WO2005039586A1 - Use of pyridinyl-pyrimidinylamino-benzamide derivatives for the treatment of amyloid related disorders - Google Patents

Use of pyridinyl-pyrimidinylamino-benzamide derivatives for the treatment of amyloid related disorders Download PDF

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Publication number
WO2005039586A1
WO2005039586A1 PCT/EP2004/012080 EP2004012080W WO2005039586A1 WO 2005039586 A1 WO2005039586 A1 WO 2005039586A1 EP 2004012080 W EP2004012080 W EP 2004012080W WO 2005039586 A1 WO2005039586 A1 WO 2005039586A1
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WIPO (PCT)
Prior art keywords
methyl
amino
pyridinyl
pyrimidinyl
benzamide
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.)
Ceased
Application number
PCT/EP2004/012080
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English (en)
French (fr)
Inventor
Graeme Bilbe
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.)
Novartis Pharma GmbH Austria
Novartis AG
Original Assignee
Novartis Pharma GmbH Austria
Novartis AG
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
Application filed by Novartis Pharma GmbH Austria, Novartis AG filed Critical Novartis Pharma GmbH Austria
Priority to JP2006536068A priority Critical patent/JP4827737B2/ja
Priority to US10/576,175 priority patent/US7687512B2/en
Publication of WO2005039586A1 publication Critical patent/WO2005039586A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • 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

Definitions

  • the invention relates also to possible tautomers of the compounds of formula
  • Substituted alkyl is alkyl as last defined, especially lower alkyl, preferably methyl; where one or more, especially up to three, substituents may be present, primarily from the group selected from halogen, especially fluorine, amino, N-lower alkylamino, N,N-di-lower alkylamino, N-lower alkanoylamino, hydroxy, cyano, carboxy, lower alkoxycarbonyl, and phenyl-lower alkoxycarbonyl. Trifluoromethyl is especially preferred.
  • the invention further relates to the use of COMPOUND or a N-Oxide or a pharmaceutically acceptable salt thereof for the manufacture of medicament having an activity on protein kinases VEGFR-2, Tie-2, c-Src, c-Met, FGFR-1 , Flt-1 , HER-2, c-Abl, c-Raf, PDGFR-beta, c- Kit, or on a combination of the above enzymes, for the treatment and/or prevention of neurological and vascular disorders related to beta-amyloid generation and/or aggregation such as neurodegenerative diseases like Alzheimer's disease, Down's Syndrome, memory and cognitive impairment, dementia, amyloid neuropathies, brain inflammation, nerve and brain trauma, vascular amyloidosis, or cerebral hemorrhage with amyloidosis.
  • neurodegenerative diseases like Alzheimer's disease, Down's Syndrome, memory and cognitive impairment
  • dementia amyloid neuropathies
  • brain inflammation nerve and brain trauma
  • vascular amyloidosis
  • HEK APPswe cells are plated in microtiter plates precoated with 10 ⁇ g/ml poly-D-lysine at 12O00 cells/well in 100 ⁇ l/well DMEM medium supplemented with 10% FCS, 0.25 mg/ml G418 sulfate, 1% penicillin streptomycin. The following day, supernatant is replaced with 90 ⁇ l/well of fresh medium and 10 ⁇ l/well of compound diluted in culture medium are added. Two types of control wells are used: cell culture medium without cells plus 10 ⁇ l/well of all compound dilutions (background signals) and cell culture medium from untreated cells (positive control). 24 hours later after compound addition, conditioned medium is collected and A ⁇ levels determined by a specific sandwich ELISA.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Cardiology (AREA)
  • Hematology (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/EP2004/012080 2003-10-27 2004-10-26 Use of pyridinyl-pyrimidinylamino-benzamide derivatives for the treatment of amyloid related disorders Ceased WO2005039586A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2006536068A JP4827737B2 (ja) 2003-10-27 2004-10-26 アミロイド関連疾患の処置のためのピリジニル−ピリミジニルアミノ−ベンズアミド誘導体の使用
US10/576,175 US7687512B2 (en) 2003-10-27 2004-10-26 Use of pyridinyl-pyrimidinylamino-benzamide derivatives for the treatment of amyloid related disorders

