NO333231B1 - Enantiomerisk rene aminoheteroarylforbindelser, farmasoytisk preparat samt anvendelser derav - Google Patents
Enantiomerisk rene aminoheteroarylforbindelser, farmasoytisk preparat samt anvendelser derav Download PDFInfo
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- NO333231B1 NO333231B1 NO20071290A NO20071290A NO333231B1 NO 333231 B1 NO333231 B1 NO 333231B1 NO 20071290 A NO20071290 A NO 20071290A NO 20071290 A NO20071290 A NO 20071290A NO 333231 B1 NO333231 B1 NO 333231B1
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- Prior art keywords
- mmol
- phenyl
- dichloro
- ethoxy
- added
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- 125000005214 aminoheteroaryl group Chemical group 0.000 title description 8
- 239000000825 pharmaceutical preparation Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 270
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 30
- 201000011510 cancer Diseases 0.000 claims abstract description 17
- 230000010261 cell growth Effects 0.000 claims abstract description 16
- 230000002159 abnormal effect Effects 0.000 claims abstract description 14
- 238000011282 treatment Methods 0.000 claims abstract description 12
- -1 -OH Chemical group 0.000 claims description 102
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 76
- 125000001072 heteroaryl group Chemical group 0.000 claims description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- 229910052757 nitrogen Inorganic materials 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 45
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 18
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 239000012453 solvate Substances 0.000 claims description 17
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 16
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 11
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 10
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- CPHQTOFPAKOGJL-RXMQYKEDSA-N 5-bromo-3-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyrazin-2-amine Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C1=NC(Br)=CN=C1N CPHQTOFPAKOGJL-RXMQYKEDSA-N 0.000 claims description 7
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 6
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 229930192474 thiophene Natural products 0.000 claims description 6
- BVOMRRWJQOJMPA-UHFFFAOYSA-N 1,2,3-trithiane Chemical compound C1CSSSC1 BVOMRRWJQOJMPA-UHFFFAOYSA-N 0.000 claims description 5
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical compound C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 claims description 5
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 5
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 claims description 5
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 5
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 5
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 5
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 claims description 5
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 5
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 5
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 5
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 claims description 5
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 5
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 claims description 5
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 5
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 5
- 150000003852 triazoles Chemical class 0.000 claims description 5
- OUNTTYYPPFOKFB-LLVKDONJSA-N 3-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyrazin-2-amine Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=NC=1C(=C1)C=NN1C1CCNCC1 OUNTTYYPPFOKFB-LLVKDONJSA-N 0.000 claims description 4
- CVNLLSCZPXZERZ-SSDOTTSWSA-N 3-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-(1h-pyrazol-4-yl)pyrazin-2-amine Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=NC=1C=1C=NNC=1 CVNLLSCZPXZERZ-SSDOTTSWSA-N 0.000 claims description 4
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims description 3
- NSMODUFDBCVKPU-GFCCVEGCSA-N 1-[4-[4-[5-amino-6-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyrazin-2-yl]pyrazol-1-yl]piperidin-1-yl]-2-hydroxyethanone Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=NC=1C(=C1)C=NN1C1CCN(C(=O)CO)CC1 NSMODUFDBCVKPU-GFCCVEGCSA-N 0.000 claims description 3
- ZGYNYCBQFKXKGY-CYBMUJFWSA-N 1-[4-[4-[6-amino-5-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]pyrazol-1-yl]piperidin-1-yl]-2-hydroxyethanone Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCN(C(=O)CO)CC1 ZGYNYCBQFKXKGY-CYBMUJFWSA-N 0.000 claims description 3
- NPLCWDKKWCIODK-CYBMUJFWSA-N 3-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]pyridin-2-amine Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCN(C)CC1 NPLCWDKKWCIODK-CYBMUJFWSA-N 0.000 claims description 3
