ES2457394T3 - Derivados de pirimidina como inhibidores de proteína cinasa - Google Patents

Derivados de pirimidina como inhibidores de proteína cinasa Download PDF

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Publication number
ES2457394T3
ES2457394T3 ES08806455T ES08806455T ES2457394T3 ES 2457394 T3 ES2457394 T3 ES 2457394T3 ES 08806455 T ES08806455 T ES 08806455T ES 08806455 T ES08806455 T ES 08806455T ES 2457394 T3 ES2457394 T3 ES 2457394T3
Authority
ES
Spain
Prior art keywords
diazepin
pyrimido
cyclopentyl
methyl
oxo
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.)
Active
Application number
ES08806455T
Other languages
English (en)
Spanish (es)
Inventor
Jonathan James Hollick
Stuart Donald Jones
Claire June Flynn
Micheal George Thomas
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cyclacel Ltd
Original Assignee
Cyclacel Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from GB0719038A external-priority patent/GB0719038D0/en
Priority claimed from GB0806844A external-priority patent/GB0806844D0/en
Application filed by Cyclacel Ltd filed Critical Cyclacel Ltd
Application granted granted Critical
Publication of ES2457394T3 publication Critical patent/ES2457394T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

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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
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • 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
    • C07D487/10—Spiro-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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (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)
  • Pulmonology (AREA)
  • Epidemiology (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Pain & Pain Management (AREA)
  • Urology & Nephrology (AREA)
  • Dermatology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
ES08806455T 2007-09-28 2008-09-29 Derivados de pirimidina como inhibidores de proteína cinasa Active ES2457394T3 (es)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GB0719038A GB0719038D0 (en) 2007-09-28 2007-09-28 Compound
GB0719038 2007-09-28
GB0806844 2008-04-15
GB0806844A GB0806844D0 (en) 2008-04-15 2008-04-15 Compound
PCT/GB2008/003305 WO2009040556A1 (en) 2007-09-28 2008-09-29 Pyrimidine derivatives as protein kinase inhibitors

Publications (1)

Publication Number Publication Date
ES2457394T3 true ES2457394T3 (es) 2014-04-25

Family

ID=40199600

Family Applications (2)

Application Number Title Priority Date Filing Date
ES08806455T Active ES2457394T3 (es) 2007-09-28 2008-09-29 Derivados de pirimidina como inhibidores de proteína cinasa
ES13156251.4T Active ES2585110T3 (es) 2007-09-28 2008-09-29 Derivados de pirimidina como inhibidores de proteína cinasa

Family Applications After (1)

Application Number Title Priority Date Filing Date
ES13156251.4T Active ES2585110T3 (es) 2007-09-28 2008-09-29 Derivados de pirimidina como inhibidores de proteína cinasa

Country Status (9)

