm Inc | Pyrazine kinase inhibitors |
| CN103159742B (zh) * | 2011-12-16 | 2015-08-12 | 北京韩美药品有限公司 | 5-氯嘧啶类化合物及其作为egfr酪氨酸激酶抑制剂的应用 |
| AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
| CN103373989B (zh) * | 2012-04-28 | 2016-04-13 | 上海医药工业研究院 | 盐酸帕唑帕尼的中间体的制备方法 |
| AU2013204563B2 (en) | 2012-05-05 | 2016-05-19 | Takeda Pharmaceutical Company Limited | Compounds for inhibiting cell proliferation in EGFR-driven cancers |
| US9505749B2 (en) | 2012-08-29 | 2016-11-29 | Amgen Inc. | Quinazolinone compounds and derivatives thereof |
| WO2014058921A2 (en) | 2012-10-08 | 2014-04-17 | Portola Pharmaceuticals, Inc. | Substituted pyrimidinyl kinase inhibitors |
| CA2888383A1 (en) | 2012-10-18 | 2014-04-24 | Bayer Pharma Aktiengesellschaft | N-(pyridin-2-yl)pyrimidin-4-amine derivatives containing a sulfone group |
| ES2595222T3 (es) | 2012-10-18 | 2016-12-28 | Bayer Pharma Aktiengesellschaft | Derivados de 5-fluoro-N-(piridin-2-il)piridin-2-amina que contienen un grupo sulfona |
| TW201418243A (zh) | 2012-11-15 | 2014-05-16 | Bayer Pharma AG | 含有磺醯亞胺基團之ｎ－（吡啶－２－基）嘧啶－４－胺衍生物 |
| SG11201503079PA (en) | 2012-11-15 | 2015-06-29 | Bayer Pharma AG | 5-FLUORO-<i>N</i>-(PYRIDIN-2-YL)PYRIDIN-2-AMINE DERIVATIVES CONTAINING A SULFOXIMINE GROUP |
| CN103864764A (zh) * | 2012-12-11 | 2014-06-18 | 齐鲁制药有限公司 | 吲唑取代的嘧啶胺衍生物、其制备方法和用途 |
| EP2935250B1 (en) * | 2012-12-17 | 2018-03-28 | Sun Pharmaceutical Industries Limited | Process for the preparation of pazopanib or salts thereof |
| WO2014097152A1 (en) | 2012-12-17 | 2014-06-26 | Ranbaxy Laboratories Limited | Process for the preparation of pazopanib or salts thereof |
| CN103910716A (zh) * | 2013-01-07 | 2014-07-09 | 华东理工大学 | 2,4-二取代-环烷基[d]嘧啶类化合物及其用途 |
| KR20150103735A (ko) | 2013-01-09 | 2015-09-11 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | 조합물 |
| FR3001154B1 (fr) | 2013-01-23 | 2015-06-26 | Guerbet Sa | Magneto-emulsion vectorisee |
| EP2968113B8 (en) | 2013-03-14 | 2020-10-28 | Forsight Vision4, Inc. | Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant |
| US9611283B1 (en) | 2013-04-10 | 2017-04-04 | Ariad Pharmaceuticals, Inc. | Methods for inhibiting cell proliferation in ALK-driven cancers |
| CN103214467B (zh) * | 2013-04-26 | 2015-09-30 | 中国人民解放军军事医学科学院微生物流行病研究所 | 5-[[4-[(2,3-二甲基-2h-吲唑-6-基)甲氨基]-2嘧啶基]氨基]-2-甲基-苯磺酰胺衍生物及其制备方法与应用 |
| CA2917096C (en) | 2013-07-04 | 2021-05-18 | Bayer Pharma Aktiengesellschaft | Sulfoximine substituted 5-fluoro-n-(pyridin-2-yl)pyridin-2-amine derivatives and their use as cdk9 kinase inhibitors |
| US11136625B2 (en) | 2013-08-28 | 2021-10-05 | Crown Bioscience, Inc. (Taicang) | Gene expression signatures predictive of subject response to a multi-kinase inhibitor and methods of using the same |
| WO2015056180A1 (en) | 2013-10-15 | 2015-04-23 | Glaxosmithkline Intellectual Property (No.2) Limited | Indoline derivatives as inhibitors of perk |
| US10730859B2 (en) | 2013-11-05 | 2020-08-04 | Laurus Labs Limited | Process for the preparation of pazopanib or a pharmaceutically acceptable salt thereof |
| CN103739550B (zh) * | 2014-01-02 | 2016-06-01 | 中国药科大学 | 2,3-二甲基-6-脲-2h-吲唑类化合物及其制备方法与应用 |
