NO332188B1 - Aminoheteroarylforbindelser samt anvendelse av slike for fremstilling av preparat for behandling av sykdom. - Google Patents
Aminoheteroarylforbindelser samt anvendelse av slike for fremstilling av preparat for behandling av sykdom. Download PDFInfo
- Publication number
- NO332188B1 NO332188B1 NO20054080A NO20054080A NO332188B1 NO 332188 B1 NO332188 B1 NO 332188B1 NO 20054080 A NO20054080 A NO 20054080A NO 20054080 A NO20054080 A NO 20054080A NO 332188 B1 NO332188 B1 NO 332188B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- pyridin
- ethoxy
- amino
- dichloro
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 59
- 201000010099 disease Diseases 0.000 title description 21
- 125000005214 aminoheteroaryl group Chemical group 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 225
- 239000000203 mixture Substances 0.000 claims abstract description 160
- 239000003112 inhibitor Substances 0.000 claims abstract description 16
- -1 (3-{6-amino-6-[1-(2,6-dichloro-phenyl)-ethoxy]-pyridin-3-yl}-phenyl)-((R)-2-pyrrolidin-1-ylmethyl-pyrrolidine -1-yl)-methanone Chemical compound 0.000 claims description 81
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 76
- 206010028980 Neoplasm Diseases 0.000 claims description 67
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- 150000003839 salts Chemical class 0.000 claims description 45
- 229910052757 nitrogen Inorganic materials 0.000 claims description 42
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 21
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 17
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- 230000002159 abnormal effect Effects 0.000 claims description 12
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- 150000002367 halogens Chemical class 0.000 claims description 12
- 230000010261 cell growth Effects 0.000 claims description 11
- 239000012453 solvate Substances 0.000 claims description 11
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 10
- 150000004677 hydrates Chemical class 0.000 claims description 10
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
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- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 4
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- AUCWHTWWTRFLTK-UHFFFAOYSA-N [4-[6-amino-5-[1-[2-fluoro-6-(trifluoromethyl)phenyl]ethoxy]pyridin-3-yl]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone Chemical compound FC=1C=CC=C(C(F)(F)F)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N(CC1)CCC1N1CCCC1 AUCWHTWWTRFLTK-UHFFFAOYSA-N 0.000 claims description 4
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- NVJXHLYVXPKGOY-UHFFFAOYSA-N 4-[6-amino-5-[1-(2,6-dichlorophenyl)ethoxy]pyridin-3-yl]-n-(2-pyrrolidin-1-ylethyl)benzamide Chemical compound ClC=1C=CC=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)NCCN1CCCC1 NVJXHLYVXPKGOY-UHFFFAOYSA-N 0.000 claims description 3
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- LPWNBBNZNCSNBM-UHFFFAOYSA-N [3-[6-amino-5-[1-(2,6-dichlorophenyl)ethoxy]pyridin-3-yl]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone Chemical compound ClC=1C=CC=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=1)=CC=CC=1C(=O)N(CC1)CCC1N1CCCC1 LPWNBBNZNCSNBM-UHFFFAOYSA-N 0.000 claims description 2
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- QWSDYGXUBMHYCQ-UHFFFAOYSA-N [4-[6-amino-5-[(2,4,6-trifluorophenyl)methoxy]pyridin-3-yl]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone Chemical compound NC1=NC=C(C=2C=CC(=CC=2)C(=O)N2CCC(CC2)N2CCCC2)C=C1OCC1=C(F)C=C(F)C=C1F QWSDYGXUBMHYCQ-UHFFFAOYSA-N 0.000 claims description 2
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- AEHVEIFJNDIFGT-CALCHBBNSA-N [4-[6-amino-5-[(3-fluoro-2-methoxyphenyl)methoxy]pyridin-3-yl]phenyl]-[(3r,5s)-3,5-dimethylpiperazin-1-yl]methanone Chemical compound COC1=C(F)C=CC=C1COC1=CC(C=2C=CC(=CC=2)C(=O)N2C[C@@H](C)N[C@@H](C)C2)=CN=C1N AEHVEIFJNDIFGT-CALCHBBNSA-N 0.000 claims description 2
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- KKZCMUIQONHMRX-UHFFFAOYSA-N [4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]-3-fluorophenyl]-(2,2-dimethylpiperazin-1-yl)methanone Chemical compound ClC=1C=CC(F)=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C(=C1)F)=CC=C1C(=O)N1CCNCC1(C)C KKZCMUIQONHMRX-UHFFFAOYSA-N 0.000 claims description 2
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- RYNWHMVYHXUHGE-UHFFFAOYSA-N [4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]phenyl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C1=CC=C(C=2C=C(OC(C)C=3C(=C(F)C=CC=3Cl)Cl)C(N)=NC=2)C=C1 RYNWHMVYHXUHGE-UHFFFAOYSA-N 0.000 claims description 2
- GCHXQZRZNXAOKV-UHFFFAOYSA-N [4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]phenyl]-(4-methyl-1,4-diazepan-1-yl)methanone Chemical compound ClC=1C=CC(F)=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CCCN(C)CC1 GCHXQZRZNXAOKV-UHFFFAOYSA-N 0.000 claims description 2
