AU2009274256B2 - Amidophenoxyindazoles useful as inhibitors of c-Met - Google Patents
Amidophenoxyindazoles useful as inhibitors of c-Met Download PDFInfo
- Publication number
- AU2009274256B2 AU2009274256B2 AU2009274256A AU2009274256A AU2009274256B2 AU 2009274256 B2 AU2009274256 B2 AU 2009274256B2 AU 2009274256 A AU2009274256 A AU 2009274256A AU 2009274256 A AU2009274256 A AU 2009274256A AU 2009274256 B2 AU2009274256 B2 AU 2009274256B2
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- Australia
- Prior art keywords
- methyl
- mmol
- fluoro
- indazol
- oxo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- OQEBGEOZZFMBAA-UHFFFAOYSA-N ethyl 1-(4-fluorophenyl)-4-methyl-2-oxopyridine-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(C)C=CN1C1=CC=C(F)C=C1 OQEBGEOZZFMBAA-UHFFFAOYSA-N 0.000 description 1
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- JVRMHJVBDNCXMM-UHFFFAOYSA-N ethyl 4,6-dimethyl-2-oxo-1-phenylpyridine-3-carboxylate Chemical compound O=C1C(C(=O)OCC)=C(C)C=C(C)N1C1=CC=CC=C1 JVRMHJVBDNCXMM-UHFFFAOYSA-N 0.000 description 1
- REVDPJKCGIMABK-UHFFFAOYSA-N ethyl 5-(2-fluoro-4-nitrophenoxy)-1-methylindazole-6-carboxylate Chemical compound CCOC(=O)C1=CC=2N(C)N=CC=2C=C1OC1=CC=C([N+]([O-])=O)C=C1F REVDPJKCGIMABK-UHFFFAOYSA-N 0.000 description 1
- YQOSIYRTYFQAAK-UHFFFAOYSA-N ethyl 5-(2-fluoro-4-nitrophenoxy)-1h-indazole-6-carboxylate Chemical compound CCOC(=O)C1=CC=2NN=CC=2C=C1OC1=CC=C([N+]([O-])=O)C=C1F YQOSIYRTYFQAAK-UHFFFAOYSA-N 0.000 description 1
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- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
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- AIVFTAPXWGSQGN-UHFFFAOYSA-N n-[4-[6-(benzhydrylamino)-1-methylindazol-5-yl]oxy-3-fluorophenyl]-1-(4-fluorophenyl)-6-methyl-2-oxopyridine-3-carboxamide Chemical compound O=C1N(C=2C=CC(F)=CC=2)C(C)=CC=C1C(=O)NC(C=C1F)=CC=C1OC1=CC=2C=NN(C)C=2C=C1NC(C=1C=CC=CC=1)C1=CC=CC=C1 AIVFTAPXWGSQGN-UHFFFAOYSA-N 0.000 description 1
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- XHXVAJHZTIXQQD-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]-5-[(4-butoxyphenyl)methyl]-2,6-dimethylpyrimidin-4-amine Chemical compound C1=CC(OCCCC)=CC=C1CC1=C(C)N=C(C)N=C1NP(=O)(N1CC1)N1CC1 XHXVAJHZTIXQQD-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- WHYQCQRHPQBZHM-UHFFFAOYSA-N pyrazole-1-carboxylic acid Chemical compound OC(=O)N1C=CC=N1 WHYQCQRHPQBZHM-UHFFFAOYSA-N 0.000 description 1
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
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- 238000002390 rotary evaporation Methods 0.000 description 1
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- 210000002966 serum Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
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- IPISOFJLWYBCAV-UHFFFAOYSA-N tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-carboxylate Chemical compound C1=NN(C(=O)OC(C)(C)C)C=C1B1OC(C)(C)C(C)(C)O1 IPISOFJLWYBCAV-UHFFFAOYSA-N 0.000 description 1
- PEINCCVZOINAMV-UHFFFAOYSA-N tert-butyl 4-[5-(2-fluoro-4-nitrophenoxy)-1-methylindazol-6-yl]pyrazole-1-carboxylate 5-(2-fluoro-4-nitrophenoxy)-1-methyl-6-(1H-pyrazol-4-yl)indazole Chemical compound FC1=C(OC=2C=C3C=NN(C3=CC2C=2C=NNC2)C)C=CC(=C1)[N+](=O)[O-].FC1=C(OC=2C=C3C=NN(C3=CC2C=2C=NN(C2)C(=O)OC(C)(C)C)C)C=CC(=C1)[N+](=O)[O-] PEINCCVZOINAMV-UHFFFAOYSA-N 0.000 description 1
- CMNHMRCJSHRCRI-UHFFFAOYSA-N tert-butyl n-[5-(2-fluoro-4-nitrophenoxy)-1-methylindazol-6-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC=1C=C2N(C)N=CC2=CC=1OC1=CC=C([N+]([O-])=O)C=C1F CMNHMRCJSHRCRI-UHFFFAOYSA-N 0.000 description 1
- JDDZBVOSDZEVBG-UHFFFAOYSA-N tert-butyl n-[5-(4-amino-2-fluorophenoxy)-1-methylindazol-6-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC=1C=C2N(C)N=CC2=CC=1OC1=CC=C(N)C=C1F JDDZBVOSDZEVBG-UHFFFAOYSA-N 0.000 description 1
