CN103917530B - 作为mtor抑制剂的吗啉代取代的脲或氨基甲酸衍生物 - Google Patents

作为mtor抑制剂的吗啉代取代的脲或氨基甲酸衍生物 Download PDF

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Publication number
CN103917530B
CN103917530B CN201280055609.8A CN201280055609A CN103917530B CN 103917530 B CN103917530 B CN 103917530B CN 201280055609 A CN201280055609 A CN 201280055609A CN 103917530 B CN103917530 B CN 103917530B
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phenyl
methylsulfonyl
urea
methylmorpholino
triazin
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Expired - Fee Related
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Chinese (zh)
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CN103917530A (zh
Inventor
R.林赫
A.D.坎斯菲尔德
D.P.哈迪
M.苏诺塞
A.莫雷尔
L.康韦里
R.阿德雷戈
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Cellzome Ltd
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Cellzome Ltd
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    • 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
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
    • C07D251/22—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to two ring carbon atoms
    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Transplantation (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pulmonology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Virology (AREA)
  • Hospice & Palliative Care (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CN201280055609.8A 2011-09-21 2012-09-21 作为mtor抑制剂的吗啉代取代的脲或氨基甲酸衍生物 Expired - Fee Related CN103917530B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP11182221 2011-09-21
EP11182221.9 2011-09-21
PCT/EP2012/068590 WO2013041652A1 (en) 2011-09-21 2012-09-21 Morpholino substituted urea or carbamate derivatives as mtor inhibitors

Publications (2)

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CN103917530A CN103917530A (zh) 2014-07-09
CN103917530B true CN103917530B (zh) 2016-08-24

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Country Status (11)

Country Link
US (1) US9175011B2 (https=)
EP (1) EP2758379B1 (https=)
JP (1) JP5995975B2 (https=)
KR (1) KR20140070616A (https=)
CN (1) CN103917530B (https=)
AU (1) AU2012311458B2 (https=)
BR (1) BR112014006743A8 (https=)
CA (1) CA2849189A1 (https=)
ES (1) ES2609606T3 (https=)
RU (1) RU2616619C2 (https=)
WO (1) WO2013041652A1 (https=)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
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
BR112014008241A2 (pt) 2011-10-07 2017-04-18 Cellzome Ltd composto, composição farmacêutica, métodos para tratar, controlar, retardar ou prevenir doenças e distúrbios, e para preparar um composto, e, uso de um composto
US9242969B2 (en) 2013-03-14 2016-01-26 Novartis Ag Biaryl amide compounds as kinase inhibitors
UY36294A (es) 2014-09-12 2016-04-29 Novartis Ag Compuestos y composiciones como inhibidores de quinasa
AU2017329090B9 (en) 2016-09-19 2019-09-05 Novartis Ag Therapeutic combinations comprising a RAF inhibitor and a ERK inhibitor
ES2952265T3 (es) 2017-05-02 2023-10-30 Novartis Ag Terapia combinada que comprende un inhibidor de Raf y trametinib
WO2020055761A1 (en) 2018-09-10 2020-03-19 Mirati Therapeutics, Inc. Combination therapies
ES3025633T3 (en) 2019-05-13 2025-06-09 Novartis Ag New crystalline forms of n-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methvlphenyl)-2(trifluoromethyl)isonicotinamide as raf inhibitors for the treatment of cancer
WO2021050743A1 (en) * 2019-09-11 2021-03-18 Yale University Compositions and methods for treating slow-flow vascular malformations
CN115109049B (zh) * 2022-08-12 2023-08-15 江西科技师范大学 含芳基脲结构的三嗪类化合物及其应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101641346A (zh) * 2007-04-02 2010-02-03 弗·哈夫曼-拉罗切有限公司 作为mglur2拮抗剂的吡啶和嘧啶衍生物
WO2010103094A1 (en) * 2009-03-13 2010-09-16 Cellzome Limited PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
WO2011107585A1 (en) * 2010-03-04 2011-09-09 Cellzome Limited Morpholino substituted urea derivatives as mtor inhibitors

