ZA200504674B - Diazepinoindole derivatives as kinase inhibitors - Google Patents
Diazepinoindole derivatives as kinase inhibitors Download PDFInfo
- Publication number
- ZA200504674B ZA200504674B ZA200504674A ZA200504674A ZA200504674B ZA 200504674 B ZA200504674 B ZA 200504674B ZA 200504674 A ZA200504674 A ZA 200504674A ZA 200504674 A ZA200504674 A ZA 200504674A ZA 200504674 B ZA200504674 B ZA 200504674B
- Authority
- ZA
- South Africa
- Prior art keywords
- phenyl
- dihydro
- diazepino
- indol
- oxo
- Prior art date
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- 229940043355 kinase inhibitor Drugs 0.000 title description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
- BSYFXFLGOGQHFU-UHFFFAOYSA-N pyrrolo[2,3-g][1,2]benzodiazepine Chemical class N1=NC=CC=C2C3=NC=CC3=CC=C21 BSYFXFLGOGQHFU-UHFFFAOYSA-N 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims description 172
- 150000001875 compounds Chemical class 0.000 claims description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims description 59
- 125000001424 substituent group Chemical group 0.000 claims description 59
- 125000001072 heteroaryl group Chemical group 0.000 claims description 55
- AHDDRJBFJBDEPW-DTWKUNHWSA-N trans-2-Phenylcyclopropanecarboxylic acid Chemical compound OC(=O)[C@@H]1C[C@H]1C1=CC=CC=C1 AHDDRJBFJBDEPW-DTWKUNHWSA-N 0.000 claims description 47
- 125000003118 aryl group Chemical group 0.000 claims description 45
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
- 150000003839 salts Chemical class 0.000 claims description 42
- 125000003342 alkenyl group Chemical group 0.000 claims description 27
- 125000000304 alkynyl group Chemical group 0.000 claims description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 19
- 101150050673 CHK1 gene Proteins 0.000 claims description 18
- -1 2-phenyl-cyclopropanecarbonyl Chemical group 0.000 claims description 15
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 12
- 102000001253 Protein Kinase Human genes 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 108060006633 protein kinase Proteins 0.000 claims description 10
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 8
- CRSYCFLQNTZJCV-UHFFFAOYSA-N 6-amino-2-phenyl-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-9-one Chemical compound C1=2C=3C=NNC(=O)C1=CC(N)=CC=2NC=3C1=CC=CC=C1 CRSYCFLQNTZJCV-UHFFFAOYSA-N 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 229940034982 antineoplastic agent Drugs 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- 230000005855 radiation Effects 0.000 claims description 3
- WUEPMEXUMQVEGN-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;2,2,2-trifluoro-n-[2-[2-[(2,2,2-trifluoroacetyl)amino]ethylamino]ethyl]acetamide Chemical compound OC(=O)C(F)(F)F.FC(F)(F)C(=O)NCCNCCNC(=O)C(F)(F)F WUEPMEXUMQVEGN-UHFFFAOYSA-N 0.000 claims description 2
- DQCWXAWRJUKYAS-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-yl)-N-(9-oxo-2-phenyl-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl)acetamide Chemical compound C1C2=CC=CC=C2CC1CC(=O)NC(C=C1C(=O)NN=CC=2C=31)=CC=3NC=2C1=CC=CC=C1 DQCWXAWRJUKYAS-UHFFFAOYSA-N 0.000 claims description 2
