JP2012532100A5 - - Google Patents
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- Publication number
- JP2012532100A5 JP2012532100A5 JP2012517506A JP2012517506A JP2012532100A5 JP 2012532100 A5 JP2012532100 A5 JP 2012532100A5 JP 2012517506 A JP2012517506 A JP 2012517506A JP 2012517506 A JP2012517506 A JP 2012517506A JP 2012532100 A5 JP2012532100 A5 JP 2012532100A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- alkyl
- cycloalkyl
- heterocyclyl
- group
- 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.)
- Granted
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 69
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- -1 trifluoromethoxy, difluoromethoxy Chemical group 0.000 claims description 52
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 47
- 150000001875 compounds Chemical class 0.000 claims description 45
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 39
- 125000004043 oxo group Chemical group O=* 0.000 claims description 39
- 229910052736 halogen Inorganic materials 0.000 claims description 38
- 150000002367 halogens Chemical group 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 37
- 239000012453 solvate Substances 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 32
- DRYRBWIFRVMRPV-UHFFFAOYSA-N quinazolin-4-amine Chemical compound C1=CC=C2C(N)=NC=NC2=C1 DRYRBWIFRVMRPV-UHFFFAOYSA-N 0.000 claims description 32
- 125000004429 atom Chemical group 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 22
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 19
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 17
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 15
- BPXYEYJNCXITEY-UHFFFAOYSA-N diazonio(trifluoromethoxy)azanide Chemical compound FC(F)(F)ON=[N+]=[N-] BPXYEYJNCXITEY-UHFFFAOYSA-N 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 230000003463 hyperproliferative effect Effects 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 7
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 6
- 101150029707 ERBB2 gene Proteins 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 5
- 206010017758 gastric cancer Diseases 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 201000011549 stomach cancer Diseases 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims description 3
- KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical compound [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 claims description 3
- SZJCILCGJYLDID-UHFFFAOYSA-N 6-[5-[(4-methyl-1,4-azaphosphinan-1-yl)methyl]furan-2-yl]-n-[3-methyl-4-(6-methylpyridin-3-yl)oxyphenyl]quinazolin-4-amine Chemical compound C1CP(C)CCN1CC1=CC=C(C=2C=C3C(NC=4C=C(C)C(OC=5C=NC(C)=CC=5)=CC=4)=NC=NC3=CC=2)O1 SZJCILCGJYLDID-UHFFFAOYSA-N 0.000 claims description 2
- SFCWQUHXQVCOQK-UHFFFAOYSA-N 6-[5-[[2-dimethylphosphanylethyl(ethyl)amino]methyl]furan-2-yl]-n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]quinazolin-4-amine Chemical compound O1C(CN(CCP(C)C)CC)=CC=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=C(F)C=CC=5)C4=CC=3)C2=C1 SFCWQUHXQVCOQK-UHFFFAOYSA-N 0.000 claims description 2
- 150000001540 azides Chemical group 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- PSERDZBSHZARJW-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[3-(2-dimethylphosphorylethylamino)prop-1-ynyl]quinazolin-4-amine Chemical compound C12=CC(C#CCNCCP(C)(=O)C)=CC=C2N=CN=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC(F)=C1 PSERDZBSHZARJW-UHFFFAOYSA-N 0.000 claims description 2
- ALTCDLWHAAMADR-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-dimethoxyphosphorylethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCCP(=O)(OC)OC)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 ALTCDLWHAAMADR-UHFFFAOYSA-N 0.000 claims description 2