- GCHURKJETQITJF-UHFFFAOYSA-N [4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound ClC=1C=CC(F)=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CCN(C)CC1 GCHURKJETQITJF-UHFFFAOYSA-N 0.000 claims description 2
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- APZWJXYBVLSYAK-LRHAYUFXSA-N [4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]phenyl]-[(3r)-3-aminopyrrolidin-1-yl]methanone Chemical compound ClC=1C=CC(F)=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CC[C@@H](N)C1 APZWJXYBVLSYAK-LRHAYUFXSA-N 0.000 claims description 2
- AWXKDRXUIGCEML-LRHAYUFXSA-N [4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]phenyl]-[(3r)-3-hydroxypyrrolidin-1-yl]methanone Chemical compound ClC=1C=CC(F)=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CC[C@@H](O)C1 AWXKDRXUIGCEML-LRHAYUFXSA-N 0.000 claims description 2
- FGXJPXSISSLIIV-DGXGNLECSA-N [4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]phenyl]-[(3r,4s)-3,4-dihydroxypyrrolidin-1-yl]methanone Chemical compound ClC=1C=CC(F)=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1C[C@H](O)[C@H](O)C1 FGXJPXSISSLIIV-DGXGNLECSA-N 0.000 claims description 2
- APZWJXYBVLSYAK-RUINGEJQSA-N [4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]phenyl]-[(3s)-3-aminopyrrolidin-1-yl]methanone Chemical compound ClC=1C=CC(F)=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CC[C@H](N)C1 APZWJXYBVLSYAK-RUINGEJQSA-N 0.000 claims description 2
- AWXKDRXUIGCEML-RUINGEJQSA-N [4-[6-amino-5-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-3-yl]phenyl]-[(3s)-3-hydroxypyrrolidin-1-yl]methanone Chemical compound ClC=1C=CC(F)=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CC[C@H](O)C1 AWXKDRXUIGCEML-RUINGEJQSA-N 0.000 claims description 2
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- OWJYVAGQUFLWBE-UHFFFAOYSA-N [4-[6-amino-5-[1-(2,6-dichlorophenyl)ethoxy]pyridin-3-yl]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound ClC=1C=CC=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CCN(C)CC1 OWJYVAGQUFLWBE-UHFFFAOYSA-N 0.000 claims description 2
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- VZYQNRXUIIMQEQ-XPKAQORNSA-N [4-[6-amino-5-[1-(2,6-dichlorophenyl)ethoxy]pyridin-3-yl]phenyl]-[(3r)-3-aminopyrrolidin-1-yl]methanone Chemical compound ClC=1C=CC=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CC[C@@H](N)C1 VZYQNRXUIIMQEQ-XPKAQORNSA-N 0.000 claims description 2
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- VZYQNRXUIIMQEQ-IBYPIGCZSA-N [4-[6-amino-5-[1-(2,6-dichlorophenyl)ethoxy]pyridin-3-yl]phenyl]-[(3s)-3-aminopyrrolidin-1-yl]methanone Chemical compound ClC=1C=CC=C(Cl)C=1C(C)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CC[C@H](N)C1 VZYQNRXUIIMQEQ-IBYPIGCZSA-N 0.000 claims description 2
- WSANBMQPGMLNPV-UHFFFAOYSA-N [4-[6-amino-5-[1-(2,6-dichlorophenyl)propoxy]pyridin-3-yl]phenyl]-(3,5-dimethylpiperazin-1-yl)methanone Chemical compound ClC=1C=CC=C(Cl)C=1C(CC)OC(C(=NC=1)N)=CC=1C(C=C1)=CC=C1C(=O)N1CC(C)NC(C)C1 WSANBMQPGMLNPV-UHFFFAOYSA-N 0.000 claims description 2
- GDNMBLFQCIKWSG-UHFFFAOYSA-N [4-[6-amino-5-[1-(2-chloro-3,6-difluorophenyl)ethoxy]pyridin-3-yl]phenyl]-(4-ethylpiperazin-1-yl)methanone Chemical compound C1CN(CC)CCN1C(=O)C1=CC=C(C=2C=C(OC(C)C=3C(=C(F)C=CC=3F)Cl)C(N)=NC=2)C=C1 GDNMBLFQCIKWSG-UHFFFAOYSA-N 0.000 claims description 2
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- 201000004916 vulva carcinoma Diseases 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 239000010457 zeolite Substances 0.000 description 1
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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
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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
- C07D213/73—Unsubstituted amino or imino radicals
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
-
- 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
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Vascular Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US44958803P | 2003-02-26 | 2003-02-26 | |
US54022904P | 2004-01-29 | 2004-01-29 | |
PCT/US2004/005495 WO2004076412A2 (en) | 2003-02-26 | 2004-02-26 | Aminoheteroaryl compounds as protein kinase inhibitors |
Publications (3)
Publication Number | Publication Date |
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NO20054080D0 NO20054080D0 (no) | 2005-09-01 |
NO20054080L NO20054080L (no) | 2005-11-21 |
NO332188B1 true NO332188B1 (no) | 2012-07-23 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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NO20054080A NO332188B1 (no) | 2003-02-26 | 2005-09-01 | Aminoheteroarylforbindelser samt anvendelse av slike for fremstilling av preparat for behandling av sykdom. |
Country Status (29)
Country | Link |
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US (2) | US7230098B2 (es) |
EP (2) | EP1603570B9 (es) |
JP (1) | JP4695588B2 (es) |
KR (1) | KR101106905B1 (es) |
CN (1) | CN103265477B (es) |
AP (1) | AP2114A (es) |
AU (1) | AU2004215428B2 (es) |
BR (1) | BRPI0407827B8 (es) |
CA (1) | CA2517256C (es) |
CY (2) | CY1113837T1 (es) |
