JP2014528436A5 - - Google Patents
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- Publication number
- JP2014528436A5 JP2014528436A5 JP2014533911A JP2014533911A JP2014528436A5 JP 2014528436 A5 JP2014528436 A5 JP 2014528436A5 JP 2014533911 A JP2014533911 A JP 2014533911A JP 2014533911 A JP2014533911 A JP 2014533911A JP 2014528436 A5 JP2014528436 A5 JP 2014528436A5
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- dioxide
- dihydrothieno
- urea
- methylmorpholino
- 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
Links
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 152
- -1 8-oxa-3-azabicyclo [3.2.1] octan-3-yl Chemical group 0.000 claims description 142
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 100
- 239000004202 carbamide Substances 0.000 claims description 100
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 80
- 150000001875 compounds Chemical class 0.000 claims description 75
- 125000000217 alkyl group Chemical group 0.000 claims description 69
- 229910052736 halogen Inorganic materials 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 7
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 claims description 5
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 206010052779 Transplant rejections Diseases 0.000 claims description 3
- 208000036142 Viral infection Diseases 0.000 claims description 3
- 230000000172 allergic effect Effects 0.000 claims description 3
- 208000010668 atopic eczema Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 208000016097 disease of metabolism Diseases 0.000 claims description 3
- 208000024908 graft versus host disease Diseases 0.000 claims description 3
- 230000001900 immune effect Effects 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 208000030159 metabolic disease Diseases 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 230000002062 proliferating effect Effects 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 230000009385 viral infection Effects 0.000 claims description 3
- CBOPGLRBWYFSAV-ZDUSSCGKSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-5,7-dihydrothieno[3,4-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CSC2 CBOPGLRBWYFSAV-ZDUSSCGKSA-N 0.000 claims description 2
- OWRMWXQMGOZNPC-AWEZNQCLSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-7,8-dihydro-5h-thiopyrano[4,3-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1CSCC2 OWRMWXQMGOZNPC-AWEZNQCLSA-N 0.000 claims description 2
- DTRRFSMNAUOSAH-AWEZNQCLSA-N 1-cyclopropyl-3-[4-[4-[(3s)-3-methylmorpholin-4-yl]-7,8-dihydro-6h-thiopyrano[3,2-d]pyrimidin-2-yl]phenyl]urea Chemical compound C[C@H]1COCCN1C1=NC(C=2C=CC(NC(=O)NC3CC3)=CC=2)=NC2=C1SCCC2 DTRRFSMNAUOSAH-AWEZNQCLSA-N 0.000 claims description 2
- HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 claims description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000006001 difluoroethyl group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
- 125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 208000026278 immune system disease Diseases 0.000 claims 2
- 208000027866 inflammatory disease Diseases 0.000 claims 2
- 230000002503 metabolic effect Effects 0.000 claims 2
- MNILDQSRDHCFJG-UHFFFAOYSA-N 3-oxa-8-azabicyclo[3.2.1]octane Chemical compound C1OCC2CCC1N2 MNILDQSRDHCFJG-UHFFFAOYSA-N 0.000 claims 1
- 206010057249 Phagocytosis Diseases 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 230000008782 phagocytosis Effects 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- 125000001153 fluoro group Chemical group F* 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000003566 oxetanyl group Chemical group 0.000 description 2
- 102000003954 Autophagy-Related Proteins Human genes 0.000 description 1
- 108010082399 Autophagy-Related Proteins Proteins 0.000 description 1
- 0 CC(C)CC(C)(C)CN(CC(C)(CO)*I*)c1c(C)c(I*)nc([Tl])n1 Chemical compound CC(C)CC(C)(C)CN(CC(C)(CO)*I*)c1c(C)c(I*)nc([Tl])n1 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11184358 | 2011-10-07 | ||
| EP11184358.7 | 2011-10-07 | ||
| US201261649995P | 2012-05-22 | 2012-05-22 | |
| US61/649,995 | 2012-05-22 | ||