- NRPUVLZXPDSMAK-GFCCVEGCSA-N 3-[(1r)-1-(2-chloro-3,6-difluorophenyl)ethoxy]-5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-2-amine Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1F)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 NRPUVLZXPDSMAK-GFCCVEGCSA-N 0.000 claims description 3
- IGRNEOXYFPOWTJ-SECBINFHSA-N 4-[5-amino-6-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyrazin-2-yl]benzoic acid Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=NC=1C1=CC=C(C(O)=O)C=C1 IGRNEOXYFPOWTJ-SECBINFHSA-N 0.000 claims description 3
- SMXJWWPPUKVIIS-OAHLLOKOSA-N 4-[6-amino-5-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]-n-[2-(dimethylamino)ethyl]-n-methylbenzamide Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C1=CC=C(C(=O)N(C)CCN(C)C)C=C1 SMXJWWPPUKVIIS-OAHLLOKOSA-N 0.000 claims description 3
- URFUZAZEKBBCEY-ZCFIWIBFSA-N 5-bromo-3-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-2-amine Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C1=CC(Br)=CN=C1N URFUZAZEKBBCEY-ZCFIWIBFSA-N 0.000 claims description 3
- IGTXHUMAYCGTDA-CQSZACIVSA-N [4-[6-amino-5-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]phenyl]-piperazin-1-ylmethanone Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CCNCC1 IGTXHUMAYCGTDA-CQSZACIVSA-N 0.000 claims description 3
- GNCSJBTWIJTFDM-LLVKDONJSA-N [4-[6-amino-5-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]phenyl]methanol Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C1=CC=C(CO)C=C1 GNCSJBTWIJTFDM-LLVKDONJSA-N 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- XYXYREBTJQXBIZ-MRXNPFEDSA-N tert-butyl 4-[4-[5-amino-6-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyrazin-2-yl]benzoyl]piperazine-1-carboxylate Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=NC=1C(C=C1)=CC=C1C(=O)N1CCN(C(=O)OC(C)(C)C)CC1 XYXYREBTJQXBIZ-MRXNPFEDSA-N 0.000 claims description 3
- SLWPVKXDTQGPAI-QGZVFWFLSA-N tert-butyl 4-[4-[6-amino-5-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]benzoyl]piperazine-1-carboxylate Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CCN(C(=O)OC(C)(C)C)CC1 SLWPVKXDTQGPAI-QGZVFWFLSA-N 0.000 claims description 3
- XPUXHXOFUXBVBM-CQSZACIVSA-N 1-[4-[4-[5-amino-6-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyrazin-2-yl]pyrazol-1-yl]piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=NC=1C(=C1)C=NN1C1CCN(C(=O)CN(C)C)CC1 XPUXHXOFUXBVBM-CQSZACIVSA-N 0.000 claims description 2
- KEQQAJTTZPKZSZ-GFCCVEGCSA-N 3-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(1-methylpiperidin-4-yl)pyrazol-4-yl]pyrazin-2-amine Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=NC=1C(=C1)C=NN1C1CCN(C)CC1 KEQQAJTTZPKZSZ-GFCCVEGCSA-N 0.000 claims description 2
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- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
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- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 208000013013 vulvar carcinoma Diseases 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
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- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/18—Oxygen or sulfur 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A61K31/4965—Non-condensed pyrazines
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
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- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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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
- 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
- C07D401/14—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 three or more hetero rings
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- C07—ORGANIC CHEMISTRY
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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
- C07D403/14—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 three or more hetero rings
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US60508604P | 2004-08-26 | 2004-08-26 | |
PCT/IB2005/002837 WO2006021884A2 (en) | 2004-08-26 | 2005-08-15 | Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors |
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NO20071290L NO20071290L (no) | 2007-05-29 |
NO333231B1 true NO333231B1 (no) | 2013-04-15 |
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NO20071290A NO333231B1 (no) | 2004-08-26 | 2007-03-09 | Enantiomerisk rene aminoheteroarylforbindelser, farmasoytisk preparat samt anvendelser derav |
NO2013008C NO2013008I2 (no) | 2004-08-26 | 2013-04-15 | Krizotinib eller et farmasøytisk akseptabelt salt, hydrat eller solvat derav |
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NO2013008C NO2013008I2 (no) | 2004-08-26 | 2013-04-15 | Krizotinib eller et farmasøytisk akseptabelt salt, hydrat eller solvat derav |