- YRWMJOLPABFTDZ-UHFFFAOYSA-N tert-butyl n-[5-[2-fluoro-4-[(6-methyl-2-oxo-1-phenylpyridine-3-carbonyl)amino]phenoxy]-1h-indazol-6-yl]carbamate Chemical compound CC1=CC=C(C(=O)NC=2C=C(F)C(OC=3C(=CC=4NN=CC=4C=3)NC(=O)OC(C)(C)C)=CC=2)C(=O)N1C1=CC=CC=C1 YRWMJOLPABFTDZ-UHFFFAOYSA-N 0.000 description 1
- 150000003527 tetrahydropyrans Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—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
- A61K31/4427—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
-
- 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
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8329408P | 2008-07-24 | 2008-07-24 | |
| US61/083,294 | 2008-07-24 | ||
| US8508208P | 2008-07-31 | 2008-07-31 | |
| US61/085,082 | 2008-07-31 | ||
| US10865908P | 2008-10-27 | 2008-10-27 | |
| US61/108,659 | 2008-10-27 | ||
| PCT/US2009/050640 WO2010011538A1 (en) | 2008-07-24 | 2009-07-15 | Amidophenoxyindazoles useful as inhibitors of c-met |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2009274256A1 AU2009274256A1 (en) | 2010-01-28 |
| AU2009274256B2 true AU2009274256B2 (en) | 2013-07-11 |
Family
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| ES2590778T3 (es) | 2011-02-28 | 2016-11-23 | Calitor Sciences, Llc | Compuestos de quinolina sustituida |
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| KR20130118612A (ko) * | 2012-04-20 | 2013-10-30 | (주)네오믹스 | 신규한 아미노피리딘 유도체 및 이의 용도 |
| EP2870178B1 (en) * | 2012-05-09 | 2017-07-12 | Eli Lilly and Company | Anti-c-met antibodies |
| JP6433922B2 (ja) * | 2013-02-27 | 2018-12-05 | アレイ バイオファーマ、インコーポレイテッド | インダゾール誘導体の調製に使用するための中間体およびその調製方法 |
| CN104140393B (zh) * | 2013-12-10 | 2016-09-21 | 郑州泰基鸿诺医药股份有限公司 | 一种芳环/芳杂环叔丁醇酯类化合物的制备方法 |
| WO2015164161A1 (en) | 2014-04-22 | 2015-10-29 | Calitor Sciences, Llc | Bicylcic pyrazolone compounds and methods of use |
| TW201716085A (zh) * | 2015-08-12 | 2017-05-16 | 應克隆公司 | 癌症之組合療法 |
| US20190336599A1 (en) * | 2016-04-15 | 2019-11-07 | Eli Lilly And Company | Combination of ramucirumab and merestinib for use in treatment of colorectal cancer |
| EP3464380B1 (en) | 2016-06-02 | 2024-11-06 | Immunocore Limited | Dosing regimen for gp100-specific tcr - anti-cd3 scfv fusion protein |
| CN109562282A (zh) * | 2016-07-29 | 2019-04-02 | 伊莱利利公司 | 用于治疗癌症的使用merestinib和抗-pd-l1或抗-pd-1抑制剂的组合疗法 |
| CN108069938A (zh) * | 2016-11-15 | 2018-05-25 | 中国药科大学 | 2,4-二取代吡啶类化合物及其制备方法和应用 |
| CN109982700A (zh) * | 2016-11-16 | 2019-07-05 | 伊莱利利公司 | 具有外显子14跳跃突变或外显子14跳跃表型的癌症的治疗 |
| EP3541383B1 (en) | 2016-11-16 | 2021-01-06 | Eli Lilly and Company | Combination therapy for cancer with exon 14 skipping mutation(s) or exon 14 skipping phenotype |
| CN107382968A (zh) * | 2017-07-06 | 2017-11-24 | 北京万全德众医药生物技术有限公司 | 一种吲哚类c‑Met抑制剂的制备方法 |
| CN107311983A (zh) * | 2017-07-06 | 2017-11-03 | 北京万全德众医药生物技术有限公司 | 吲哚类小分子c‑met抑制剂 |
| US10180422B1 (en) | 2017-08-22 | 2019-01-15 | Scripps Health | Methods of treating a neuroendocrine tumor |
| EP3480201A1 (en) | 2017-11-06 | 2019-05-08 | Oncostellae, S.L. | New analogs as androgen receptor and glucocorticoid receptor modulators |
| EP3719012B1 (en) | 2017-11-24 | 2024-03-06 | Medshine Discovery Inc. | N-[4-[(2-amino-4-pyridinyl)oxy]-3-fluorophenyl]-3-(4-fluorophenyl)-1,2,3,4-tetrahydro-2,4-dioxo-5-pyrimidinecarboxamide derivatives as c-met/axl inhibitors for the treatment of tumors |
| US20210177828A1 (en) * | 2018-01-17 | 2021-06-17 | Nanjing Transthera Biosciences Co., Ltd. | Tam family kinase /and csf1r kinase inhibitor and use thereof |
| AU2019237715B2 (en) | 2018-03-08 | 2021-01-28 | Wellmarker Bio Co., Ltd. | Thienopyridine derivatives and pharmaceutical composition comprising same |
| EP3842425B1 (en) * | 2018-08-24 | 2024-05-22 | TransThera Sciences (Nanjing), Inc. | Novel quinoline derivative inhibitor |
| CN112739691B (zh) * | 2018-09-03 | 2023-05-23 | 泰励生物科技（上海）有限公司 | 用作抗癌药的trk抑制剂 |
| CN112771053A (zh) | 2019-09-06 | 2021-05-07 | 伟迈可生物有限公司 | 基于生物标志物的治疗组合物 |
| CN117355533A (zh) * | 2021-06-22 | 2024-01-05 | 株式会社Lg化学 | 作为蛋白激酶抑制剂的新型化合物 |
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