| CN104829542B (zh) * | 2014-02-10 | 2018-02-02 | 中国科学院上海药物研究所 | 苯胺嘧啶类化合物、其制备方法和医药用途 |
| EP3116877A1 (en) | 2014-03-11 | 2017-01-18 | Glaxosmithkline Intellectual Property (No. 2) Limited | Chemical compounds acting as perk inhibitors |
| CA2942119A1 (en) | 2014-03-13 | 2015-09-17 | Bayer Pharma Aktiengesellschaft | 5-fluoro-n-(pyridin-2-yl)pyridin-2-amine derivatives containing a sulfone group |
| US9790189B2 (en) | 2014-04-01 | 2017-10-17 | Bayer Pharma Aktiengesellschaft | Disubstituted 5-fluoro pyrimidine derivatives containing a sulfondiimine group |
| CN106459084B (zh) | 2014-04-11 | 2019-04-19 | 拜耳医药股份有限公司 | 大环化合物 |
| US9856263B2 (en) | 2014-04-28 | 2018-01-02 | Pfizer Inc. | Heteroaromatic compounds and their use as dopamine D1 ligands |
| MX2017001818A (es) | 2014-08-08 | 2017-05-30 | Forsight Vision4 Inc | Formulaciones estables y solubles de inhibidores de receptor de quinasa tirosina y metodos de preparacion de los mismos. |
| WO2016055935A1 (en) | 2014-10-06 | 2016-04-14 | Glaxosmithkline Intellectual Property (No.2) Limited | Combination of lysine-specific demethylase 1 inhibitor and thrombopoietin agonist |
| CA2964696C (en) | 2014-10-16 | 2022-09-06 | Bayer Pharma Aktiengesellschaft | Fluorinated benzofuranyl-pyrimidine derivatives containing a sulfoximine group |
| EP3207037B1 (en) | 2014-10-16 | 2019-01-23 | Bayer Pharma Aktiengesellschaft | Fluorinated benzofuranyl-pyrimidine derivatives containing a sulfone group |
| AU2016205311B2 (en) | 2015-01-08 | 2022-02-17 | The Board Of Trustees Of The Leland Stanford Junior University | Factors and cells that provide for induction of bone, bone marrow, and cartilage |
| SG11201705767PA (en) | 2015-01-13 | 2017-08-30 | Univ Kyoto | Agent for preventing and/or treating amyotrophic lateral sclerosis |
| KR101705980B1 (ko) * | 2015-06-12 | 2017-02-13 | 중앙대학교 산학협력단 | 신규 파조파닙 유도체 및 이를 함유하는 약학조성물 |
| CN105237523B (zh) * | 2015-10-08 | 2018-06-01 | 深圳市博圣康生物科技有限公司 | 嘧啶衍生物及其制备方法、用途 |
| WO2017098421A1 (en) | 2015-12-08 | 2017-06-15 | Glaxosmithkline Intellectual Property Development Limited | Benzothiadiazine compounds |
| WO2017153952A1 (en) | 2016-03-10 | 2017-09-14 | Glaxosmithkline Intellectual Property Development Limited | 5-sulfamoyl-2-hydroxybenzamide derivatives |
| EP3228630A1 (en) | 2016-04-07 | 2017-10-11 | IMBA-Institut für Molekulare Biotechnologie GmbH | Combination of an apelin antagonist and an angiogenesis inhibitor for the treatment of cancer |
| KR20190015748A (ko) | 2016-06-08 | 2019-02-14 | 글락소스미스클라인 인털렉츄얼 프로퍼티 디벨로프먼트 리미티드 | Atf4 경로 억제제로서의 화학적 화합물 |
| US10851053B2 (en) | 2016-06-08 | 2020-12-01 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds |
| WO2018015879A1 (en) | 2016-07-20 | 2018-01-25 | Glaxosmithkline Intellectual Property Development Limited | Isoquinoline derivatives as perk inhibitors |
| WO2018100536A1 (en) | 2016-12-01 | 2018-06-07 | Glaxosmithkline Intellectual Property Development Limited | Methods of treating cancer |
| NZ754994A (en) | 2016-12-22 | 2022-12-23 | Amgen Inc | Benzisothiazole, isothiazolo[3,4-b]pyridine, quinazoline, phthalazine, pyrido[2,3-d]pyridazine and pyrido[2,3-d]pyrimidine derivatives as kras g12c inhibitors for treating lung, pancreatic or colorectal cancer |