- CZLDSCXHCDKQFT-UHFFFAOYSA-N 2-fluoro-N-(9-oxo-2-phenyl-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl)-3-(trifluoromethyl)benzamide Chemical compound C1=CC=C(C(F)(F)F)C(F)=C1C(=O)NC1=CC(NC(C=2C=CC=CC=2)=C2C=NNC3=O)=C2C3=C1 CZLDSCXHCDKQFT-UHFFFAOYSA-N 0.000 claims description 2
- MVBMKCBHWGCQSV-UHFFFAOYSA-N 9-oxo-2-phenyl-N-(2-phenylcyclopropyl)-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaene-6-carboxamide Chemical compound C=1C(=C23)NC(C=4C=CC=CC=4)=C3C=NNC(=O)C2=CC=1C(=O)NC1CC1C1=CC=CC=C1 MVBMKCBHWGCQSV-UHFFFAOYSA-N 0.000 claims description 2
- SKMKTYFTYJMUAV-UHFFFAOYSA-N N-[1-(4-fluorophenyl)ethyl]-9-oxo-2-phenyl-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaene-6-carboxamide Chemical compound C=1C=C(F)C=CC=1C(C)NC(=O)C(C=C1C(=O)NN=CC=2C=31)=CC=3NC=2C1=CC=CC=C1 SKMKTYFTYJMUAV-UHFFFAOYSA-N 0.000 claims description 2
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims 10
- NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical compound N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 claims 5
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 claims 4
- DPKSIAPPUDIZGD-JOCHJYFZSA-N (2R)-2-hydroxy-N-(9-oxo-2-phenyl-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl)-2-phenylacetamide Chemical compound O=C([C@H](O)C=1C=CC=CC=1)NC(C=C1C(=O)NN=CC=2C=31)=CC=3NC=2C1=CC=CC=C1 DPKSIAPPUDIZGD-JOCHJYFZSA-N 0.000 claims 2
- NFXMJZRICBRUKE-UHFFFAOYSA-N 2-(3,4-dihydro-1H-isoquinolin-2-yl)-N-(9-oxo-2-phenyl-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl)acetamide Chemical compound C1CC2=CC=CC=C2CN1CC(=O)NC(C=C1C(=O)NN=CC=2C=31)=CC=3NC=2C1=CC=CC=C1 NFXMJZRICBRUKE-UHFFFAOYSA-N 0.000 claims 2
- AHDDRJBFJBDEPW-UHFFFAOYSA-N 2-phenylcyclopropane-1-carboxylic acid Chemical compound OC(=O)C1CC1C1=CC=CC=C1 AHDDRJBFJBDEPW-UHFFFAOYSA-N 0.000 claims 2
- HXEACLLIILLPRG-RXMQYKEDSA-N D-pipecolic acid Chemical compound OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 2
- 208000035269 cancer or benign tumor Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 claims 2
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 claims 2
- VHMBMZURJCYWQL-QWHCGFSZSA-N (1R,2R)-N-(2-bromo-9-oxo-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl)-2-phenylcyclopropane-1-carboxamide Chemical compound C1([C@@H]2C[C@H]2C(=O)NC=2C=C3NC(=C4C3=C(C(NN=C4)=O)C=2)Br)=CC=CC=C1 VHMBMZURJCYWQL-QWHCGFSZSA-N 0.000 claims 1
- VWJCDWQVWASWJL-ZWKOTPCHSA-N (1R,2R)-N-(9-oxo-2-pyridin-3-yl-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl)-2-phenylcyclopropane-1-carboxamide Chemical compound O=C([C@H]1[C@@H](C1)C=1C=CC=CC=1)NC(C=C1C(=O)NN=CC=2C=31)=CC=3NC=2C1=CC=CN=C1 VWJCDWQVWASWJL-ZWKOTPCHSA-N 0.000 claims 1
- SZTQDTNQGMICST-ZWKOTPCHSA-N (1R,2R)-N-[2-[3-(dimethylamino)propyl]-9-oxo-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl]-2-phenylcyclopropane-1-carboxamide Chemical compound C1([C@@H]2C[C@H]2C(=O)NC=2C=C3NC(=C4C3=C(C(NN=C4)=O)C=2)CCCN(C)C)=CC=CC=C1 SZTQDTNQGMICST-ZWKOTPCHSA-N 0.000 claims 1
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- TWYJYUIFEPPLLC-ZMBIFBSDSA-N (2R)-2-amino-2-(4-hydroxyphenyl)-N-(9-oxo-2-phenyl-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl)acetamide hydrochloride Chemical compound Cl.O=C([C@H](N)C=1C=CC(O)=CC=1)NC(C=C1C(=O)NN=CC=2C=31)=CC=3NC=2C1=CC=CC=C1 TWYJYUIFEPPLLC-ZMBIFBSDSA-N 0.000 claims 1