- WZTNHMOZMRMQJP-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(dimethylphosphorylmethylamino)methyl]furan-2-yl]quinazolin-4-amine Chemical compound O1C(CNCP(C)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 WZTNHMOZMRMQJP-UHFFFAOYSA-N 0.000 claims description 2
- ZOKOPJAIVDTBRI-UHFFFAOYSA-N n-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[[4-(dimethylphosphorylmethyl)piperazin-1-yl]methyl]furan-2-yl]quinazolin-4-amine Chemical compound C1CN(CP(C)(=O)C)CCN1CC1=CC=C(C=2C=C3C(NC=4C=C(Cl)C(OCC=5C=C(F)C=CC=5)=CC=4)=NC=NC3=CC=2)O1 ZOKOPJAIVDTBRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000004437 phosphorous atom Chemical group 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 2
- FSUZZBKJXRIBMD-UHFFFAOYSA-N 2-[2-dimethylphosphorylethyl-[[5-[4-[[1-[(3-fluorophenyl)methyl]indazol-5-yl]amino]quinazolin-6-yl]furan-2-yl]methyl]amino]ethanol Chemical compound O1C(CN(CCO)CCP(C)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=C(F)C=CC=5)C4=CC=3)C2=C1 FSUZZBKJXRIBMD-UHFFFAOYSA-N 0.000 claims 1
- NJONAMZJCQXASF-UHFFFAOYSA-N 6-[5-[(2-dimethylphosphorylethylamino)methyl]furan-2-yl]-n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]quinazolin-4-amine Chemical class O1C(CNCCP(C)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C4C=NN(CC=5C=C(F)C=CC=5)C4=CC=3)C2=C1 NJONAMZJCQXASF-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 description 5
- 0 C*(c1ccc(*)[o]1)=C Chemical compound C*(c1ccc(*)[o]1)=C 0.000 description 3
- WXKJDVKKRORIGP-UHFFFAOYSA-N CC(N(CCP(C)(C)=O)CC1=CC=C(C(C=C23)=CC=C2N=CN=C3NC2=CC=C3N(CC4=CC(F)=CC=C4)N=CC3=C2)O1)O Chemical compound CC(N(CCP(C)(C)=O)CC1=CC=C(C(C=C23)=CC=C2N=CN=C3NC2=CC=C3N(CC4=CC(F)=CC=C4)N=CC3=C2)O1)O WXKJDVKKRORIGP-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22255109P | 2009-07-02 | 2009-07-02 | |
| US61/222,551 | 2009-07-02 | ||
| PCT/US2010/001897 WO2011002523A1 (en) | 2009-07-02 | 2010-07-02 | Phosphorus containing quinazoline compounds and methods of use |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2012532100A JP2012532100A (ja) | 2012-12-13 |
| JP2012532100A5 true JP2012532100A5 (https=) | 2013-08-15 |
| JP5721709B2 JP5721709B2 (ja) | 2015-05-20 |
Family
ID=43411348
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012517506A Active JP5721709B2 (ja) | 2009-07-02 | 2010-07-02 | リンを含むキナゾリン化合物および使用方法 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8987284B2 (https=) |
| EP (1) | EP2448409A4 (https=) |
| JP (1) | JP5721709B2 (https=) |
| KR (1) | KR20120090025A (https=) |
| CN (1) | CN102711472B (https=) |
| AU (1) | AU2010266725A1 (https=) |
| BR (1) | BRPI1015363A2 (https=) |
| CA (1) | CA2804190A1 (https=) |
| IL (1) | IL217222A0 (https=) |
| MX (1) | MX2012000166A (https=) |
| RU (1) | RU2012103492A (https=) |
| SG (1) | SG177451A1 (https=) |
| WO (1) | WO2011002523A1 (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG177451A1 (en) | 2009-07-02 | 2012-02-28 | Newgen Therapeutics Inc | Phosphorus containing quinazoline compounds and methods of use |
| US8916574B2 (en) | 2009-09-28 | 2014-12-23 | Qilu Pharmaceutical Co., Ltd. | 4-(substituted anilino)-quinazoline derivatives useful as tyrosine kinase inhibitors |
| EP2714703B1 (en) | 2011-05-31 | 2021-03-10 | Newgen Therapeutics, Inc. | Tricyclic inhibitors of poly(adp-ribose)polymerase |
| CN103772411B (zh) * | 2013-04-28 | 2016-08-03 | 复旦大学 | 含硫6-呋喃基喹唑啉-4-胺化合物及其制备方法和用途 |
| CN104558040B (zh) * | 2015-01-30 | 2017-04-05 | 江苏康缘药业股份有限公司 | 含磷取代的喹唑啉衍生物的晶型及其制备方法和应用 |
| CN104558043B (zh) * | 2015-01-30 | 2017-01-11 | 江苏康缘药业股份有限公司 | 含磷取代的喹唑啉衍生物的新晶型及其制备方法和应用 |
| CN104610364B (zh) * | 2015-01-30 | 2017-03-29 | 江苏康缘药业股份有限公司 | 含磷取代的喹唑啉衍生物的新晶型及其制备方法和应用 |
| CN104558042B (zh) * | 2015-01-30 | 2017-03-29 | 江苏康缘药业股份有限公司 | 含磷取代的喹唑啉衍生物的新晶型及其制备方法和应用 |
| CN104558041B (zh) * | 2015-01-30 | 2017-01-11 | 江苏康缘药业股份有限公司 | 含磷取代的喹唑啉衍生物的新晶型及其制备方法和应用 |