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0325031.3A GB0325031D0 (en) 2003-10-27 2003-10-27 Organic compounds
GB0325031.3 2003-10-27

Publications (1)

Publication Number Publication Date
WO2005039586A1 true WO2005039586A1 (en) 2005-05-06

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PCT/EP2004/012080 Ceased WO2005039586A1 (en) 2003-10-27 2004-10-26 Use of pyridinyl-pyrimidinylamino-benzamide derivatives for the treatment of amyloid related disorders

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US (1) US7687512B2 (https=)
JP (1) JP4827737B2 (https=)
GB (1) GB0325031D0 (https=)
WO (1) WO2005039586A1 (https=)

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WO2006117185A1 (en) * 2005-05-02 2006-11-09 Novartis Ag Pyrimidylaminobenzamide derivatives for hypereosinophilic syndrome
WO2007015870A2 (en) 2005-07-20 2007-02-08 Novartis Ag Crystalline forms of 4-methyl-n-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide
WO2008153959A1 (en) * 2007-06-07 2008-12-18 Intra-Cellular Therapies, Inc. Novel heterocycle compounds and uses thereof
WO2008153974A1 (en) 2007-06-07 2008-12-18 Intra-Cellular Therapies, Inc. Novel heterocycle compounds and uses thereof
US7683060B2 (en) 2006-08-07 2010-03-23 Incyte Corporation Triazolotriazines as kinase inhibitors
WO2010060074A1 (en) * 2008-11-24 2010-05-27 Teva Pharmaceutical Industries Ltd. Preparation of nilotinib and intermediates thereof
US7767675B2 (en) 2006-11-22 2010-08-03 Incyte Corporation Imidazotriazines and imidazopyrimidines as kinase inhibitors
WO2011016861A2 (en) 2009-08-05 2011-02-10 Intra-Cellular Therapies, Inc. Novel regulatory proteins and inhibitors
WO2011162835A1 (en) 2010-02-03 2011-12-29 Incyte Corporation Imidazo[1,2-b][1,2,4]triazines as c-met inhibitors
CN102316738A (zh) * 2009-02-18 2012-01-11 盛泰萨路申有限公司 作为激酶抑制剂的酰胺类
US8202999B2 (en) 2005-01-07 2012-06-19 Synta Pharmaceuticals Corp. Compounds for inflammation and immune-related uses
US8227477B2 (en) 2008-11-05 2012-07-24 Greta Sterimbaum Nilotinib HCl crystalline forms
US8349293B2 (en) 2007-03-22 2013-01-08 Guerbet Use of metal nanoparticles in the diagnosis of Alzheimer's disease
WO2013014170A1 (en) 2011-07-27 2013-01-31 Ab Science Oxazole and thiazole derivatives as selective protein kinase inhibitors (c-kit)
US8420645B2 (en) 2008-05-21 2013-04-16 Incyte Corporation Salts of 2-fluoro-N-methyl-4-[7-(quinolin-6-yl-methyl)-imidazo[1,2-b][1,2,4]triazin-2-yl]benzamide and processes related to preparing the same
US8501760B2 (en) 2006-09-27 2013-08-06 Novartis Ag Pharmaceutical compositions comprising nilotinib or its salt
US8604045B2 (en) 2005-12-06 2013-12-10 Novartis Ag Pyrimidylaminobenzamide derivatives for treatment of neurofibromatosis
WO2016206551A1 (zh) * 2015-06-24 2016-12-29 北京键凯科技有限公司 Src蛋白抑制剂在制备预防和/治疗阿尔兹海默病药物中的应用
CN106905298A (zh) * 2015-12-22 2017-06-30 江苏先声药业有限公司 盐酸尼洛替尼杂质的制备方法
EP4238566A1 (en) * 2012-05-02 2023-09-06 Georgetown University Treating amyotrophic lateral sclerosis with tyrosine kinase inhibitors
US12246009B2 (en) 2018-11-20 2025-03-11 Georgetown University Compositions and methods for treating neurodegenerative, myodegenerative, and lysosomal storage disorders