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Families Citing this family (174)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK1603570T5 (da) * | 2003-02-26 | 2013-12-09 | Sugen Inc | Aminoheteroarylforbindelser som proteinkinaseinhibitorer |
MY150088A (en) | 2003-05-19 | 2013-11-29 | Irm Llc | Immunosuppressant compounds and compositions |
ES2355923T3 (es) * | 2004-08-26 | 2011-04-01 | Pfizer, Inc. | Compuestos de aminoheteroarilo sustituidos con pirazol como inhibidores de proteina quinasa. |
ES2341351T3 (es) * | 2004-08-26 | 2010-06-18 | Pfizer, Inc. | Compuestos de aminoheteroarilo enantiomericamente puros como inhibidores de proteina cinasas. |
PL1959955T3 (pl) * | 2005-12-05 | 2011-04-29 | Pfizer Prod Inc | Sposób traktowania nieprawidłowego wzrostu komórek |
AU2006323025B2 (en) * | 2005-12-05 | 2012-07-05 | Pfizer Products Inc. | Polymorphs of a c-Met/HGFR inhibitor |
RU2008141761A (ru) * | 2006-03-22 | 2010-04-27 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | ИНГИБИТОРЫ с-МЕТ ПРОТЕИНКИНАЗЫ |
US8168383B2 (en) | 2006-04-14 | 2012-05-01 | Cell Signaling Technology, Inc. | Gene defects and mutant ALK kinase in human solid tumors |
SI2450437T1 (sl) | 2006-04-14 | 2017-12-29 | Cell Signaling Technology Inc. | Okvarjenost genov in mutantna ALK kinaza v človeških solidnih tumorjih |
CA2660836A1 (en) * | 2006-08-07 | 2008-02-21 | Incyte Corporation | Triazolotriazines as kinase inhibitors |
GB0621607D0 (en) * | 2006-10-31 | 2006-12-06 | Chroma Therapeutics Ltd | Inhibitors of c-Met |
EA026126B1 (ru) | 2006-11-22 | 2017-03-31 | Инсайт Холдингс Корпорейшн | Имидазотриазины и имидазопиримидины в качестве ингибиторов киназы |
US8455513B2 (en) | 2007-01-10 | 2013-06-04 | Aerie Pharmaceuticals, Inc. | 6-aminoisoquinoline compounds |
JP2010516680A (ja) * | 2007-01-19 | 2010-05-20 | エックスカバリー,インコーポレイテッド | キナーゼ阻害薬化合物 |
US8715665B2 (en) | 2007-04-13 | 2014-05-06 | The General Hospital Corporation | Methods for treating cancer resistant to ErbB therapeutics |
US8748143B2 (en) | 2007-09-13 | 2014-06-10 | Codexis, Inc. | Ketoreductase polypeptides for the reduction of acetophenones |
WO2009099982A1 (en) * | 2008-02-04 | 2009-08-13 | Osi Pharmaceuticals, Inc. | 2-aminopyridine kinase inhibitors |
AR070317A1 (es) * | 2008-02-06 | 2010-03-31 | Osi Pharm Inc | Furo (3,2-c) piridina y tieno (3,2-c) piridinas |
EP2269993B1 (en) | 2008-04-23 | 2013-02-27 | Kyowa Hakko Kirin Co., Ltd. | 2-aminoquinazoline derivative |
WO2009143211A2 (en) | 2008-05-21 | 2009-11-26 | Incyte Corporation | Salts of 2-fluoro-n-methyl-4-[7-(quinolin-6-yl-methyl)- imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide and processes related to preparing the same |
EP2143441A1 (en) | 2008-07-08 | 2010-01-13 | Pierre Fabre Medicament | Combination of a c-Met antagonist and an aminoheteroaryl compound for the treatment of cancer |
US8450344B2 (en) | 2008-07-25 | 2013-05-28 | Aerie Pharmaceuticals, Inc. | Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds |
JP2012509342A (ja) | 2008-11-20 | 2012-04-19 | オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド | 置換ピロロ[2,3−b]−ピリジンおよび−ピラジン |
CA2746764A1 (en) | 2008-12-18 | 2010-06-24 | Novartis Ag | New polymorphic form of 1- (4- { l- [ (e) -4-cyclohexyl--3-trifluoromethyl-benzyloxyimino] -ethyl) -2-ethyl-benzy l) -azetidine-3-carboxylic |
CN102300862B (zh) | 2008-12-19 | 2016-11-23 | 沃泰克斯药物股份有限公司 | 用作atr激酶抑制剂的化合物 |
CA2929545C (en) | 2009-05-01 | 2019-04-09 | Aerie Pharmaceuticals, Inc. | Dual mechanism inhibitors for the treatment of disease |
PT2975024T (pt) * | 2009-06-10 | 2018-05-14 | Chugai Pharmaceutical Co Ltd | Compostos tetracíclicos |
DE102009056886A1 (de) | 2009-12-03 | 2011-06-09 | Bayer Schering Pharma Aktiengesellschaft | cMet-Inhibitoren zur Behandlung der Endometriose |
BR112012019302B1 (pt) | 2010-02-03 | 2022-06-21 | Incyte Holdings Corporation | Imidazo[1,2-b] [1,2,4]triazinas como inibidores de c-met, composição que as compreende e métodos in vitro de inibir a atividade de c-met cinase, de inibir a via de sinalização da hgf/c-met cinase em uma célula e de inibir a atividade proliferativa de uma célula |
JP2013525476A (ja) * | 2010-05-04 | 2013-06-20 | ファイザー・インク | Alk阻害剤としての複素環式誘導体 |
EP2569287B1 (en) | 2010-05-12 | 2014-07-09 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
EP2569286B1 (en) * | 2010-05-12 | 2014-08-20 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
NZ603477A (en) | 2010-05-12 | 2014-09-26 | Vertex Pharma | Compounds useful as inhibitors of atr kinase |
AR081039A1 (es) | 2010-05-14 | 2012-05-30 | Osi Pharmaceuticals Llc | Inhibidores biciclicos fusionados de quinasa |
JP2013526570A (ja) | 2010-05-14 | 2013-06-24 | オーエスアイ・ファーマシューティカルズ,エルエルシー | 縮合二環式キナーゼ阻害剤 |