| CN105388242A (zh) * | 2015-11-11 | 2016-03-09 | 江苏康缘药业股份有限公司 | 二对甲苯磺酸缘生替尼原料药中残留溶剂的检测方法 |
| CN105424831B (zh) * | 2015-11-11 | 2017-11-10 | 江苏康缘药业股份有限公司 | 二对甲苯磺酸缘生替尼原料药中有效成分的定量检测方法 |
| CN105237573B (zh) * | 2015-11-11 | 2017-10-24 | 江苏康缘药业股份有限公司 | 二对甲苯磺酸缘生替尼的制备方法 |
| CN105606717B (zh) * | 2015-11-11 | 2017-10-24 | 江苏康缘药业股份有限公司 | 二对甲苯磺酸缘生替尼原料药中有关物质的检测方法 |
| CN108285421A (zh) * | 2018-01-26 | 2018-07-17 | 黑龙江鑫创生物科技开发有限公司 | 一种微通道反应器合成拉帕替尼中间体的方法 |
| EP4013749B1 (en) | 2019-08-15 | 2026-03-11 | Black Diamond Therapeutics, Inc. | Alkynyl quinazoline compounds |
| CN113995728B (zh) * | 2020-07-28 | 2023-03-14 | 江苏康缘药业股份有限公司 | 一种药物组合物及制备方法 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ID19609A (id) | 1996-07-13 | 1998-07-23 | Glaxo Group Ltd | Senyawa-senyawa heterosiklik |
| TR200102505T2 (tr) * | 1999-02-27 | 2003-01-21 | Boehringer Ingelheim Pharma Kg | 4-amino-kinazolin ve kinolin türevleri. |
| DE19911509A1 (de) | 1999-03-15 | 2000-09-21 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| ATE377597T1 (de) | 1999-07-09 | 2007-11-15 | Glaxo Group Ltd | Anilinochinazoline als protein-tyrosin- kinasehemmer |
| US6894057B2 (en) | 2002-03-08 | 2005-05-17 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| DE10217689A1 (de) | 2002-04-19 | 2003-11-13 | Boehringer Ingelheim Pharma | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, ihre Verwendung und Verfahren zu ihrer Herstellung |
| AU2003231765B9 (en) | 2002-04-26 | 2010-01-28 | Gilead Sciences, Inc. | Cellular accumulation of phosphonate analogs of HIV protease inhibitor compounds and the compounds as such |
| WO2004046101A2 (en) | 2002-11-20 | 2004-06-03 | Array Biopharma, Inc. | Cyanoguanidines and cyanoamidines as erbb2 and egfr inhibitors |
| DE10307165A1 (de) | 2003-02-20 | 2004-09-02 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, ihre Verwendung und Verfahren zu ihrer Herstellung |
| US7223749B2 (en) * | 2003-02-20 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
| DE10349113A1 (de) * | 2003-10-17 | 2005-05-12 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung von Aminocrotonylverbindungen |
| JP2007510667A (ja) | 2003-11-07 | 2007-04-26 | スミスクライン ビーチャム （コーク） リミテッド | 癌の治療法 |
| US20070208023A1 (en) * | 2004-04-16 | 2007-09-06 | Smithkline Beecham Corporation | Cancer Treatment Method |
| KR20080098490A (ko) | 2006-01-13 | 2008-11-10 | 파마시클릭스, 인코포레이티드 | 티로신 키나제 억제제 및 이의 용도 |
| JP5241513B2 (ja) * | 2006-01-26 | 2013-07-17 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | アミノクロトニルアミノ置換キナゾリン誘導体の合成方法 |
| US20080234267A1 (en) | 2007-03-20 | 2008-09-25 | Karen Elizabeth Lackey | Compounds and Methods of Treatment |
| SG177451A1 (en) | 2009-07-02 | 2012-02-28 | Newgen Therapeutics Inc | Phosphorus containing quinazoline compounds and methods of use |
-
2010
- 2010-07-02 SG SG2011097581A patent/SG177451A1/en unknown
- 2010-07-02 CA CA2804190A patent/CA2804190A1/en not_active Abandoned
- 2010-07-02 WO PCT/US2010/001897 patent/WO2011002523A1/en not_active Ceased
- 2010-07-02 KR KR1020127002859A patent/KR20120090025A/ko not_active Withdrawn
- 2010-07-02 BR BRPI1015363-2A patent/BRPI1015363A2/pt not_active IP Right Cessation
- 2010-07-02 JP JP2012517506A patent/JP5721709B2/ja active Active
- 2010-07-02 RU RU2012103492/04A patent/RU2012103492A/ru not_active Application Discontinuation
- 2010-07-02 MX MX2012000166A patent/MX2012000166A/es not_active Application Discontinuation
- 2010-07-02 AU AU2010266725A patent/AU2010266725A1/en not_active Abandoned
- 2010-07-02 US US13/380,808 patent/US8987284B2/en active Active
- 2010-07-02 CN CN201080039138.2A patent/CN102711472B/zh active Active
- 2010-07-02 EP EP10794499.3A patent/EP2448409A4/en not_active Withdrawn
-
2011
- 2011-12-27 IL IL217222A patent/IL217222A0/en unknown
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