TW202304908A - 四氫吡啶并嘧啶化合物 - Google Patents
四氫吡啶并嘧啶化合物 Download PDFInfo
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- TW202304908A TW202304908A TW111113796A TW111113796A TW202304908A TW 202304908 A TW202304908 A TW 202304908A TW 111113796 A TW111113796 A TW 111113796A TW 111113796 A TW111113796 A TW 111113796A TW 202304908 A TW202304908 A TW 202304908A
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- Taiwan
- Prior art keywords
- oxy
- fluorophenyl
- tetrahydropyrimidine
- pyrimidin
- tetrahydropyrido
- Prior art date
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- -1 Tetrahydropyridopyrimidine compound Chemical class 0.000 title claims abstract description 192
- 150000001875 compounds Chemical class 0.000 claims description 229
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 105
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 100
- 150000003839 salts Chemical class 0.000 claims description 35
- 239000003112 inhibitor Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- WJXZFAHQZCAGHQ-UHFFFAOYSA-N CN(CC1)CCC1N(CC1)CC2=C1C(OC(C=C1)=CC=C1NC(C(C(N1C(C=C3)=CC=C3F)=O)=CN(CC3CC3)C1=O)=O)=NC=N2 Chemical compound CN(CC1)CCC1N(CC1)CC2=C1C(OC(C=C1)=CC=C1NC(C(C(N1C(C=C3)=CC=C3F)=O)=CN(CC3CC3)C1=O)=O)=NC=N2 WJXZFAHQZCAGHQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000002246 antineoplastic agent Substances 0.000 claims description 4
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims 1
- WYEUDIXCTGHYOQ-UHFFFAOYSA-N N-[3-fluoro-4-[[7-(1-methylpiperidine-4-carbonyl)-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]oxy]phenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide Chemical compound CC(C)N(C=C(C(NC(C=C1)=CC(F)=C1OC1=NC=NC(C2)=C1CCN2C(C1CCN(C)CC1)=O)=O)C(N1C(C=C2)=CC=C2F)=O)C1=O WYEUDIXCTGHYOQ-UHFFFAOYSA-N 0.000 claims 1
- KHOIPUORMKAOKA-UHFFFAOYSA-N N-[4-[[7-(cyclobutanecarbonyl)-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]oxy]-3-fluorophenyl]-3-(4-fluorophenyl)-2,4-dioxo-1-propan-2-ylpyrimidine-5-carboxamide Chemical compound CC(C)N(C=C(C(NC(C=C1)=CC(F)=C1OC1=NC=NC(C2)=C1CCN2C(C1CCC1)=O)=O)C(N1C(C=C2)=CC=C2F)=O)C1=O KHOIPUORMKAOKA-UHFFFAOYSA-N 0.000 claims 1
- XUWPSMYXXJRCCG-UHFFFAOYSA-N O=C(C1CC1)N(CC1)CC2=C1C(OC(C=CC(NC(C(C(N1C(C=C3)=CC=C3F)=O)=CN(C3CC3)C1=O)=O)=C1)=C1F)=NC=N2 Chemical compound O=C(C1CC1)N(CC1)CC2=C1C(OC(C=CC(NC(C(C(N1C(C=C3)=CC=C3F)=O)=CN(C3CC3)C1=O)=O)=C1)=C1F)=NC=N2 XUWPSMYXXJRCCG-UHFFFAOYSA-N 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 718
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 405
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- 239000000243 solution Substances 0.000 description 237
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- 239000012044 organic layer Substances 0.000 description 215
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 189
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 142
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- RXBYRTSOWREATF-UHFFFAOYSA-N 1,2,3,4-tetrahydroacridine Chemical compound C1=CC=C2C=C(CCCC3)C3=NC2=C1 RXBYRTSOWREATF-UHFFFAOYSA-N 0.000 description 16
- 239000002244 precipitate Substances 0.000 description 16
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
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- 108091000080 Phosphotransferase Proteins 0.000 description 12
- 102000020233 phosphotransferase Human genes 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- WGJUBVJZKNTGRC-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2CNCCC2=C1 WGJUBVJZKNTGRC-UHFFFAOYSA-N 0.000 description 11