WO2011145035A1 (en) | 2010-05-17 | 2011-11-24 | Indian Incozen Therapeutics Pvt. Ltd. | Novel 3,5-disubstitued-3h-imidazo[4,5-b]pyridine and 3,5- disubstitued -3h-[1,2,3]triazolo[4,5-b] pyridine compounds as modulators of protein kinases |
WO2012003338A1 (en) | 2010-07-01 | 2012-01-05 | Takeda Pharmaceutical Company Limited | COMBINATION OF A cMET INHIBITOR AND AN ANTIBODY TO HGF AND/OR cMET |
EP3698788A1 (en) | 2010-08-20 | 2020-08-26 | Chugai Seiyaku Kabushiki Kaisha | Composition comprising tetracyclic compound |
WO2012042421A1 (en) | 2010-09-29 | 2012-04-05 | Pfizer Inc. | Method of treating abnormal cell growth |
CN102464667B (zh) * | 2010-11-03 | 2014-06-04 | 中国科学院上海药物研究所 | 一类五元杂环并嘧啶类化合物及其制备方法和用途 |
JP5965923B2 (ja) * | 2011-02-24 | 2016-08-10 | ジエンス ハンセン ファーマセウティカル カンパニー リミテッド | プロテインキナーゼ阻害剤としてのリン含有化合物 |
US9145390B2 (en) | 2011-03-03 | 2015-09-29 | Concert Pharmaceuticals, Inc. | Derivatives of pyrazole-substituted amino-heteroaryl compounds |
MX2013010067A (es) * | 2011-03-03 | 2014-01-31 | Concert Pharmaceuticals Inc | Derivados de compuestos de amino-heteroarilo sustituidos con pirazol. |
CN102718745A (zh) * | 2011-03-30 | 2012-10-10 | 中国科学院上海药物研究所 | 新型胺基吡啶类化合物、其制备方法、包含此类化合物的药物组合物及其用途 |
EP2710003A1 (en) | 2011-05-16 | 2014-03-26 | OSI Pharmaceuticals, LLC | Fused bicyclic kinase inhibitors |
CN102850328B (zh) * | 2011-07-01 | 2014-12-24 | 苏州东南药业股份有限公司 | 吡啶类化合物、其制备方法、包含该化合物的药物组合物及其用途 |
KR20140041906A (ko) | 2011-08-02 | 2014-04-04 | 화이자 인코포레이티드 | 암의 치료에 사용하기 위한 크리조티닙 |
EP2758387A4 (en) * | 2011-09-21 | 2015-03-11 | Teligene Ltd | Pyridine compounds as kinase inhibitors |
MX2014003785A (es) | 2011-09-30 | 2014-07-24 | Vertex Phamaceuticals Inc | Tratamiento del cancer de pancreas y del cancer de pulmon de celulas no pequeñas con inhibidores de atr. |
EP2940017B1 (en) | 2011-09-30 | 2019-08-28 | Vertex Pharmaceuticals Incorporated | Process for making compounds useful as inhibitors of ATR kinase |
CN103204844A (zh) * | 2012-01-17 | 2013-07-17 | 上海艾力斯医药科技有限公司 | 氨基杂芳基化合物及其制备方法与应用 |
EP2804605A4 (en) * | 2012-01-20 | 2015-07-08 | Acucela Inc | SUBSTITUTED HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF DISEASES |
EP2620140A1 (en) | 2012-01-26 | 2013-07-31 | ratiopharm GmbH | Crizotinib containing compositions |
JP5823066B2 (ja) | 2012-03-06 | 2015-11-25 | ファイザー・インク | 増殖性疾患の治療のための大環状誘導体 |
CN107082779A (zh) | 2012-03-30 | 2017-08-22 | 理森制药股份公司 | 作为c‑met 蛋白激酶调节剂的新化合物 |
NZ720511A (en) | 2012-04-05 | 2016-12-23 | Vertex Pharma | Compounds useful as inhibitors of atr kinase and combination therapies thereof |
CN106349222B (zh) * | 2012-04-22 | 2019-03-05 | 东南大学 | 克里唑替尼前药及其制备方法与用途 |
CN103387535B (zh) * | 2012-05-10 | 2016-06-01 | 广东东阳光药业有限公司 | 取代的炔基吡啶化合物及其使用方法和用途 |
CN103420987B (zh) * | 2012-05-15 | 2015-11-25 | 上海医药工业研究院 | 吡啶衍生物及其制备方法 |
CN103420906B (zh) * | 2012-05-21 | 2015-09-09 | 南京圣和药业股份有限公司 | 新型酪氨酸蛋白激酶抑制剂 |
WO2013181251A1 (en) | 2012-05-29 | 2013-12-05 | Ratiopharm Gmbh | Crizotinib hydrochloride salt in crystalline |
WO2013192512A1 (en) * | 2012-06-22 | 2013-12-27 | Concert Pharmaceuticals, Inc. | Derivatives of pyrazole-substituted amino-heteroaryl compounds |
CN103509008A (zh) * | 2012-06-22 | 2014-01-15 | 康瑟特制药公司 | 吡唑取代的氨基-杂芳基化合物的衍生物 |
WO2014020467A2 (en) | 2012-07-30 | 2014-02-06 | Fresenius Kabi Oncology Ltd | Process for the preparation of pyrazole substituted aminoheteroaryl compounds |
EP2892530A1 (en) | 2012-08-27 | 2015-07-15 | CeMM - FORSCHUNGSZENTRUM FÜR MOLEKULARE MEDIZIN GmbH | Aminoheteroaryl compounds as mth1 inhibitors |
US9651555B2 (en) | 2012-09-24 | 2017-05-16 | Ventana Medical Systems, Inc. | Method of identifying treatment responsive non-small cell lung cancer using anaplastic lymphoma kinase (ALK) as a marker |
HUE040055T2 (hu) | 2012-09-25 | 2019-02-28 | Chugai Pharmaceutical Co Ltd | RET inhibitor |
DK2904406T3 (en) | 2012-10-04 | 2018-06-18 | Vertex Pharma | METHOD OF DETERMINING THE ATR INHIBITION, INCREASED DNA DAMAGE |
WO2014081816A1 (en) * | 2012-11-21 | 2014-05-30 | Concert Pharmaceuticals, Inc. | Fluoro-derivatives of pyrazole-substituted amino-heteroaryl compounds |
CN104016979B (zh) * | 2012-11-23 | 2017-05-03 | 广东东阳光药业有限公司 | 取代的环化合物及其使用方法和用途 |
WO2014089324A1 (en) * | 2012-12-07 | 2014-06-12 | Calitor Sciences, Llc | Substituted cyclic compounds and methods of use |
TWI498325B (zh) * | 2013-01-18 | 2015-09-01 | Hoffmann La Roche | 3-取代吡唑及其用途 |
WO2014115169A2 (en) * | 2013-01-24 | 2014-07-31 | Hetero Research Foundation | Crizotinib solid dispersion |
JP6200520B2 (ja) * | 2013-02-02 | 2017-09-20 | 正大天晴薬業集団股▲ふん▼有限公司 | 置換2−アミノピリジンプロテインキナーゼ阻害剤 |
WO2014139391A1 (en) * | 2013-03-11 | 2014-09-18 | Teligene Ltd | Substituted pyridine compounds as kinases inhibitors |
EP4335507A3 (en) | 2013-03-15 | 2024-06-05 | Aerie Pharmaceuticals, Inc. | Combination therapy |
WO2014203177A1 (en) * | 2013-06-18 | 2014-12-24 | Shilpa Medicare Limited | Amorphous (r) -3- [1- (2, 6-dichloro-3-fluorophenyl) methoxy] -5- [1- (piperidin-4- yl) -1h-pyrazol-4-yl] pyridin-2-amine |