| WO2018148533A1 (en) | 2017-02-09 | 2018-08-16 | Georgetown University | Compositions and methods for treating lysosomal storage disorders |
| ES2900199T3 (es) | 2017-03-28 | 2022-03-16 | Bayer Ag | Novedosos compuestos macrocíclicos inhibidores de PTEFB |
| WO2018177889A1 (en) | 2017-03-28 | 2018-10-04 | Bayer Aktiengesellschaft | Novel ptefb inhibiting macrocyclic compounds |
| US11166953B2 (en) | 2017-04-17 | 2021-11-09 | Yale University | Compounds, compositions and methods of treating or preventing acute lung injury |
| JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
| WO2018225093A1 (en) | 2017-06-07 | 2018-12-13 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds as atf4 pathway inhibitors |
| BR112020000122A2 (pt) | 2017-07-03 | 2020-07-07 | Glaxosmithkline Intellectual Property Development Limited | derivados da n-(3-(2-(4-clorofenóxi)acetamido)biciclo[1.1.1] pentan-1-il)-2-ciclobutano-1-carboxamida e compostos relacionados como inibidores do atf4 para tratamento contra o câncer e outras doenças |
| CA3068395A1 (en) | 2017-07-03 | 2019-01-10 | Glaxosmithkline Intellectual Property Development Limited | 2-(4-chlorophenoxy)-n-((1-(2-(4-chlorophenoxy)ethynazetidin-3-yl)methyl)acetamide derivatives and related compounds as atf4 inhibitors for treating cancer and other diseases |
| WO2019021208A1 (en) | 2017-07-27 | 2019-01-31 | Glaxosmithkline Intellectual Property Development Limited | USEFUL INDAZOLE DERIVATIVES AS PERK INHIBITORS |
| CN107619407B (zh) * | 2017-08-10 | 2019-05-24 | 山东大学 | 基于帕唑帕尼结构的hdac和vegfr双靶点抑制剂及其制备方法和应用 |
| TW201922721A (zh) | 2017-09-07 | 2019-06-16 | 英商葛蘭素史克智慧財產發展有限公司 | 化學化合物 |
| ES2928576T3 (es) | 2017-09-08 | 2022-11-21 | Amgen Inc | Inhibidores de KRAS G12C y métodos de uso de los mismos |
| WO2019053617A1 (en) | 2017-09-12 | 2019-03-21 | Glaxosmithkline Intellectual Property Development Limited | CHEMICAL COMPOUNDS |
| CN111727183B (zh) | 2018-02-13 | 2023-12-29 | 拜耳公司 | 5-氟-4-(4-氟-2-甲氧基苯基)-n-{4-[(s-甲基磺亚胺酰基)甲基]吡啶-2-基}吡啶-2-胺用于治疗弥漫性大b细胞淋巴瘤中的用途 |
| WO2019193541A1 (en) | 2018-04-06 | 2019-10-10 | Glaxosmithkline Intellectual Property Development Limited | Bicyclic aromatic ring derivatives of formula (i) as atf4 inhibitors |
| WO2019193540A1 (en) | 2018-04-06 | 2019-10-10 | Glaxosmithkline Intellectual Property Development Limited | Heteroaryl derivatives of formula (i) as atf4 inhibitors |
| WO2019053500A1 (en) | 2018-04-17 | 2019-03-21 | Alvogen Malta Operations (Row) Ltd | PHARMACEUTICAL COMPOSITION OF SOLID DOSAGE FORM CONTAINING PAZOPANIB AND PROCESS FOR PREPARING THE SAME |
| MA52501A (fr) | 2018-05-04 | 2021-03-10 | Amgen Inc | Inhibiteurs de kras g12c et leurs procédés d'utilisation |
| CA3099118A1 (en) | 2018-05-04 | 2019-11-07 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| EP3790886B1 (en) | 2018-05-10 | 2024-06-26 | Amgen Inc. | Kras g12c inhibitors for the treatment of cancer |
| EP3802535B1 (en) | 2018-06-01 | 2022-12-14 | Amgen, Inc | Kras g12c inhibitors and methods of using the same |