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 11
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- WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 10
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000005222 photoaffinity labeling Methods 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 239000012460 protein solution Substances 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 229910001426 radium ion Inorganic materials 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- GACGLJQNRZCHSH-UHFFFAOYSA-N tert-butyl 1,2-diazaspiro[3.3]heptane-2-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1NC2(C1)CCC2 GACGLJQNRZCHSH-UHFFFAOYSA-N 0.000 description 1
- PSRHRFNKESVOEL-UHFFFAOYSA-N tert-butyl 4-(2-oxoethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC=O)CC1 PSRHRFNKESVOEL-UHFFFAOYSA-N 0.000 description 1
- UHNCQJLEINZUNT-UHFFFAOYSA-N tert-butyl 4-oxo-1,5,6,8-tetrahydropyrido[3,4-d]pyrimidine-7-carboxylate Chemical compound N1=CNC(=O)C2=C1CN(C(=O)OC(C)(C)C)CC2 UHNCQJLEINZUNT-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- 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
- A61K31/495—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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021-068414 | 2021-04-14 | ||
| JP2021068414 | 2021-04-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202304908A true TW202304908A (zh) | 2023-02-01 |
Family
ID=83640095
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW111113796A TW202304908A (zh) | 2021-04-14 | 2022-04-12 | 四氫吡啶并嘧啶化合物 |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPWO2022220227A1 (enrdf_load_stackoverflow) |
| TW (1) | TW202304908A (enrdf_load_stackoverflow) |
| WO (1) | WO2022220227A1 (enrdf_load_stackoverflow) |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20140378T1 (en) * | 2006-12-29 | 2014-05-23 | Rigel Pharmaceuticals, Inc. | Polycyclic heteroaryl substituted triazoles useful as axl inhibitors |
| US8349838B2 (en) * | 2008-07-09 | 2013-01-08 | Rigel Pharmaceuticals, Inc. | Polycyclic heteroaryl substituted triazoles useful as Axl inhibitors |
| CA2749843C (en) * | 2009-01-16 | 2017-09-05 | Rigel Pharmaceuticals, Inc. | Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer |
| ES2937952T3 (es) * | 2011-04-01 | 2023-04-03 | Univ Utah Res Found | Análogos de N-fenilpirimidina-2-amina sustituidos como inhibidores de la cinasa AXL |
| KR20140090678A (ko) * | 2011-11-14 | 2014-07-17 | 세파론, 인코포레이티드 | AXL 및 c-MET 키나제 억제제로서의 우라실 유도체 |
| SMT201700065T1 (it) * | 2012-01-31 | 2017-03-08 | Daiichi Sankyo Co Ltd | Derivato piridonico |
| TWI649308B (zh) * | 2013-07-24 | 2019-02-01 | 小野藥品工業股份有限公司 | 喹啉衍生物 |
| MY193536A (en) * | 2014-02-04 | 2022-10-18 | Astellas Pharma Inc | Pharmaceutical composition comprising diamino heterocyclic carboxamide compound as active ingredient |
| TWI690525B (zh) * | 2014-07-07 | 2020-04-11 | 日商第一三共股份有限公司 | 具有四氫吡喃基甲基之吡啶酮衍生物及其用途 |
| EP3233829B1 (en) * | 2014-12-18 | 2019-08-14 | Pfizer Inc | Pyrimidine and triazine derivatives and their use as axl inhibitors |
-
2022
- 2022-04-12 WO PCT/JP2022/017548 patent/WO2022220227A1/ja not_active Ceased
- 2022-04-12 TW TW111113796A patent/TW202304908A/zh unknown
- 2022-04-12 JP JP2023514646A patent/JPWO2022220227A1/ja not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| WO2022220227A1 (ja) | 2022-10-20 |
| JPWO2022220227A1 (enrdf_load_stackoverflow) | 2022-10-20 |
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