CN104650049B (zh) * | 2013-08-28 | 2018-06-08 | 广东东阳光药业有限公司 | 取代的吡啶化合物及其使用方法和用途 |
WO2015034729A1 (en) * | 2013-09-05 | 2015-03-12 | Calitor Sciences, Llc | Substituted pyridine compounds and methods of use |
WO2015036898A2 (en) * | 2013-09-10 | 2015-03-19 | Shilpa Medicare Limited | Novel salts of crizotinib and their preparation |
JP6537500B2 (ja) * | 2013-09-20 | 2019-07-03 | ビオマリン プハルマセウトイカル インコーポレイテッド | 疾患治療用のグルコシルセラミドシンターゼ阻害剤 |
CN104513253A (zh) | 2013-10-01 | 2015-04-15 | 南京波尔泰药业科技有限公司 | 用于治疗增殖性疾病的大环化合物 |
US20160280798A1 (en) | 2013-11-06 | 2016-09-29 | The United States Of America, As Represented By The Secretary Department Of Health & Human Service | Alk antibodies, conjugates, and chimeric antigen receptors, and their use |
CN103755627B (zh) * | 2014-01-09 | 2016-02-17 | 定陶县友帮化工有限公司 | 2-氨基-3-羟基-5-氯吡啶的合成方法 |
MX2016009896A (es) * | 2014-01-29 | 2017-01-11 | Neuropore Therapies Inc | Heteroaril amidas como inhibidores de agregacion de proteina. |
JP6247992B2 (ja) * | 2014-04-17 | 2017-12-13 | 株式会社ダイセル | ハロゲン化合物の製造方法 |
WO2015163448A1 (ja) | 2014-04-25 | 2015-10-29 | 中外製薬株式会社 | 4環性化合物を高用量含有する製剤 |
WO2015163447A1 (ja) | 2014-04-25 | 2015-10-29 | 中外製薬株式会社 | 4環性化合物の新規結晶 |
ES2762641T3 (es) | 2014-07-31 | 2020-05-25 | Chia Tai Tianqing Pharmaceutical Group Co Ltd | Inhibidores de proteína quinasa de 2-aminopiridina sustituida con piridina |
TWI765410B (zh) | 2014-08-08 | 2022-05-21 | 日商中外製藥股份有限公司 | 4環性化合物的非晶質體的用途 |
CN105348265A (zh) * | 2014-08-19 | 2016-02-24 | 蔡苹 | 一种具有ALK和c-Met抑制活性的2,4-二取代杂环三氮唑类化合物的制备和应用 |
WO2016032927A1 (en) | 2014-08-25 | 2016-03-03 | Pfizer Inc. | Combination of a pd-1 antagonist and an alk inhibitor for treating cancer |
CN105820113B (zh) * | 2015-01-07 | 2018-04-20 | 爱技特科技(北京)有限公司 | 一种克唑替尼手性中间体的制备方法 |
US11077093B2 (en) | 2015-01-16 | 2021-08-03 | Chugai Seiyaku Kabushiki Kaisha | Combination drug |
CN104693184A (zh) * | 2015-03-17 | 2015-06-10 | 安润医药科技(苏州)有限公司 | 克唑替尼的合成方法 |
WO2017059357A1 (en) | 2015-09-30 | 2017-04-06 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of dna damaging agents and atr inhibitors |
CA3000386A1 (en) | 2015-09-30 | 2017-04-06 | Merck Patent Gmbh | Combination of a pd-1 axis binding antagonist and an alk inhibitor for treating alk-negative cancer |
US9643927B1 (en) | 2015-11-17 | 2017-05-09 | Aerie Pharmaceuticals, Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
AU2015414743B2 (en) * | 2015-11-17 | 2019-07-18 | Alcon Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
ES2905823T3 (es) | 2016-05-20 | 2022-04-12 | Biohaven Therapeutics Ltd | Uso de riluzol, profármacos de riluzol o análogos de riluzol con inmunoterapias para tratar cánceres |
CN106083708A (zh) * | 2016-06-30 | 2016-11-09 | 浙江大学 | 含2‑吡啶酮环侧链的2‑氨基吡啶衍生物及制备和应用 |
MX2019002396A (es) | 2016-08-31 | 2019-07-08 | Aerie Pharmaceuticals Inc | Composiciones oftalmicas. |
MX2019007643A (es) | 2016-12-22 | 2019-09-09 | Amgen Inc | Benzoisotiazol, isotiazolo[3,4-b]piridina, quinazolina, ftalazina, pirido[2,3-d]piridazina y derivados de pirido[2,3-d]pirimidina como inhibirores de kras g12c para tratar el cancer de pulmon, pancreatico o colorrectal. |
CN106831720B (zh) * | 2017-01-21 | 2019-04-16 | 河北科技大学 | 双-4-(1h-吡唑-1-基)哌啶-1-甲酸叔丁酯的合成方法及其应用 |
MX2019011784A (es) | 2017-03-31 | 2019-11-18 | Aerie Pharmaceuticals Inc | Compuestos de aril ciclopropil-amino-isoquinolinil amida. |
JOP20190272A1 (ar) | 2017-05-22 | 2019-11-21 | Amgen Inc | مثبطات kras g12c وطرق لاستخدامها |
US10180422B1 (en) | 2017-08-22 | 2019-01-15 | Scripps Health | Methods of treating a neuroendocrine tumor |
EP4403175A3 (en) | 2017-09-08 | 2024-10-02 | Amgen Inc. | Inhibitors of kras g12c and methods of using the same |
JP6635999B2 (ja) * | 2017-10-13 | 2020-01-29 | 株式会社ダイセル | カリウム塩の製造方法、及びカリウム塩 |
CN108191833A (zh) * | 2018-01-17 | 2018-06-22 | 浙江树人学院 | 克唑替尼衍生物及其制备方法和应用 |
CN110396088B (zh) * | 2018-04-25 | 2024-03-12 | 珠海宇繁生物科技有限责任公司 | Hpk1激酶抑制剂、制备方法及其应用 |
WO2019206049A1 (en) * | 2018-04-25 | 2019-10-31 | Zhuhai Yufan Biotechnologies Co., Ltd | Hpk1 inhibitors, preparation method and application thereof |
AU2019262599B2 (en) | 2018-05-04 | 2023-10-12 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
WO2019213516A1 (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 |
AU2019278998B2 (en) | 2018-06-01 | 2023-11-09 | 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 |
US11285156B2 (en) | 2018-06-12 | 2022-03-29 | Amgen Inc. | Substituted piperazines as KRAS G12C inhibitors |
TWI825163B (zh) | 2018-09-04 | 2023-12-11 | 日商中外製藥股份有限公司 | 四環性化合物的製造方法 |
CA3112391A1 (en) | 2018-09-14 | 2020-03-19 | Aerie Pharmaceuticals, Inc. | Aryl cyclopropyl-amino-isoquinolinyl amide 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 |
MX2021007157A (es) | 2018-12-20 | 2021-08-16 | Amgen Inc | Heteroarilamidas utiles como inhibidores de kif18a. |