| CA3099799A1 (en) | 2018-06-11 | 2019-12-19 | Amgen Inc. | Kras g12c inhibitors for treating cancer |
| MA51848A (fr) | 2018-06-12 | 2021-04-21 | Amgen Inc | Inhibiteurs de kras g12c et leurs procédés d'utilisation |
| AU2019285066B2 (en) | 2018-06-15 | 2024-06-13 | Handa Pharmaceuticals, Inc. | Kinase inhibitor salts and compositions thereof |
| WO2020007822A1 (en) | 2018-07-02 | 2020-01-09 | Conservatoire National Des Arts Et Metiers (Cnam) | Bismuth metallic (0) nanoparticles, process of manufacturing and uses thereof |
| EP3820843A1 (en) | 2018-07-09 | 2021-05-19 | GlaxoSmithKline Intellectual Property Development Limited | Chemical compounds |
| WO2020031107A1 (en) | 2018-08-08 | 2020-02-13 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds |
| JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法 |
| JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法 |
| US11053226B2 (en) | 2018-11-19 | 2021-07-06 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| EP4342473A3 (en) | 2018-11-30 | 2024-05-15 | GlaxoSmithKline Intellectual Property Development Limited | Compounds useful in hiv therapy |
| MA54550A (fr) | 2018-12-20 | 2022-03-30 | Amgen Inc | Inhibiteurs de kif18a |
| AU2019401495B2 (en) | 2018-12-20 | 2025-06-26 | Amgen Inc. | Heteroaryl amides useful as KIF18A inhibitors |
| MA54546A (fr) | 2018-12-20 | 2022-03-30 | Amgen Inc | Amides d'hétéroaryle utiles en tant qu'inhibiteurs de kif18a |
| EA202191730A1 (ru) | 2018-12-20 | 2021-08-24 | Эмджен Инк. | Ингибиторы kif18a |
| US20220040324A1 (en) | 2018-12-21 | 2022-02-10 | Daiichi Sankyo Company, Limited | Combination of antibody-drug conjugate and kinase inhibitor |
| KR20210146287A (ko) | 2019-03-01 | 2021-12-03 | 레볼루션 메디슨즈, 인크. | 이환식 헤테로아릴 화합물 및 이의 용도 |
| CN113727758A (zh) | 2019-03-01 | 2021-11-30 | 锐新医药公司 | 双环杂环基化合物及其用途 |
| EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
| EP3972973A1 (en) | 2019-05-21 | 2022-03-30 | Amgen Inc. | Solid state forms |
| WO2021018941A1 (en) | 2019-07-31 | 2021-02-04 | Glaxosmithkline Intellectual Property Development Limited | Methods of treating cancer |
| CN114391012B (zh) | 2019-08-02 | 2025-10-31 | 美国安进公司 | 作为kif18a抑制剂的吡啶衍生物 |
| ES3051918T3 (en) | 2019-08-02 | 2025-12-30 | Amgen Inc | Kif18a inhibitors |
| WO2021026098A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
| JP7640521B2 (ja) | 2019-08-02 | 2025-03-05 | アムジエン・インコーポレーテツド | Ｋｉｆ１８ａ阻害剤として有用なヘテロアリールアミド |
| CN110746402B (zh) * | 2019-09-21 | 2021-01-15 | 温州医科大学 | 一种2-n-芳基-4-n-芳基-5-氟嘧啶类化合物及其制备方法和应用 |
| EP4048671B1 (en) | 2019-10-24 | 2026-03-18 | Amgen Inc. | Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer |
| JP7823816B2 (ja) | 2019-11-04 | 2026-03-04 | レヴォリューション・メディスンズ，インコーポレイテッド | Ｒａｓ阻害剤 |
| KR20220109407A (ko) | 2019-11-04 | 2022-08-04 | 레볼루션 메디슨즈, 인크. | Ras 억제제 |
| EP4054719B1 (en) | 2019-11-04 | 2026-02-11 | Revolution Medicines, Inc. | Ras inhibitors |
| BR112022008858A2 (pt) | 2019-11-08 | 2022-09-06 | Revolution Medicines Inc | Composto, composição farmacêutica e métodos para inibir sos1 em um sujeito, para inibir a interação de sos1 e uma proteína, para tratar ou prevenir uma doença e para tratar ou prevenir câncer |