- AHRFABYUKRWAOZ-ZMBIFBSDSA-N (2R)-2-amino-2-cyclohexyl-N-(9-oxo-2-phenyl-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl)acetamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1([C@@H](N)C(=O)NC=2C=C3C(=O)NN=CC4=C(C=5C=CC=CC=5)NC(=C34)C=2)CCCCC1 AHRFABYUKRWAOZ-ZMBIFBSDSA-N 0.000 claims 1
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- SOXNMWXZIMFNRZ-UHFFFAOYSA-N N-[2-[3-[(dimethylamino)methyl]phenyl]-9-oxo-3,10,11-triazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13),11-pentaen-6-yl]-2-fluoro-3-(trifluoromethyl)benzamide Chemical compound CN(C)CC1=CC=CC(C2=C3C4=C(C(NN=C3)=O)C=C(NC(=O)C=3C(=C(C=CC=3)C(F)(F)F)F)C=C4N2)=C1 SOXNMWXZIMFNRZ-UHFFFAOYSA-N 0.000 description 1
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- QCOXCILKVHKOGO-UHFFFAOYSA-N n-(2-nitramidoethyl)nitramide Chemical compound [O-][N+](=O)NCCN[N+]([O-])=O QCOXCILKVHKOGO-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/06—Peri-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/06—Peri-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43939603P | 2003-01-09 | 2003-01-09 |
Publications (1)
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|---|---|
| ZA200504674B true ZA200504674B (en) | 2006-07-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200504674A ZA200504674B (en) | 2003-01-09 | 2005-06-08 | Diazepinoindole derivatives as kinase inhibitors |
Country Status (35)
| Country | Link |
|---|---|
| US (3) | US6967198B2 (hr) |
| EP (2) | EP1947102A1 (hr) |
| JP (1) | JP3990718B2 (hr) |
| KR (1) | KR100697746B1 (hr) |
| CN (1) | CN1759118B (hr) |
| AP (1) | AP2048A (hr) |
| AT (1) | ATE404564T1 (hr) |
| AU (1) | AU2004203977B2 (hr) |
| BR (1) | BRPI0406701A (hr) |
| CA (1) | CA2512683C (hr) |
| CR (1) | CR7899A (hr) |
| CY (1) | CY1108408T1 (hr) |
| DE (1) | DE602004015724D1 (hr) |
| DK (1) | DK1585749T3 (hr) |
| EA (1) | EA009337B1 (hr) |
| EC (1) | ECSP055911A (hr) |
| ES (1) | ES2309484T3 (hr) |
| GE (1) | GEP20084367B (hr) |
| HK (1) | HK1086257A1 (hr) |
| HR (1) | HRP20050624A2 (hr) |
| IL (1) | IL169082A (hr) |
| IS (1) | IS7884A (hr) |
| MA (1) | MA27703A1 (hr) |
| MX (1) | MXPA05007352A (hr) |
| NO (1) | NO20053775L (hr) |
| NZ (1) | NZ540638A (hr) |
| OA (1) | OA13017A (hr) |
| PL (1) | PL378372A1 (hr) |
| PT (1) | PT1585749E (hr) |
| RS (1) | RS20050522A (hr) |
| SI (1) | SI1585749T1 (hr) |
| TN (1) | TNSN05176A1 (hr) |
| UA (1) | UA80733C2 (hr) |
| WO (1) | WO2004063198A1 (hr) |
| ZA (1) | ZA200504674B (hr) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1467730A4 (en) * | 2002-01-22 | 2010-03-10 | Univ California | Non-steroid ligands for the glucocorticoid receptor, compositions and uses thereof |
| EA009337B1 (ru) * | 2003-01-09 | 2007-12-28 | Пфайзер Инк. | Трициклические соединения, представляющие собой ингибиторы протеинкиназ, для увеличения эффективности противоопухолевых агентов и лучевой терапии |
| JP2008530575A (ja) * | 2005-02-18 | 2008-08-07 | アストラゼネカ アクチボラグ | Ｃｈｋ１阻害薬に対する応答性を判定する方法 |
| KR100912998B1 (ko) | 2005-03-29 | 2009-08-20 | 이코스 코포레이션 | Ｃｈｋ1 억제에 유용한 헤테로아릴 우레아 유도체 |
| GB0510390D0 (en) * | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| NZ565378A (en) | 2005-06-29 | 2011-03-31 | Threshold Pharmaceuticals Inc | Phosphoramidate alkylator prodrugs |