| PCT/EP2012/069676 WO2013050508A1 (en) | 2011-10-07 | 2012-10-05 | Morpholino substituted bicyclic pyrimidine urea or carbamate derivatives as mtor inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014528436A JP2014528436A (ja) | 2014-10-27 |
| JP2014528436A5 true JP2014528436A5 (enExample) | 2015-11-19 |
| JP5995977B2 JP5995977B2 (ja) | 2016-09-21 |
Family
ID=48043187
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014533911A Expired - Fee Related JP5995977B2 (ja) | 2011-10-07 | 2012-10-05 | Ｍｔｏｒ阻害剤としてのモルホリノ置換二環式ピリミジン尿素またはカルバメート誘導体 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US9242993B2 (enExample) |
| EP (1) | EP2763985B1 (enExample) |
| JP (1) | JP5995977B2 (enExample) |
| KR (1) | KR20140084130A (enExample) |
| CN (1) | CN103946222B (enExample) |
| AU (1) | AU2012320465B2 (enExample) |
| BR (1) | BR112014008241A2 (enExample) |
| CA (1) | CA2850852A1 (enExample) |
| ES (1) | ES2592219T3 (enExample) |
| MX (1) | MX341577B (enExample) |
| RU (1) | RU2609208C2 (enExample) |
| WO (1) | WO2013050508A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9249129B2 (en) | 2010-03-04 | 2016-02-02 | Cellzome Limited | Morpholino substituted urea derivatives as mTOR inhibitors |
| KR20140070616A (ko) | 2011-09-21 | 2014-06-10 | 셀좀 리미티드 | Mtor 저해제로서의 모르폴리노 치환된 우레아 또는 카바메이트 유도체 |
| WO2017156350A1 (en) | 2016-03-09 | 2017-09-14 | K-Gen, Inc. | Methods of cancer treatment |
| CN106117242B (zh) * | 2016-06-27 | 2018-08-03 | 山东大学 | 四氢噻喃并嘧啶类衍生物及其制备方法与应用 |
| FR3075795A1 (fr) * | 2017-12-21 | 2019-06-28 | Galderma Research & Development | Nouveaux composes inhibiteurs de mtor |
| EP3849535A4 (en) | 2018-09-10 | 2022-06-29 | Mirati Therapeutics, Inc. | Combination therapies |
| CN111205310B (zh) * | 2018-11-22 | 2023-12-19 | 上海迪诺医药科技有限公司 | 杂环稠合嘧啶衍生物、其药物组合物及应用 |
| WO2021143821A1 (zh) * | 2020-01-17 | 2021-07-22 | 江苏恒瑞医药股份有限公司 | 稠合杂芳基类衍生物、其制备方法及其在医药上的应用 |
| AU2022272184A1 (en) | 2021-05-11 | 2023-11-30 | Oric Pharmaceuticals, Inc. | Polo like kinase 4 inhibitors |
Family Cites Families (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0961780T3 (da) | 1997-02-12 | 2007-08-27 | Electrophoretics Ltd | Proteinmarkörer for lungecancer og anvendelse deraf |
| GB9714249D0 (en) | 1997-07-08 | 1997-09-10 | Angiogene Pharm Ltd | Vascular damaging agents |
| ATE401312T1 (de) | 1997-12-15 | 2008-08-15 | Astellas Pharma Inc | Pyrimidin-5-carboxamid-derivate |
| JP3893026B2 (ja) | 1999-02-10 | 2007-03-14 | アストラゼネカ アクチボラグ | 血管形成阻害剤としてのキナゾリン誘導体 |
| ES2306306T3 (es) | 1999-11-05 | 2008-11-01 | Astrazeneca Ab | Nuevos derivados de quinazolina. |
| DK1255752T3 (da) | 2000-02-15 | 2007-11-26 | Sugen Inc | Pyrrolsubstituerede 2-indolinonproteinkinaseinhibitorer |
| NZ534544A (en) * | 2002-02-28 | 2007-05-31 | Novartis Ag | N- {5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl} -4-(3-pyridyl)-2-pyrimidine-amine coated stents |
| US7135298B2 (en) | 2003-03-26 | 2006-11-14 | The Burnham Institute For Medical Research | Screening assay for agents that alter target of Rapamycin activity |
| BRPI0418022A (pt) * | 2003-12-22 | 2007-04-17 | Novartis Ag | biomarcadores para sensibilidade de doenças proliferativas a inibidores de mtor |
| AU2005302004A1 (en) * | 2004-10-28 | 2006-05-11 | Wyeth | Use of an mTOR inhibitor in treatment of uterine leiomyoma |
| GB0503961D0 (en) * | 2005-02-25 | 2005-04-06 | Kudos Pharm Ltd | Compounds |
| WO2006117560A1 (en) | 2005-05-05 | 2006-11-09 | Astrazeneca Ab | Pyrazolyl-amino- substituted pyrimidines and their use in the treatment of cancer |
| CA2611365C (en) | 2005-06-14 | 2014-02-11 | Cellzome Ag | Process for the identification of novel enzyme interacting compounds |
| EP1887359B1 (en) | 2006-08-03 | 2008-11-12 | Cellzome Ag | Methods for the identification of PI3K interacting molecules and for the purification of PI3K |
| CA2660758A1 (en) | 2006-08-24 | 2008-02-27 | Astrazeneca Ab | Morpholino pyrimidine derivatives useful in the treatment of proliferative disorders |
| US7888352B2 (en) * | 2006-12-07 | 2011-02-15 | Piramed Limited | Phosphoinositide 3-kinase inhibitor compounds and methods of use |
| US20080233127A1 (en) | 2007-03-21 | 2008-09-25 | Wyeth | Imidazolopyrimidine analogs and their use as pi3 kinase and mtor inhibitors |