Country Link
US (3) US8563542B2 (enExample)
EP (2) EP2610256B1 (enExample)
JP (2) JP5410432B2 (enExample)
CN (1) CN101878216B (enExample)
CA (1) CA2700979C (enExample)
ES (2) ES2457394T3 (enExample)
PL (2) PL2205603T3 (enExample)
RU (2) RU2478100C2 (enExample)
WO (1) WO2009040556A1 (enExample)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE479434T1 (de) 2006-02-14 2010-09-15 Vertex Pharma Als protein-kinase-inhibitoren nutzbare dyhydrodiazepine
AU2008287339A1 (en) 2007-08-15 2009-02-19 Vertex Pharmaceuticals Incorporated 4-(9-(3, 3-difluorocyclopentyl) -5, 7, 7-trimethyl-6-oxo-6, 7, 8, 9-tetrahydro-5H-pyrimido [4, 5-b][1, 4] diazepin-2-ylamino)-3-methoxybenzamide Derivatives as Inhibitors of the Human Protein Kinases PLK1 to PLK4 for the Treatment of Proliferative Diseases
BRPI0817315A2 (pt) 2007-09-25 2015-03-17 Takeda Pharmaceutical Inibidores de quinase do tipo polo
CN101878216B (zh) 2007-09-28 2013-07-10 西克拉塞尔有限公司 作为蛋白激酶抑制剂的嘧啶衍生物
CA2728729C (en) 2008-06-23 2016-09-27 Vertex Pharmaceuticals Incorporated Protein kinase inhibitors
EP2318412B1 (en) 2008-06-23 2013-08-14 Vertex Pharmceuticals Incorporated Protein kinase inhibitors
GEP20207129B (en) 2009-06-17 2020-07-10 Vertex Pharma Inhibitors of influenza viruses replication
SG179207A1 (en) 2009-09-25 2012-04-27 Vertex Pharma Methods for preparing pyrimidine derivatives useful as protein kinase inhibitors
MX2012003484A (es) 2009-09-25 2012-04-20 Vertex Pharma Metodos para preparar derivados de pirimidina utiles como inhibidores de proteina cinasa.
AU2011260323A1 (en) 2010-06-04 2012-11-15 F. Hoffmann-La Roche Ag Aminopyrimidine derivatives as LRRK2 modulators
KR101566091B1 (ko) 2010-11-10 2015-11-04 에프. 호프만-라 로슈 아게 Lrrk2 조절제로서 피라졸 아미노피리미딘 유도체
RU2013132681A (ru) 2010-12-16 2015-01-27 Вертекс Фармасьютикалз Инкорпорейтед Ингибиторы репликации вирусов гриппа
UA118010C2 (uk) 2011-08-01 2018-11-12 Вертекс Фармасьютікалз Інкорпорейтед Інгібітори реплікації вірусів грипу
GB201205752D0 (en) * 2012-03-30 2012-05-16 Cyclacel Ltd Treatment
EP2970317A4 (en) 2013-03-15 2016-11-02 Dana Farber Cancer Inst Inc PYRIMIDODIAZEPINONE COMPOUNDS AND METHOD FOR THE TREATMENT OF DISEASES
BR112016001457A2 (pt) 2013-07-25 2017-08-29 Dana Farber Cancer Inst Inc Inibidores de fatores de transcrição e usos dos mesmos
PT3068776T (pt) 2013-11-13 2019-08-26 Vertex Pharma Inibidores da replicação de vírus da gripe
HUE038820T2 (hu) 2013-11-13 2018-11-28 Vertex Pharma Eljárás influenzavírusok replikációjának inhibitorai elõállítására
EP3099693A4 (en) * 2014-01-31 2017-08-16 Dana-Farber Cancer Institute, Inc. Uses of diazepane derivatives
MX2016009974A (es) 2014-01-31 2016-10-31 Dana Farber Cancer Inst Inc Derivados de diaminopirimidina bencensulfona y sus usos.
KR101517414B1 (ko) * 2014-04-24 2015-05-04 고려대학교 산학협력단 염증성 질환의 예방 또는 치료용 약학 조성물
RU2017104897A (ru) 2014-08-08 2018-09-10 Дана-Фарбер Кэнсер Инститьют, Инк. Производные диазепана и их применения
DK3233882T3 (da) 2014-12-16 2020-01-27 Kayla Therapeutics Fluorinerede cykliske dinukleotider til cytokininduktion
WO2016183120A1 (en) 2015-05-13 2016-11-17 Vertex Pharmaceuticals Incorporated Inhibitors of influenza viruses replication
EP3294717B1 (en) 2015-05-13 2020-07-29 Vertex Pharmaceuticals Inc. Methods of preparing inhibitors of influenza viruses replication
CA2986441A1 (en) 2015-06-12 2016-12-15 Dana-Farber Cancer Institute, Inc. Combination therapy of transcription inhibitors and kinase inhibitors
US11306105B2 (en) 2015-09-11 2022-04-19 Dana-Farber Cancer Institute, Inc. Cyano thienotriazolodiazepines and uses thereof
RU2018112953A (ru) 2015-09-11 2019-10-14 Дана-Фарбер Кэнсер Инститьют, Инк. Ацетамидтиенотриазолодиазепины и пути их применения
WO2017066428A1 (en) 2015-10-13 2017-04-20 H. Lee Moffitt Cancer Center & Research Institute, Inc. Brd4-kinase inhibitors as cancer therapeutics
CR20180336A (es) 2015-11-25 2018-08-06 Dana Farber Cancer Inst Inc Inhibidores de bromodominio bivalentes y usos de los mismos
JP2019512459A (ja) * 2016-03-04 2019-05-16 アンホイ ニュー スター ファーマシューティカル デベロップメント カンパニー，リミテッド ７員環化合物、その調製方法、その医薬組成物、およびその使用
AU2017248186B2 (en) * 2016-04-07 2021-10-21 Dana-Farber Cancer Institute, Inc. Pyrimido-diazepinone kinase scaffold compounds and methods of treating PI3K-mediated disorders
JP2021501785A (ja) 2017-11-02 2021-01-21 カリコ ライフ サイエンシーズ エルエルシー 統合的ストレス経路の調節剤
SG11202004009TA (en) * 2017-11-02 2020-05-28 Calico Life Sciences Llc Modulators of the integrated stress pathway
ES3036562T3 (en) * 2019-08-16 2025-09-22 Cyclacel Pharmaceuticals Inc Crystalline forms of pyrimidino diazepine derivative
US12570660B2 (en) * 2019-08-16 2026-03-10 Cyclacel Pharmaceuticals, Inc Process for the preparation of a pyrimidino-diazepine derivative
AU2020356484A1 (en) 2019-09-27 2022-03-17 Dana-Farber Cancer Institute, Inc. ERK5 degraders as therapeutics in cancer and inflammatory diseases
WO2023196943A1 (en) 2022-04-08 2023-10-12 Inhibrx, Inc. Dr5 agonist and plk1 inhibitor or cdk inhibitor combination therapy