DK (2) | DK2476667T3 (es) |
EA (1) | EA010727B1 (es) |
EC (1) | ECSP055988A (es) |
ES (2) | ES2401330T3 (es) |
GE (1) | GEP20084341B (es) |
HR (1) | HRP20050714B1 (es) |
IL (1) | IL170291A (es) |
IS (1) | IS2910B (es) |
MA (1) | MA27713A1 (es) |
ME (1) | MEP52808A (es) |
MX (1) | MXPA05009063A (es) |
NO (1) | NO332188B1 (es) |
NZ (1) | NZ541861A (es) |
OA (1) | OA13151A (es) |
PL (1) | PL216368B1 (es) |
PT (2) | PT2476667E (es) |
RS (1) | RS53118B (es) |
TN (1) | TNSN05208A1 (es) |
WO (1) | WO2004076412A2 (es) |
Families Citing this family (180)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MXPA05009063A (es) * | 2003-02-26 | 2005-12-12 | Sugen Inc | Compuestos de aminoheteroarilo como inhibidores de proteina cinasa. |
MXPA06009547A (es) * | 2004-02-23 | 2007-01-26 | Dana Farber Cancer Inst Inc | Metodo para tratar el crecimiento celular anormal usando inhibidores de c-met y m-tor. |
EP1719762B1 (en) | 2004-02-27 | 2012-06-27 | Eisai R&D Management Co., Ltd. | Novel pyridine derivative and pyrimidine derivative (1) |
AU2005228899A1 (en) * | 2004-03-30 | 2005-10-13 | Novartis Vaccines And Diagnostics, Inc. | Substituted thiophene derivatives as anti-cancer agents |
US8008301B2 (en) | 2004-04-01 | 2011-08-30 | Eli Lilly And Company | Histamine H3 receptor agents, preparation and therapeutic uses |
JP4777974B2 (ja) * | 2004-04-01 | 2011-09-21 | イーライ リリー アンド カンパニー | ヒスタミンh3受容体作用物質、製剤および治療的使用 |
MX2007002274A (es) | 2004-08-23 | 2007-05-07 | Lilly Co Eli | Agentes del receptor de histamina h3. preparacion y usos terapeuticos. |
PL1786785T3 (pl) * | 2004-08-26 | 2010-08-31 | Pfizer | Enancjomerycznie czyste związki aminoheteroarylowe jako kinazy białkowe |
MX2007002247A (es) * | 2004-08-26 | 2007-04-20 | Pfizer | Biotransformacion enantioselectiva para la preparacion de intermedios de inhibidores de la proteina tirosina quinasa. |
PT1784396E (pt) * | 2004-08-26 | 2011-01-27 | Pfizer | Compostos amino-heteroarílicos substituídos com pirazole como inibidores de proteína quinases |
CA2578075A1 (en) * | 2004-08-26 | 2006-03-02 | Pfizer Inc. | Aminoheteroaryl compounds as protein tyrosine kinase inhibitors |
GT200600042A (es) * | 2005-02-10 | 2006-09-27 | Aventis Pharma Inc | Compuestos de bis arilo y heteroarilo sustituido como antagonistas selectivos de 5ht2a |
AU2006218404A1 (en) * | 2005-03-03 | 2006-09-08 | Sirtris Pharmaceuticals, Inc. | N-phenyl benzamide derivatives as sirtuin modulators |
WO2006124748A2 (en) * | 2005-05-13 | 2006-11-23 | Lexicon Genetics Incorporated | Multicyclic compounds and methods of their use |
US8088928B2 (en) * | 2005-08-04 | 2012-01-03 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
US7855289B2 (en) * | 2005-08-04 | 2010-12-21 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
DK1910384T3 (da) * | 2005-08-04 | 2012-12-17 | Sirtris Pharmaceuticals Inc | Imidazo [2,1-b] thiazol-derivater som sirtuinmodulerende forbindelser |
US8093401B2 (en) * | 2005-08-04 | 2012-01-10 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
WO2007023768A1 (ja) * | 2005-08-24 | 2007-03-01 | Eisai R & D Management Co., Ltd. | 新規ピリジン誘導体およびピリミジン誘導体(3) |
SI1959955T1 (sl) * | 2005-12-05 | 2011-02-28 | Pfizer Prod Inc | Postopek zdravljenja abnormalne celične rasti |
RU2387650C2 (ru) * | 2005-12-05 | 2010-04-27 | Пфайзер Продактс Инк. | Полиморфы с-met/hgfr ингибитора |
PE20070978A1 (es) * | 2006-02-14 | 2007-11-15 | Novartis Ag | COMPUESTOS HETEROCICLICOS COMO INHIBIDORES DE FOSFATIDILINOSITOL 3-QUINASAS (PI3Ks) |
JP2009529047A (ja) | 2006-03-07 | 2009-08-13 | アレイ バイオファーマ、インコーポレイテッド | ヘテロ二環系ピラゾール化合物およびその使用 |
WO2007111904A2 (en) * | 2006-03-22 | 2007-10-04 | Vertex Pharmaceuticals Incorporated | C-met protein kinase inhibitors for the treatment of proliferative disorders |
ES2637592T3 (es) | 2006-04-14 | 2017-10-13 | Cell Signaling Technology, Inc. | Defectos de genes y quinasa ALK mutante en tumores sólidos humanos |
US8168383B2 (en) | 2006-04-14 | 2012-05-01 | Cell Signaling Technology, Inc. | Gene defects and mutant ALK kinase in human solid tumors |
US7601716B2 (en) | 2006-05-01 | 2009-10-13 | Cephalon, Inc. | Pyridopyrazines and derivatives thereof as ALK and c-Met inhibitors |
MX2008014953A (es) * | 2006-05-26 | 2009-03-05 | Bayer Healthcare Llc | Combinaciones de medicamentos con diarilureas sustituidas para el tratamiento de cancer. |
CA2655128A1 (en) * | 2006-06-08 | 2007-12-21 | Array Biopharma Inc. | Quinoline compounds and methods of use |
JP2010500365A (ja) | 2006-08-07 | 2010-01-07 | インサイト・コーポレイション | キナーゼ阻害剤としてのトリアゾロトリアジン |
ATE535520T1 (de) * | 2006-08-23 | 2011-12-15 | Eisai R&D Man Co Ltd | Salz eines phenoxypyridinderivats oder kristall davon und verfahren zu dessen herstellung |
US7790885B2 (en) | 2006-08-31 | 2010-09-07 | Eisai R&D Management Co., Ltd. | Process for preparing phenoxypyridine derivatives |
WO2008042867A2 (en) * | 2006-09-29 | 2008-04-10 | Emiliem Inc. | Modulators of multiple kinases |
EP2222647B1 (en) | 2006-10-23 | 2015-08-05 | Cephalon, Inc. | Fused bicyclic derivatives of 2,4-diaminopyrimidine as alk and c-met inhibitors |