| JP2023501528A (ja) | 2019-11-14 | 2023-01-18 | アムジエン・インコーポレーテツド | Ｋｒａｓ ｇ１２ｃ阻害剤化合物の改善された合成 |
| WO2021097207A1 (en) | 2019-11-14 | 2021-05-20 | Amgen Inc. | Improved synthesis of kras g12c inhibitor compound |
| WO2021108683A1 (en) | 2019-11-27 | 2021-06-03 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| CN114929279A (zh) | 2020-01-07 | 2022-08-19 | 锐新医药公司 | Shp2抑制剂给药和治疗癌症的方法 |
| WO2021236935A1 (en) | 2020-05-22 | 2021-11-25 | Qx Therapeutics Inc. | Compositions and methods for treating lung injuries associated with viral infections |
| CA3183032A1 (en) | 2020-06-18 | 2021-12-23 | Mallika Singh | Methods for delaying, preventing, and treating acquired resistance to ras inhibitors |
| WO2022040446A1 (en) | 2020-08-19 | 2022-02-24 | Nanocopoeia, Llc | Amorphous pazopanib particles and pharmaceutical compositions thereof |
| MX2023002248A (es) | 2020-09-03 | 2023-05-16 | Revolution Medicines Inc | Uso de inhibidores de sos1 para tratar neoplasias malignas con mutaciones de shp2. |
| CR20230165A (es) | 2020-09-15 | 2023-06-02 | Revolution Medicines Inc | Derivados indólicos como inhibidores de ras en el tratamiento del cáncer |
| CN116528869A (zh) * | 2020-11-27 | 2023-08-01 | 安锐生物医药科技(广州)有限公司 | 氨基杂芳基激酶抑制剂 |
| CN117396472A (zh) | 2020-12-22 | 2024-01-12 | 上海齐鲁锐格医药研发有限公司 | Sos1抑制剂及其用途 |
| IL308193A (en) | 2021-05-05 | 2024-01-01 | Revolution Medicines Inc | RAS inhibitors |
| CR20230558A (es) | 2021-05-05 | 2024-01-24 | Revolution Medicines Inc | Inhibidores de ras para el tratamiento del cáncer |
| WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| WO2023081923A1 (en) | 2021-11-08 | 2023-05-11 | Frequency Therapeutics, Inc. | Platelet-derived growth factor receptor (pdgfr) alpha inhibitors and uses thereof |
| JP2025500878A (ja) | 2021-12-17 | 2025-01-15 | ジェンザイム・コーポレーション | Ｓｈｐ２阻害剤としてのピラゾロピラジン化合物 |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| IL314883A (en) | 2022-03-07 | 2024-10-01 | Amgen Inc | A process for preparing 4-methyl-2-propan-2-yl-pyridine-3-carbonitrile |
| CN119136806A (zh) | 2022-03-08 | 2024-12-13 | 锐新医药公司 | 用于治疗免疫难治性肺癌的方法 |
| AU2023274540A1 (en) | 2022-05-24 | 2024-12-12 | Daiichi Sankyo Company, Limited | Dosage regimen of an anti-cdh6 antibody-drug conjugate |
| AR129423A1 (es) | 2022-05-27 | 2024-08-21 | Viiv Healthcare Co | Compuestos útiles en la terapia contra el hiv |
| WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| PE20251879A1 (es) | 2022-10-14 | 2025-07-22 | Black Diamond Therapeutics Inc | Metodos de tratamiento del cancer usando derivados de isoquinolina o 6-aza-quinolina |
| AU2024241633A1 (en) | 2023-03-30 | 2025-11-06 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| PE20260039A1 (es) | 2023-04-07 | 2026-01-09 | Revolution Medicines Inc | Inhibidores macrociclicos de ras |
| WO2024211663A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
| CN121100123A (zh) | 2023-04-14 | 2025-12-09 | 锐新医药公司 | Ras抑制剂的结晶形式 |
| TW202448897A (zh) | 2023-04-14 | 2024-12-16 | 美商銳新醫藥公司 | Ｒａｓ抑制劑之結晶形式、含有其之組合物及其使用方法 |
| WO2024229406A1 (en) | 2023-05-04 | 2024-11-07 | Revolution Medicines, Inc. | Combination therapy for a ras related disease or disorder |