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9117635D0 (en) 1991-08-15 1991-10-02 British Telecomm Phase shifter
GB0302220D0 (en) 2003-01-30 2003-03-05 Cyclacel Ltd Use
DE50307267D1 (de) * 2003-02-26 2007-06-21 Boehringer Ingelheim Pharma Dihydropteridinone, verfahren zu deren herstellung und deren verwendung als arzneimittel
US6861422B2 (en) 2003-02-26 2005-03-01 Boehringer Ingelheim Pharma Gmbh & Co. Kg Dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions
US8710009B2 (en) 2004-05-26 2014-04-29 The Texas A&M University System HSP20 inhibits amyloidogenesis and neurotoxicity
EP1799684B1 (en) * 2004-10-04 2014-12-03 Millennium Pharmaceuticals, Inc. Lactam compounds useful as protein kinase inhibitors
AU2006262283B2 (en) 2005-06-24 2011-10-13 Eli Lilly And Company Tetrahydrocarbazole derivatives useful as androgen receptor modulators (SARM)
US7439358B2 (en) 2006-02-08 2008-10-21 Boehringer Ingelheim International Gmbh Specific salt, anhydrous and crystalline form of a dihydropteridione derivative
ATE479434T1 (de) 2006-02-14 2010-09-15 Vertex Pharma Als protein-kinase-inhibitoren nutzbare dyhydrodiazepine
TW200808325A (en) * 2006-07-06 2008-02-16 Astrazeneca Ab Novel compounds
CN101636399B (zh) * 2007-03-22 2012-04-18 武田药品工业株式会社 可用作plk1抑制剂的取代的嘧啶并二氮杂*
BRPI0817315A2 (pt) * 2007-09-25 2015-03-17 Takeda Pharmaceutical Inibidores de quinase do tipo polo
CN101878216B (zh) 2007-09-28 2013-07-10 西克拉塞尔有限公司 作为蛋白激酶抑制剂的嘧啶衍生物
WO2009067547A1 (en) * 2007-11-19 2009-05-28 Takeda Pharmaceutical Company Limited Polo-like kinase inhibitors
US8710068B2 (en) 2009-01-19 2014-04-29 The Trustees Of The University Of Pennsylvania Method of treating cancer using a survivin inhibitor
GB201205752D0 (en) 2012-03-30 2012-05-16 Cyclacel Ltd Treatment

Also Published As

Publication number Publication date
CA2700979C (en) 2017-06-20
JP5410432B2 (ja) 2014-02-05
EP2205603A1 (en) 2010-07-14
EP2610256B1 (en) 2016-04-27
EP2610256A1 (en) 2013-07-03
US9133199B2 (en) 2015-09-15
ES2585110T3 (es) 2016-10-03
HK1146042A1 (en) 2011-05-13
CN101878216A (zh) 2010-11-03
EP2205603B1 (en) 2014-01-15
PL2610256T3 (pl) 2016-11-30
CA2700979A1 (en) 2009-04-02
WO2009040556A1 (en) 2009-04-02
JP2010540509A (ja) 2010-12-24
RU2478100C2 (ru) 2013-03-27
RU2623221C2 (ru) 2017-06-23
PL2205603T3 (pl) 2014-07-31
JP2014076994A (ja) 2014-05-01
US9493471B2 (en) 2016-11-15
US20150344486A1 (en) 2015-12-03
US20140066436A1 (en) 2014-03-06
US20110046093A1 (en) 2011-02-24
HK1187895A1 (en) 2014-04-17
RU2010116759A (ru) 2011-11-10
JP5863196B2 (ja) 2016-02-16
CN101878216B (zh) 2013-07-10
RU2013108456A (ru) 2014-09-10
US8563542B2 (en) 2013-10-22

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