GB0621607D0 (en) * | 2006-10-31 | 2006-12-06 | Chroma Therapeutics Ltd | Inhibitors of c-Met |
AU2007323725B2 (en) | 2006-11-22 | 2014-02-20 | Incyte Holdings Corporation | Imidazotriazines and imidazopyrimidines as kinase inhibitors |
CA2672167C (en) | 2006-12-14 | 2016-01-26 | Bayer Schering Pharma Aktiengesellschaft | Dihydropyridine derivatives useful as protein kinase inhibitors |
WO2008087736A1 (ja) * | 2007-01-19 | 2008-07-24 | Ube Industries, Ltd. | アラルキルオキシ又はヘテロアラルキルオキシ基を有する芳香族アミンの製法 |
ES2531002T3 (es) | 2007-01-19 | 2015-03-09 | Xcovery Inc | Compuestos inhibidores de quinasa |
US8715665B2 (en) | 2007-04-13 | 2014-05-06 | The General Hospital Corporation | Methods for treating cancer resistant to ErbB therapeutics |
JP5496876B2 (ja) * | 2007-04-16 | 2014-05-21 | アッヴィ・インコーポレイテッド | 7−置換されていないインドール系Mcl−1阻害薬 |
US8263585B2 (en) | 2007-05-04 | 2012-09-11 | Novartis Ag | Organic compounds |
CL2008001822A1 (es) * | 2007-06-20 | 2009-03-13 | Sirtris Pharmaceuticals Inc | Compuestos derivados de tiazolo[5,4-b]piridina; composicion farmaceutica que comprende a dichos compuestos; y uso del compuesto en el tratamiento de la resistencia a la insulina, sindrome metabolico, diabetes, entre otras. |
US20100190777A1 (en) | 2007-07-17 | 2010-07-29 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
CA2694275A1 (en) * | 2007-07-26 | 2009-01-29 | Novartis Ag | Organic compounds |
JP5973131B2 (ja) | 2007-09-13 | 2016-08-23 | コデクシス, インコーポレイテッド | アセトフェノンの還元のためのケトレダクターゼポリペプチド |
CN101868455B (zh) * | 2007-10-23 | 2013-11-13 | 阿勒根公司 | 治疗性的取代的内酰胺 |
JP2011502984A (ja) * | 2007-11-01 | 2011-01-27 | サートリス ファーマシューティカルズ, インコーポレイテッド | サーチュインモジュレーターとしてのアミド誘導体 |
US20110009381A1 (en) * | 2007-11-08 | 2011-01-13 | Sirtis Pharmaceuticals, Inc. | Solubilized thiazolopyridines |
JP2009132660A (ja) | 2007-11-30 | 2009-06-18 | Eisai R & D Management Co Ltd | 食道癌治療用組成物 |
WO2009073224A1 (en) * | 2007-12-07 | 2009-06-11 | Ambit Biosciences Corp. | Methods of treating certain diseases using pyrimidine derivatives |
JP2009203226A (ja) * | 2008-01-31 | 2009-09-10 | Eisai R & D Management Co Ltd | ピリジン誘導体およびピリミジン誘導体を含有するレセプターチロシンキナーゼ阻害剤 |
JPWO2009096198A1 (ja) * | 2008-02-01 | 2011-05-26 | 一般社団法人ファルマIp | 新規ビアリール誘導体 |
EP2265270A1 (en) * | 2008-02-04 | 2010-12-29 | 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 |
WO2009104520A1 (ja) * | 2008-02-18 | 2009-08-27 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | フェノキシピリジン誘導体の製造方法(2) |
US20110092452A1 (en) * | 2008-03-05 | 2011-04-21 | The Regents Of The University Of Michigan | Compositions and methods for diagnosing and treating pancreatic cancer |
US8268834B2 (en) * | 2008-03-19 | 2012-09-18 | Novartis Ag | Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme |
FR2928923B1 (fr) | 2008-03-21 | 2010-04-23 | Sanofi Aventis | Derives polysubstitues de 2-heteroaryl-6-phenyl-imidazo °1,2-a!pyridines, leur preparation et leur application en therapeutiques |
FR2928924B1 (fr) | 2008-03-21 | 2010-04-23 | Sanofi Aventis | Derives polysubstitues de 6-heteroaryle-imidazo°1,2-a! pyridines, leur preparation et leur application en therapeutique |
FR2928922B1 (fr) | 2008-03-21 | 2010-04-23 | Sanofi Aventis | Derives de 2-aryl-6-phenyl-imidazo°1,2-a!pyridines polysubstitues, leur preparation et leur application en therapeutique |
US20110039860A1 (en) * | 2008-05-07 | 2011-02-17 | Cangming Yang | Soluble epoxide hydrolase inhibitors, compositions containing such compounds and methods of treatment |
NZ602791A (en) | 2008-05-21 | 2014-04-30 | Incyte Corp | 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 |
PL2303018T3 (pl) * | 2008-06-19 | 2016-06-30 | Xcovery Holdings Inc | Podstawione związki pirydazynokarboksyamidowe jako związki będące inhibitorami kinazy |
CN102137939A (zh) * | 2008-08-29 | 2011-07-27 | 霍夫曼-拉罗奇有限公司 | 不依赖vegf的肿瘤的诊断和治疗 |
WO2010046780A2 (en) * | 2008-10-22 | 2010-04-29 | Institut Pasteur Korea | Anti viral 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 |
WO2010077624A1 (en) * | 2008-12-09 | 2010-07-08 | Merck Sharp & Dohme Corp. | Biaryl carboxamides |
EP2376502B1 (en) | 2008-12-19 | 2015-06-17 | GlaxoSmithKline LLC | Thiazolopyridine sirtuin modulating compounds |
SG10201607592PA (en) | 2008-12-19 | 2016-11-29 | Vertex Pharma | Pyrazine derivatives useful as inhibitors of atr kinase |
JP2012102018A (ja) * | 2009-03-03 | 2012-05-31 | Astellas Pharma Inc | アミド化合物 |
TW201100441A (en) | 2009-06-01 | 2011-01-01 | Osi Pharm Inc | Amino pyrimidine anticancer compounds |
DE102009056886A1 (de) | 2009-12-03 | 2011-06-09 | Bayer Schering Pharma Aktiengesellschaft | cMet-Inhibitoren zur Behandlung der Endometriose |
EA025304B1 (ru) | 2010-02-03 | 2016-12-30 | Инсайт Холдингс Корпорейшн | ИМИДАЗО[1,2-b][1,2,4]ТРИАЗИНЫ В КАЧЕСТВЕ c-Met ИНГИБИТОРОВ |
EP2566858A2 (en) | 2010-05-04 | 2013-03-13 | Pfizer Inc. | Heterocyclic derivatives as alk inhibitors |
JP2013526540A (ja) | 2010-05-12 | 2013-06-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Atrキナーゼ阻害剤として有用な化合物 |