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WO2007076875A2 (en) * 2006-01-06 2007-07-12 Aarhus Universitet Compounds acting on the serotonin transporter
MX2009004314A (es) 2006-11-13 2009-05-05 Pfizer Prod Inc Diaril, dipiridinil y arilpiridinilderivados y usos de los mismos.
US8242271B2 (en) 2007-06-04 2012-08-14 Avila Therapeutics, Inc. Heterocyclic compounds and uses thereof
WO2009036066A1 (en) * 2007-09-10 2009-03-19 Curis, Inc. Vegfr inhibitors containing a zinc binding moiety
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US20110243957A1 (en) * 2008-09-24 2011-10-06 University Of South Florida Materials and methods for preventing or treating neurodegenerative conditions associated with abeta peptide accumulation
EP2340244A4 (en) * 2008-10-14 2012-07-25 Ning Xi COMPOUNDS AND APPLICATION PROCEDURES
ES2578990T3 (es) * 2009-03-21 2016-08-03 Sunshine Lake Pharma Co., Ltd. Derivados de amino éster, sales de los mismos y métodos de uso
EP2483406A2 (en) 2009-09-30 2012-08-08 President and Fellows of Harvard College Methods for modulation of autophagy through the modulation of autophagy-inhibiting gene products
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EP3080103B9 (en) * 2013-12-11 2018-09-19 Biogen MA Inc. Biaryl compounds useful for the treatment of human diseases in oncology, neurology and immunology
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US11426406B2 (en) 2017-02-09 2022-08-30 Georgetown University Compositions and methods for treating lysosomal storage disorders
WO2018207154A1 (en) * 2017-05-12 2018-11-15 The Hong Kong University Of Science And Technology Heterocyclic compounds as epha4 inhibitors
WO2020056132A1 (en) * 2018-09-13 2020-03-19 University Of Southern California Novel fgfr inhibitors and uses thereof
CA3132730A1 (en) * 2019-03-05 2020-09-10 Hongyi & Associates Llc Compounds for treating neurodegenerative diseases and cancers

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US8202999B2 (en) 2005-01-07 2012-06-19 Synta Pharmaceuticals Corp. Compounds for inflammation and immune-related uses
US7666874B2 (en) 2005-05-02 2010-02-23 Novartis Ag Pyrimidylaminobenzamide derivatives for hypereosinophilic syndrome
WO2006117185A1 (en) * 2005-05-02 2006-11-09 Novartis Ag Pyrimidylaminobenzamide derivatives for hypereosinophilic syndrome
EP2266572A1 (en) * 2005-05-02 2010-12-29 Novartis AG Use of pyrimidylaminobenzamide derivatives for the treatment of hypereosinophilic syndrome
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AU2012201453C1 (en) * 2005-07-20 2024-05-23 Novartis Ag Crystalline forms of 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide
TWI406661B (zh) * 2005-07-20 2013-09-01 Novartis Ag ４-甲基-ｎ-〔３-（４-甲基-咪唑-１-基）-５-三氟甲基-苯基〕-３-（４-吡啶-３-基-嘧啶-２基胺基）-苯甲醯胺之結晶型
NO341930B1 (no) * 2005-07-20 2018-02-19 Novartis Ag Krystallinske former for 4-metyl-N-[3-(4-metylimidazol-1-yl)-5-trifluormetylfenyl]-3-(4-pyridin-3-ylpyrimidin-2-ylamino)benzamid
EA013464B1 (ru) * 2005-07-20 2010-04-30 Новартис Аг Кристаллические формы 4-метил-n-[3-(4-метилимидазол-1-ил)-5-трифторметилфенил]-3-(4-пиридин-3-илпиримидин-2-иламино)бензамида
KR101651288B1 (ko) 2005-07-20 2016-08-25 노파르티스 아게 4-메틸-ｎ-［3-(4-메틸-이미다졸-1-일)-5-트리플루오로메틸페닐］-3-(4-피리딘-3-일-피리미딘-2-일아미노)벤즈아미드의 결정 형태
EP2535337A1 (en) * 2005-07-20 2012-12-19 Novartis AG Crystalline forms of 4-methyl-n-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide sulfate and its amorphous form
US8829015B2 (en) 2005-07-20 2014-09-09 Novartis Ag Crystalline forms of 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide
US8415363B2 (en) 2005-07-20 2013-04-09 Novartis Ag Crystalline forms of 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide
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