| WO2007022273A2 (en) | 2005-08-15 | 2007-02-22 | The Regents Of The University Of California | Vegf-activated fas ligands |
| US8143052B2 (en) | 2005-08-25 | 2012-03-27 | Ube Industries, Ltd. | Process for preparing optically active (S or R)-α amino acid and (R or S)-α amino acid ester in one phase organic reaction medium |
| US7645885B2 (en) * | 2005-08-26 | 2010-01-12 | The Regents Of The University Of California | Non-steroidal antiandrogens |
| EP2004655A1 (en) * | 2006-04-04 | 2008-12-24 | Pfizer Products Incorporated | Polymorphic forms of (2r,z)-2-amino-2-cyclohexyl-n-(5-(1-methyl-1h-pyrazol-4 l)-1-oxo-2,6-dihydro-1h-ý1,2¨diazepinoý4,5,6-cd¨indol-8-yl)acetamide |
| WO2007113671A1 (en) * | 2006-04-04 | 2007-10-11 | Pfizer Products Inc. | Combination therapy of (2r,z)-2-amino-2-cyclohexyl-n-(5-(1-methyl-1h-pyrazol-4-yl)-1-oxo-2,6-dihydro-1h-[1,2]diazepino[4,5,6-cd]indol-8-yl)acetamide |
| JP2010510222A (ja) * | 2006-11-17 | 2010-04-02 | シェーリング コーポレイション | 増殖性障害に対する併用療法 |
| US8158656B2 (en) * | 2008-05-16 | 2012-04-17 | Shenzhen Chipscreen Biosciences Ltd. | 2-indolinone derivatives as multi-target protein kinase inhibitors and histone deacetylase inhibitors |
| ES2378513T3 (es) * | 2008-08-06 | 2012-04-13 | Pfizer Inc. | Compuestos 2-heterociclilamino piracinas sustituidas en posición 6 como inhibidores de CHK-1 |
| EP2346881A1 (en) * | 2008-10-10 | 2011-07-27 | Priaxon AG | Novel compounds which modulate kinase activity |
| US8314108B2 (en) | 2008-12-17 | 2012-11-20 | Eli Lilly And Company | 5-(5-(2-(3-aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-ylamino)pyrazine-2-carbonitrile, pharmaceutically acceptable salts thereof, or solvate of salts |
| US8663210B2 (en) | 2009-05-13 | 2014-03-04 | Novian Health, Inc. | Methods and apparatus for performing interstitial laser therapy and interstitial brachytherapy |
| US8211901B2 (en) | 2009-05-22 | 2012-07-03 | Shenzhen Chipscreen Biosciences Ltd. | Naphthamide derivatives as multi-target protein kinase inhibitors and histone deacetylase inhibitors |
| CN101906076B (zh) | 2009-06-04 | 2013-03-13 | 深圳微芯生物科技有限责任公司 | 作为蛋白激酶抑制剂和组蛋白去乙酰化酶抑制剂的萘酰胺衍生物、其制备方法及应用 |
| BR112013028665A2 (pt) | 2011-05-06 | 2016-09-06 | Zafgen Inc | compostos de sulfonamida tricíclicos e métodos para fazer e usar os mesmos |
| US9254299B2 (en) | 2011-12-22 | 2016-02-09 | Threshold Pharmaceuticals, Inc. | Administration of hypoxia activated prodrugs in combination with Chk1 inhibitors for treating cancer |
| DK2797921T3 (en) * | 2011-12-31 | 2017-10-02 | Beigene Ltd | FUSED TETRA- OR PENTA-CYCLIC DIHYDRODIAZEPINOCARBAZOLONES AS PARB INHIBITORS |
| EA027241B1 (ru) | 2011-12-31 | 2017-07-31 | Бейджен, Лтд. | Конденсированные тетра- или пентациклические пиридофталазиноны в качестве ингибиторов parp |
| CN102746211B (zh) * | 2012-06-27 | 2015-05-27 | 上海泰坦化学有限公司 | 一种取代吲哚-3-甲醛类化合物的制备方法 |
| TWI633107B (zh) * | 2013-05-22 | 2018-08-21 | 開曼群島商百濟神州生物科技有限公司 | 作為ｐａｒｐ抑制劑的稠合四或五環二氫二氮呯并咔唑酮 |
| CA2938626A1 (en) | 2013-07-26 | 2015-01-29 | John Rothman | Compositions to improve the therapeutic benefit of bisantrene |
| US10071109B2 (en) | 2013-11-06 | 2018-09-11 | Molecular Templates, Inc. | Predictive biomarker for hypoxia-activated prodrug therapy |