WO2011143423A2 (en) * | 2010-05-12 | 2011-11-17 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
CA2798763A1 (en) | 2010-05-12 | 2011-11-17 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
US20130072495A1 (en) | 2010-05-14 | 2013-03-21 | OSI Pharmaceuticals, LLC | Fused bicyclic kinase inhibitors |
AR081039A1 (es) | 2010-05-14 | 2012-05-30 | Osi Pharmaceuticals Llc | Inhibidores biciclicos fusionados de quinasa |
US9526648B2 (en) | 2010-06-13 | 2016-12-27 | Synerz Medical, Inc. | Intragastric device for treating obesity |
US10010439B2 (en) | 2010-06-13 | 2018-07-03 | Synerz Medical, Inc. | Intragastric device for treating obesity |
US8628554B2 (en) | 2010-06-13 | 2014-01-14 | Virender K. Sharma | Intragastric device for treating obesity |
US10420665B2 (en) | 2010-06-13 | 2019-09-24 | W. L. Gore & Associates, Inc. | Intragastric device for treating obesity |
MX2012014776A (es) | 2010-06-25 | 2013-01-29 | Eisai R&D Man Co Ltd | Agente antitumoral que emplea compuestos con efecto inhibidor de cinasas combinados. |
US9120752B2 (en) | 2010-07-16 | 2015-09-01 | Purdue Pharma, L.P. | Pyridine compounds as sodium channel blockers |
WO2012042421A1 (en) | 2010-09-29 | 2012-04-05 | Pfizer Inc. | Method of treating abnormal cell growth |
US9126947B2 (en) | 2010-10-08 | 2015-09-08 | Xcovery Holding Company Llc | Substituted pyridazine carboxamide compounds |
EP2646448B1 (en) | 2010-11-29 | 2017-08-30 | OSI Pharmaceuticals, LLC | Macrocyclic kinase inhibitors |
GB201021103D0 (en) | 2010-12-13 | 2011-01-26 | Univ Leuven Kath | New compounds for the treatment of neurodegenerative diseases |
CA2824970C (en) | 2011-02-11 | 2016-05-03 | Batmark Limited | Inhaler component |
RU2598849C2 (ru) * | 2011-02-24 | 2016-09-27 | Цзянсу Хэнсох Фармасьютикал Ко., Лтд. | Содержащие фосфор соединения в качестве ингибиторов протеинкина3 |
US9145390B2 (en) | 2011-03-03 | 2015-09-29 | Concert Pharmaceuticals, Inc. | Derivatives of pyrazole-substituted amino-heteroaryl compounds |
JO3438B1 (ar) * | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
BR112013028895A2 (pt) | 2011-05-10 | 2016-08-09 | Bayer Ip Gmbh | (tio)carbonilamidinas bicíclicas |
EP2710003A1 (en) | 2011-05-16 | 2014-03-26 | OSI Pharmaceuticals, LLC | Fused bicyclic kinase inhibitors |
JP2014517079A (ja) | 2011-06-22 | 2014-07-17 | バーテックス ファーマシューティカルズ インコーポレイテッド | Atrキナーゼ阻害剤として有用な化合物 |
EP2739617A4 (en) * | 2011-07-27 | 2015-01-28 | Nanjing Allgen Pharma Co Ltd | SPIROCYCLIC MOLECULES AS PROTEIN KINASE INHIBITORS |
KR20140041906A (ko) | 2011-08-02 | 2014-04-04 | 화이자 인코포레이티드 | 암의 치료에 사용하기 위한 크리조티닙 |
WO2013049859A1 (en) | 2011-09-30 | 2013-04-04 | Vertex Pharmaceuticals Incorporated | Treating pancreatic cancer and non-small cell lung cancer with atr inhibitors |
EP2940017B1 (en) | 2011-09-30 | 2019-08-28 | Vertex Pharmaceuticals Incorporated | Process for making compounds useful as inhibitors of ATR kinase |
LT2822953T (lt) | 2012-03-06 | 2017-04-10 | Pfizer Inc. | Makrocikliniai dariniai, skirti proliferacinių ligų gydymui |
WO2013136170A1 (en) | 2012-03-16 | 2013-09-19 | Purdue Pharma L.P. | Substituted pyridines as sodium channel blockers |
CN108478577A (zh) | 2012-04-05 | 2018-09-04 | 沃泰克斯药物股份有限公司 | 可用作atr激酶抑制剂的化合物及其组合疗法 |
WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
JP6340361B2 (ja) * | 2012-04-13 | 2018-06-06 | エピザイム,インコーポレイティド | がんを処置するための組合せ治療 |
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 |
WO2013177092A1 (en) * | 2012-05-23 | 2013-11-28 | Sunshine Lake Pharma Co., Ltd. | Substituted alkynyl pyridine compounds and methods of use |
CA2880896C (en) | 2012-06-26 | 2021-11-16 | Del Mar Pharmaceuticals | Methods for treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or ahi1 dysregulations or mutations employing dianhydrogalactitol, diacetyldianhydrogalactitol, dibromodulcitol, or analogs or derivatives thereof |
GB201211310D0 (en) * | 2012-06-26 | 2012-08-08 | Chroma Therapeutics Ltd | CSF-1R kinase inhibitors |
WO2014046730A1 (en) | 2012-09-24 | 2014-03-27 | Ventana Medical Systems, Inc. | Method of identifying treatment responsive non-small cell lung cancer using anaplastic lymphoma kinase (alk) as a marker |
WO2014055756A1 (en) | 2012-10-04 | 2014-04-10 | Vertex Pharmaceuticals Incorporated | Method for measuring atr inhibition mediated increases in dna damage |
US20150299170A1 (en) * | 2012-11-21 | 2015-10-22 | Concert Pharmaceuticals, Inc. | Fluoro-derivatives of pyrazole-substituted amino-heteroaryl compounds |
LT3418281T (lt) | 2012-12-07 | 2021-01-11 | Vertex Pharmaceuticals Inc. | Pirazolo[1,5-a]pirimidinai, naudotini kaip atr kinazės inhibitoriai, skirti vėžinių ligų gydymui |
WO2014096941A1 (en) | 2012-12-20 | 2014-06-26 | Purdue Pharma L.P. | Cyclic sulfonamides as sodium channel blockers |
KR20150098605A (ko) | 2012-12-21 | 2015-08-28 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 퀴놀린 유도체의 비정질 형태 및 그의 제조방법 |
KR101791762B1 (ko) * | 2013-02-02 | 2017-11-20 | 치아타이 티안큉 파마수티컬 그룹 주식회사 | 치환된 2-아미노피리딘 단백질 키나제 억제제 |