| US20080234262A1 (en) | 2007-03-21 | 2008-09-25 | Wyeth | Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors |
| NZ580372A (en) | 2007-04-18 | 2012-01-12 | Pfizer Prod Inc | Pyrimidine and triazine derivatives including a sulfonamide group for the treatment of abnormal cell growth such as cancer |
| EP2178563A2 (en) | 2007-07-06 | 2010-04-28 | OSI Pharmaceuticals, Inc. | Combination anti-cancer therapy comprising an inhibitor of both mtorc1 and mtorc2 |
| AR067478A1 (es) | 2007-07-09 | 2009-10-14 | Astrazeneca Ab | Compuestos derivados de morfolina pirimidina |
| WO2009007751A2 (en) | 2007-07-09 | 2009-01-15 | Astrazeneca Ab | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| WO2009007749A2 (en) | 2007-07-09 | 2009-01-15 | Astrazeneca Ab | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| ATE554075T1 (de) | 2007-07-09 | 2012-05-15 | Astrazeneca Ab | Bei mit mtor-kinase und/oder pi3k in zusammenhang stehenden krankheiten angewendete morpholinopyrimidinderivate |
| CN101224207A (zh) | 2007-10-12 | 2008-07-23 | 中国科学院上海有机化学研究所 | 具有诱导自吞噬治疗错误折叠蛋白聚集所致疾病的药物及其筛选方法 |
| ATE528408T1 (de) | 2008-02-04 | 2011-10-15 | Cellzome Ag | Selektivitätsprofilerstellung von mit pi3k wechselwirkenden molekülen gegen mehrere ziele |
| AP2775A (en) | 2008-05-23 | 2013-09-30 | Wyeth Llc | Triazine compounds as P13 kinase and MTOR inhibitors |
| WO2010014939A1 (en) | 2008-07-31 | 2010-02-04 | Genentech, Inc. | Pyrimidine compounds, compositions and methods of use |
| GB2465405A (en) * | 2008-11-10 | 2010-05-19 | Univ Basel | Triazine, pyrimidine and pyridine analogues and their use in therapy |
| WO2010096619A1 (en) | 2009-02-23 | 2010-08-26 | Wyeth Llc | Process, purification and crystallization of 1-(4-{[4-(dimethylamino)piperidin-1-yl]carbonyl}phenyl)-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea |
| EP2406258B1 (en) | 2009-03-13 | 2014-12-03 | Cellzome Limited | PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS |
| WO2010120987A1 (en) * | 2009-04-17 | 2010-10-21 | Wyeth Llc | Ring fused, ureidoaryl- and carbamoylaryl-bridged morpholino-pyrimidine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
| WO2010120994A2 (en) | 2009-04-17 | 2010-10-21 | Wyeth Llc | Ureidoaryl-and carbamoylaryl-morpholino- pyrimidine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their synthesis |
| WO2010120998A1 (en) | 2009-04-17 | 2010-10-21 | Wyeth Llc | Pyrimidine compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
| CA2766151A1 (en) * | 2009-06-24 | 2010-12-29 | Genentech, Inc. | Oxo-heterocycle fused pyrimidine compounds, compositions and methods of use |
| WO2011011716A1 (en) | 2009-07-23 | 2011-01-27 | The Trustees Of Princeton University | Inhibitors of mtor kinase as anti-viral agents |
| US9249129B2 (en) | 2010-03-04 | 2016-02-02 | Cellzome Limited | Morpholino substituted urea derivatives as mTOR inhibitors |
| EP2694511A1 (en) | 2011-04-04 | 2014-02-12 | Cellzome Limited | Dihydropyrrolo pyrimidine derivatives as mtor inhibitors |
| KR20140070616A (ko) | 2011-09-21 | 2014-06-10 | 셀좀 리미티드 | Mtor 저해제로서의 모르폴리노 치환된 우레아 또는 카바메이트 유도체 |
-
2012
- 2012-10-05 BR BR112014008241A patent/BR112014008241A2/pt not_active Application Discontinuation
- 2012-10-05 CN CN201280057967.2A patent/CN103946222B/zh not_active Expired - Fee Related
- 2012-10-05 RU RU2014109748A patent/RU2609208C2/ru not_active IP Right Cessation
- 2012-10-05 US US14/350,167 patent/US9242993B2/en not_active Expired - Fee Related
- 2012-10-05 KR KR1020147012152A patent/KR20140084130A/ko not_active Ceased
- 2012-10-05 CA CA2850852A patent/CA2850852A1/en not_active Abandoned
- 2012-10-05 ES ES12769098.0T patent/ES2592219T3/es active Active
- 2012-10-05 MX MX2014004161A patent/MX341577B/es active IP Right Grant
- 2012-10-05 EP EP12769098.0A patent/EP2763985B1/en active Active
- 2012-10-05 AU AU2012320465A patent/AU2012320465B2/en not_active Ceased
- 2012-10-05 JP JP2014533911A patent/JP5995977B2/ja not_active Expired - Fee Related
- 2012-10-05 WO PCT/EP2012/069676 patent/WO2013050508A1/en not_active Ceased
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