CA2779184A1 - Inhibiteurs de proteine kinase - Google Patents
Inhibiteurs de proteine kinase Download PDFInfo
- Publication number
- CA2779184A1 CA2779184A1 CA2779184A CA2779184A CA2779184A1 CA 2779184 A1 CA2779184 A1 CA 2779184A1 CA 2779184 A CA2779184 A CA 2779184A CA 2779184 A CA2779184 A CA 2779184A CA 2779184 A1 CA2779184 A1 CA 2779184A1
- Authority
- CA
- Canada
- Prior art keywords
- mmol
- compound
- alkyl
- added
- substituted
- 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.)
- Abandoned
Links
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 title description 2
- 239000003909 protein kinase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 10
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 abstract description 12
- 102000001253 Protein Kinase Human genes 0.000 abstract description 11
- 108060006633 protein kinase Proteins 0.000 abstract description 11
- 239000000543 intermediate Substances 0.000 description 99
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 43
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
- 230000002829 reductive effect Effects 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 238000000746 purification Methods 0.000 description 24
- 239000007787 solid Substances 0.000 description 23
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
- 108091000080 Phosphotransferase Proteins 0.000 description 20
- -1 cornpositions Substances 0.000 description 20
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- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
- 150000003839 salts Chemical class 0.000 description 14
- 239000003039 volatile agent Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 12
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- 125000001424 substituent group Chemical group 0.000 description 11
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- 235000019270 ammonium chloride Nutrition 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
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- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
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- 125000004122 cyclic group Chemical group 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 229940125904 compound 1 Drugs 0.000 description 8
- 150000002431 hydrogen Chemical class 0.000 description 8
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 229910000024 caesium carbonate Inorganic materials 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000012230 colorless oil Substances 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- 125000000392 cycloalkenyl group Chemical group 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
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- 238000004366 reverse phase liquid chromatography Methods 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 4
- 229940126657 Compound 17 Drugs 0.000 description 4
- 241000282414 Homo sapiens Species 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 4
- 239000002585 base Substances 0.000 description 4
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- 239000000284 extract Substances 0.000 description 4
- 125000001183 hydrocarbyl group Chemical group 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
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- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 4
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- 238000010189 synthetic method Methods 0.000 description 4
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- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 3
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
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
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (13)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2779184A CA2779184A1 (fr) | 2012-05-31 | 2012-05-31 | Inhibiteurs de proteine kinase |
| US14/404,497 US9796716B2 (en) | 2012-05-31 | 2013-05-28 | Selective inhibitors of Tec and Src protein kinase families |
| KR1020197011438A KR20190043648A (ko) | 2012-05-31 | 2013-05-28 | 단백질 키나제 저해제 |
| EP13796590.1A EP2855484A4 (fr) | 2012-05-31 | 2013-05-28 | Inhibiteurs de protéine kinases |
| RU2014145285A RU2678767C2 (ru) | 2012-05-31 | 2013-05-28 | Ингибиторы протеинкиназ |
| CA2874211A CA2874211A1 (fr) | 2012-05-31 | 2013-05-28 | Inhibiteurs de proteine kinases |
| CN201380028248.2A CN104379586B (zh) | 2012-05-31 | 2013-05-28 | 蛋白激酶抑制剂 |
| KR1020147036372A KR101972990B1 (ko) | 2012-05-31 | 2013-05-28 | 단백질 키나제 저해제 |
| PCT/CA2013/000513 WO2013177668A1 (fr) | 2012-05-31 | 2013-05-28 | Inhibiteurs de protéine kinases |
| IN2338MUN2014 IN2014MN02338A (fr) | 2012-05-31 | 2013-05-28 | |
| BR112014029718A BR112014029718A2 (pt) | 2012-05-31 | 2013-05-28 | inibidores da proteína quinase |
| JP2015514295A JP6175495B2 (ja) | 2012-05-31 | 2013-05-28 | プロテインキナーゼ阻害薬 |
| HK15109229.7A HK1208460A1 (en) | 2012-05-31 | 2015-09-18 | Protein kinase inhibitors |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2779184A CA2779184A1 (fr) | 2012-05-31 | 2012-05-31 | Inhibiteurs de proteine kinase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2779184A1 true CA2779184A1 (fr) | 2013-11-30 |
Family
ID=49714083
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2779184A Abandoned CA2779184A1 (fr) | 2012-05-31 | 2012-05-31 | Inhibiteurs de proteine kinase |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2779184A1 (fr) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015074138A1 (fr) * | 2013-11-21 | 2015-05-28 | Pharmascience Inc. | Inhibiteurs de protéines kinases |
| WO2015077866A1 (fr) * | 2013-11-26 | 2015-06-04 | Pharmascience Inc. | Inhibiteurs de protéines kinases |
| WO2016187723A1 (fr) * | 2015-05-27 | 2016-12-01 | Pharmascience Inc. | Inhibiteurs de la famille des enzymes kinases tec |
| CN108290850A (zh) * | 2015-12-07 | 2018-07-17 | Dic株式会社 | 聚合性化合物的制造方法 |
-
2012
- 2012-05-31 CA CA2779184A patent/CA2779184A1/fr not_active Abandoned
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015074138A1 (fr) * | 2013-11-21 | 2015-05-28 | Pharmascience Inc. | Inhibiteurs de protéines kinases |
| US9822120B2 (en) | 2013-11-21 | 2017-11-21 | Pharmascience Inc. | Protein kinase inhibitors |
| WO2015077866A1 (fr) * | 2013-11-26 | 2015-06-04 | Pharmascience Inc. | Inhibiteurs de protéines kinases |
| WO2016187723A1 (fr) * | 2015-05-27 | 2016-12-01 | Pharmascience Inc. | Inhibiteurs de la famille des enzymes kinases tec |
| CN108290850A (zh) * | 2015-12-07 | 2018-07-17 | Dic株式会社 | 聚合性化合物的制造方法 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20150602 |
|
| FZDE | Discontinued |
Effective date: 20150602 |