JP2016512815A (ja) | 2013-03-15 | 2016-05-09 | バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated | Atrキナーゼの阻害剤として有用な縮合ピラゾロピリミジン誘導体 |
US11491154B2 (en) | 2013-04-08 | 2022-11-08 | Dennis M. Brown | Therapeutic benefit of suboptimally administered chemical compounds |
JP6411379B2 (ja) | 2013-05-14 | 2018-10-24 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | レンバチニブ化合物に対する子宮内膜がん対象の応答性を予測及び評価するためのバイオマーカー |
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 |
RU2550346C2 (ru) | 2013-09-26 | 2015-05-10 | Общество с ограниченной ответственностью "Отечественные Фармацевтические Технологии" ООО"ФармТех" | Новые химические соединения (варианты) и их применение для лечения онкологических заболеваний |
RU2643361C2 (ru) | 2013-09-30 | 2018-02-01 | Кореа Рисёч Инститьют Оф Кемикал Текнолоджи | Новые производные триазолопиразина и их применение |
WO2015069922A2 (en) | 2013-11-06 | 2015-05-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Alk antibodies, conjugates, and chimeric antigen receptors, and their use |
PT3077397T (pt) | 2013-12-06 | 2020-01-22 | Vertex Pharma | Composto de 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]pirazolo[1,5-a]pirimidin-3-carboxamida útil como inibidor da atr quinase, a sua preparação, diferentes formas sólidas e derivados radiomarcados do mesmo |
KR20160100329A (ko) | 2013-12-20 | 2016-08-23 | 3-브이 바이오사이언시스, 인코포레이티드 | 지질 합성의 헤테로사이클릭 조절물질 및 이들의 조합물 |
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 |
US10231965B2 (en) | 2014-02-20 | 2019-03-19 | Ignyta, Inc. | Molecules for administration to ROS1 mutant cancer cells |
JP2017516458A (ja) | 2014-03-24 | 2017-06-22 | ジェネンテック, インコーポレイテッド | c−met拮抗剤による癌治療及びc−met拮抗剤のHGF発現との相関 |
US10730866B2 (en) | 2014-04-07 | 2020-08-04 | Purdue Pharma L.P. | Indole derivatives and use thereof |
WO2015167825A1 (en) | 2014-04-29 | 2015-11-05 | Emory University | Prostaglandin receptor ep2 antagonists, derivatives, compositions, and uses related thereto |
WO2015172747A1 (en) * | 2014-05-16 | 2015-11-19 | Zhaoyin Wang | Spirocyclic molecules as mth1 inhibitors |
RS60013B1 (sr) | 2014-06-05 | 2020-04-30 | Vertex Pharma | Radioaktivno obeleženi derivati jedinjenja 2-amino-6-fluoro-n-[5-fluoropiridin-3-il]pirazolo[1,5-a]pirimidin-3-karboksamida, korisnog kao inhibitora atr kinaze, dobijanje pomenutog jedinjenja i njegovi različiti čvrsti oblici |
CA2950780C (en) | 2014-06-17 | 2023-05-16 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of chk1 and atr inhibitors |
WO2016019909A1 (zh) * | 2014-08-07 | 2016-02-11 | 江苏豪森药业股份有限公司 | 一种抗癌化合物的新晶型及其制备方法和用途 |
WO2016028971A1 (en) | 2014-08-21 | 2016-02-25 | Bristol-Myers Squibb Company | Tied-back benzamide derivatives as potent rock inhibitors |
ES2926687T3 (es) | 2014-08-28 | 2022-10-27 | Eisai R&D Man Co Ltd | Derivado de quinolina muy puro y método para su producción |
JP6678679B2 (ja) | 2014-10-13 | 2020-04-08 | エイトリン ファーマシューティカルズ エルエルシー | 毛細血管拡張性運動失調症およびRad3関連(ATR)プロテインキナーゼ阻害剤 |
GB2535427A (en) | 2014-11-07 | 2016-08-24 | Nicoventures Holdings Ltd | Solution |
UY36391A (es) * | 2014-11-05 | 2016-06-01 | Flexus Biosciences Inc | Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido1), sus métodos de síntesis y composiciones farmacèuticas que las contienen |
JP6902466B2 (ja) * | 2014-11-07 | 2021-07-14 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | ミオカルディン関連転写因子および血清応答因子(mrtf/srf)媒介性遺伝子転写の阻害剤ならびにその使用方法 |
AU2015355220B2 (en) | 2014-12-02 | 2020-02-27 | Ignyta, Inc. | Combinations for the treatment of neuroblastoma |
EP3789027A1 (en) | 2015-01-13 | 2021-03-10 | Kyoto University | Bosutinib, sunitinib, tivozanib, imatinib, nilotinib, rebastinib or bafetinib for preventing and/or treating amyotrophic lateral sclerosis |
MA41598A (fr) * | 2015-02-25 | 2018-01-02 | Constellation Pharmaceuticals Inc | Composés thérapeutiques de pyridazine et leurs utilisations |
US20180028662A1 (en) | 2015-02-25 | 2018-02-01 | Eisai R&D Management Co., Ltd. | Method for Suppressing Bitterness of Quinoline Derivative |
CA2978226A1 (en) | 2015-03-04 | 2016-09-09 | Merck Sharpe & Dohme Corp. | Combination of a pd-1 antagonist and a vegfr/fgfr/ret tyrosine kinase inhibitor for treating cancer |
WO2016198691A1 (en) | 2015-06-11 | 2016-12-15 | Basilea Pharmaceutica Ag | Efflux-pump inhibitors and therapeutic uses thereof |
CA2988707C (en) | 2015-06-16 | 2023-10-10 | Eisai R&D Management Co., Ltd. | Combination of cbp/catenin inhibitor and immune checkpoint inhibitor for treating cancer |
US10405627B2 (en) * | 2015-07-14 | 2019-09-10 | Michael Charles Boland, III | Luggage with fold out table |
AU2016331955B2 (en) | 2015-09-30 | 2022-07-21 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of DNA damaging agents and ATR inhibitors |
AU2016370846B2 (en) | 2015-12-18 | 2022-08-25 | Ignyta, Inc. | Combinations for the treatment of cancer |
US11129808B2 (en) | 2016-03-15 | 2021-09-28 | University Of South Florida | PKC-delta-I inhibitor formulations and uses thereof |