| CA2950780C (en) | 2014-06-17 | 2023-05-16 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of chk1 and atr inhibitors |
| US10457680B2 (en) * | 2015-08-25 | 2019-10-29 | Beigene, Ltd. | Process for preparing a PARP inhibitor, crystalline forms, and uses thereof |
| 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 |
| EP3519051B1 (en) | 2016-09-27 | 2021-09-22 | Beigene, Ltd. | Treatment of cancers using combination comprising parp inhibitors |
| JP6541635B2 (ja) * | 2016-10-28 | 2019-07-10 | ベイジーン リミテッド | Ｐａｒｐ阻害剤としての縮合四環式または縮合五環式ジヒドロジアゼピノカルバゾロン |
| US10899763B2 (en) | 2017-02-28 | 2021-01-26 | Beigene, Ltd. | Crystalline forms of salts of fused penta-cyclic dihydrodiazepinocarbazolones, and uses thereof |
| US11661581B2 (en) * | 2017-05-25 | 2023-05-30 | University Of Massachusetts | Use of CDK inhibitors to enhance growth and self-renewal of progenitor cells |
| RU2764243C2 (ru) * | 2017-09-22 | 2022-01-14 | ДЖУБИЛАНТ ЭПИПЭД ЭлЭлСи | Гетероциклические соединения в качестве ингибиторов PAD |
| EP3461480A1 (en) | 2017-09-27 | 2019-04-03 | Onxeo | Combination of a dna damage response cell cycle checkpoint inhibitors and belinostat for treating cancer |
| WO2020154608A1 (en) * | 2019-01-25 | 2020-07-30 | Numedii, Inc. | Method for treating idiopathic pulmonary fibrosis |
| WO2021018298A1 (zh) * | 2019-08-01 | 2021-02-04 | 南京明德新药研发有限公司 | 作为parp抑制剂吲哚并七元酰肟化合物 |
| WO2021104461A1 (zh) | 2019-11-29 | 2021-06-03 | 南京明德新药研发有限公司 | 二氮杂吲哚类衍生物及其作为Chk1抑制剂的应用 |
| WO2022011458A1 (en) * | 2020-07-13 | 2022-01-20 | Ontario Institute For Cancer Research (Oicr) | Nicotinamide phosphoribosyltransferase (nampt) inhibitor-conjugates and uses thereof |
| CN115698019A (zh) * | 2020-07-31 | 2023-02-03 | 正大天晴药业集团股份有限公司 | 用作parp抑制剂的吲哚并七元酰肟类似物的结晶及其制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9722320D0 (en) | 1997-10-22 | 1997-12-17 | Janssen Pharmaceutica Nv | Human cell cycle checkpoint proteins |
| US6383744B1 (en) | 1998-07-10 | 2002-05-07 | Incyte Genomics, Inc. | Human checkpoint kinase |
| WO2000016781A1 (en) | 1998-09-18 | 2000-03-30 | Smithkline Beecham Corporation | Chk1 kinase inhibitors |
| PT1140936E (pt) * | 1999-01-11 | 2004-06-30 | Agouron Pharma | Inibidores triciclicos de poli(adp-ribose) polimerases |
| ES2302699T3 (es) | 1999-08-27 | 2008-08-01 | Novartis Vaccines And Diagnostics, Inc. | Oligonucleotidos quimericos antisentido y formulaciones de transfeccion celular de los mismos. |
| ECSP003637A (es) | 1999-08-31 | 2002-03-25 | Agouron Pharma | Inhibidores triciclicos de poli (adp-ribosa) polimerasas |
| US6670167B1 (en) | 1999-11-01 | 2003-12-30 | Agouron Pharmaceuticals, Inc. | Catalytic domain of the human effector cell cycle checkpoint protein kinase materials and methods for identification of inhibitors thereof |
| DE60019318T2 (de) | 1999-09-22 | 2006-03-09 | Canbas Co., Ltd., Numazu | Zusammensetzungen und verfahren zur inhibierung vom zellulären g2-übergang und sensitisierung von zellen gegen dna-schädigenden wirkstoffe |
| US6211164B1 (en) | 2000-03-10 | 2001-04-03 | Abbott Laboratories | Antisense oligonucleotides of the human chk1 gene and uses thereof |
| AU3652102A (en) * | 2000-12-01 | 2002-06-11 | Guilford Pharm Inc | Compounds and their uses |