CA3123227A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
WO2020132651A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
MA54543A (fr) | 2018-12-20 | 2022-03-30 | Amgen Inc | Inhibiteurs de kif18a |
WO2020130125A1 (ja) | 2018-12-21 | 2020-06-25 | 第一三共株式会社 | 抗体-薬物コンジュゲートとキナーゼ阻害剤の組み合わせ |
CN113767100A (zh) | 2019-03-01 | 2021-12-07 | 锐新医药公司 | 双环杂芳基化合物及其用途 |
AU2020232616A1 (en) | 2019-03-01 | 2021-09-09 | Revolution Medicines, Inc. | Bicyclic heterocyclyl compounds and uses thereof |
EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
KR20220011670A (ko) | 2019-05-21 | 2022-01-28 | 암젠 인크 | 고체 상태 형태 |
US20220281843A1 (en) | 2019-08-02 | 2022-09-08 | Amgen Inc. | Kif18a inhibitors |
US20240254100A1 (en) | 2019-08-02 | 2024-08-01 | Amgen Inc. | Kif18a inhibitors |
US20220372018A1 (en) | 2019-08-02 | 2022-11-24 | Amgen Inc. | Kif18a inhibitors |
AU2020326627A1 (en) | 2019-08-02 | 2022-03-17 | Amgen Inc. | KIF18A inhibitors |
US20220354951A1 (en) | 2019-08-02 | 2022-11-10 | Onehealthcompany, Inc. | Treatment of Canine Cancers |
WO2021055728A1 (en) | 2019-09-18 | 2021-03-25 | Merck Sharp & Dohme Corp. | Small molecule inhibitors of kras g12c mutant |
CN112552293A (zh) * | 2019-09-25 | 2021-03-26 | 珠海宇繁生物科技有限责任公司 | 一种protac小分子化合物及其应用 |
JP2022552873A (ja) | 2019-10-24 | 2022-12-20 | アムジエン・インコーポレーテツド | がんの治療におけるkras g12c及びkras g12d阻害剤として有用なピリドピリミジン誘導体 |
IL292438A (en) | 2019-10-28 | 2022-06-01 | Merck Sharp & Dohme | Small molecules that inhibit the g12c mutant of kras |
WO2021085653A1 (en) | 2019-10-31 | 2021-05-06 | Taiho Pharmaceutical Co., Ltd. | 4-aminobut-2-enamide derivatives and salts thereof |
AU2020379734A1 (en) | 2019-11-04 | 2022-05-05 | Revolution Medicines, Inc. | Ras inhibitors |
US11739074B2 (en) | 2019-11-04 | 2023-08-29 | Revolution Medicines, Inc. | Ras inhibitors |
TW202132314A (zh) | 2019-11-04 | 2021-09-01 | 美商銳新醫藥公司 | Ras抑制劑 |
JP2023500328A (ja) | 2019-11-08 | 2023-01-05 | レボリューション メディシンズ インコーポレイテッド | 二環式ヘテロアリール化合物及びその使用 |
US20230192681A1 (en) | 2019-11-14 | 2023-06-22 | Amgen Inc. | Improved synthesis of kras g12c inhibitor compound |
AR120456A1 (es) | 2019-11-14 | 2022-02-16 | Amgen Inc | Síntesis mejorada del compuesto inhibidor de g12c de kras |
WO2021108683A1 (en) | 2019-11-27 | 2021-06-03 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
WO2021106231A1 (en) | 2019-11-29 | 2021-06-03 | Taiho Pharmaceutical Co., Ltd. | A compound having inhibitory activity against kras g12d mutation |
JP2023509701A (ja) | 2020-01-07 | 2023-03-09 | 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 | Shp2阻害剤投薬およびがんを処置する方法 |
WO2021196655A1 (zh) * | 2020-04-03 | 2021-10-07 | 中国药科大学 | 含苯并咪唑结构的化合物及其制备方法与用途 |
US20230174518A1 (en) | 2020-04-24 | 2023-06-08 | Taiho Pharmaceutical Co., Ltd. | Kras g12d protein inhibitors |
US20230181536A1 (en) | 2020-04-24 | 2023-06-15 | Taiho Pharmaceutical Co., Ltd. | Anticancer combination therapy with n-(1-acryloyl-azetidin-3-yl)-2-((1h-indazol-3-yl)amino)methyl)-1h-imidazole-5-carboxamide inhibitor of kras-g12c |
CN115916194A (zh) | 2020-06-18 | 2023-04-04 | 锐新医药公司 | 用于延迟、预防和治疗针对ras抑制剂的获得性抗性的方法 |
JP7373664B2 (ja) | 2020-07-15 | 2023-11-02 | 大鵬薬品工業株式会社 | 腫瘍の治療に使用されるピリミジン化合物を含む組み合わせ |
WO2022060583A1 (en) | 2020-09-03 | 2022-03-24 | Revolution Medicines, Inc. | Use of sos1 inhibitors to treat malignancies with shp2 mutations |
AU2021345111A1 (en) | 2020-09-15 | 2023-04-06 | Revolution Medicines, Inc. | Indole derivatives as Ras inhibitors in the treatment of cancer |
CN114437058A (zh) * | 2020-10-30 | 2022-05-06 | 珠海宇繁生物科技有限责任公司 | 氘代hpk1激酶抑制剂及其制备方法和应用 |
AU2021409816A1 (en) | 2020-12-22 | 2023-07-06 | Qilu Regor Therapeutics Inc. | Sos1 inhibitors and uses thereof |
WO2022235864A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Ras inhibitors |
CN117616031A (zh) | 2021-05-05 | 2024-02-27 | 锐新医药公司 | 用于治疗癌症的ras抑制剂 |
WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
WO2022250170A1 (en) | 2021-05-28 | 2022-12-01 | Taiho Pharmaceutical Co., Ltd. | Small molecule inhibitors of kras mutated proteins |
AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
WO2023114954A1 (en) | 2021-12-17 | 2023-06-22 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
WO2023172940A1 (en) | 2022-03-08 | 2023-09-14 | Revolution Medicines, Inc. | Methods for treating immune refractory lung cancer |
CN114767676B (zh) * | 2022-04-22 | 2024-04-19 | 珠海宇繁生物科技有限责任公司 | Hpk1激酶抑制剂在预防和/或治疗人的病原体感染中的应用 |
WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
WO2024081916A1 (en) | 2022-10-14 | 2024-04-18 | Black Diamond Therapeutics, Inc. | Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives |
WO2024206858A1 (en) | 2023-03-30 | 2024-10-03 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
WO2024211712A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