WO2017180723A1 (en) | 2016-04-12 | 2017-10-19 | Atrin Pharmaceuticals LLC | Ataxia telengiectasia and rad3-related (atr) inhibitors and methods of their use |
US10779980B2 (en) | 2016-04-27 | 2020-09-22 | Synerz Medical, Inc. | Intragastric device for treating obesity |
WO2017201585A1 (en) * | 2016-05-26 | 2017-11-30 | Genea Ip Holdings Pty Ltd | Modulators of dux4 for regulation of muscle function |
TWI646094B (zh) | 2016-06-01 | 2019-01-01 | 大陸商貝達藥業股份有限公司 | Crystal form of inhibitory protein kinase active compound and application thereof |
WO2018110669A1 (en) | 2016-12-15 | 2018-06-21 | Ono Pharmaceutical Co., Ltd. | Activator of trek (twik related k+ channels) channels |
CN106866627B (zh) * | 2017-01-24 | 2021-09-14 | 南方医科大学 | 3-(1-(氨基吡啶氧基)乙基)苯甲酰胺衍生物及其合成方法和应用 |
US11028058B2 (en) | 2017-07-18 | 2021-06-08 | Nuvation Bio Inc. | Heterocyclic compounds as adenosine antagonists |
MX2020000693A (es) | 2017-07-18 | 2020-07-29 | Nuvation Bio Inc | Compuestos de 1,8-naftiridinona, y usos de los mismos. |
BR112020000793A2 (pt) | 2017-07-19 | 2020-07-14 | Ignyta, Inc. | composições farmacêuticas e formas de dosagem |
EP3697390A1 (en) | 2017-10-17 | 2020-08-26 | Ignyta, Inc. | Pharmaceutical compositions and dosage forms |
CN107794282B (zh) * | 2017-11-20 | 2020-12-25 | 浙江工业大学 | 一种克唑替尼手性中间体的制备方法及菌株 |
WO2019154665A1 (en) * | 2018-02-07 | 2019-08-15 | Basf Se | New pyridine carboxamides |
WO2019174601A1 (en) * | 2018-03-15 | 2019-09-19 | Fujian Haixi Pharmaceuticals Co., Ltd | Heteroaryl compounds as kinase inhibitor |
CN110372664A (zh) * | 2018-04-13 | 2019-10-25 | 华东理工大学 | 选择性jak2抑制剂及其应用 |
WO2019206049A1 (en) * | 2018-04-25 | 2019-10-31 | Zhuhai Yufan Biotechnologies Co., Ltd | Hpk1 inhibitors, preparation method and application thereof |
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 |
CN108947895B (zh) * | 2018-08-22 | 2021-09-24 | 肇庆中彩机电技术研发有限公司 | 一种抗癌活性的化合物 |
JP2022517418A (ja) * | 2019-01-18 | 2022-03-08 | ニューベイション・バイオ・インコーポレイテッド | アデノシンアンタゴニストとしてのヘテロ環式化合物 |
CN113939291A (zh) | 2019-01-18 | 2022-01-14 | 诺维逊生物股份有限公司 | 1,8-萘啶酮化合物及其用途 |
KR20210116550A (ko) * | 2019-01-18 | 2021-09-27 | 누베이션 바이오 인크. | 아데노신 길항제로서의 헤테로시클릭 화합물 |
JP7345901B2 (ja) | 2019-05-14 | 2023-09-19 | テリジーン リミテッド | キナーゼ阻害剤として有用な置換大員環類 |
KR102426921B1 (ko) | 2019-09-24 | 2022-07-29 | 주식회사 이노보테라퓨틱스 | 헤테로아릴아미도피리딘올 유도체 및 이를 유효성분으로 포함하는 자가면역질환의 예방 또는 치료용 약학적 조성물 |
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 |
KR102344185B1 (ko) * | 2020-02-26 | 2021-12-27 | 계명대학교 산학협력단 | 신규한 Pim 키나아제 억제제 및 이의 용도 |
CN113493437B (zh) * | 2020-04-03 | 2022-07-26 | 中国药科大学 | 含苯并咪唑结构的化合物及其制备方法和用途 |
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 |
WO2023086671A1 (en) * | 2021-11-15 | 2023-05-19 | The Broad Institute, Inc. | Compounds, compositions, and methods for inducing antimicrobial intracellular activity and for preventing and treating microbial infections |
Family Cites Families (71)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4725601A (en) | 1985-06-04 | 1988-02-16 | Fujisawa Pharmaceutical Co., Ltd. | Certain imidazo[1,2-a]pyridines useful in the treatment of ulcers |
US4966849A (en) | 1985-09-20 | 1990-10-30 | President And Fellows Of Harvard College | CDNA and genes for human angiogenin (angiogenesis factor) and methods of expression |
US5217999A (en) | 1987-12-24 | 1993-06-08 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Styryl compounds which inhibit EGF receptor protein tyrosine kinase |
GB8827305D0 (en) | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
ES2064101T3 (es) | 1990-04-02 | 1995-01-16 | Pfizer | Compuestos de acido bencilfosfonico inhibidores de la quinasa de tirosina. |
US5302606A (en) | 1990-04-16 | 1994-04-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase |
WO1992020642A1 (en) * | 1991-05-10 | 1992-11-26 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
JPH06503095A (ja) | 1991-05-29 | 1994-04-07 | ファイザー・インコーポレーテッド | 三環式ポリヒドロキシ系のチロシンキナーゼ阻害薬 |
US5587458A (en) | 1991-10-07 | 1996-12-24 | Aronex Pharmaceuticals, Inc. | Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof |
GB9201693D0 (en) | 1992-01-27 | 1992-03-11 | Smithkline Beecham Intercredit | Compounds |
CA2372813A1 (en) | 1992-02-06 | 1993-08-19 | L.L. Houston | Biosynthetic binding protein for cancer marker |
AU672224B2 (en) | 1992-08-06 | 1996-09-26 | Warner-Lambert Company | 2-thioindoles (selenoindoles) and related disulfides (selenides) which inhibit protein tyrosine kinases and whichhave antitumor properties |
US5330992A (en) | 1992-10-23 | 1994-07-19 | Sterling Winthrop Inc. | 1-cyclopropyl-4-pyridyl-quinolinones |
DE69233803D1 (de) | 1992-10-28 | 2011-03-31 | Genentech Inc | Verwendung von vaskulären Endothelwachstumsfaktor-Antagonisten |
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 |
GB9226855D0 (en) | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
US5455258A (en) | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
US5521190A (en) * | 1993-05-27 | 1996-05-28 | Fmc Corporation | Insecticidal pterdines and 8-deazapteridines |