Family Cites Families (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69837529T2 (de) 1997-02-12 2007-07-26 Electrophoretics Ltd., Cobham Proteinmarker für lungenkrebs und deren verwendung
GB9714249D0 (en) 1997-07-08 1997-09-10 Angiogene Pharm Ltd Vascular damaging agents
AU1507199A (en) 1997-12-15 1999-07-05 Yamanouchi Pharmaceutical Co., Ltd. Novel pyrimidine-5-carboxamide derivatives
SK288365B6 (sk) 1999-02-10 2016-07-01 Astrazeneca Ab Medziprodukty pre chinazolínové deriváty ako inhibítory angiogenézy
CZ301689B6 (cs) 1999-11-05 2010-05-26 Astrazeneca Ab Derivát chinazolinu a farmaceutický prostredek, který ho obsahuje
SI1255752T1 (sl) 2000-02-15 2007-12-31 Pharmacia & Upjohn Co Llc S pirolom substituirani zaviralci 2-indolinon protein kinaza
US7135298B2 (en) 2003-03-26 2006-11-14 The Burnham Institute For Medical Research Screening assay for agents that alter target of Rapamycin activity
CN101218229A (zh) 2005-05-05 2008-07-09 阿斯利康(瑞典)有限公司 吡唑基-氨基取代的嘧啶及其在癌症治疗中的应用
PL1891446T3 (pl) 2005-06-14 2013-08-30 Cellzome Gmbh Sposób identyfikacji nowych związków oddziałujących z enzymami
GB0616747D0 (en) * 2006-08-24 2006-10-04 Astrazeneca Ab Novel compounds
ATE414281T1 (de) 2006-08-03 2008-11-15 Cellzome Ag Verfahren zur identifizierung von molekülen die mit pi3k interagieren und verfahren zur reinigung von pi3k
MX2009002046A (es) 2006-08-24 2009-03-06 Astrazeneca Ab Derivados de morfolino pirimidina utiles en el tratamiento de trastornos proliferativos.
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
BRPI0810411B8 (pt) 2007-04-18 2021-05-25 Pfizer Prod Inc derivados de sulfonil amida para o tratamento de crescimento celular anormal, seu sos, bem como composição farmacêutica
EP2178563A2 (en) 2007-07-06 2010-04-28 OSI Pharmaceuticals, Inc. Combination anti-cancer therapy comprising an inhibitor of both mtorc1 and mtorc2
CA2692945A1 (en) 2007-07-09 2009-01-15 Astrazeneca Ab Compounds - 945
EP2178866A2 (en) 2007-07-09 2010-04-28 AstraZeneca AB Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases
WO2009007751A2 (en) 2007-07-09 2009-01-15 Astrazeneca Ab Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases
CN101809002B (zh) 2007-07-09 2013-03-27 阿斯利康(瑞典)有限公司 用于与mtor激酶和/或pi3k相关的疾病中的吗啉代嘧啶衍生物
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
WO2009093981A1 (en) * 2008-01-23 2009-07-30 S Bio Pte Ltd Triazine compounds as kinase inhibitors
US20110111972A1 (en) 2008-02-04 2011-05-12 Cellzome Ag Selectivity profiling of pi3k interacting molecules against multiple targets
AP2775A (en) 2008-05-23 2013-09-30 Wyeth Llc Triazine compounds as P13 kinase and MTOR inhibitors
AR073354A1 (es) 2008-07-31 2010-11-03 Genentech Inc Compuestos de pirimidina, composiciones farmaceuticas y su uso en el tratamiento del cancer.
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
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
JP5649643B2 (ja) 2009-04-17 2015-01-07 ワイス・エルエルシー ピリミジン化合物、ｍＴＯＲキナーゼおよびＰＩ３キナーゼ阻害剤としてのそれらの使用、ならびにそれらの合成
US20140018354A9 (en) 2009-07-23 2014-01-16 Nathaniel Moorman Inhibitors of mtor kinase as anti-viral agents
JP2014510122A (ja) 2011-04-04 2014-04-24 セルゾーム リミテッド ｍＴＯＲ阻害剤としてのジヒドロピロロピリミジン誘導体
BR112014008241A2 (pt) 2011-10-07 2017-04-18 Cellzome Ltd composto, composição farmacêutica, métodos para tratar, controlar, retardar ou prevenir doenças e distúrbios, e para preparar um composto, e, uso de um composto

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101641346A (zh) * 2007-04-02 2010-02-03 弗·哈夫曼-拉罗切有限公司 作为mglur2拮抗剂的吡啶和嘧啶衍生物
WO2010103094A1 (en) * 2009-03-13 2010-09-16 Cellzome Limited PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
WO2011107585A1 (en) * 2010-03-04 2011-09-09 Cellzome Limited Morpholino substituted urea derivatives as mtor inhibitors

Also Published As

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ES2609606T3 (es) 2017-04-21
KR20140070616A (ko) 2014-06-10
EP2758379B1 (en) 2016-10-19
WO2013041652A1 (en) 2013-03-28
CN103917530A (zh) 2014-07-09
BR112014006743A8 (pt) 2018-01-09
CA2849189A1 (en) 2013-03-28
AU2012311458B2 (en) 2016-02-04
JP2014530197A (ja) 2014-11-17
EP2758379A1 (en) 2014-07-30
BR112014006743A2 (pt) 2017-04-11
RU2014109747A (ru) 2015-10-27
JP5995975B2 (ja) 2016-09-21
US20140378438A1 (en) 2014-12-25
US9175011B2 (en) 2015-11-03
RU2616619C2 (ru) 2017-04-18
AU2012311458A1 (en) 2014-04-10

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