| US20250049810A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| TW202530228A (zh) | 2023-10-12 | 2025-08-01 | 美商銳新醫藥公司 | Ｒａｓ抑制劑 |
| TW202542151A (zh) | 2023-12-22 | 2025-11-01 | 美商銳格醫藥有限公司 | Ｓｏｓ１抑制劑及其用途 |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| TW202547461A (zh) | 2024-05-17 | 2025-12-16 | 美商銳新醫藥公司 | Ｒａｓ抑制劑 |
| WO2025253311A1 (en) | 2024-06-04 | 2025-12-11 | Hetero Labs Limited | 1,2-dicarboxamide compounds as kinase inhibitors |
| WO2025255438A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025265060A1 (en) | 2024-06-21 | 2025-12-26 | Revolution Medicines, Inc. | Therapeutic compositions and methods for managing treatment-related effects |
| WO2026006747A1 (en) | 2024-06-28 | 2026-01-02 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026015825A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Use of ras inhibitor for treating pancreatic cancer |
| WO2026015796A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015801A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015790A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026050446A1 (en) | 2024-08-29 | 2026-03-05 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2861560D1 (en) | 1977-11-28 | 1982-03-04 | Barry Boettcher | Complexes of bivalent copper, methods of preparation thereof and compositions containing said complexes |
| CA2124206C (en) | 1991-11-25 | 2001-02-27 | John Eugene Macor | Indole derivatives |
| CN1102144C (zh) | 1994-08-13 | 2003-02-26 | 株式会社柳韩洋行 | 新的嘧啶衍生物及其制备方法 |
| US5730977A (en) | 1995-08-21 | 1998-03-24 | Mitsui Toatsu Chemicals, Inc. | Anti-VEGF human monoclonal antibody |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| JP4471404B2 (ja) | 1996-02-13 | 2010-06-02 | アストラゼネカ ユーケイ リミテッド | Ｖｅｇｆインヒビターとしてのキナゾリン誘導体 |
| ATE211134T1 (de) | 1996-03-05 | 2002-01-15 | 4-anilinochinazolin derivate | |
| DE19610799C1 (de) | 1996-03-19 | 1997-09-04 | Siemens Ag | Zündeinrichtung zum Auslösen eines Rückhaltemittels in einem Kraftfahrzeug |
| GB9707800D0 (en) | 1996-05-06 | 1997-06-04 | Zeneca Ltd | Chemical compounds |
| GB9622363D0 (en) | 1996-10-28 | 1997-01-08 | Celltech Therapeutics Ltd | Chemical compounds |
| AU734009B2 (en) | 1997-05-30 | 2001-05-31 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| ATE368665T1 (de) | 1997-08-22 | 2007-08-15 | Astrazeneca Ab | Oxindolylchinazolinderivate als angiogenesehemmer |
| CA2303830A1 (en) | 1997-09-26 | 1999-04-08 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| NZ506679A (en) | 1998-03-27 | 2002-11-26 | Janssen Pharmaceutica Nv | HIV inhibiting pyrimidine derivatives |
| AU4077499A (en) | 1998-05-15 | 1999-12-06 | Glaxo Group Limited | Infrared thermography |
| UA60365C2 (uk) | 1998-06-04 | 2003-10-15 | Пфайзер Продактс Інк. | Похідні ізотіазолу, спосіб їх одержання, фармацевтична композиція та спосіб лікування гіперпроліферативного захворювання у ссавця |
| WO2000002871A1 (en) | 1998-07-10 | 2000-01-20 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
| US6022307A (en) | 1998-07-14 | 2000-02-08 | American Cyanamid Company | Substituted dibenzothiophenes having antiangiogenic activity |