| UA76977C2 (en) | 2001-03-02 | 2006-10-16 | Icos Corp | Aryl- and heteroaryl substituted chk1 inhibitors and their use as radiosensitizers and chemosensitizers |
| EA009337B1 (ru) * | 2003-01-09 | 2007-12-28 | Пфайзер Инк. | Трициклические соединения, представляющие собой ингибиторы протеинкиназ, для увеличения эффективности противоопухолевых агентов и лучевой терапии |
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2004
- 2004-01-05 EA EA200500893A patent/EA009337B1/ru not_active IP Right Cessation
- 2004-01-05 BR BR0406701-0A patent/BRPI0406701A/pt not_active IP Right Cessation
- 2004-01-05 KR KR1020057012806A patent/KR100697746B1/ko not_active IP Right Cessation
- 2004-01-05 JP JP2006500278A patent/JP3990718B2/ja not_active Expired - Fee Related
- 2004-01-05 ES ES04700145T patent/ES2309484T3/es not_active Expired - Lifetime
- 2004-01-05 OA OA1200500197A patent/OA13017A/en unknown
- 2004-01-05 NZ NZ540638A patent/NZ540638A/en unknown
- 2004-01-05 CA CA2512683A patent/CA2512683C/en not_active Expired - Fee Related
- 2004-01-05 RS YUP-2005/0522A patent/RS20050522A/sr unknown
- 2004-01-05 MX MXPA05007352A patent/MXPA05007352A/es active IP Right Grant
- 2004-01-05 AP AP2005003353A patent/AP2048A/xx active
- 2004-01-05 PT PT04700145T patent/PT1585749E/pt unknown
- 2004-01-05 GE GEAP20048886A patent/GEP20084367B/en unknown
- 2004-01-05 AU AU2004203977A patent/AU2004203977B2/en not_active Ceased
- 2004-01-05 DE DE602004015724T patent/DE602004015724D1/de not_active Expired - Lifetime
- 2004-01-05 CN CN2004800063838A patent/CN1759118B/zh not_active Expired - Fee Related
- 2004-01-05 AT AT04700145T patent/ATE404564T1/de not_active IP Right Cessation
- 2004-01-05 PL PL378372A patent/PL378372A1/pl not_active Application Discontinuation
- 2004-01-05 WO PCT/IB2004/000026 patent/WO2004063198A1/en active IP Right Grant
- 2004-01-05 DK DK04700145T patent/DK1585749T3/da active
- 2004-01-05 EP EP08155745A patent/EP1947102A1/en not_active Withdrawn
- 2004-01-05 EP EP04700145A patent/EP1585749B1/en not_active Expired - Lifetime
- 2004-01-05 SI SI200430830T patent/SI1585749T1/sl unknown
- 2004-01-09 US US10/754,171 patent/US6967198B2/en not_active Expired - Fee Related
- 2004-05-01 UA UAA200506730A patent/UA80733C2/uk unknown
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2005
- 2005-06-08 IL IL169082A patent/IL169082A/en not_active IP Right Cessation
- 2005-06-08 ZA ZA200504674A patent/ZA200504674B/en unknown
- 2005-06-09 IS IS7884A patent/IS7884A/is unknown
- 2005-07-07 HR HR20050624A patent/HRP20050624A2/hr not_active Application Discontinuation
- 2005-07-08 CR CR7899A patent/CR7899A/es unknown
- 2005-07-08 EC EC2005005911A patent/ECSP055911A/es unknown
- 2005-07-08 MA MA28375A patent/MA27703A1/fr unknown
- 2005-07-08 TN TNP2005000176A patent/TNSN05176A1/fr unknown
- 2005-07-22 US US11/187,089 patent/US7132533B2/en not_active Expired - Fee Related
- 2005-08-08 NO NO20053775A patent/NO20053775L/no unknown
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2006
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- 2006-06-23 US US11/426,132 patent/US7462713B2/en not_active Expired - Fee Related
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2008
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