WO2024211663A1 (en) | 2023-04-07 | 2024-10-10 | Revolution Medicines, Inc. | Condensed macrocyclic compounds as ras inhibitors |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NO20054080L (no) * | 2003-02-26 | 2005-11-21 | Uszhang Jennifer R | Aminoheteroarylforbindelser som roteinkinaseinhibitorer |
Family Cites Families (79)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB129611A (en) | 1919-04-15 | 1919-07-17 | John Norman Riddell Hannam | Improvements in Stropping or Sharpening Devices for Safety Razor Blades. |
GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
US5376645A (en) | 1990-01-23 | 1994-12-27 | University Of Kansas | Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof |
US5587458A (en) | 1991-10-07 | 1996-12-24 | Aronex Pharmaceuticals, Inc. | Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof |
CA2372813A1 (en) | 1992-02-06 | 1993-08-19 | L.L. Houston | Biosynthetic binding protein for cancer marker |
US6177401B1 (en) | 1992-11-13 | 2001-01-23 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften | Use of organic compounds for the inhibition of Flk-1 mediated vasculogenesis and angiogenesis |
US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
IL112248A0 (en) | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
US5863949A (en) | 1995-03-08 | 1999-01-26 | Pfizer Inc | Arylsulfonylamino hydroxamic acid derivatives |
US5861510A (en) | 1995-04-20 | 1999-01-19 | Pfizer Inc | Arylsulfonyl hydroxamic acid derivatives as MMP and TNF inhibitors |
US5747498A (en) | 1996-05-28 | 1998-05-05 | Pfizer Inc. | Alkynyl and azido-substituted 4-anilinoquinazolines |
US5880141A (en) | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
GB9518953D0 (en) | 1995-09-15 | 1995-11-15 | Pfizer Ltd | Pharmaceutical formulations |
GB9520822D0 (en) | 1995-10-11 | 1995-12-13 | Wellcome Found | Therapeutically active compounds |
GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
ES2183905T3 (es) | 1995-12-20 | 2003-04-01 | Hoffmann La Roche | Inhibidores de metaloproteasa de matriz. |
IL125954A (en) | 1996-03-05 | 2003-06-24 | Zeneca Ltd | Quinazoline derivatives, processes for their preparation, pharmaceutical compositions containing them and use thereof in the manufacture of medicaments having an antiangiogenic and/or vascular permeability reducing effect |
AU2710597A (en) | 1996-06-27 | 1998-01-14 | Pfizer Inc. | Derivatives of 2-(2-oxo-ethylidene)-imidazolidin-4-one and their use as farnesyl protein transferase inhibitors |
EP0818442A3 (en) | 1996-07-12 | 1998-12-30 | Pfizer Inc. | Cyclic sulphone derivatives as inhibitors of metalloproteinases and of the production of tumour necrosis factor |
HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
JP4386967B2 (ja) | 1996-07-13 | 2009-12-16 | グラクソ、グループ、リミテッド | プロテインチロシンキナーゼ阻害剤としての縮合複素環式化合物 |
BR9710362A (pt) | 1996-07-13 | 1999-08-17 | Glaxo Group Ltd | Composto formula-ao farmaceutica utiliza-ao de um composto processos de tratamento de um ser humano ou animal sofrendo de uma mediada por atividade anormal de cinase de proteina tirosina e para a prepara-ao de um composto |
DE19628569A1 (de) | 1996-07-16 | 1998-01-22 | Bayer Ag | Substituierte N-(5-Isothiazolyl)-thioamide |
EP0923585B1 (en) | 1996-07-18 | 2002-05-08 | Pfizer Inc. | Phosphinate based inhibitors of matrix metalloproteases |
CN1228083A (zh) | 1996-08-23 | 1999-09-08 | 美国辉瑞有限公司 | 芳基磺酰氨基异羟肟酸衍生物 |
ID18494A (id) | 1996-10-02 | 1998-04-16 | Novartis Ag | Turunan pirazola leburan dan proses pembuatannya |
WO2000035296A1 (en) | 1996-11-27 | 2000-06-22 | Wm. Wrigley Jr. Company | Improved release of medicament active agents from a chewing gum coating |
WO1998030566A1 (en) | 1997-01-06 | 1998-07-16 | Pfizer Inc. | Cyclic sulfone derivatives |
NZ336840A (en) | 1997-02-03 | 2001-01-26 | Pfizer Prod Inc | Arylsulfonylamino hydroxamic acid derivatives useful in the treatment of tumor necrosis factor and matrix metalloproteinase mediated diseases |
JP2000507975A (ja) | 1997-02-07 | 2000-06-27 | ファイザー・インク | N−ヒドロキシ−β−スルホニルプロピオンアミド誘導体類及びそれらのマトリックスメタロプロテイナーゼ阻害薬としての使用 |
IL131123A0 (en) | 1997-02-11 | 2001-01-28 | Pfizer | Arylsulfonyl hydroxamic acid derivatives |
EP0984930B1 (en) | 1997-05-07 | 2005-04-06 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
CA2291709A1 (en) | 1997-05-30 | 1998-12-03 | Merck & Co., Inc. | Novel angiogenesis inhibitors |
GB9711643D0 (en) | 1997-06-05 | 1997-07-30 | Janssen Pharmaceutica Nv | Glass thermoplastic systems |
NZ502309A (en) * | 1997-08-08 | 2002-02-01 | Pfizer Prod Inc | Aryloxyarylsulfonylamino hydroxamic acid derivatives and pharmaceutical use |
DE69838172T2 (de) | 1997-08-22 | 2008-04-10 | Astrazeneca Ab | Oxindolylchinazolinderivate als angiogenesehemmer |
JP2001518470A (ja) | 1997-09-26 | 2001-10-16 | メルク エンド カムパニー インコーポレーテッド | 新規な血管形成阻害剤 |