| DE69932828T2 (de) | 1998-08-29 | 2007-10-18 | Astrazeneca Ab | Pyrimidine verbindungen |
| DE69933680T2 (de) | 1998-08-29 | 2007-08-23 | Astrazeneca Ab | Pyrimidine verbindungen |
| CA2341409A1 (en) | 1998-08-31 | 2000-03-09 | Merck And Co., Inc. | Novel angiogenesis inhibitors |
| EP1109823B1 (en) | 1998-09-08 | 2005-11-16 | Agouron Pharmaceuticals, Inc. | Modifications of the vegf receptor-2 protein and methods of use |
| DK1119567T3 (da) | 1998-10-08 | 2005-07-25 | Astrazeneca Ab | Quinazolinderivater |
| GB9828511D0 (en) | 1998-12-24 | 1999-02-17 | Zeneca Ltd | Chemical compounds |
| JP2002535318A (ja) | 1999-01-22 | 2002-10-22 | アムジエン・インコーポレーテツド | キナーゼ阻害薬 |
| DK1553097T3 (da) | 1999-02-10 | 2010-12-13 | Astrazeneca Ab | Quinazolinderivat som angiogeneseinhibitor og mellemprodukter dertil |
| WO2000052470A1 (fr) | 1999-03-04 | 2000-09-08 | Kyowa Hakko Kogyo Co., Ltd. | Moyen de diagnostic et de traitement de la leucemie |
| GB9905075D0 (en) | 1999-03-06 | 1999-04-28 | Zeneca Ltd | Chemical compounds |
| US6245759B1 (en) | 1999-03-11 | 2001-06-12 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| GB9907658D0 (en) | 1999-04-06 | 1999-05-26 | Zeneca Ltd | Chemical compounds |
| CO5170501A1 (es) | 1999-04-14 | 2002-06-27 | Novartis Ag | AZOLES SUSTITUIDOS UTILES PARA EL TRATAMIENTO DE ENFERMEDADES MEDIADAS POR TNFa eIL-1 Y ENFERMEDADES DEL METABOLISMO OSEO |
| CO5170498A1 (es) * | 1999-05-28 | 2002-06-27 | Abbott Lab | Biaril sulfonamidas son utiles como inhibidores de proliferacion celular |
| GB9914258D0 (en) * | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| DE60006541D1 (de) | 1999-06-30 | 2003-12-18 | Merck & Co Inc | Src-kinase hemmende verbindungen |
| GB9918035D0 (en) | 1999-07-30 | 1999-09-29 | Novartis Ag | Organic compounds |
| GB9919778D0 (en) | 1999-08-21 | 1999-10-27 | Zeneca Ltd | Chemical compounds |
| IL148385A0 (en) | 1999-09-10 | 2002-09-12 | Merck & Co Inc | Tyrosine kinase inhibitors |
| ATE396978T1 (de) * | 1999-10-07 | 2008-06-15 | Amgen Inc | Triazin-kinase-hemmer |
| EP1244650B1 (fr) * | 1999-11-29 | 2003-06-25 | Aventis Pharma S.A. | Derives arylamines et leur application comme agent antitelomerase |
| EP1246823A1 (en) | 1999-12-28 | 2002-10-09 | Pharmacopeia, Inc. | Pyrimidine and triazine kinase inhibitors |
| MXPA02007957A (es) * | 2000-02-17 | 2002-11-29 | Amgen Inc | Inhibidores de cinasas. |
| GB0004890D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004888D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0004887D0 (en) | 2000-03-01 | 2000-04-19 | Astrazeneca Uk Ltd | Chemical compounds |
| JP2004501070A (ja) | 2000-03-31 | 2004-01-15 | イムクローン システムズ インコーポレイティド | 血管内皮成長因子受容体アンタゴニストによる非固形哺乳類腫瘍の処理 |
| DK1318997T3 (da) | 2000-09-15 | 2006-09-25 | Vertex Pharma | Pyrazolforbindelser der er nyttige som proteinkinase-inhibitorer |
| AUPR213700A0 (en) | 2000-12-18 | 2001-01-25 | Biota Scientific Management Pty Ltd | Antiviral agents |
| ATE430742T1 (de) * | 2000-12-21 | 2009-05-15 | Smithkline Beecham Corp | Pyrimidinamine als angiogenesemodulatoren |
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2001
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