JPH07109260A (ja) * | 1993-10-12 | 1995-04-25 | Fuji Photo Film Co Ltd | 5−アミノ−2−ニトロピリジン誘導体及び2,5−ジアミノ−3−ヒドロキシピリジン誘導体の製造方法 |
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 |
EP0821671B1 (en) | 1995-04-20 | 2000-12-27 | 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 |
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 |
DK0780386T3 (da) | 1995-12-20 | 2003-02-03 | Hoffmann La Roche | Matrixmetalloproteaseinhibitorer |
CN1116286C (zh) | 1996-03-05 | 2003-07-30 | 曾尼卡有限公司 | 4-苯胺基喹唑啉衍生物 |
HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
DK0912559T3 (da) | 1996-07-13 | 2003-03-10 | Glaxo Group Ltd | Kondenserede heterocykliske forbindelser som proteintyrosinkinaseinhibitorer |
US6207669B1 (en) | 1996-07-13 | 2001-03-27 | Glaxo Wellcome Inc. | Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors |
TR199900066T2 (xx) | 1996-07-18 | 1999-04-21 | Pfizer Inc. | Matriks metalloproteazlar�n fosfinat bazl� inhibit�rleri |
PL331895A1 (en) | 1996-08-23 | 1999-08-16 | Pfizer | Arylosulphonylamino derivatives of hydroxamic acid |
ID18494A (id) | 1996-10-02 | 1998-04-16 | Novartis Ag | Turunan pirazola leburan dan proses pembuatannya |
US6077864A (en) | 1997-01-06 | 2000-06-20 | Pfizer Inc. | Cyclic sulfone derivatives |
BR9807815A (pt) | 1997-02-03 | 2000-03-08 | Pfizer Prod Inc | Derivados de ácido arilsulfonilamino-hidroxâmico |
WO1998034915A1 (en) | 1997-02-07 | 1998-08-13 | Pfizer Inc. | N-hydroxy-beta-sulfonyl-propionamide derivatives and their use as inhibitors of matrix metalloproteinases |
HUP0000657A3 (en) | 1997-02-11 | 2000-10-30 | Pfizer | N-arylsulfonyl-piperidine, -morpholine hydroxamic acid derivatives and pharmaceutical compositions containing them |
SE9700661D0 (sv) * | 1997-02-25 | 1997-02-25 | Astra Ab | New compounds |
EP0984930B1 (en) | 1997-05-07 | 2005-04-06 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
JP2002501532A (ja) | 1997-05-30 | 2002-01-15 | メルク エンド カンパニー インコーポレーテッド | 新規血管形成阻害薬 |
WO1999010349A1 (en) | 1997-08-22 | 1999-03-04 | Zeneca Limited | Oxindolylquinazoline derivatives as angiogenesis inhibitors |
EP1017682A4 (en) | 1997-09-26 | 2000-11-08 | Merck & Co Inc | NEW ANGIOGENESIS INHIBITORS |
EP1028964A1 (en) | 1997-11-11 | 2000-08-23 | Pfizer Products Inc. | Thienopyrimidine and thienopyridine derivatives useful as anticancer agents |
GB9725782D0 (en) | 1997-12-05 | 1998-02-04 | Pfizer Ltd | Therapeutic agents |
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 |
PA8469501A1 (es) | 1998-04-10 | 2000-09-29 | Pfizer Prod Inc | Hidroxamidas del acido (4-arilsulfonilamino)-tetrahidropiran-4-carboxilico |
PA8469401A1 (es) | 1998-04-10 | 2000-05-24 | Pfizer Prod Inc | Derivados biciclicos del acido hidroxamico |
SE9801526D0 (sv) * | 1998-04-29 | 1998-04-29 | Astra Ab | New compounds |
AU759226B2 (en) | 1998-05-29 | 2003-04-10 | Sugen, Inc. | Pyrrole substituted 2-indolinone protein kinase inhibitors |
US20010002396A1 (en) * | 1998-07-16 | 2001-05-31 | Charles Achkar | Compositions and methods of treating skin conditions |
CN1340051A (zh) | 1999-02-11 | 2002-03-13 | 辉瑞产品公司 | 可用作抗癌剂的杂芳基取代的喹啉-2-酮衍生物 |
GB9908410D0 (en) | 1999-04-13 | 1999-06-09 | Pfizer Ltd | Pyridines |
JP2003523942A (ja) | 1999-06-30 | 2003-08-12 | メルク エンド カムパニー インコーポレーテッド | Srcキナーゼ阻害剤化合物 |
HN2001000008A (es) * | 2000-01-21 | 2003-12-11 | Inc Agouron Pharmaceuticals | Compuesto de amida y composiciones farmaceuticas para inhibir proteinquinasas, y su modo de empleo |
ME00415B (me) | 2000-02-15 | 2011-10-10 | Pharmacia & Upjohn Co Llc | Pirol supstituisani 2-indol protein kinazni inhibitori |
EE200200453A (et) | 2000-02-16 | 2003-12-15 | Neurogen Corporation | Asendatud arüülpürasiinid |
CN102336679A (zh) | 2000-07-07 | 2012-02-01 | 塔夫茨大学信托人 | 7-取代的四环素化合物 |
WO2002024681A2 (en) * | 2000-09-20 | 2002-03-28 | Ortho-Mcneil Pharmaceutical, Inc. | Pyrazine derivatives as modulators of tyrosine kinases |
GB0101577D0 (en) | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
WO2002064594A2 (en) * | 2001-02-12 | 2002-08-22 | F. Hoffmann-La Roche Ag | 6-substituted pyrido-pyrimidines |
US6825198B2 (en) * | 2001-06-21 | 2004-11-30 | Pfizer Inc | 5-HT receptor ligands and uses thereof |
BR0214309A (pt) | 2001-11-21 | 2004-10-13 | Upjohn Co | Derivados aril-1,4-pirazina substituìdos |
MXPA05009063A (es) * | 2003-02-26 | 2005-12-12 | Sugen Inc | Compuestos de aminoheteroarilo como inhibidores de proteina cinasa. |
PT1784396E (pt) * | 2004-08-26 | 2011-01-27 | Pfizer | Compostos amino-heteroarílicos substituídos com pirazole como inibidores de proteína quinases |
PL1786785T3 (pl) * | 2004-08-26 | 2010-08-31 | Pfizer | Enancjomerycznie czyste związki aminoheteroarylowe jako kinazy białkowe |
US10181126B2 (en) | 2012-03-13 | 2019-01-15 | American Express Travel Related Services Company, Inc. | Systems and methods for tailoring marketing |
US10884952B2 (en) | 2016-09-30 | 2021-01-05 | Intel Corporation | Enforcing memory operand types using protection keys |
JP6943759B2 (ja) | 2017-12-28 | 2021-10-06 | 株式会社東海理化電機製作所 | シフト装置 |
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