PL340589A1 (en) | 1997-11-11 | 2001-02-12 | Pfizer Prod Inc | Derivatives of thienepyrimidine and thienepyridine useful as anticarcinogenic agents |
GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
JPH11236333A (ja) | 1997-12-30 | 1999-08-31 | Pfizer Prod Inc | 抗ガン剤として有用なイミダゾリン−4−オン誘導体 |
GB9800575D0 (en) | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
GB9801690D0 (en) | 1998-01-27 | 1998-03-25 | Pfizer Ltd | Therapeutic agents |
ES2220004T3 (es) | 1998-04-10 | 2004-12-01 | Pfizer Products Inc. | Derivados del acido ciclobutil-ariloxiarilsulfonilaminohidroxamico. |
PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
SK287132B6 (sk) | 1998-05-29 | 2009-12-07 | Sugen, Inc. | Farmaceutická kompozícia obsahujúca pyrolom substituovaný 2-indolinón, súprava obsahujúca uvedenú kompozíciu a použitie pyrolom substituovaného 2-indolinónu |
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 |
EP1107962B1 (en) | 1998-08-27 | 2005-02-23 | Pfizer Products Inc. | Quinolin-2-one derivatives useful as anticancer agents |
CZ2001660A3 (cs) | 1998-08-27 | 2002-05-15 | Pfizer Products Inc. | Alkynylsubstituované chinolin-2-ony, farmaceutické kompozice a způsoby léčení na jejich bázi a způsob výroby těchto sloučenin |
PT1004578E (pt) | 1998-11-05 | 2004-06-30 | Pfizer Prod Inc | Derivados hidroxamida do acido 5-oxo-pirrolidino-2-carboxilico |
EP1006113A1 (en) | 1998-12-02 | 2000-06-07 | Pfizer Products Inc. | Derivatives of 2-(2-oxo-ethylidene)-imidazolidin-4-one and their use to inhibit abnormal cell growth |
US6649645B1 (en) | 1998-12-23 | 2003-11-18 | Pharmacia Corporation | Combination therapy of radiation and a COX-2 inhibitor for treatment of neoplasia |
WO2000038715A2 (en) | 1998-12-23 | 2000-07-06 | G.D. Searle & Co. | Use of an integrin antagonist and radiation in the treatment of neoplasia |
US6682736B1 (en) | 1998-12-23 | 2004-01-27 | Abgenix, Inc. | Human monoclonal antibodies to CTLA-4 |
UA71945C2 (en) | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
JP3270834B2 (ja) | 1999-01-27 | 2002-04-02 | ファイザー・プロダクツ・インク | 抗がん剤として有用なヘテロ芳香族二環式誘導体 |
AU2124800A (en) | 1999-02-11 | 2000-08-29 | Pfizer Products Inc. | Heteroaryl-substituted quinolin-2-one derivatives useful as anticancer agents |
US6586447B1 (en) | 1999-04-01 | 2003-07-01 | Pfizer Inc | 3,3-disubstituted-oxindole derivatives useful as anticancer agents |
US6511993B1 (en) * | 1999-06-03 | 2003-01-28 | Kevin Neil Dack | Metalloprotease inhibitors |
EP1081137A1 (en) | 1999-08-12 | 2001-03-07 | Pfizer Products Inc. | Selective inhibitors of aggrecanase in osteoarthritis treatment |
DE60008206T2 (de) | 1999-11-30 | 2004-12-02 | Pfizer Products Inc., Groton | Chinolinderivate verwendbar zur Hemmung der Farnesyl-Protein Transferase |
UA75055C2 (uk) * | 1999-11-30 | 2006-03-15 | Пфайзер Продактс Інк. | Похідні бензоімідазолу, що використовуються як антипроліферативний засіб, фармацевтична композиція на їх основі |
HN2000000266A (es) | 2000-01-21 | 2001-05-21 | Pfizer Prod Inc | Compuesto anticanceroso y metodo de separacion de enantiomeros util para sintetizar dicho compuesto. |
DE122010000004I1 (de) * | 2000-02-15 | 2010-04-15 | Sugen Inc | Pyrrol substituierte indolin-2-on protein kinase inhibitoren |
US6844357B2 (en) | 2000-05-01 | 2005-01-18 | Pfizer Inc. | Substituted quinolin-2-one derivatives useful as antiproliferative agents |
SE0102439D0 (sv) | 2001-07-05 | 2001-07-05 | Astrazeneca Ab | New compounds |
SE0102438D0 (sv) | 2001-07-05 | 2001-07-05 | Astrazeneca Ab | New compounds |
US20060063782A1 (en) | 2002-07-03 | 2006-03-23 | Murray Christopher W | 3-Hetero arylmethoxy ! pyridines and their analogues as p38 map kinase inhibitors |
SE0203754D0 (sv) | 2002-12-17 | 2002-12-17 | Astrazeneca Ab | New compounds |
CN1777427A (zh) * | 2003-02-26 | 2006-05-24 | 苏根公司 | 作为蛋白激酶抑制剂的氨基杂芳基化合物 |
WO2005002673A1 (en) | 2003-07-03 | 2005-01-13 | Astex Therapeutics Limited | Raf kinase inhibitors |
ES2355923T3 (es) * | 2004-08-26 | 2011-04-01 | Pfizer, Inc. | Compuestos de aminoheteroarilo sustituidos con pirazol como inhibidores de proteina quinasa. |
ES2341351T3 (es) * | 2004-08-26 | 2010-06-18 | Pfizer, Inc. | Compuestos de aminoheteroarilo enantiomericamente puros como inhibidores de proteina cinasas. |
CN101027404A (zh) * | 2004-08-26 | 2007-08-29 | 辉瑞大药厂 | 对映选择性生物转化制备蛋白酪氨酸激酶抑制剂中间体 |
JP2008510792A (ja) * | 2004-08-26 | 2008-04-10 | ファイザー・インク | タンパク質チロシンキナーゼ阻害剤としてのアミノヘテロアリール化合物 |
PL1959955T3 (pl) * | 2005-12-05 | 2011-04-29 | Pfizer Prod Inc | Sposób traktowania nieprawidłowego wzrostu komórek |
AU2006323025B2 (en) * | 2005-12-05 | 2012-07-05 | Pfizer Products Inc. | Polymorphs of a c-Met/HGFR inhibitor |
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NO20054080L (no) * | 2003-02-26 | 2005-11-21 | Uszhang Jennifer R | Aminoheteroarylforbindelser som roteinkinaseinhibitorer |
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